Clinical trial NCT05289037
Conditions: COVID-19
Keywords: Adaptive COVAIL Covid-19 Multivalent Omicron SARS-CoV-2 Vaccine Variants
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Start date: 2022-03-30; Completion date: 2023-11-27
Enrollment: 1270 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This phase 2 clinical trial will evaluate the safety and immunogenicity of additional doses of prototype and variant (alone or in combination) vaccine candidates in previously vaccinated participants with or without prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and will evaluate innate, cellular, and humoral immune responses to inform on how to shift the immune response to cover new variants as they emerge. A randomized open-label, non-placebo controlled, multi-site, multi-stage clinical trial in individuals, 18 years of age and older, who are in a stable state of health, has received a complete authorized/approved vaccine series (primary series + booster either with homologous or heterologous vaccine products) \>/ = 16 weeks prior to enrollment. Subjects will be stratified by i) age (18-64 years and = 65 years of age) (however arms 16 and 17 or stage 4 will only enroll participants between the ages of 18-49 years) and ii) history of confirmed prior SARS-CoV-2 infection, and randomly assigned to receive one of several variant vaccines. Enrollment will target a goal of approximately 45% of each of the variant vaccine arms to be in older adults (= 65 years of age) for stages 1, 2 and 3 and approximately 20% to have had confirmed COVID-19 for all 4 stages. The primary objective is to evaluate humoral immune responses of candidate SARS-CoV-2 variant vaccines, alone or in combination.

Detailed description:
This phase 2 clinical trial will evaluate the safety and immunogenicity of additional doses of prototype and variant (alone or in combination) vaccine candidates in previously vaccinated participants with or without prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and will evaluate innate, cellular, and humoral immune responses to inform on how to shift the immune response to cover new variants as they emerge. A randomized open-label, non-placebo controlled, multi-site, multi-stage clinical trial in individuals, 18 years of age and older, who are in a stable state of health, has received a complete authorized/approved vaccine series (primary series + booster either with homologous or heterologous vaccine products) \>/= 16 weeks prior to enrollment. Subjects will be stratified by i) age (18-64 years and = 65 years of age) (however arms 16 and 17 or stage 4 will only enroll participants between the ages of 18-49 years) and ii) history of confirmed prior SARS-CoV-2 infection, and randomly assigned to receive one of several variant vaccines. Enrollment will target a goal of approximately 45% of each of the variant vaccine arms to be in older adults (= 65 years of age) for stages 1, 2 and 3 and approximately 20% to have had confirmed COVID-19 for all 4 stages. This is an adaptive design and may add arms of new vaccine platforms and/or variant lineage spike vaccines as needed. The study arms will be conducted in different stages (that could overlap) depending on public health needs and the availability of study products (starting with the available mRNA vaccines). The primary objective is to evaluate humoral immune responses of candidate SARS-CoV-2 variant vaccines, alone or in combination. The secondary objective is to evaluate the safety of candidate SARS-CoV-2 variant vaccines, as assessed by: a) Local and systemic solicited Adverse Events for 7 days following each vaccine dose; b) Unsolicited Adverse Events from Dose 1 to 28 days following each vaccine dose; c) Serious Adverse Events (SAEs), Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interests (AESIs), New Onset of Chronic Medical (NOCMCs) and Adverse Events (AEs) leading to withdrawal from the study from Dose 1 to 12 months after last vaccine dose.

Arms: arm 1: mRNA-1273 administered through 0.2 mg/ml intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=100 arm 2: 0.1 mg/ml of mRNA-1273.351 and 0.2 mg/ml of mRNA-1273.529 mg/ml administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=100 arm 3: 0.1 mg/ml of mRNA-1273.351 and 0.2 mg/ml of mRNA-1273.529 mg/ml administered through intramuscular injection in the deltoid muscle on Day 1 and Day 57 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=100 arm 4: 0.2 mg/ml of mRNA-1273.617.2 and 0.2 mg/ml of mRNA-1273.529 administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=100 arm 5: 0.2 mg/ml of mRNA-1273.529 administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=100 arm 6: 0.2 mg/ml of mRNA-1273.529 and mRNA-1273 0.2 mg/ml administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=100 arm 7: 500 mcg/mL of BNT162b2 (Wildtype) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=50 arm 8: 500 mcg/mL of BNT162b2 (Beta) and 500 mcg/mL of BNT162b2 (Omicron) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=50 arm 9: 500 mcg/mL of BNT162b2 (Omicron) administered through intramuscular injection in the deltoid muscle on Day 1 and Day 57 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=50 arm 10: 500 mcg/mL of BNT162b2 (Beta) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=50 arm 11: 500 mcg/mL of BNT162b2 (Beta) and 500 mcg/mL of BNT162b2 (Wildtype) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=50 arm 12: 500 mcg/mL of BNT162b2 (Omicron) and 500 mcg/mL of BNT162b2 (Wildtype) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=50 arm 13: 500 mcg/mL CoV2 preS dTM-AS03 \[D614\] (prototype) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=50 arm 14: 500 mcg/mL CoV2 preS dTM-AS03 \[B.1.351\] (Beta) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=50 arm 15: 500 mcg/mL CoV2 preS dTM-AS03 \[D614 + B.1.351\] (prototype + Beta) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=50 arm 16: 100 mcg/mL BNT162b2 bivalent (wildtype and Omicron BA.1) + Wildtype (Prototype) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 49 years; ( 45% in \> / = 49 years) N=100 arm 17: 100 mcg/mL BNT162b2 bivalent (wildtype and Omicron BA.4/BA.5) + Wildtype (Prototype) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 49 years; ( 45% in \> / = 49 years) N=100
Interventions: intervention 1: AS03 intervention 2: BNT162b2 intervention 3: BNT162b2 (B.1.1.529) intervention 4: BNT162b2 (B.1.351) intervention 5: BNT162b2 bivalent (wildtype and Omicron BA.1) intervention 6: BNT162b2 bivalent (wildtype and Omicron BA.4/BA.5) intervention 7: CoV2 preS dTM [B.1.351] intervention 8: CoV2 preS dTM/D614 intervention 9: CoV2 preS dTM/D614+B.1.351 intervention 10: mRNA-1273 intervention 11: mRNA-1273.351 intervention 12: mRNA-1273.529 intervention 13: mRNA-1273.617.2 intervention 14: Sodium Chloride, 0.9%
Intervention descriptions: intervention 1: AS03 oil-in-water emulsion adjuvant. intervention 2: A nucleoside-modified messenger RNA (modRNA) encoding the viral spike glycoprotein (S) of SARS-CoV-2. intervention 3: A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer contains mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain. intervention 4: A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer contains mRNA that encodes for the prefusion stabilized S protein of the B.1.351 (Beta) variant SARS-CoV-2 strain. intervention 5: A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer. Contains mRNA that encodes for the prefusion stabilized S protein of the Omicron BA.1 variant SARS-CoV-2 strain and the ancestral strain of SARS-CoV-2. intervention 6: A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer. Contains mRNA that encodes for the prefusion stabilized S protein of the Omicron BA.4/BA.5 variant SARS-CoV-2 strain and the ancestral strain of SARS-CoV-2. intervention 7: Is a liquid formulation made of recombinant protein placed in a formulation buffer that contains the spike protein sequence of the B.1.351 (Beta) variant SARS-CoV-2 strain. intervention 8: Is a liquid formulation made of recombinant protein placed in a formulation buffer. The antigen solution contains the spike protein sequence of the ancestral strain of SARS-CoV-2. intervention 9: Is a liquid formulation made of recombinant protein placed in a formulation buffer contains the spike protein sequences of the ancestral and B.1.351 (Beta) variant SARS-CoV-2 strains intervention 10: Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized spike (S) protein of the 2019 novel coronavirus (2019-nCoV). intervention 11: Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the pre fusion stabilized spike (S) protein of the B.1.351 variant SARS-CoV-2 strain. intervention 12: Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain. intervention 13: Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized S protein of the B.1.617.2 (Delta) variant SARS-CoV-2 strain. intervention 14: 0.9% Sodium Chloride Injection

Protocol documents:
ICF_000.pdf: 
Division of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious 
Diseases (NIAID), National Institutes of Health (NIH) / Protocol Number 22-0004 
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INFORMED CONSENT FORM 
AND 
AUTHORIZATION TO USE AND DISCLOSE PROTECTED HEALTH INFORMATION 
 
Sponsor / Study Title: 
  
Division of Microbiology and Infectious Diseases (DMID), 
National Institute of Allergy and Infectious Diseases (NIAID), 
National Institutes of Health (NIH) / “Phase 2 Clinical Trial to 
Optimize Immune Coverage of SARS-CoV-2 Existing and 
Emerging Variants” 
 
Protocol Number: 
 
22-0004 
Principal Investigator: 
(Study Doctor) 
 
«PiFullName» 
 
Telephone: 
 
«IcfPhoneNumber» 
 
Address: 
«PiLocations» 
 
 
KEY INFORMATION  
You are being asked to take part in this study because we would like to know if giving additional 
doses of the original vaccines against SARS-CoV-2 (the virus that causes COVID-19) or 
experimental versions of these vaccines with different variant strains are safe and how they 
may affect the immune system.  
 
• Being in the study is voluntary – it is your choice.  
• Your participation in this study will last for about 12 to 24 months. 
• Procedures will include collection of health information, injections, blood draws, and 
potentially a nasal swab of your nose.  
• There are risks from participating. 
o The most common risk is pain at the site of injection. 
o One of the most serious risks is anaphylaxis, or severe allergic reaction to the 
study vaccine. See the “Risks of Participation” section in this consent form for 
more information.  You should discuss these risks in detail with the study team. 
o There is risk of loss of confidentiality of your health information. 
• You might not benefit from being in this research study. There may be benefit to getting 
a second booster of the original vaccine against SARS-CoV-2 if you are an adult 50 years 
or older, but we do not know whether vaccines based on the new variants will offer 
benefit. 
• As part of this study, we are obtaining extra blood samples from you, and one to two 
nasal swabs if you have symptoms consistent with COVID-19 or test positive for COVID-
19 outside of the study. We will use your coded information, leftover samples, and extra 


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samples for secondary research (the research is not planned yet). It will include genetic 
research. When you give consent, you will take part in the vaccine study and allow for 
secondary research. 
 
Please read this form carefully. Take your time to ask the study doctor or study staff as many 
questions about the study as you would like. The study doctor or study staff can explain words 
or information that you do not understand. Reading this form and talking to the study doctor or 
study staff may help you decide whether to take part or not. If you decide to take part in this 
study, you must sign your name at the end of this form and date it.  
 
BACKGROUND  
The purpose of this study is to learn about the safety and immunogenicity (ability to provoke an 
immune response, which can indicate how well a vaccine works) of booster vaccines to SARS-
CoV-2. Multiple SARS-CoV-2 vaccines have been studied in large studies with tens of thousands 
of participants, and have been granted either Emergency Use Authorization (EUA) or approval 
by the United States Food and Drug Administration (FDA) and are being used in the national 
COVID-19 vaccination campaign.  All the current vaccines  approved or authorized under EUA 
deliver the spike protein (the protein that allows the virus to enter human cells) to the immune 
system to generate immunity to that specific viral protein. 
 
Messenger ribonucleic acid (mRNA) vaccines include the genetic code of the spike protein. 
Moderna and Pfizer/BioNTech have both received FDA approval for a vaccine using this strategy 
that is given as a two-dose primary series. Adenovirus vaccines use defective adenoviruses 
(common cold viruses that cannot grow) carrying the code for spike protein inside the viral 
particles, delivering the instructions to make the spike protein. Johnson & Johnson in 
partnership with Janssen has received EUA in the U.S. for a vaccine using a human adenovirus 
26 (Ad26) vector in 2020. The Johnson & Johnson vaccine primary series is a single dose 
vaccine.  Additionally, Sanofi-GSK has developed a third vaccine type, an adjuvanted 
recombinant protein subunit vaccine, which contains copies of the spike protein itself with an 
adjuvant. Adjuvants are ingredients added to help a vaccine work better by increasing the immune 
response. The adjuvant in the Sanofi-GSK vaccine is called AS03.  The Sanofi-GSK vaccine is still 
considered experimental but has been tested in a phase 3 clinical trial and shown to be 
effective in protecting against COVID-19 and Sanofi-GSK is in the process of applying for FDA 
EUA.  
 
Since EUA of the Moderna, Pfizer and Johnson & Johnson vaccines, billions of people around 
the world have since been vaccinated against symptomatic COVID-19 and severe disease. In 
further study, scientists and researchers have found that the protection against COVID-19 
provided by these vaccines wanes over time and additional doses may be needed to continue 
to prevent COVID-19. The FDA gave EUA for a booster dose (3rd doses of Moderna or 
Pfizer/BioNTech and a 2nd dose of Johnson & Johnson) in Fall 2021 and the Centers for Disease 
Control and Prevention (CDC) now recommends that all adults receive booster doses at least 2 
months after a primary Johnson & Johnson vaccine or at least 5 months after the second dose 
of Moderna or Pfizer/BioNTech. 


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Additionally, the FDA has now expanded the EUA for Moderna and Pfizer for a second booster 
at least 4 months from the last dose for adults 50 years and older. The CDC guidance also now 
allows for second booster dose to be given to adults 50 years and older who, based on age or 
medical history, continue to be at risk for serious COVID-19 illnesses and those who received 2 
doses of the Johnson & Johnson vaccine.  
 
However, current primary and booster doses of all three vaccines deliver spike protein based 
on the strain of the virus from early 2020, and the spike protein over the course of the 
pandemic continues to change with ongoing circulation of the virus. These changes have led to 
new strains, also called variants, which continue to cause surges of new cases around the 
world. It’s possible that updated variant versions of the vaccines will be needed in the future. 
Booster vaccines using updated spike proteins to reflect the circulating variants, or using 
different vaccine delivery types, may improve the immune response to prevent infection 
longer, more effectively, or from more variants.  
 
The remaining sections describe more about the research study. Members of the study team 
will talk with you about the information in this document. You are encouraged to ask any 
questions and discuss this study with family, friends, and anyone you choose. If you decide to 
take part in this study, you will be asked to sign and date this consent form. A copy of this 
signed and dated consent will be given to you to keep. Signing and dating this consent form 
indicates that you understand your involvement in the study, the risks of participating and that 
you agree to take part in the study. 
 
PURPOSE OF THIS RESEARCH STUDY  
The purpose of this research is to test additional vaccine booster shots that use different vaccine 
types and/or variant spikes to see if these new combinations are safe and to evaluate the immune 
system responses. Vaccines tell your germ-fighting cells to make antibodies and other substances 
to fight infections. All the study vaccines are intended to train the immune system so that if the 
person is then infected with the SARS-CoV-2 virus, they have a “head start” and the infection can 
be stopped or made less severe. Based on what we know, we would anticipate any of the vaccines 
used in this study to boost antibodies and provide similar protection as if you received a second 
booster dose of the original vaccine. However, using a booster vaccine that has one or more 
different variant spikes, or the original spike in combination with variant spikes, may improve 
protection against variant strains. 
This study uses vaccines that have received FDA approval or EUA and also experimental vaccines 
that are still under investigation. The vaccines used in this study include different vaccine types, 
the variant spikes, or both together as experimental vaccine approaches.  
Experimental means the study vaccine is not approved for routine use by the FDA; however, the 
FDA is allowing experimental variant vaccines to be used that have been developed in the same 
manner as approved vaccines. Some of the vaccines used in this study may include: 
• A low dose Moderna vaccine, mRNA-1273, 50 mcg, granted FDA EUA as a booster 


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• Moderna mRNA study vaccines updated with three new variants: B.1.351 (Beta variant), 
B.1.617.2 (Delta variant) and B.1.1.519 (Omicron variant) 
• Moderna mRNA study vaccines containing a combination of 2 or more variants 
• A Pfizer mRNA vaccine, BNT162b2, 30 mcg, granted FDA EUA as a booster 
• Pfizer mRNA vaccines updated with two new variants B.1.351 (Beta variant) and 
B.1.1.519 (Omicron variant) 
• Pfizer mRNA study vaccines containing a combination of 2 or more variants 
• A Sanofi-GSK recombinant protein vaccine, CoV2 preS dTM-AS03, 5 mcg dose  
• A Sanofi-GSK recombinant protein vaccine updated with the B.1.351 (Beta) variant 
• A Sanofi-GSK recombinant protein vaccine containing a combination of 2 variants (2.5 
mcg dose for each variant) 
• Variant study vaccines using different technologies to deliver spike protein 
 
Groups of participants who have already received the Moderna primary series (2 doses) and 
booster, the Pfizer primary series (2 doses) and booster, or Janssen vaccine (1 dose) and 
booster as recommended by the CDC will be enrolled. Immune responses to additional booster 
doses may also differ based on age and whether or not someone has been infected and 
recovered from SARS-CoV-2. We have therefore designed the study to have at least 45% of 
adults aged 65 years or older and 20% of participants who are fully vaccinated and have 
recovered from COVID-19.  
 
This study will be enrolled in at least 3 stages. We anticipate about 600 individuals will be 
enrolled in Stage 1 and receive one of the Moderna vaccines as described in Table 1 below 
which will include mRNA for one or more strains or variants. In Stage 2, we will enroll 
approximately 300 participants who will receive one of the Pfizer vaccines as described in Table 
2 below which will include mRNA for one or more strains or variants.  In Stage 3, we will enroll 
approximately 150 participants who will receive one of the Sanofi-GSK vaccines as described in 
Table 3 below which will include spike protein for one or more strains or variants.  You will not 
be able to choose to be part of a specific arm (group) or receive a specific study vaccine. This 
will be randomly assigned. For stage 1, in one arm of the study participants will receive 2 doses 
at least 8 weeks apart. Because this is an adaptive trial, additional stages and the number of 
participants to be enrolled, as well as the specific study vaccines to be given in future stages, 
are still yet to be determined.  
 
 
 


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Table 1: Stage 1 Study Treatment Arms 
Arm 
Number of 
participants 
First Study vaccination (Day 1) 
Second Study vaccination (day 57) 
1 
100 
Moderna mRNA Prototype Vaccine 
NA 
2 
100 
Moderna mRNA Beta/Omicron Vaccine 
NA 
3 
100 
Moderna mRNA Beta/Omicron Vaccine 
Moderna mRNA Beta/Omicron 
Vaccine 
4 
100 
Moderna mRNA Delta/Omicron Vaccine 
NA 
5 
100 
Moderna mRNA Omicron Vaccine 
NA 
6 
100 
Moderna mRNA Prototype/Omicron 
Vaccine 
NA 
NA = Not Applicable 
 
Table 1: Stage 2 Study Treatment Arms 
Arm 
Number of 
participants 
First Study vaccination (Day 1) 
Second Study 
vaccination (day 57) 
1 
50 
Pfizer mRNA Prototype Vaccine 
NA 
2 
50 
Pfizer mRNA Beta/Omicron Vaccine 
NA 
3 
50 
Pfizer mRNA Omicron Vaccine 
NA 
4 
50 
Pfizer mRNA Beta Vaccine 
NA 
5 
50 
Pfizer mRNA Prototype/Beta Vaccine 
NA 
6 
50 
Pfizer mRNA Prototype/Omicron Vaccine 
NA 
NA = Not Applicable 
 
Table 2: Stage 3 Study Treatment Arms 
Arm 
Number of 
participants 
First Study vaccination (Day 1) 
Second Study 
vaccination (day 57) 
1 
50 
Sanofi-GSK Prototype Vaccine 
NA 
2 
50 
Sanofi-GSK Beta Vaccine 
NA 
3 
50 
Sanofi-GSK Protype/Beta Vaccine 
NA 
NA = Not Applicable 
 
Most participants will attend 8 or 9 in-person study visits, including an initial screening visit 
(that may be combined with the first study vaccination visit), one study vaccination visit, and 7 
in-person follow-up visits. They will be in the study for up to approximately 13 months, if they 
have a separate screening visit, or 12 months, if the screening visit is combined with the first 
study vaccination visit. Study visits may include a physical exam, and all but one (the visit seven 
days after the study vaccination) will include a blood draw. Participants in Arm 3 of stage 1 will 
have 12-13 in-person study visits including an initial screening visit (that may be combined with 
the first study vaccination visit), two study vaccination visits, and 10 in-person follow-up visits. 


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They will be in the study for up to approximately 15 months, if they have a separate screening 
visit, or 14 months, if the screening visit is combined with the first study vaccination visit. 
 
SELECTION OF STUDY POPULATION 
All stages of the study include adults aged 18 years or older who are in stable state of health. 
We will screen you for eligibility before performing any further study activities or giving you a 
study vaccination. 
 
You are not eligible for this research study if: 
 
• You have been diagnosed with COVID-19 in the past 4 months 
• You have a history of receiving a SARS-CoV-2 plasma antibody infusion or SARS-CoV-2 
monoclonal antibody infusion (in the last 90 days) 
• You have received non-COVID-19 vaccine (within 28 days prior to the first dose with 
study vaccine, except for influenza vaccine) 
• You have received any experimental vaccine or drug in the past 28 days, OR plan to 
receive one during your study participation 
• You have received an experimental coronavirus vaccine 
• You have any serious chronic medical or psychiatric conditions 
• You are on certain medications 
• You are pregnant or breastfeeding a child 
• You have a history of hypersensitivity or a severe allergic reaction to vaccine or to 
polyethylene glycol (PEG), polysorbate or nanolipid particles which are components of 
the vaccines  
• You have a prior history of myocarditis (inflammation of the heart muscle) or 
pericarditis (inflammation of the lining outside of the heart) (Stages 1 and 2 only)  
• You have any medical condition the study doctor feels would make your participation 
unsafe 
 
WHAT WILL HAPPEN DURING THE STUDY? 
If you are assigned to receive 1 dose of study vaccine, your participation in this study will last 
approximately 12 months and will include approximately 8 or 9 in-person study visits and 1 
phone call.  If you receive 2 doses of a vaccine, your participation will be 14 months and will 
include 12 or 13 in–person study visits and 2 phone calls.  
 
Screening 
You will have a Screening Visit to check if you are eligible to enroll in this study. The Screening 
Visit may be combined with the first study vaccination visit. If it is a separate visit, it will take 
about 60 minutes and will include: 
 
• Reviewing, signing and dating the consent form 
• Collecting information about your medical and mental health history, medications, and 
vaccination history 


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• A physical exam if needed 
• Checking vital signs (blood pressure, pulse, respiratory [breathing] rate, temperature) 
• Measuring height and weight 
• For participants of childbearing potential, a urine pregnancy test 
 
General Study Visit Procedures 
Study visits that include a study vaccination will generally last about 2-3 hours and other visits 
will generally last about 30 minutes. The first study vaccination visit may be combined with the 
screening visit and will include the screening visit procedures. Visits may include: 
 
• Questions about your recent medical history and medications, illnesses or symptoms, 
and side effects or reactions 
• Collecting vital signs (heart rate, blood pressure, temperature) before a study 
vaccination and at other visits if needed 
• Having a physical exam if needed 
• Collection of blood samples at almost all of the study clinic visits (and if you can become 
pregnant, urine for pregnancy testing at each of the vaccination visits) 
• Study vaccination or assessment of the site of a previous study vaccination if needed 
• Review of symptoms after vaccination during telephone calls 
 
Single Vaccine Arm: The single study vaccination will be given on Day 1. 
 
Two Vaccines Arm: The two study vaccinations will be given on Days 1 and 57. 
 
At the study vaccination visits we will review your medical history to confirm that you are 
eligible for a study vaccination. 
 
You will receive an injection of the study vaccine in the deltoid (shoulder) muscle of your upper 
arm at each study vaccination visit. You will stay in the clinic for at least 30 minutes after the 
study vaccination for study staff to check for any immediate reactions. 
 
We will give you a memory aid (like a diary card), thermometer, and ruler (to measure the size 
of any redness or swelling at the vaccination site) with instructions to record your temperature 
and any side effects. At home, you will complete the daily memory aid, beginning on the 
evening of the day of each study vaccination and continuing daily for the next seven days. 
About seven days after each study vaccination visit the study staff will call you to check-in and 
make sure you did not need to see a doctor for any side effects. The memory aid will include 
contact information should you need to contact the study team. You will be instructed to bring 
the memory aid with you to your next scheduled clinic visit. 
 
We will ask you to keep track of any unexpected symptoms you develop after being vaccinated. 
You will be asked to recall these symptoms at your safety phone call visit, approximately 1 week 
after being vaccinated.  


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If you become sick or have any reactions after a study vaccination, you should immediately 
contact the study staff. We may ask you to come to the clinic for an extra study visit. The staff 
may perform additional research or safety procedures, if needed. 
 
Follow Up Visits 
In addition to the study vaccination visits, you will also come to the clinic (or speak with us by 
phone) for follow up visits as described below. Follow-up visits will take about 30 minutes. 
 
Single Vaccine Arm: Day 4, Day 8 or one week (phone call only), 2 weeks, 4 weeks, 3, 6, 9 and 
12 months following vaccination. 
 
Two Vaccine Arm: Day 4, Day 8 or one week (phone call only), 2 weeks, 4 weeks, 2 months and 
3 days, 1 week (phone call only), 2 weeks, 4 weeks, 3, 6, 9 and 12 months following the second 
vaccination.   
 
The study staff will call you periodically during your study participation to check on your health 
status or to remind you of an upcoming visit or for other reasons. We may also contact you by 
email or text message when appropriate. 
 
Information about your study participation and study results may be included in your electronic 
health record.  If you have concerns about this or wish to obtain more detail, you should discuss 
this with the study team. 
 
Unscheduled Visits 
You may be asked to come back to the study clinic at other times if needed, for example, if you 
have a serious reaction to vaccine. The study doctor will determine what activities will be 
needed after reviewing any symptoms that you are having, which may include drawing your 
blood and/or performing an electrocardiogram (ECG). 
 
You may also have an unscheduled visit if you develop an illness suspicious for COVID-19 or test 
positive for COVID-19 outside of the study. At that visit 1-2 nasal samples may be collected.  
 
Laboratory Testing of Specimens 
The blood specimens collected from you will be used for research tests of the immune response 
to the study vaccine. These tests will measure how your body developed an immune response 
to the study vaccine. We will look at your antibodies, which are proteins that your body uses to 
fight off the virus.  We will also look at how different cells of your immune system help to fight 
the virus. Finally, we may use some of the blood samples to test for a cardiac marker of 
inflammation of the heart muscle.  
 
Some of the testing in this study will include genetic testing to see how your cells work to 
develop immune responses. We will not do genetic tests that check for diseases or biomarkers 
for cancer. You will not receive the results of the genetic testing.  


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We will use some samples to develop better ways to test a person’s response to the study 
vaccine. Giving blood samples for the research tests will not benefit you. It may benefit others 
by leading to new approaches in vaccine development or treatments for coronavirus infection. 
The results of these tests are useful only for research purposes. Your individual results will not 
be available to you or your regular doctor and will not be placed in your medical record. 
 
Nasal swabs will be used to test for the presence of the virus that causes COVID-19 and, if 
positive, for genetic sequencing of the virus, allowing us to determine what variant has caused 
you COVID-19.  We will let you know if your COVID-19 test at the study site is positive. Since 
sequencing may be done weeks or months after collection and processed in batches, we will be 
unable to share the results of this testing with you. 
 
Blood and nasal swab samples for these research tests may be sent to a central storage facility 
or sent directly to the research testing laboratories. These samples will not be labeled with your 
name or initials, or any other information that could readily identify you. These samples will be 
labeled only with a barcode and a unique tracking number (ID code) to help protect your 
confidentiality. Staff at the central storage facility and research testing laboratories will not 
know your identity, or even the study identifier you were assigned. However, the study staff 
who enrolled you will keep a list in a secure area with your name, contact information and the 
ID code (called a code key) that can link the samples to you, if needed. Access to the code key is 
limited to study staff working at the research site where your samples were collected. 
 
We may remove the codes from your information or samples so that we cannot identify you 
and use these in other research. These de-identified samples may be shared with other 
researchers without your additional consent. 
 
Leftover and Extra Blood Samples 
Some of the blood collected for measuring immune responses to the vaccines may not be 
needed to do the research tests. We plan to store and use these leftover samples and your 
information (identified only by ID codes) for secondary research. Secondary research is 
research that is not part of this study but will be performed in the future. You will not be told 
about the future research. 
 
We will also collect extra blood samples at each visit to store and use for secondary and 
future research. Secondary and future research will be limited to COVID-19 vaccines and may 
help us understand how the booster vaccines work or to develop new tests. If you do not want 
to give leftover and extra samples for future and secondary research, you cannot enroll in this 
study. 
 
Blood samples will be stored indefinitely at a site determined by the National Institutes of 
Health (NIH). Leftover and extra blood samples will be labeled only with a barcode and an ID 
code (not with your name, initials, or any other information that could readily identify you). 


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These leftover and extra blood samples will be stored with the same confidentiality measures 
used for the main specimens.  
 
Leftover and extra blood samples may be used in the future for research about this study 
vaccine and your body’s response to this study vaccine. This may include genetic testing. 
Genetic testing will look at the material in your immune cells that tells each immune cell in your 
body how to work. Future genetic testing may inform development of COVID-19 vaccines, or be 
used for studies of coronaviruses. You will not be contacted about the types of future research. 
The genetic testing is for research purposes only and it will not be able to tell you about 
relatives, paternity, or country of origin. The genetic research testing done in this study will not 
tell you about diseases that you may get in the future. We will not give you the results from the 
genetic research testing. 
 
At any time during this study or after this study is over, extra blood samples may be shared with 
other study doctors/institutions and used for future and secondary research, including genetic 
testing. Also, after future genetic testing, the resulting data may be shared with other 
researchers. We will share your future genetic information through a “closed” database, also 
called a restricted data repository. NIH gives permission to other researchers to use your future 
genetic information only for research purposes. To qualify, researchers must receive approval 
from NIH to access and use the future genetic information. A summary of data from all 
participants may be shared in an “open” database, also called an unrestricted data repository, 
but this will not contain your individual data. The risk of anyone identifying you with this 
information is very unlikely. However, there is still a risk of loss of confidentiality.  
 
Your individual data will not contain information that can easily identify you. It may be possible 
to identify you with your DNA; however, the researchers must follow rules specifically to not 
identify you. If you change your mind and want to remove your data from the database, you 
should contact the research site that collected your data. If possible, your data can be removed 
for further research. Your data cannot be removed if it has already been used. 
 
Leftover and extra blood samples will be used only for research purposes. This may include 
reproducing or growing your cells. These blood samples will not be sold or used directly for 
production of any commercial product. However, the research studies in this study or in the 
future may lead to identification of antibodies or other treatments that could indirectly lead to 
a commercial product that protects against viral infection or disease. 
 
Although the results of any future research may be patentable or have commercial profit, you 
will not receive payment if this happens. You will have no legal or financial interest in any 
commercial development resulting from any future research. 
 
If these blood samples are tested in the future, the results may be published. You will not be 
identified in such publication. In other words, the publication will not contain any information 
about you that would enable someone to determine your identity. 
 


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By signing and dating this consent form, you are agreeing to the collection, storage and future 
research use of your blood samples and information collected for this study. There are no 
benefits to you in the collection, storage and future research use of your blood samples. Future 
research tests may benefit others by leading to new approaches in the development of vaccines 
or treatments for coronavirus infections. The results of any future research testing will be kept 
confidential in the same way as the results of other testing done for this study. The results of 
any future research will not be available to you or your regular doctor and will not be placed in 
your medical record. 
 
You may change your mind about future and secondary research and withdraw consent for the 
storage and use of your coded samples or information at any time. You will need to contact the 
study doctor using the contact information listed on page 1 of this form. If you have visits after 
this, we will stop collecting extra blood. 
 
Your samples will be removed from future use when the vaccine study is completed. Only 
stored samples with an ID code and not used in this research can be removed or destroyed. 
Research that has already begun using your specimens cannot be withdrawn. For example, if 
some research with your specimens and data has already been completed, the information 
from that research may still be used. Also, for example, if the specimens and data have been 
shared already with other researchers, it might not be possible to withdraw the specimens and 
data. 
 
Ask us if you have questions about how your blood samples may be used. 
 
POTENTIAL RISKS AND DISCOMFORTS 
There may be some risks to participation in this study. You may experience one or more of the 
risks or side effects explained below. You should discuss these with the study doctor or study 
staff. Many side effects go away shortly if treated, but in some cases, side effects can be 
serious, long lasting, or permanent. The Moderna mRNA-1273 50 mcg study vaccine and Pfizer 
BNT162b2 30 mcg study vaccine have been granted EUA by the FDA to be used as a booster 
dose. All of the other study vaccines will be given under experimental authorization in this 
study.  The Moderna variant vaccines (beta strain, omicron strain and delta strain), either alone 
or in combination, are experimental and have been given to only a few hundred humans. 
Similarly, the Pfizer variant vaccines (beta strain and omicron strain), either alone or in 
combination, are experimental and have been given to only a few hundred humans. There may 
be risks that we do not know about right now.  Side effects may occur more frequently with the 
booster doses compared with the first vaccine. 
 
The possible risks of participating in this study include those associated with having blood 
drawn, reactions to the injection, adverse effects (side effects) of the study vaccine(s), having 
nasal swab(s) collected, and the possibility of a breach of confidentiality. 
 
Having your blood taken can cause pain and may also cause lightheadedness or fainting. The 
needle stick can cause bruising, which can be prevented or reduced by putting pressure on the 


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site for a few minutes after the needle is removed. It is possible to get an infection at the site of 
the needle stick. To reduce the risk of infection after the blood draw or study vaccine injection, 
the study doctor or study staff will wipe the area clean with alcohol and use sterile equipment. 
Throughout this study, the amount of blood collected will not exceed 17 tablespoons (246 mL) 
in any 8-week period (which is less than the amount of blood allowed to be drawn during that 
time frame under the American Association of Blood Banks standards) if you are receiving one 
dose vaccine or 24 tablespoons (354 mL) if you are receiving 2 vaccine doses. 
 
The risks associated with having nasal swabs collected may include discomfort, eyes watering, 
bleeding, minor irritation and sneezing.  
 
Data placed in the NIH-designated database will have identifiers removed, such as name, 
address, and identification numbers. Because it may be possible to re-identify genetic data, 
even if access to data is controlled, confidentiality cannot be guaranteed. There may be other 
risks that are unknown. 
 
Risks and side effects you may experience with the study vaccines  
 
After a study vaccination, a person might experience: 
 
• Mild to moderate events: 
o A sore arm 
o Redness, swelling, hardness, or itching at injection site 
o Fever, chills, or fatigue (feeling tired) 
o Flu-like illness 
o Headache, muscle aches, pain and stiffness in the joints 
o Nausea or vomiting 
o Fainting 
o Swelling of lymph nodes in the neck or armpit 
o Decreased appetite 
o Lethargy (feeling sluggish or having little energy) 
o Night sweats 
o Malaise (a feeling of discomfort or feeling ill) 
o Diarrhea 
 
Events such as a sore arm, fever, chills, fatigue, headache, muscle aches, pain and stiffness in 
joints, and nausea are more common after a second vaccination and may occur more 
commonly after additional booster vaccinations.  
 
In a study of the Moderna mRNA-1273 booster vaccine, given as a single 50 mcg dose, 
headache, fatigue, muscle aches, joint aches, nausea or vomiting, chills, or a combination of 
those events, occurred in about three-quarters of people after vaccination. Fever occurred in 
about one in 10 people receiving the 50 mcg Moderna booster and pain at the injection site 
occurred in about eight in ten people. 


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In another study of the Moderna mRNA beta variant vaccine, given as a 50 mcg booster dose, 
fatigue, headache, muscle aches, joint aches, chills, nausea or vomiting, rash, or a combination 
of those events, occurred in six in ten people after vaccine.  Pain at the injection site occurred in  
eight in 10 participants.  
 
Similarly, in a study of the Pfizer BNT162b2 booster vaccine given as a single 30 mcg dose,  
reactions to the vaccine were mild to moderate and there were no serious side effects. Pain at 
the injection site occurred most often in 8 out of 10 participants, and other common reactions 
included:  
• Fatigue (feeling tired) 
• Headache 
• Muscle/joint pain 
• Chills  
 
In a study of the Sanofi-GSK CoV2 preS dTM-AS03 vaccine given as 5 mcg booster dose to 
previously vaccinated participants, pain at the injection was reported in 8 out of 10 
participants, which was more frequent in younger participants.   
 
Other common reactions included: 
• Headache 
• Fatigue 
• Muscle aches 
• Joint aches 
• Fever  
 
Most reactions were mild. 
 
About one in a one hundred people who received the Moderna mRNA-1273 primary series, 
given as two doses of 100 mcg vaccination, had a delayed reaction in the vaccinated arm, with 
redness and/or pain and/or itching starting about seven days after the vaccination. These 
events usually resolved over several days. There have also been reports of skin reactions, facial 
and lip swelling in people who have received cosmetic dermal fillers or implants. 
 
In prior studies, swollen glands have been reported in less than 1% of participants receiving the 
Pfizer BNT162b2 vaccine and were also seen after the booster, but more frequently than with 
the first or second doses.  
 
• Severe events could occur very rarely: 
o In prior studies with related study vaccines, less than 5% of participants receiving 
the Moderna mRNA-1273 vaccine and less than 1% of people receiving the Pfizer 
BNT162b2 vaccine had local pain and soreness around the vaccination site that 


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was considered “severe,” meaning that it prevented them from performing their 
usual activities for some period of time. 
o Rarely, an injection could cause an ulceration (open sore), abscess (a pocket of 
pus caused by the body fighting infection) or necrosis (dead tissue) at the 
injection site. 
o An immediate allergic reaction called anaphylaxis (also known as allergic shock) 
may occur after receiving vaccines or medications.  
o Anaphylaxis reactions have occurred after administration of the Moderna and 
Pfizer mRNA COVID-19 vaccines in vaccination campaigns under Emergency Use 
Authorization (EUA) in the United States.  Most of these reactions started within 
30 minutes of vaccination, most of those people had a prior history of allergy, 
and nearly all were women. The currently estimated risk of an anaphylactic 
reaction to the mRNA vaccines is about 2-5 events per million first vaccinations. 
 
This type of reaction may include symptoms such as: 
 Skin rash (hives) 
 Sweating 
 A feeling of dread 
 Swelling around the mouth, throat and eyes 
 Wheezing 
 Difficulty breathing 
 Increased pulse 
 Fainting or feeling dizzy due to low blood pressure 
 Inability to breathe without assistance  
 
If these reactions occur, emergency medications administered by study 
personnel can usually stop them. Most people who experience anaphylaxis 
recover completely. Rarely, people can die. 
o Myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of 
the lining outside the heart) have occurred in some people who have received 
the mRNA vaccines. In most of these people, symptoms began within a few days 
following receipt of the second dose of the vaccine. The chance of having this 
occur is very low. You should seek medical attention right away if you have any 
of the following symptoms after receiving the vaccine: chest pain, shortness of 
breath, or feelings of a fast-beating, pounding, or fluttering heart. 
o One of the vaccines that you get in this study may contain a substance called 
AS03, which is an ‘adjuvant’. This substance may improve the immune response 
to the vaccine. People who have received vaccines that contain an adjuvant, 
have very rarely (up to 1 in 10,000 people) developed illnesses called 
“autoimmune diseases”, which can sometimes be serious and lifelong. 
Autoimmune diseases may develop when immune cells that normally protect 
you from illness, attack your own organs instead. These illnesses have also 
developed in people who have not received these vaccines. 


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o An increased risk of narcolepsy was observed in some individuals after 
vaccination with a flu vaccine containing AS03 (called Pandemrix) during the 
H1N1 pandemic in 2009-2010. Narcolepsy is an illness that affects your brain and 
causes uncontrollable sleepiness. People with narcolepsy sometimes go limp or 
fall asleep suddenly, such as while talking or driving, and it can be a lifelong 
problem. This study vaccine contains AS03. A similar risk of narcolepsy was not 
identified with other vaccines containing AS03. Currently available data suggest 
that the cases of narcolepsy seen immediately following the 2009-2010 
pandemic in some people were most likely triggered by a reaction in those 
people to a protein from the flu virus itself that was also present in pandemic flu 
vaccines used at the time. Research is continuing to assess whether either of the 
main components of the 2009-2010 flu pandemic vaccine (e.g., the viral proteins 
in the form used in the vaccine or the AS03 adjuvant) may have contributed to 
the reaction. 
o Additionally, any reaction other than the above events could be severe. 
 
If you had an allergic reaction after being vaccinated in the past, or if you are allergic to any 
product, including polyethylene glycol (PEG), which is in the study vaccines, you must tell the 
study doctor or study staff before you decide to sign and date this informed consent form. If 
you have an allergy to some products, you will not be able to take part in this study. Serious 
allergic reactions can be life-threatening. 
 
It is possible that receiving the study vaccines may change how your regular medications, 
vaccines, or supplements work. It is very important that you tell the study doctor about any 
medications, supplements, or vaccines before you take them during the study. 
 
If you stop or change the dose of your regular medication, therapy, or supplements to be in the 
study, your health might get worse. Please tell the study doctor or study staff right away if you 
have any problems when you stop or change your regular medication, therapy, or supplements. 
 
Please tell the study doctor or study staff right away if you have any side effects. Please tell 
them if you have any other problems with your health or the way you feel during the study, 
whether or not you think these problems are related to the study vaccine. 
 
Ask the study doctor if you have questions about the signs or symptoms of any side effects that 
you read about in this consent form. 
 
Risks Related to Pregnancy 
You cannot be enrolled in this study if you are: 
• Pregnant 
• Nursing a child 
 
COVID-19 vaccines appear to be safe in pregnancy, but there may be unknown risks to the 
embryo, fetus, or nursing child. Nobody knows what all of these risks are right now.  If you can 


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become pregnant, you must have a negative urine pregnancy test before each study 
vaccination. You cannot participate in this study if you are breastfeeding. 
 
If you become pregnant while you are in this study (through three months after the last 
vaccination), you should report this immediately to the study staff. With your permission, the 
study doctor or study staff will ask about your health, collect information from you through the 
outcome of your pregnancy, and collect scheduled blood samples. The study doctor may share 
this information with the study sponsor and with the Advarra Institutional Review Board (IRB), a 
group of people who review research studies to protect the rights and welfare of research 
participants. 
 
BENEFITS 
You may not benefit from being in this study. There may be benefit to getting a second booster 
of the original vaccine against SARS-CoV-2 if you are an adult 50 years or older, but we do not 
know whether vaccines based on the new variants will offer benefit. 
 
However, the results of this research might benefit others by contributing knowledge that could 
lead to development of booster vaccine schedules for new strain variants of the SARS-CoV-2 
virus.  
 
ALTERNATIVES TO PARTICIPATION  
The only alternative is to not participate in this study. You also may be able to receive a second 
booster outside of the study. 
 
NEW FINDINGS  
We will contact you about any new information and explain how this may affect your health, 
wellbeing, or willingness to stay in this study. You may be asked to sign and date a revised 
consent form if this occurs. 
 
STUDY INFORMATION 
When the results of this study are available, which will likely be a year or more after your last 
visit, we will attempt to provide you with a summary of those results, and a summary will be 
posted on http://www.ClinicalTrials.gov. If you move after your last study visit, it is your 
responsibility to provide us with your new address if you want to receive this information. 
 
SOURCE OF FUNDING FOR THE STUDY 
The study site is receiving payment from the NIH, National Institute of Allergy and Infectious 
Diseases (NIAID), Division of Microbiology and Infectious Diseases (DMID), the sponsor of the 
study.  
 
Moderna, Pfizer and Sanofi-GSK, the companies that make the study vaccines, are providing the 
vaccines for this study to the NIH without charge. 
 
 
 


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COMPENSATION FOR PARTICIPATION 
«Compensation» 
 
You will be paid for your time and expenses related to participation in the study. You will 
receive $XX for each study visit where you are required to come to the clinic and $XX for a 
safety telephone call. Therefore, if you are in a group that received one dose of study vaccine 
you will receive $XXX and if you are in a group that received 2 doses of study vaccine you will 
receive $XXX. You will not be compensated for any missed visits. For illnesses you will be 
compensated $XX for each illness event where a swab is collected.  
 
You will be paid ___________ [“following each completed visit”, “monthly”, “quarterly”, “at 
the end of your participation in the research study”, “following each completed visit or at the 
end of your participation in the research study, whichever you prefer”]. 
 
If you have any questions regarding your compensation for participation, please contact the 
study staff.   
 
COST OF PARTICIPATION 
While you are in the study, you still need to get regular medical care. You (and/or your health 
care payer) will still have to pay for the costs of your regular medical care that are not a part of 
this study. You will not have to pay to receive the study vaccine. There are no costs for the 
study visits, tests or procedures performed as part of this study. 
 
To find out more about costs, ask the study staff. 
 
COMPENSATION FOR INJURY  
If you are injured as a result of being in this study, you should notify the study doctor as soon as 
possible. If there is an emergency, call 911 right away or go to the emergency room and contact 
your study doctor as soon as you can. If you tell the study staff that you think you have been 
injured then they will help you get the care you need. 
 
If you are directly injured by the vaccine being studied, or by medical procedures needed 
because of this study, and you receive medical care for the injury, you may need to pay for that 
care. The study site will provide short-term medical care for any injury resulting from your 
participation in research here, but you might not be reimbursed for care covered and paid for 
by a third party like your health insurance provider, or costs such as required co-payments or 
deductibles related to that coverage.  No long-term medical care or financial compensation for 
research related injury will be provided by the NIH or the Federal Government.  
 
You do not give up any of your legal rights by signing and dating this form. 
 
A Declaration under the Public Readiness and Emergency Preparedness (PREP) Act was issued 
by the Secretary of the United States Department of Health and Human Services on March 10, 
2020. This Declaration limits the legal rights of a participant in clinical studies utilizing COVID-19 


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countermeasures, such as the study vaccines, mRNA-1273, used in this study. Because this 
study is covered by the PREP Act Declaration, covered persons, such as the manufacturers, 
study sponsor, researchers, healthcare providers and others have liability immunity (that is, 
they cannot be sued by you or your family under the laws of the United States). 
 
If you believe that you may have been harmed as a result of this study, certain claims for 
serious injury or death caused by the countermeasure may be eligible for compensation 
through the Countermeasures Injury Compensation Program (CICP). This is a program set up by 
the Health Resources and Services Administration (HRSA) of the United States Government. 
Information about this program can be found at https://www.hrsa.gov/cicp/about/index.html 
or by calling 1-855-266-2427. If you are eligible for this program, you must file a claim within 
one year of the administration or use of the covered countermeasure. A factsheet on CICP and 
how to file a Request for Benefits Package to the CICP Summary, will be provided to you. 
 
CONFIDENTIALITY   
Paper documents containing personal information about you will be maintained in locked file 
cabinets. Computerized information will be maintained in password-restricted files. Only 
people who are involved in the conduct, oversight, or auditing of this study will be allowed 
access. 
 
The authority to collect this information is provided by Title 42, Section 285f, of the US Code of 
Laws, which specifies that the general purpose of the National Institute of Allergy and Infectious 
Diseases is the conduct and support of research, training, health information dissemination, 
and other programs with respect to allergic and immunologic diseases and disorders and 
infectious diseases, including tropical diseases. 
 
By signing and dating this consent form you are giving permission for representatives of the 
NIH, the Office for Human Research Protections (OHRP), the FDA, and Advarra IRB (a group of 
people who review research studies to protect the rights and welfare of research participants), 
as well as the study doctor and other employees of the study site involved with this research 
study, to inspect sections of your medical and research records related to this study. 
 
The FDA may choose to inspect your records since you are a participant in this research study. 
When a study is submitted to the FDA, the study doctor agrees to allow the FDA access to the 
study records. The FDA will treat the information as confidential, but on rare occasions 
disclosure to third parties may be required by law. Therefore, absolute protection of 
confidentiality cannot be promised. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law. This Web site will not include information that can identify you. At most, the Web 
site will include a summary of the results. You can search this Web site at any time.  
 
 
 


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CERTIFICATE OF CONFIDENTIALITY  
To help us protect your privacy, we have a Certificate of Confidentiality from the NIH. Study 
staff cannot provide to any person not connected with the research your name, or any 
materials that contain identifiable, sensitive information about you, unless permitted by a legal 
exception, such as state laws that require reporting of some contagious diseases. The most 
important protection provided by the Certificate is that the study staff cannot be forced to 
provide any of your identifiable, sensitive information, in any Federal, State, or local civil, 
criminal, administrative, legislative, or other proceeding, such as if there is a court subpoena, 
without your permission. 
 
The study team will use the Certificate to resist any demands for information that would 
identify you. 
 
Your information protected by the Certificate may still be disclosed or used when the 
information: 
 
1. Is disclosed to people connected with the research; for example, information may be 
used for auditing or program evaluation internally by the NIH; or 
2. Is required to be disclosed by Federal, State, or local laws, for example, when 
information must be disclosed to meet the legal requirements of the FDA. This does not 
include disclosure for use during legal proceedings as noted above; 
3. Is necessary for your medical treatment and you have consented to this disclosure; 
4. Is for other scientific research as allowed by applicable federal regulations; 
5. Is disclosed with your consent. 
 
The Certificate will not be used to prevent disclosure to state or local authorities of harm to self 
or others including, for example, child abuse and neglect, and by signing and dating below you 
consent to those disclosures. 
 
 
 


Division of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious 
Diseases (NIAID), National Institutes of Health (NIH) / Protocol Number 22-0004 
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«PiFullName» 
Advarra IRB Approved Version 31 May 2022 
Revised «PIApprovalDate» 
 
AUTHORIZATION TO USE AND DISCLOSE PROTECTED HEALTH INFORMATION 
If you decide to be in this study, the study doctor and study staff will use and share health data 
about you to conduct the study. Health data may include your name, address, phone number, 
date of birth, medical history and information about your study visits including all tests.  
 
Health data may come from your study records or from existing records kept by your doctor or 
other health care workers.  
 
For this study, the study staff may share health data about you with authorized users including: 
 
• The Department of Health and Human Services 
• The OHRP 
• Additional governmental agencies in the United States 
• Advarra IRB 
• Your regular doctor 
• The Food and Drug Administration (FDA) and other US federal and state agencies. 
• A public health authority that is authorized by law to collect or receive such information 
for the purpose of preventing or controlling disease, injury, or disability, and conducting 
public health surveillance, investigations, or interventions. 
• Outside individuals and companies, such as laboratories and data storage companies, 
that work with the researchers and sponsor and need to access your information to 
conduct this study. 
• Other research doctors and medical centers participating in this study 
 
Your health data will be used to conduct and oversee the research, including for instance: 
 
• To do the research 
• To study the results 
• To see if the research was done correctly 
 
If the results of this study are made public information that identifies you will not be used. 
 
Once your health data has been shared with authorized users, it may no longer be protected by 
federal privacy law and could possibly be used or disclosed in ways other than those listed here.  
 
Your permission to use and share health data about you will last indefinitely. In California and 
any other state that requires an expiration date, the Authorization will expire 50 years after you 
sign and date this authorization document. 
 
You may revoke (take back) your permission to use and share health data about you at any time 
by writing to the study doctor at the address listed on the first page of this form. If you do this, 
you will not be able to stay in this study. No new health data that identifies you will be gathered 


Division of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious 
Diseases (NIAID), National Institutes of Health (NIH) / Protocol Number 22-0004 
Page 21 of 24   
 
 
«PiFullName» 
Advarra IRB Approved Version 31 May 2022 
Revised «PIApprovalDate» 
 
after your written request is received. However, health data about you that has already been 
gathered may still be used and given to others as described in this form.  
 
Your right to access your health data in the study records will be suspended during the study to 
keep from changing the study results. When the study is over, you can access your study health 
data. 
 
If you decide not to sign and date this form, you will not be able to take part in the study. 
 
STATEMENT OF AUTHORIZATION 
I have read this form and its contents were explained. My questions have been answered. I 
voluntarily agree to allow study staff to collect, use and share my health data as specified in this 
form. I will receive a signed and dated copy of this form for my records. I am not giving up any 
of my legal rights by signing and dating this form.  
 
 
________________________________________ 
 
 
Printed Name of Participant 
 
 
________________________________________ 
 
____________________  
Signature of Participant 
 
 
 
 
Date 
 
 
 
 


Division of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious 
Diseases (NIAID), National Institutes of Health (NIH) / Protocol Number 22-0004 
Page 22 of 24   
 
 
«PiFullName» 
Advarra IRB Approved Version 31 May 2022 
Revised «PIApprovalDate» 
 
WHOM TO CONTACT ABOUT THIS STUDY 
During the study, if you experience any medical problems, suffer a research-related injury, or 
have questions, concerns or complaints about the study such as: 
 
• Whom to contact in the case of a research-related injury or illness; 
• Payment or compensation for being in the study, if any; 
• Your responsibilities as a research participant; 
• Eligibility to participate in the study; 
• The study doctor’s or study site’s decision to exclude you from participation; 
• Results of tests and/or procedures; 
 
Please contact the study doctor at the telephone number listed on the first page of this 
consent document.  
 
If you seek emergency care, or hospitalization is required, alert the treating physician that you 
are participating in this research study.  
 
An institutional review board (IRB) is an independent committee established to help protect the 
rights of research participants. If you have any questions about your rights as a research 
participant, contact: 
 
• By mail: 
Study Subject Adviser 
Advarra IRB 
6100 Merriweather Dr., Suite 600 
Columbia, MD 21044 
• or call toll free:    877-992-4724 
• or by email:          adviser@advarra.com 
 
Please reference the following number when contacting the Study Subject Adviser: 
Pro00062043. 
 
 
 


Division of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious 
Diseases (NIAID), National Institutes of Health (NIH) / Protocol Number 22-0004 
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«PiFullName» 
Advarra IRB Approved Version 31 May 2022 
Revised «PIApprovalDate» 
 
VOLUNTARY PARTICIPATION / WITHDRAWAL  
Your signature and date on this consent form means that you have received the information 
about this study and that you agree to be a part of the study. Your participation in this study is 
voluntary. You may decide not to participate, or you may discontinue participation at any time 
without penalty if you agree to participate and then decide that you no longer want to be in the 
study. Your decision will not result in any penalty or loss of benefits to which you are entitled. 
 
You will be given a copy of this signed and dated consent form to keep. You are not giving up 
any of your rights by signing and dating this consent form. Even after you have signed and 
dated this consent form, you may change your mind at any time. Please contact the study staff 
if you decide to stop taking part in this study. 
 
The study doctor or sponsor may decide to stop you from taking part in this study at any time, 
without your consent. You could be removed from the study for any of the following reasons: 
 
• You miss research visits 
• You are unable to comply with study procedures or instructions 
• You withhold information about your health history or medications 
• Reasons related to your health  
• If you have a serious reaction to the study vaccine 
• Because the entire study is stopped (the sponsor may stop the study at any time) 
• If you do not later consent to any future changes that may be made to the study 
• If you become pregnant 
• Any other reason 
 
If you decide to stop or the study doctor withdraws you, we may ask you to come for a final 
visit. This visit may include activities listed in the general study visits. We will stop collecting 
your information and specimens for research when you withdraw your consent for the research 
or are withdrawn by the study doctor. However, any information and specimens collected prior 
to withdrawal may continue to be used for this study. 
 
Advarra Institutional Review Board (IRB), the FDA, other regulatory agencies, or the sponsor 
(NIH) who oversee the conduct of this study can stop the study at any time for safety concerns 
or other issues. 
 
 
 


Division of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious 
Diseases (NIAID), National Institutes of Health (NIH) / Protocol Number 22-0004 
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CONSENT  
I have read (or have had read to me) and understand the information in this informed consent 
document. I have had an opportunity to ask questions and all of my questions have been 
answered to my satisfaction. I agree to participate in this study. I will receive a copy of this 
signed and dated consent document. 
 
 
________________________________________ 
 
 
Printed Name of Participant 
 
 
________________________________________ 
 
____________________  
Signature of Participant 
 
 
 
 
Date 
 
 
I attest that the participant named above had enough time to consider this information, had an 
opportunity to ask questions, and voluntarily agreed to be in this study. 
 
 
 
  
Printed Name of Person Obtaining Consent 
 
 
 
 
        
 
    _____   
Signature of Person Obtaining Consent     
            Date 

SAP_002.pdf: 
CLINICAL RESEARCH IN INFECTIOUS DISEASES 
 
 
 
STATISTICAL ANALYSIS PLAN 
for 
DMID Protocol: 22-0004 
 
Study Title: 
Phase 2 Clinical Trial to Optimize Immune Coverage 
of SARS-CoV-2 Existing and Emerging Variants 
 
COVID-19 VAriant Immunologic Landscape Trial 
(COVAIL) 
 
NCT05289037 
 
Version 1.0 
 
DATE: 10OCT2023 
 
RESTRICTED 
 
 


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STUDY TITLE 
Protocol Number Code: 
DMID Protocol: 22-0004 
Development Phase: 
Phase 2 
Products: 
Moderna [mRNA-1273, mRNA-1273.351, mRNA-1273.529, mRNA-
1273.617.2] 
Pfizer [BNT162b2 (wildtype), BNT162b2 (B.1.351, Beta), BNT162b2 
(B1.1.529, Omicron), BNT162b2 bivalent  (wildtype and  Omicron BA.1) 
and BNT162b2 bivalent (wildtype and Omicron BA.4/BA.5)] 
Sanofi [CoV2 preS dTM-AS03 [D614] (prototype), CoV2 preS dTM-
AS03 [B.1.351] (Beta), and CoV2 preS dTM-AS03 [D614 + B.1.351] 
(prototype + Beta)] 
Form/Route: 
Injection 
Indication Studied: 
COVID-19 
Sponsor: 
Division of Microbiology and Infectious Diseases 
National Institute of Allergy and Infectious Diseases 
National Institutes of Health 
Clinical Trial Initiation Date: 
30MAR2022 
Clinical Trial Completion Date: 
Ongoing 
Date of the Analysis Plan: 
10 October 2023 
Version Number: 
1.0 
This study was performed in compliance with Good Clinical Practice. 
Information contained in this publication is the property of Division of Microbiology and Infectious Diseases and is confidential. This 
information may not be disclosed to third parties without written authorization from Division of Microbiology and Infectious Diseases. This 
report may not be reproduced, stored in a retrieval system or transmitted in any form or by any means - electronic, mechanical, recording or 
otherwise - without the prior authorization from Division of Microbiology and Infectious Diseases. This document must be returned to Division 
of Microbiology and Infectious Diseases upon request. 
 


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TABLE OF CONTENTS 
STUDY TITLE ................................................................................................................................2 
TABLE OF CONTENTS .................................................................................................................3 
LIST OF ABBREVIATIONS ..........................................................................................................6 
1. 
PREFACE .....................................................................................................................8 
2. 
INTRODUCTION ........................................................................................................9 
2.1. 
Purpose of the Analyses ..............................................................................................12 
3. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................13 
3.1. 
Study Definitions and Derived Variables ...................................................................14 
4. 
INVESTIGATIONAL PLAN .....................................................................................15 
4.1. 
Overall Study Design and Plan ...................................................................................15 
4.2. 
Discussion of Study Design, Including the Choice of Control Groups ......................15 
4.3. 
Selection of Study Population ....................................................................................16 
4.4. 
Treatments ..................................................................................................................18 
4.4.1. 
Treatments Administered ............................................................................................18 
4.4.2. 
Identity of Investigational Product(s) .........................................................................18 
4.4.3. 
Method of Assigning Subjects to Treatment Groups (Randomization) .....................19 
4.4.4. 
Selection of Doses in the Study ..................................................................................19 
4.4.5. 
Selection and Timing of Dose for Each Subject .........................................................20 
4.4.6. 
Blinding ......................................................................................................................20 
4.4.7. 
Prior and Concomitant Therapy ..................................................................................20 
4.4.8. 
Treatment Compliance ................................................................................................20 
4.5. 
Immunogenicity and Safety Variables ........................................................................21 
5. 
SAMPLE SIZE CONSIDERATIONS .......................................................................25 
6. 
GENERAL STATISTICAL CONSIDERATIONS ....................................................26 
6.1. 
General Principles .......................................................................................................26 
6.2. 
Timing of Analyses .....................................................................................................26 
6.3. 
Analysis Populations ..................................................................................................26 
6.3.1. 
Modified Intention-to-Treat (mITT) Population ........................................................26 
6.3.2. 
Per Protocol Population ..............................................................................................26 
6.3.3. 
Safety Population ........................................................................................................26 


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6.4. 
Covariates and Subgroups ..........................................................................................26 
6.5. 
Missing Data ...............................................................................................................27 
6.6. 
Interim Analyses and Data Monitoring ......................................................................27 
6.7. 
Multicenter Studies .....................................................................................................27 
6.8. 
Multiple Comparisons/Multiplicity ............................................................................27 
7. 
STUDY SUBJECTS ...................................................................................................28 
7.1. 
Disposition of Subjects ...............................................................................................28 
7.2. 
Protocol Deviations ....................................................................................................28 
8. 
IMMUNOGENICITY EVALUATION .....................................................................29 
8.1. 
Primary Immunogenicity Analyses ............................................................................29 
8.2. 
Secondary Immunogenicity Analyses ........................................................................30 
8.3. 
Exploratory Immunogenicity/Efficacy Analyses .......................................................30 
8.3.1. 
T-cells .........................................................................................................................30 
8.3.2. 
B-cells .........................................................................................................................30 
8.3.3. 
Breakthrough Infections .............................................................................................30 
8.3.4. 
Sequencing Results of Breakthrough Infections .........................................................31 
9. 
SAFETY EVALUATION ..........................................................................................32 
9.1. 
Demographic and Other Baseline Characteristics ......................................................32 
9.1.1. 
Prior and Concurrent Medical Conditions ..................................................................32 
9.1.2. 
Prior and Concomitant Medications ...........................................................................32 
9.2. 
Measurements of Treatment Compliance ...................................................................32 
9.3. 
Adverse Events ...........................................................................................................33 
9.3.1. 
Solicited Events and Symptoms .................................................................................33 
9.3.2. 
Unsolicited Adverse Events ........................................................................................33 
9.4. 
Deaths, Serious Adverse Events and other Significant Adverse Events ....................34 
9.5. 
Pregnancies .................................................................................................................34 
9.6. 
Clinical Laboratory Evaluations .................................................................................34 
9.7. 
Vital Signs and Physical Evaluations .........................................................................34 
9.8. 
Concomitant Medications ...........................................................................................34 
9.9. 
Other Safety Measures ................................................................................................34 
10. 
PHARMACOKINETICS ...........................................................................................35 


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11. 
IMMUNOGENICITY ................................................................................................36 
12. 
OTHER ANALYSES .................................................................................................37 
13. 
REPORTING CONVENTIONS ................................................................................38 
14. 
TECHNICAL DETAILS ............................................................................................39 
15. 
SUMMARY OF CHANGES IN THE CONDUCT OF THE STUDY OR 
PLANNED ANALYSES ............................................................................................40 
16. 
REFERENCES ...........................................................................................................41 
17. 
LISTING OF TABLES, FIGURES, AND LISTINGS ..............................................44 
APPENDICES ...............................................................................................................................45 
APPENDIX 1. TABLE MOCK-UPS..........................................................................................46 
APPENDIX 2. FIGURE MOCK-UPS ......................................................................................227 
APPENDIX 3. LISTINGS MOCK-UPS ...................................................................................383 
 


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LIST OF ABBREVIATIONS 
AE 
Adverse Event 
CI 
Confidence Interval 
CRF 
Case Report Form 
DMID 
Division of Microbiology and Infectious Diseases 
DSMB 
Data and Safety Monitoring Board 
EDC 
Electronic Data Capture 
ECLIA 
Electrochemiluminescence Immunoassay 
GMT 
Geometric Mean Titer 
FRNT 
Focus Reduction Neutralization Assay 
GMFD 
Geometric Mean Fold Drop 
GMFR 
Geometric Mean Fold Rise 
GMR 
Geometric Mean Ratio 
ICH 
International Conference on Harmonisation 
IRB 
Institutional Review Board 
ITT 
Intention to Treat 
LLOD 
Lower Limit of Detection 
MedDRA 
Medical Dictionary for Regulatory Activities  
mITT 
Modified Intention to Treat 
N 
Number (typically refers to subjects) 
NIH 
National Institutes of Health 
PI 
Principal Investigator 
PP 
Per Protocol 
PsVNA 
Pseudovirus Neutralization Assay 
PT 
Preferred Term 
SAE 
Serious Adverse Event 
SD 
Standard Deviation 
SDCC 
Statistical and Data Coordinating Center 
SMC 
Safety Monitoring Committee 
SOC  
System Organ Class 
 
 


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SOP 
Standard Operating Procedures 
WHO 
World Health Organization 
 


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1. 
PREFACE 
The Statistical Analysis Plan (SAP) for “Phase 2 Clinical Trial to Optimize Immune Coverage of SARS-CoV-
2 Existing and Emerging Variants” (DMID Protocol 22-0004) describes and expands upon the statistical 
information presented in the protocol.  
This document describes all planned analyses and provides reasons and justifications for these analyses. It 
also includes sample tables, listings, and figures planned for the final analyses. Regarding the final analyses 
and Clinical Study Report (CSR), this SAP follows the International Conference on Harmonisation of 
Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Guidelines, as indicated in 
Topic E3 (Structure and Content of Clinical Study Reports), and more generally is consistent with Topic E8 
(General Considerations for Clinical Trials) and Topic E9 (Statistical Principles for Clinical Trials). The 
structure and content of the SAP provides sufficient detail to meet the requirements identified by the FDA and 
ICH, while all work planned and reported for this SAP will follow internationally accepted guidelines 
published by the American Statistical Association and the Royal Statistical Society for statistical practice. 
This document contains four sections: (1) a review of the study design, (2) general statistical considerations, 
(3) comprehensive statistical analysis methods for immunogenicity and safety outcomes, and (4) a list of 
proposed tables and figures. Within the table, figure, and listing mock-ups (Appendix 1, Appendix 2, and 
Appendix 3), references to CSR sections are included. Any deviation from this SAP will be described and 
justified in protocol amendments and/or in the CSR, as appropriate. The reader of this SAP is encouraged to 
also review the study protocol for details on conduct of the study and the operational aspects of clinical 
assessments. 
 


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2. 
INTRODUCTION 
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was first detected in Wuhan, Hubei 
Province, China in December 2019. The corresponding illness designation, coronavirus disease 2019 
(COVID-19), was declared as a pandemic respiratory illness in March 2020 [1]. As of 18 August 2022, it has 
infected close to 600 million people worldwide and resulted in more than 6 million deaths, including close to 
1 million in the United States [1, 2].  
Six Phase 3 efficacy trials of SARS-CoV-2 vaccine constructs were conducted and are in long-term follow-up 
in the U.S. The ModernaTX, Inc mRNA-1273 and Pfizer/BioNTech BNT162b2 mRNA platforms encode for 
the full-length spike (S) protein of SARS-CoV-2, modified to introduce 2 proline residues to stabilize the S 
protein (S-2P) in a prefusion conformation, derived from the Wuhan-Hu-1 strain (prototype) [3]. The Janssen 
Pharmaceutical/Johnson & Johnson COVID-19 Vaccine (Ad26.COV.2) is composed of recombinant, 
replication-incompetent human adenovirus type 26, encoding a prefusion-stabilized SARS-CoV-2 spike 
antigen [4].  Studies of the Pfizer and Moderna mRNA vaccines demonstrated high efficacy against all 
symptomatic and severe disease and received Emergency Use Authorization (EUA) on December 12 and 18, 
2020, respectively and full FDA approval on August 23, 2021 and January 31, 2022. Similarly, Janssen 
Pharmaceuticals reported 66% vaccine efficacy with a single dose and high-level protection against severe 
disease and death. FDA EUA was issued on February 26, 2021. Novavax’s NVX-CoV2373, a recombinant 
nanoparticle vaccine containing the full-length spike protein received FDA EUA on July 13, 2022[ 5].  
AstraZeneca/Oxford’s ChAdOx-2, a recombinant, replication-incompetent chimpanzee adenovirus vector that 
expresses the spike protein, and Sanofi/GSK’s adjuvanted recombinant spike protein vaccine are currently not 
licensed [6, 7]. Despite widespread vaccine distribution and availability, and high coverage among adults in 
the United States (87.4% of the US population ≥ 18 years of age have received at least one dose) [8], ongoing 
waves of the pandemic continue to cause significant disease burden, notable for increasing incidence of 
breakthrough infections in fully vaccinated individuals. Studies have suggested that vaccine protection against 
symptomatic SARS-CoV-2 infection wanes over time though protection against severe COVID-19 outcomes 
remains relatively intact [9, 10, 11, 12]. However, the evolution of variant strains may favor immune escape 
or reinfection among previously infected or vaccinated individuals. A variant first identified in late 2020 
(B.1.351), is associated with increased transmission, higher viral burden, and possibly increased mortality in 
infected persons [13]. Another variant identified in December 2020 (B.1.617.2) is associated with increased 
transmission, higher risk of severe disease and hospitalization than the ancestral strain [14]. B.1.617.2 was the 
dominant strain worldwide before being replaced by B.1.1.529 in November 2021 which is characterized by a 
replication advantage, higher re-infection rates and evasion of humoral immunity mediated by more than 30 
mutations in the spike protein [15]. 
Recent data suggest that a booster dose given as either a third dose for most vaccines (mRNA, protein and 
ChAdOx-2) or a second dose for Janssen improved vaccine effectiveness against new variants in the short 
term [16, 17, 18]. Data on immunogenicity with booster doses of BNT162b2, mRNA-1273, and 
AD26.COV2.S demonstrated higher antibody titers to D614G after either homologous and heterologous 
prime-boost combinations [19]. The result is better neutralizing activity against B.1.351, B.1.617.2 and 
B.1.1.529 [20, 21, 22]. In an open label phase 2 study of participants who received a single 50 mcg booster 
dose of mRNA-1273 ≥ 6 months after a primary series, a 13-fold rise in antibody titers against D614G were 
noted from pre-boost levels as well as a 17-fold rise in in titers against the B.1.617.2 variant [20]. In another 
study, participants boosted with 50 mcg of mRNA-1273 demonstrated ID50 GMTs against the omicron variant 
20 times higher than those described 1 month after the second vaccination of the primary series; these titers 
were 2.9 times lower than titers for the D614G variant [21]. 


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The Sanofi/GSK adjuvanted recombinant prefusion spike protein vaccine (CoV2 preS dTM-AS03 [D614]) 
was developed from an established, platform used for influenza vaccines. A phase 2 study showed the safety 
and immunogenicity of a two-dose primary series of CoV2 preS dTM-AS03 [D614] in adults who were 
SARS-CoV-2 naïve and those who were previously infected [23]. The dose-finding results informed selection 
of the adjuvanted formulation with 10 mcg antigen as primary dose and the adjuvanted formulation with 5 
mcg antigen as boost dose for further evaluation. Neutralizing antibody titers were higher in non-naïve 
participants after one dose than in naïve participants after two doses. In addition, 5 mcg booster dose 
increased neutralizing antibody titers when used as a heterologous (18-30 times) or homologous (≥ 84 times) 
boost compared to pre boost [24]. Interim results from an international phase 3 trial showed 57.9% (95% 
confidence interval 26.5% to 76.7%) efficacy of the two-dose primary series against any symptomatic disease 
and 75% efficacy against moderate or severe COVID-19 with an acceptable safety and reactogenicity profile 
[24]. 
FDA EUA was subsequently issued for a booster 30 ug dose of Pfizer BNT162b2 on September 24, 2021, 50 
ug booster dose of Moderna mRNA-1273 on October 21, 2021, and a 5×1010 viral particles booster dose of 
J&J AD26.COV2 on October 21, 2021. This was recommended for adults 18 years of age and older who 
received a FDA authorized and CDC recommended primary booster series with an mRNA vaccine at least 5 
months prior or a primary series with AD26.COV2 at least 2 months prior. The Sanofi/GSK vaccine is 
currently undergoing regulatory review for approval of their vaccine candidate for the prevention of  
COVID-19. 
Published reports have also provided some early evidence for the safety and immunogenicity of a fourth dose 
of an mRNA vaccine. An open-label study of healthcare workers in Israel suggests that a fourth dose was 
well-tolerated and restored neutralizing antibody titers for variants to levels similar to those after a third dose 
[25]. Notably, this study did not include older adults, and rates of infection with B.1.1.529 (omicron) were 
similar for the control and Pfizer or Moderna 4th dose groups. In a retrospective study conducted by the Israeli 
Ministry of Health, of 1,138,681 adults aged 60 to 100 years of age, a fourth dose of mRNA was associated 
with 2 times lower rate of confirmed infection 12 or more days after vaccination compared to those who had 
only received 3 doses and the rate of severe illness was lower by a factor of 4.3 [26]. However, the added 
protection of an additional booster shot is small in absolute terms since less than 0.1% mortality was noted 
after a 3rd dose. Additionally, a separate study of adults age 60 or older suggests that vaccine effectiveness of 
a fourth dose against infection wanes quickly declining from a peak of 64% to 29% within 2 months though 
effectiveness of >73% was maintained against severe disease [27]. 
On March 29, 2022, the FDA authorized an additional booster dose of an mRNA vaccine for adults 50 years 
of age or older, or for those with immunocompromising conditions (12 years and older with 
immunocompromising conditions could receive a second booster with the Pfizer vaccine and 18 years and 
older could receive a second booster with the Moderna vaccine). Subsequent to this authorization, the CDC 
updated vaccination guidance to permit an additional booster dose for these groups in recognition of the 
increased and ongoing risk for severe disease in these populations. 
The emergence of variant strains has raised concerns about the breadth and duration of immunity and 
protection achieved by the current vaccines. Studies of vaccine immunogenicity for early variants of concern 
demonstrated those vaccinated to prototype vaccine may have reduced neutralizing activity to the variants 
[28]. For variants like B.1.351, pivotal studies testing both viral vector and adjuvanted protein technologies 
had lower efficacy in regions where B.1.351 was known to be circulating [29, 30]. Moreover, sera from 
individuals vaccinated with mRNA-based vaccines had a 6-to-9-fold reduction in neutralizing activity against 
a B.1.351-matched pseudovirion relative to a Wuhan-matched pseudovirion [10, 11]. Similarly, sera from 


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individuals vaccinated with mRNA-1273 had an 8-fold reduction in neutralizing activity against the B.1.617.2 
variant compared to titers against the D614G variant [21]. 
Studies have also demonstrated 6.7 fold reduction in neutralizing activity for Pfizer BNT162b2 against 
B.1.351 with two doses of Pfizer BNT162b2 [31]. Additionally, in one assessment of sera obtained from 
individuals vaccinated with Pfizer BNT162b2, obtained one month after the second dose, a 25 fold reduction 
in neutralizing antibody geometric mean titers against B.1.1.529 was noted compared to the wild-type virus 
[32]. Neutralizing activity has been shown to be partially restored by vaccination with a third dose of Pfizer 
BNT162b2. However, even with three doses, neutralizing activity was 4 times lower against B.1.1.529 and 3 
times lower against B.1.351 compared to B.1.617.2 and 7-8 times lower compared to wild-type virus [33]. 
Thus, additional vaccinations, higher doses or variant specific vaccines may improve protection against 
current and emerging variants of concern.  
Vaccine manufacturers have performed some trials of candidate variant vaccines. For example, a phase 2a 
open label clinical trial to examine the immunological benefit of boosting subjects previously vaccinated 6 
months prior with mRNA-1273 with mRNA-1273.351, a B.1.351 strain-specific mRNA construct (50 mcg), 
or mRNA-1273.211 (50 mcg) showed 61.6 and 33.7 times higher titers against B.1.351 compared to titers 
from participants one month after the second dose of the primary series, with similar titers against B.1.617.2 
[22]. Similar findings were seen from a study of a boost with a bivalent mRNA-1273.213 vaccine (a 1:1 mix 
of beta and delta variant mRNA) [21]. 
Similarly, several BNT162b2-based variant vaccines that target these variants are also being developed 
including BNT162b2 (B.1.617.2), BNT162b2 (B.1.351) and BNT162b2 (B.1.1.529).  In addition, Sanofi has 
developed a SARS-CoV2 prefusion Spike delta TM with AS03 adjuvant (CoV2 preS dTM-AS03 [B.1.351]) 
monovalent vaccine and a SARS-CoV2 prefusion Spike delta TM with AS03 adjuvant bivalent vaccine 
(D614/B.1.351 (CoV2 preS dTM-AS03 [D614 + B.1.351]). In a nonhuman primate model, these vaccines 
used as boosters induced cross-neutralizing antibodies against variants of concern including Delta and 
Omicron [34]. 
However, current efforts are directed towards modifying the existing vaccines to include the current 
circulating Omicron variant, though this may not be the circulating variant during the next wave of COVID-
19. It is therefore important to look beyond Omicron, and understand the immunologic landscape and how we 
can use prototype and variant vaccines alone or in combination to address emerging variants.  
For seasonal influenza viruses, the antigenic, viral genetic and epidemiological data guide annual updates of 
the seasonal influenza virus vaccines. Antigenic cartography is a visualization tool aimed at understanding the 
relationship among SARS-CoV-2 variants of concern (VOCs) in terms of their ability to induce cross-
neutralizing antibodies. A recent study using the antigenic mapping approach showed that Omicron represents 
the first widely circulating new major SARS-CoV-2 variant [35]. Though the dimensions of the cartography, 
representing new VOCs that could circulate in the future, remain largely unknown, a better understanding of 
diverse immune landscape induced by vaccination and natural infection could lead, along with vaccine 
modification, to more durable and broadly protective immunity. The update in vaccine formulations proposed 
in this study will still rely on similar platforms, route of administration and dosing, though will include an 
update of immunogens with VOCs alone or in combination that could result in broadly cross reactive 
serological and cellular immune responses especially in groups with high risk for mortality (e.g., older adults). 
This phase 2 clinical trial will evaluate the safety and immunogenicity of additional doses of vaccine to 
expand and optimize immune coverage of the existing and emerging antigenic space. Utilizing several 
prototype and variant specific COVID-19 vaccines based on mRNA and other approved platforms, we 
propose to evaluate innate, cellular, and humoral immune responses elicited from different vaccine 


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candidates. As part of an adaptive design, we anticipate adding groups with other variant-lineage spike 
proteins and other vaccine platforms, subject to availability. 
2.1. 
Purpose of the Analyses 
These analyses will assess the immunogenicity and safety of additional doses of prototype and variant (alone 
or in combination) vaccine candidates in previously vaccinated participants with or without prior SARS-CoV-
2 infection, and will evaluate innate, cellular, and humoral immune responses to inform on how to shift the 
immune response to cover new variants as they emerge. 
Data may be disseminated to public health officials and partners as needed and included in publications and 
presentations to inform the global scientific community. Early analyses will include safety and 
immunogenicity as described in Protocol v5.0 Sections 9.4.6.1, 9.4.6.2, and 9.4.6.3. Further, the protocol team 
will review data periodically to confirm no halting criteria have been met as described in Protocol v5.0 
Section 7.1.1.  


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3. 
STUDY OBJECTIVES AND ENDPOINTS 
Table 1: 
Objectives and Endpoints (Outcome Measures) 
OBJECTIVES 
ENDPOINTS (OUTCOME MEASURES) 
Primary 
• To evaluate humoral immune responses of 
candidate SARS-CoV-2 variant vaccines 
• Response rate and magnitude of SARS-CoV-
2-specific antibody binding and 
neutralization titers in serum samples as 
assessed via a range of assays at all 
timepoints 
Secondary 
• To evaluate the safety of candidate SARS-
CoV-2 variant vaccines 
• Local and systemic solicited Adverse Events 
for 7 days following each vaccine dose 
• Unsolicited Adverse Events from Dose 1 to 
28 days following each vaccine dose 
• SAEs, MAAEs, NOCMCs, AESIs, and AEs 
leading to withdrawal from the study from 
Dose 1 to 12 months after the last vaccine 
dose  
Exploratory 
• To assess, in at least a subset of samples, the 
B cell immune response of candidate SARS-
CoV-2 variant vaccines 
• Magnitude, phenotype, and percentage of 
SARS-CoV-2-specific B cells, as measured 
by flow cytometry and targeted B cell subset 
analysis at selected time points post-
vaccination 
• To assess, in at least a subset of samples, the 
SARS-CoV-2 spike protein-specific T cell 
responses of candidate SARS-CoV-2 variant 
vaccines 
• Magnitude, phenotype, and percentage of 
cytokine-producing S protein T cells as 
measured by flow cytometry at selected time 
points post-vaccination. 
• To assess, in at least a subset of samples, the 
magnitude, phenotype, and percentage of 
innate immune cells with candidate SARS-
CoV-2 variant vaccines 
• Magnitude, phenotype, and percentage of 
innate immune cells as measured by flow 
cytometry at D1 and 14 days after each 
vaccination 
• To assess, in at least a subset of samples, the 
function potential of SARS-CoV-2 specific 
antibodies to mediate Fc-effector functions 
• Characterization of antigen-specific antibody 
by a) subclass, b) isotype, c) ability to 
interact with Fc receptors, d) innate immune 


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OBJECTIVES 
ENDPOINTS (OUTCOME MEASURES) 
across candidate SARS-CoV-2 variant 
vaccines 
receptors, e) lectin-like molecules, and f) 
lectins at different times post-vaccination 
• Functional Fc effector assessments which 
may include quantification of antigen-
specific antibody-mediated NK cell 
activation (ADCC-NK) levels, antibody-
dependent cellular phagocytosis (ADCP) 
levels, antibody-dependent complement 
deposition (ADCD) and/or antibody-
dependent neutrophil activation/phagocytosis 
levels at different times post-vaccination 
• To evaluate breakthrough SARS-CoV-2 
infection by sequencing strains for variant 
spike lineage and assessing anti-
nucleocapsid serology 
• Sequence analysis on breakthrough NAAT-
confirmed SARS-CoV-2 strains at any time 
post-vaccination 
• Anti-nucleocapsid immunoassay at different 
times post-vaccination 
3.1. 
Study Definitions and Derived Variables  
For calculations using the baseline value, the value obtained pre-fourth vaccination (Day 1) will be used.  
If a value falls below the lower limit of detection for the immunogenicity assay, the value will be replaced by 
one-half the lower limit of detection in analyses. 
Subjects infected at baseline will be defined as by either self-report or positive for N-antibody. 
Major protocol deviations will be defined by the sponsor. 
Unless otherwise noted Omicron refers to B.1.1.529/BA.1. 


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4. 
INVESTIGATIONAL PLAN 
4.1. 
Overall Study Design and Plan 
This is a Phase 2 randomized, adaptive, open label, non-placebo controlled multi-site, multi-stage clinical trial 
in individuals, 18 years of age and older, who are in stable state of health, have received a complete 
authorized/approved vaccine series (primary series + booster either with homologous or heterologous vaccine 
products) and meet all other eligibility criteria. 
Approximately 1500 subjects will be enrolled at up to 30 clinical research sites. At enrollment, subjects will 
be stratified by i) age (18-64 and ≥ 65 years of age) (however arms 16 and 17 or stage 4 will only enroll 
participants between the ages of 18-49 years) and ii) confirmed prior SARS-CoV-2 infection, and randomly 
assigned to one of several study arms of variant vaccines. The study will target the enrollment of 
approximately 45% older adults (≥ 65 years of age) for stages 1, 2, and 3. Additionally, the study will target to 
enroll approximately 20% of participants with a history of confirmed SARS-CoV-2 infection. It is estimated 
that another 10-30% will have undiagnosed prior infection. Taken together, we anticipate about 40% of the 
total enrolled participants will have prior infection. The study team will decide, based on latest epidemiology, 
if enrollment of participants in any particular groups are slowed in order to ensure good representation of 
previously infected and not previously infected. 
The adaptive design of this study will include additional arms, an increase in sample size, or additional 
vaccine doses or different dosing and provide rapid information about the immunogenicity and the safety of 
candidate SARS-CoV-2 variant vaccines to inform near term public health policy. This trial will provide 
proof of concept on how variant vaccines could shift the immune response to become more specific to the 
VOCs’ antigens or broaden the antigenic landscape for emergent variants. 
Screening can occur up to 28 days prior to the first dose of study product or on Day 1 prior to administration 
of Dose 1. Safety will be assessed during the study and blood will be drawn for immunogenicity assays at 
enrollment and in-person follow-up visits. Swabs will be self-collected or collected by staff at unscheduled 
illness visits to evaluate breakthrough SARS-CoV-2 infection (symptomatic infection or asymptomatic 
infection with a positive SARS-CoV-2 test outside the study). A summary of the four currently planned stages 
can be found in Table 2. 
4.2. 
Discussion of Study Design, Including the Choice of Control Groups 
This phase 2 study is an open-label study, without administration of a placebo formulation. An open-label 
study will facilitate the need for rapid review and dissemination of study data for public health reasons. Safety 
findings are not expected to be dissimilar from Phase 1/2/3 studies conducted for similar vaccine constructs. 
Randomization will improve comparisons between different arms. Each stage will contain an arm with a 
monovalent prototype vaccine (except for stage 4). 
Selected arms will assess 2 study doses of vaccine candidates to assess if 2 doses provide a more durable and 
specific response to variant viruses. 
An interval of 4 months was chosen since a recent study performed by the investigators showed that an 
interval of 3 months between primary series and boost had acceptable safety and immunogenicity responses 
[19]. 


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4.3. 
Selection of Study Population 
All participants will have received a complete (primary and booster) US approved/authorized vaccine series. 
The US population has received either homologous primary series and boost (i.e. Moderna mRNA-1273 for 
1st dose, second dose, and booster), or heterologous boosters, and some were infected with SARS-CoV-2 
either prior to or after vaccination. This trial will enroll this immunologically diverse population, to ensure 
any findings are applicable to the larger population. 
Based on CDC data about use of primary vaccine or boost (https://covid.cdc.gov/covid data-
tracker/#vaccinations_vacc-total-admin-rate-total), it is estimated that of people in the US that have received a 
primary vaccine series and booster: 
• 50% will have received Pfizer primary series and Pfizer boost, 
• 37% will have received Moderna primary series and Moderna boost, 
• 4% will have received Pfizer primary series and Moderna boost, 
• 3% will have received Moderna primary series and Pfizer boost, 
• 1% will have received Janssen primary series and Janssen boost, 
• 2% will have received Janssen primary series and Moderna boost,  
• 2% will have received Janssen primary series and Pfizer boost. 
Additionally, approximately 20% of the US population has been infected with SARS-CoV-2, likely higher 
with asymptomatic infections [36].  
It is anticipated the enrollment into this trial will be similar to these proportions. 
Subject Inclusion and Exclusion Criteria must be confirmed by a study clinician, licensed to make medical 
diagnoses and listed on the Form FDA 1572. No exemptions are granted on Subject Inclusion or Exclusion 
Criteria in DMID-sponsored studies. 
Inclusion Criteria 
Participants must meet all the following criteria to be eligible to participate in this study: 
1. Individuals ≥ 18 years of age at the time of consent (18-49 years for stage 4). 
2. Confirmed receipt of a complete primary and booster COVID-19 vaccine series, either homologous or 
heterologous, with an FDA authorized/approved vaccine at least 16 weeks prior to study vaccine  
dose 1 
3. Willing and able to comply with all scheduled visits, vaccination plan, laboratory tests and other study 
procedures 
4. Determined by medical history, targeted physical examination and clinical judgement of the investigator 
to be in stable state of health 
Note: Participants with pre-existing stable chronic medical conditions defined as condition not 
requiring significant change in therapy or hospitalization for worsening disease within 4 weeks form 
enrollment, can be included at the discretion of the investigator. 
Exclusion Criteria 
Participants meeting any of the following criteria will be excluded from participation in this study: 


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1. Confirmed SARS-CoV-2 infection < 16 weeks prior to any study vaccine dose 
2. Pregnant and breastfeeding participants 
3. Prior administration of an investigational coronavirus vaccine at any time or SARS-CoV-2 
immunoglobulin, monoclonal antibody or plasma antibody therapy in the preceding 3 months 
Note: Subjects that participated in clinical trials of products that are now FDA approved/authorized 
are allowed to participate. 
4. Current/planned simultaneous patriation in another interventional study or receipt of any 
investigational study product within 28 days prior to vaccine study dose(s) 
5. A history of anaphylaxis, urticaria, or other significant adverse reaction requiring medical intervention 
after receipt of a vaccine, polyethylene glycol (PEG), or nanolipid particles. 
6. A history of myocarditis or pericarditis at any time prior to enrollment (for subjects in stages 1, 2 and 
4). 
7. Received or plans to receive a vaccine within 28 days prior to or after any dose of study vaccine. 
Note: Receipt of seasonal influenza vaccine is allowed at any time 
8. Bleeding disorder diagnosed by a healthcare provider (e.g., factor deficiency, coagulopathy, or platelet 
disorder requiring special precautions) or bleeding difficulties with intramuscular injections or blood 
draws. 
9. Current or previous diagnosis of an immunocompromising condition or other immunosuppressive 
condition. 
10. Advanced liver or kidney diseases. 
11. Advanced (CD4 count < 200) and/or untreated HIV, untreated Hepatitis B or untreated Hepatitis C. 
12. Received oral, intramuscular or intravenous systemic immunosuppressants, or immune-modifying 
drugs for >14 days in total within 6 months prior to any study vaccine dose (for corticosteroids ≥ 20 
mg/day of prednisone equivalent).  
Note: Topical medications are allowed. 
13. Received immunoglobulin or blood-derived products, within 3 months prior any study vaccine dose. 
14. Received chemotherapy, immunotherapy or radiation therapy within 6 months prior to any study 
vaccine dose. 
15. Study personnel or an immediate family member or household member of study personnel. 
16. Is acutely ill or febrile 72 hours prior to or at vaccine dosing (fever defined as ≥ 38.0°C/100.4°F). 
Participants meeting this criterion may be rescheduled within the relevant window periods. 
Note: Afebrile participants with minor illnesses can be enrolled at the discretion of the Investigator, as 
long as the illness is not suggestive of COVID-19. 
17. Plan to receive a COVID-19 booster vaccine outside of the study within the next 180 days. (for 
subjects in Stage 4 only) 
 
 


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Exclusion of Specific Populations 
The effects of SARS-CoV-2 vaccines on the developing fetus are not known, though there are data to suggest 
that mRNA vaccines are safe. Pregnant subjects will not be eligible for the trial as the immune responses to 
vaccines can be different than non-pregnant subjects. Children will not be included in this trial as presently 
there are limited safety data in adults for the variant strains. 
4.4. 
Treatments 
4.4.1. 
Treatments Administered  
Seventeen treatment arms administer various combinations of COVID-19 vaccines (Table 2). 
4.4.2. 
Identity of Investigational Product(s) 
Products: mRNA-1273 (Prototype), mRNA-1273.351 (Beta), mRNA-1273.617.2 (Delta), and 
mRNA-1273.529 (Omicron) 
mRNA-1273 (0.2 mg/mL) is an LNP dispersion containing an mRNA that encodes for the pre-fusion 
stabilized S protein of the Wuhan-Hu-1 strain of SARS-CoV-2. mRNA-1273 consists of an mRNA Drug 
Substance that is manufactured into LNPs composed of the proprietary ionizable lipid, SM-102, and 3 
commercially available lipids, cholesterol, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), and 
PEG2000 DMG. 
mRNA-1273.351 (0.1 mg/mL) is formulated in the same way but contains mRNA that encodes for the 
prefusion stabilized S protein of the B.1.351 (Beta) variant SARS-CoV-2 strain. 
mRNA-1273.617.2 (0.2 mg/mL) is formulated in the same way but contains mRNA that encodes for the 
prefusion stabilized S protein of the B.1.617.2 (Delta) variant SARS-CoV-2 strain. 
mRNA-1273.529 (0.2 mg/mL) is formulated in the same way but contains mRNA that encodes for the 
prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain. 
BNT162b2 (wildtype), BNT162b2 (B.1.351, Beta), BNT162b2 (B1.1.529, Omicron), BNT162b2 bivalent  
(wildtype and  Omicron BA.1) and BNT162b2 bivalent (wildtype and Omicron BA.4/BA.5) 
BNT162b2 (500 mcg/mL for stage 2) is a preservative-free, sterile dispersion of RNA formulated in LNP in 
aqueous cryoprotectant buffer. mRNA encodes for the pre fusion stabilized S protein of the ancestral strain of 
SARS-CoV-2.  
BNT162b2 (B.1.351) (500 mcg/mL for stage 2) is formulated in the same way but contains mRNA that 
encodes for the prefusion stabilized S protein of the B.1.351 (Beta) variant SARS-CoV-2 strain. 
BNT162b2 (B.1.1.529)(500 mcg/mL for stage 2) is formulated in the same way but contains mRNA that 
encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain. 
BNT162b2 bivalent (wildtype and  Omicron BA.1 100mcg/mL for stage 4) is formulated in the same way 
but contains mRNA that encodes for the prefusion stabilized S protein of the Omicron BA.1 variant SARS-
CoV-2 strain and the ancestral strain of SARS-CoV-2.. 
BNT162b2 bivalent (wildtype and  Omicron BA.4/BA.5 100mcg/mL for stage 4) is formulated in the 
same way but contains mRNA that encodes for the prefusion stabilized S protein of the Omicron BA.4/BA.5 
variant SARS-CoV-2 strain and the ancestral strain of SARS-CoV-2. 


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CoV2 preS dTM-AS03 [D614] (prototype), CoV2 preS dTM-AS03 [B.1.351] (Beta), and CoV2 preS 
dTM-AS03 [D614 + B.1.351] (prototype + Beta) 
CoV2 preS dTM-AS03 [D614] (Recombinant COVID-19 Vaccine 20 mcg/mL + AS03) is a liquid 
formulation made of recombinant protein placed in a formulation buffer and to be mixed with equal volumes 
of AS03 adjuvant (supplied separately) at the study site before administration. The antigen solution contains 
the Spike protein sequence of the ancestral strain of SARS-CoV-2.  AS03 is an adjuvant system containing  
α-tocopherol and squalene in an oil/water emulsion. For this formulation, the antigen and AS03 vials are not 
packaged in a carton box together but are supplied as individual vials. 
CoV2 preS dTM-AS03 [B.1.351] (Recombinant COVID-19 Vaccine B1.351 20 mcg/mL+ AS03) is 
formulated in the same way but contains the Spike protein sequence of the B.1.351 (Beta) variant SARS-
CoV-2 strain.  Both antigen and AS03 vials are packaged in a carton box. 
CoV2 preS dTM-AS03 [D614 + B.1.351] (Recombinant COVID-19 Bivalent Vaccine 10/10 mcg/mL + 
AS03) is formulated in the same way but contains the Spike protein sequences of the ancestral and B.1.351 
(Beta) variant SARS-CoV-2 strains.  Both antigen and AS03 vials are packaged in a carton box. 
Diluent: 0.9% NaCl for injection, USP 
The USP grade 0.9% NaCl or normal saline for injection is a sterile, nonpyrogenic, isotonicsolution; each mL 
contains NaCl 9 mg. It contains no bacteriostatic agent, antimicrobial agent,preservatives, or added buffer and 
is supplied only in single-dose containers. This product should be used to dilute the vaccine to the desired 
concentration. 
4.4.3. 
Method of Assigning Subjects to Treatment Groups (Randomization) 
Subjects will be randomized to study intervention in an equal allocation ratio within each stage.  The study 
will be open label and study sites will administer product to a subject according to which study arm the 
subject has been assigned. Sites will be asked to recruit for all arms within a stage. 
4.4.4. 
Selection of Doses in the Study 
The dosages of mRNA vaccines selected are those authorized for booster doses under EUA, and previously 
shown in prior studies to elicit good immune responses with no major safety concerns. 
In an open label study of participants in the Moderna Phase 3 clinical trial who received a single 50 mcg 
booster dose of mRNA-1273 ≥ 6 months after a primary series, a 13 fold rise in antibody titers against D614G 
was noted from pre-boost levels as well as a 17-fold rise in in titers against the B.1.617.2 variant [20]. This is 
now the CDC recommended dose for booster vaccinations with the Moderna mRNA-1273 product in 
immunocompetent adults, to be given at least 5 months from the last inoculation in the primary series [37]. 
Similarly, in a recent study, boosting with a 50 mcg total antigen dose of a bivalent mRNA-1273.213 vaccine 
(a 1:1 mix of beta and delta variant mRNA) produced only modestly lower antibody titers than using a 100 
mcg booster dose [21]. A separate study evaluating safety and immunogenicity of multiple boost strategies 
suggests that a heterologous boost strategy generates antibody and neutralizing responses and that 100 mcg of 
mRNA-1273 (the authorized dose at the time) is likely higher than needed for a booster dose after primary 
mRNA series [38]. In addition, surveillance data indicate that following an mRNA boost, local and systemic 
reactions are less common and myocarditis is rarely reported, suggesting that the currently authorized doses 
are safe [39]. These findings support the evaluation of mRNA-1273, mRNA-1273.351, mRNA-1273.617.2 
and mRNA-1273.529 at total dosages of 50 mcg per vaccination.  


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For BNT162b2, the dose is the same for primary or booster doses in adults. In an open-label clinical study, 
immunogenicity and safety of a fourth dose of either 30 mcg of BNT162b2 (Pfizer–BioNTech) or 50 mcg of 
mRNA-1273 (Moderna) administered 4 months after the third dose was assessed in 154 and 120 health care 
workers, respectively [25]. After the fourth dose, both messenger RNA (mRNA) vaccines increased neutralizing 
antibody titers to D614G, B.1.617.2 and B.1.1.529 by a factor of 9 to 10 and were slightly higher than those 
achieved after the third dose [25]. There were no significant adverse events with only mild system and local 
reactogenicity reported which was comparable with previous doses of mRNA vaccines. The bivalent booster of 
BNT162b2 was authorized by the FDA based on pre-clinical data (Omicron BA.4/BA.5 + prototype) [40].  
For CoV2 preS dTM-AS03 vaccines, none are currently approved. The dose used for booster vaccination is as 
established in the phase 2 trial and is the adjuvanted formulation with 5 mcg for any variant vaccine candidate 
in stage 3 [24]. That booster dose increased neutralizing antibody titers when used as a heterologous (18-30 
times) or homologous (≥ 84 times) boost [24]. However, no data exist on CoV2 preS dTM-AS03 vaccines as a 
second boost after primary series with mRNA or adenoviral vectored vaccines. 
4.4.5. 
Selection and Timing of Dose for Each Subject 
Subjects will be randomly assigned to a study intervention. Subjects assigned to the arm receiving 2 doses 
will receive dose 2 eight weeks after dose 1. 
4.4.6. 
Blinding 
This study is unblinded. 
4.4.7. 
Prior and Concomitant Therapy  
Concomitant medications include prescription medications and vaccinations taken within 28 days of screening 
or Day 1. Topical, ophthalmic and OTC medications, herbal supplements and vitamins will not be collected. 
This information is asked to assess eligibility. Only COVID-19 vaccination received at any time in the past 
will be captured in the trial database.  After enrollment, immunosuppressant drugs, COVID-19 vaccines 
received outside of the study as well as COVID-19 related treatment and prophylaxis should be reported at 
any time during study participation and captured in the trial database. At each study visit, if there are new 
SAEs, concomitant medications should be recorded on the appropriate DCF and not included in the database 
unless these are immunosuppressant drugs, COVID-19 vaccines received outside of the study or COVID-19 
related treatment and prophylaxis. 
4.4.8. 
Treatment Compliance 
Subjects in all treatment arms except for treatment arm 3 will receive a single dose of study product 
administered in the clinic. Subjects in treatment arm 3 will receive 2 total doses (Days 1 and 57) of study 
product administered in the clinic. 
 
 


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4.5. 
Immunogenicity and Safety Variables 
Immunogenicity 
Humoral Immunogenicity Assays: 
The following humoral immunogenicity assays may be performed: 
• IgG ELISA or Multiplex MSD antibody binding assays to SARS-CoV-2 proteins (may include 
nucleocapsid protein, and multiple variant Receptor Binding Domains (RBD) and variant spike 
proteins). 
• Neutralization assays using SARS-CoV-2 variant specific S-pseudotyped viruses. 
• Neutralization assays using different strains of live SARS-CoV-2. 
• Characterization of antigen-specific antibody by a) subclass, b) isotype, c) ability to interact with 
Fc receptors, d) innate immune receptors, e) lectin-like molecules and f) lectins at different times 
post-vaccination.   
• Functional Fc effector assays which may include quantification of antigen specific antibody-
mediated NK cell activation (ADCC-NK) levels, antibody-dependent cellular phagocytosis 
(ADCP) activity, Antibody-dependent complement deposition (ADCD) and/or Antibody-
dependent neutrophil activation/phagocytosis activity.  
Cellular Immunology Assays: 
This trial may also investigate innate, B and T cell immune responses using multiparametric flow cytometry. 
Refer to the protocol-specific immune monitoring plan for details. 
Safety 
All safety endpoints for this trial are obtained by reporting of adverse events. 
• New symptoms will be queried with broad open-ended questions at the Day 8 telephone call and 
by specifically asking about symptoms of chest pain, shortness of breath or palpitations that may 
represent myocarditis and/or pericarditis. 
• Data on new medical conditions, doctors' office visits (outside of routine care), emergency room 
visits, and hospitalizations will be collected. 
• Memory Aid: All subjects will complete a Memory Aid from the time of each vaccination through 
7 days after each vaccination. Subjects will be asked to confirm completion of the Memory Aid 
and will be queried on the presence of any grade 3 symptoms. Based on the information provided, 
subjects may be asked to return to the clinic for evaluation. Fourteen days after each vaccination, 
Memory Aids are reviewed thoroughly with the subject and confirmed data recorded in the CRF. 
As these vaccines are similar to licensed vaccines, there are no laboratory assessments for safety that will be 
done for this trial. 
Adverse Events 
AE means any untoward medical occurrence associated with the use of an intervention in humans, whether or 
not considered intervention-related [21 CFR 312.32 (a)]. An AE can therefore be any unfavorable and 
unintended sign, symptom or disease temporally associated with the use of medicinal (investigational) 
product. 


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Any medical condition that is present at the time that the subject is screened will be considered as baseline 
and not reported as an AE. However, if the severity of any pre-existing medical condition increases, it should 
be recorded as an AE. 
AEs can be further divided into solicited AEs and unsolicited AEs. Solicited AEs are those that are described 
in the package insert as local or systemic reactogenicity occurring in the first 7 days after vaccination. 
Unsolicited AEs are those events that the subject reports occurring without being queried about the specific 
event.  
AEs will be assessed for severity and relationship to study intervention. Reporting of all AEs, solicited and 
unsolicited, will occur during the period from study product administration on Day 1 through 28 days after 
each vaccination. After 28 days post last vaccination through the end of study, only SAEs, Protocol Specified 
AESIs, MAAEs, NOCMCs, and AEs leading to withdrawal from the study will be reported. 
All AEs, solicited and unsolicited, will be captured on the appropriate DCF. Solicited AEs will be regarded as 
related to the study product and will not require separate entry into the AE log. Information to be collected for 
unsolicited AEs includes event description, date of onset, assessment of severity, relationship to study product 
and alternate etiology (assessed only by those with the training and authority to make a diagnosis and listed on 
the Form FDA 1572 as the participating site PI or appropriate sub-investigator), date of resolution, 
seriousness, and outcome. AEs occurring during the study-collection and reporting period will be documented 
appropriately regardless of relationship. 
AEs will be followed to resolution or stabilization. 
Solicited Adverse Events 
Solicited AEs are anticipated local and systemic AEs for which consistent collection of information is desired. 
Study clinicians will follow and collect resolution information for any reactogenicity symptoms that are not 
resolved within 7 days. 
Solicited AEs (i.e., reactogenicity) will be collected using a memory aid and confirmed data recorded on the 
appropriate DCF from the time of each vaccination through 7 days post each vaccination. 
For this study, solicited AEs will be: 
• Injection site Pain 
• Injection site Erythema 
• Injection site Edema/Induration 
• Headache 
• Fatigue 
• Myalgia 
• Arthralgia 
• Nausea 
• Fever 
• Chills 
Unsolicited Adverse Events 
All AEs spontaneously reported by the subject and/or in response to an open question from study staff or 
revealed by observation, physical examination or other diagnostic procedures must be recorded on the 
appropriate DCF. 


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Unsolicited AEs of all severities will be reported from the time of study product administration through 28 
days post each vaccination. 
After 28 days post last vaccination through the end of study, only SAEs, AESIs, NOCMCs, MAAEs, and AEs 
leading to withdrawal from the study will be reported. 
Serious Adverse Events 
An SAE is defined in 21 CFR 312.32 as follows: “An AE or suspected adverse reaction is considered serious 
if, in the view of either the participating site PI or appropriate sub-investigator or the sponsor, it results in any 
of the following outcomes: 
• Death, 
• a life-threatening AE, 
• inpatient hospitalization or prolongation of existing hospitalization, 
• a persistent or significant incapacity or substantial disruption of the ability to conduct normal life 
functions, 
• or a congenital anomaly/birth defect. 
Important medical events that may not result in death, be life-threatening, or require hospitalization may be 
considered serious when, based upon appropriate medical judgment, they may jeopardize the patient or 
subject and may require medical or surgical intervention to prevent one of the outcomes listed in this 
definition. Examples of such medical events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, or 
the development of drug dependency or drug abuse.” 
“Life-threatening” refers to an AE that at occurrence represents an immediate risk of death to a subject. An 
event that may cause death if it occurs in a more severe form is not considered life-threatening. Similarly, a 
hospital admission for an elective procedure is not considered an SAE. 
All SAEs, as with any AE, will be assessed for severity and relationship to study intervention. 
All SAEs will be recorded on the appropriate SAE DCF. 
All SAEs will be followed through resolution or stabilization by a study clinician, licensed to make medical 
diagnoses and listed on the Form FDA 1572 as the participating site PI or appropriate sub-investigator. 
All SAEs will be reviewed and evaluated by DMID and will be sent to the DSMB (for periodic review unless 
related) and IRB/IEC as needed. 
Adverse Events of Special Interest (AESIs) 
AESIs represent any events for which additional data (besides the standard AE data) are desired. An adverse 
event of special interest (serious or nonserious) is one of scientific and medical concern specific to the 
sponsor’s product or program, for which ongoing monitoring and rapid communication by the investigator to 
the sponsor is required. Such an event may require further investigation in order to characterize and 
understand it. Depending on the nature of the event, rapid communication by the trial sponsor to other parties 
(e.g., regulators) may also be required. These may be at the request of the regulatory agency, industry partner 
or DMID, and driven by a regulatory requirement, or known or potential risk from the product or class.  
Protocol Specified AESIs are listed in Appendix A of the protocol. In addition, for stage 3, AESIs will also 
include a list of pIMD. 


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Potential immune-mediated diseases (pIMDs) 
pIMDs are a subset of AESIs that include autoimmune diseases and other inflammatory and/or neurologic 
disorders of interest which may or may not have an autoimmune etiology. AESIs that need to be recorded and 
reported as pIMDs for Stage 3 participants are listed in Appendix A of the protocol. 
However, the investigator will exercise their medical and scientific judgement in deciding whether other 
diseases have an autoimmune origin (that is pathophysiology involving systemic or organspecific pathogenic 
autoantibodies) and should also be recorded as a pIMD. 
When there is enough evidence to make any of the diagnoses mentioned in Appendix A of the protocol, the 
AESI must be reported as a pIMD. Symptoms, signs or conditions which might (or might not) represent the 
above diagnoses, should be recorded and reported as AEs but not as pIMDs until the final or definitive 
diagnosis has been determined, and alternative diagnoses have been eliminated or shown to be less likely. 
New Onset of Chronic Medical Conditions (NOCMCs)  
NOCMCs are defined as any new ICD diagnosis (per current International Statistical Classification of 
Diseases and Related Health Problems) that is applied to the subject during the course of the study, after 
receipt of the study agent, that is expected to continue for at least 3 months and requires continued health care 
intervention. 
Medically Attended Adverse Events (MAAEs)  
MAAEs are defined as a hospitalization < 24 hours, emergency room visit or an otherwise unscheduled visit 
to or from medical personnel for any reason; and considered related or possibly related to study product. 
Time Period and Frequency for Event Assessment and Follow-Up 
For this study: 
• Solicited Adverse Events will be collected for 7 days following each vaccine dose. 
• Unsolicited AEs will be collected until 28 days after each vaccination. 
• AESIs, NOCMCs, MAAEs, SAEs, and AEs leading to withdrawal from the study will be collected 
from Day 1 through the end of the study. 
SARS-CoV-2 infection 
Confirmed SARS-CoV-2 infection at any time during the study defined as a positive RT-PCR test performed 
by the site or using a non-site testing method (RT-PCT or antigen test), will be documented. While this event 
would occur on study, it is not typical AE and therefore captured as an exploratory efficacy assessment.  


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5. 
SAMPLE SIZE CONSIDERATIONS 
Sample Size Calculations for the Safety Endpoints 
Rare AEs are not demonstrable in a clinical study of this size; however, the probabilities of observing one or 
more AEs given various true event rates are presented in Table 5. With the assumption that all enrolled 
subjects will likely complete immunizations and safety visits in this relatively short study duration, the 
following statistical considerations apply. With approximately 100 subjects there is a greater than 99.9% 
chance of observing at least one AE of probability 10%. With approximately 50 subjects, there is a 99.5% 
chance of observing at least one AE of probability 10%. With approximately 25 subjects, there is a 92.8% 
chance of observing at least one AE of probability 10%. Finally, with approximately 15 subjects, there is a 
79.4% chance of observing at least one AE of probability 10%. Therefore, if no AEs of a given type occur in a 
group (or strata/subgroup), we can be relatively confident that they will occur in fewer than 10% of people if 
the vaccine is implemented.  
Sample Size Calculations for the Immunogenicity Endpoints 
The primary objective of this study is to evaluate the magnitude and durability of SARS-CoV-2 specific 
antibody titers in serum samples. This objective is descriptive in nature and will be accomplished by 
estimating 95% confidence intervals (CI) for the geometric mean titer (GMT) at each timepoint when samples 
are collected. 
The precision with which the GMT can be estimated from observed data depends on the standard deviation 
(SD) of the measurements, on the logarithmic scale, and the sample size. Table 6 displays two-sided 95% 
confidence intervals for the GMT for several values of the observed antibody titer.  


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6. 
GENERAL STATISTICAL CONSIDERATIONS 
6.1. 
General Principles 
Unless otherwise noted, continuous variables will be summarized using the following descriptive statistics: n 
(non-missing sample size), mean, standard deviation, median, maximum, and minimum. The frequency and 
percentages (based on the non-missing sample size) of observed levels will be reported for all categorical 
measures. In general, all data will be listed, sorted by vaccine arm and subject, and when appropriate by visit 
number within subject. Summary tables will be structured with a column for each variant and will be 
annotated with the total population size relevant to that table/cohort, including any missing observations. 
6.2. 
Timing of Analyses 
Interim analyses will occur as needed. Statistical analyses of immunogenicity endpoints, by vaccine arm, may 
be performed when subjects have completed key immunogenicity visits. 
6.3. 
Analysis Populations 
A tabular listing of all subjects, visits, and observations excluded from the immunogenicity analysis will be 
provided in the CSR (Listing 5). 
6.3.1. 
Modified Intention-to-Treat (mITT) Population 
The modified intention-to-treat (mITT) population includes all subjects who received at least one dose of 
vaccine and contributed both pre- and at least one post-vaccination venous blood sample for immunogenicity 
testing for which valid results were reported.  
6.3.2. 
Per Protocol Population 
In the final analysis, protocol deviations will be reviewed to determine which protocol deviations may affect 
the analysis. The per protocol (PP) population will then be defined. The PP population will, at minimum, 
exclude the following from the mITT Population: 
• Data from all available visits for subjects found to be ineligible at baseline. 
• Data from all visits subsequent to the protocol deviations that are considered to affect the science. 
• Data from any visit that occurs substantially out of window. 
6.3.3. 
Safety Population 
The safety analysis population includes all enrolled subjects who received at least one dose of study vaccine. 
This population will be summarized according to the actual study vaccine received, not necessarily the 
vaccine to which a subject was randomized. 
6.4. 
Covariates and Subgroups 
Subgroup analyses, by age group and infection status, will be completed. Analyses for each subgroup will 
include descriptive summaries and confidence intervals but no formal hypothesis testing, following 
recommendations for subgroup analyses that may inflate false positive conclusion rates and lack statistical 
power. Additional exploratory subgroup analyses may be performed as required. 


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6.5. 
Missing Data 
There are no imputations planned for missing data. 
For immunogenicity assays, any values below the lower limit of detection will be imputed as one-half of the 
lower limit of detection for analysis purposes. Any such imputations will be noted in the corresponding 
analysis. 
6.6. 
Interim Analyses and Data Monitoring 
Cumulative safety information, study status, and primary endpoint results may be published, presented at a 
public forum, or presented as summaries aggregated by vaccination group at the discretion of the sponsor 
while the study is ongoing. None of the interim analyses will include any formal statistical hypothesis testing; 
therefore, p-value adjustment will not be made to any analyses. 
6.7. 
Multicenter Studies 
Data will be pooled across all clinical sites. Center effects are not anticipated because the sites are using 
standardized procedures for vaccination and assessment of solicited and unsolicited adverse events, and the 
study relies on central laboratories for the assessment of immunogenicity endpoints. 
6.8. 
Multiple Comparisons/Multiplicity 
No hypothesis testing will be conducted, therefore, there are no p-value adjustments planned for multiple 
comparisons. Confidence intervals may be adjusted as appropriate. 


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7.
STUDY SUBJECTS
7.1. 
Disposition of Subjects 
Table 11 will present a summary of the reasons that subjects were screened but not enrolled. 
The composition of analysis populations, including reasons for subject exclusion, by vaccination arm, is 
presented in Table 10. 
The disposition of subjects in the study will be tabulated by vaccination group (Table 9). The table shows the 
total number of subjects screened, enrolled, receiving at least 1 dose, receiving 2 doses (if applicable), 
discontinued dosing or terminated from study follow-up and the number completing the study. 
A flowchart showing the disposition of study subjects, adapted from the Consort Statement [41] will be 
included (Figure 1). This figure will present the number of subjects screened, enrolled, lost to follow-up, and 
analyzed, by vaccination arm. 
A listing of subjects who discontinued dosing or terminated from study follow-up and the reason will be 
included in Listing 1. 
7.2. 
Protocol Deviations 
A summary of subject-specific protocol deviations will be presented by the reason for the deviation, the 
deviation category, and vaccination group for all subjects (Table 7) as well as similar summaries for major 
subject-specific protocol deviations that may affect analyses (Table 8). All subject-specific protocol 
deviations and non-subject specific protocol deviations will be included in Appendix 3 as data listings 
(Listing 2 and Listing 3, respectively). 


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8. 
IMMUNOGENICITY EVALUATION 
8.1. 
Primary Immunogenicity Analyses   
Descriptive summaries of immunogenicity data will be presented for the mITT population. If there are 
protocol deviations which may affect the analysis, an analysis of the per-protocol (PP) population may also be 
performed. 
The results of three immunological assays will be analyzed. The 10-plex (ECLIA) assay is a fit-for-purpose 
assay that reports antibody concentrations as arbitrary units (AU) interpolated from ECL signal of internal 
standards or reports as area under the curve (AUC) and is used to assess antibody binding for variants of 
concern. The results of the 10-plex ECLIA assay will be summarized for each group at each timepoint by the 
geometric mean (GM), geometric mean fold rise (GMFR) from baseline (Day 1), geometric mean ratio 
(GMR) against D614G, and geometric mean fold drop (GMFD) from Day 29 (and Day 85 for 2 dose group) 
along with corresponding 95% confidence intervals (CIs). GMFR is defined as the ratio of the result at a 
timepoint divided by the result at Day 1. GMR is defined as the ratio of the result for a variant of concern to 
D614G (e.g. Beta to D614G). GMFD is defined as the ratio of the result at Day 29 (or day 85) divided by the 
result at a timepoint following day Day 29 (or Day 85). Seropositive rate is the proportion of subjects with a 
result above the lower limit of detection. The lower limit of detection will be annotated in the tables and 
figures where applicable. Summaries of the 10-plex ECLIA results are shown starting with Table 15 and 
ending with Table 122. Graphical displays will include geometric mean over time (starting with Figure 2 and 
ending with Figure 109), and distribution of responses over time (starting with Table 326 and ending with 
Table 433). 
The SARS-CoV-2 pseudovirus neutralization assay (PsVNA) and focus reduction neutralization test (FRNT) 
will be run using serial dilutions against available variants (e.g. Beta, Delta, Omicron). From these assays, 
ID50, which estimates the amount of antibodies required for a neutralization rate of 50%, will be reported. 
Neutralization titers will be summarized by the GM, GMFR, GMR, GMFD, and seropositive rate with 
corresponding 95% CIs, for each group at each timepoint. The summaries of PsVNA results are shown 
starting with Table 123 and ending with Table 230, and the summaries of FRNT results are shown starting 
with Table 231 and ending with Table 338. Graphical displays for PsVNA and FRNT will include geometric 
mean over time (starting with Figure 110 and ending with Figure 325) and distributions of responses over 
time (starting with Figure 434 and ending with Figure 649). 
The immunogenicity timepoints for single-dose arms are Study Days 1, 15, 29, 91, 181, 271, and 366. The 
timepoints for the two-dose arm are Study Days 1, 15, 29, 57, 71, 85, 147, 237, 327, and 422. CIs for GM, 
GMFR, GMR, and GMFD will be calculated using the Student’s t-distribution and CIs for seropositive rates 
will be calculated using the Clopper-Pearson binomial method. If additional immunological assays are 
determined to be necessary, then the results will be summarized in a similar manner to that of the assays 
described above. 
The ELISA SARS-CoV-2 Nucleoprotein IgG (N-Protein) assay will be used to test for antibodies to the N-
protein as an indicator of previous COVID-19 infection during the course of the study. This assay will return 
a result of negative or positive for previous COVID-19 infection. The result may be used in subgroup 
analyses. 
For the pseudovirus neutralization assay, an ANCOVA model will be implemented to obtain estimates of the 
treatment group effect adjusted for prior infection status (determined by the N-Protein assay or self-report), 
log10 of baseline antibody titers, and age group. A log10 transformation will be applied to the dependent 
variable, which will be antibody titers, to obtain the treatment effect estimates as ratios of each treatment 


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group relative to the prototype treatment arm. The ANCOVA model will be applied to all immunogenicity 
study time points in single dose arms. Estimates and 95% CIs will be reported for the treatment group effects, 
and a Bonferroni adjustment will be applied to adjust the CIs for the number of treatment group comparisons. 
The model will be estimated for the mITT population as well as the subsample of the mITT population of 
subjects who do not have a history of COVID-19 infection, as determined by the N-Protein assay or self 
report. When the model is applied to the sample of uninfected subjects, prior infection status will not be 
included as a covariate (Table 339, Table 340, Table 341, and Table 342). 
Correlations between the results from samples tested at different labs (e.g. PsVNA) may be calculated to 
evaluate the consistency of results across testing facilities. 
Individual immunogenicity responses are shown in Listing 8. 
8.2. 
Secondary Immunogenicity Analyses 
See Section 9 for safety analyses which are the secondary endpoints of this study. 
8.3. 
Exploratory Immunogenicity/Efficacy Analyses 
8.3.1. 
T-cells 
The magnitude, phenotype and percentage of cytokine expressing S protein specific T cells will be 
summarized at selected timepoints by vaccination group. Mean percentages of CD4 and CD8 T cells 
expressing cytokines and proportions of responders with 95% CI, along with median, minimum, and 
maximum, will be presented by peptide pool stimulation (starting with Table 343 and ending with Table 414). 
Distributions of T cell percentages will be graphically displayed (starting with Figure 650 and ending with 
Figure 757). 
Individual T-cell responses are shown in Listing 9. 
8.3.2. 
B-cells 
Antigen-specific memory B cells were defined as CD3, CD8, CD14, CD16, and CD56 negative, but CD19, 
CD20, CD27, IgG or IgA (both on the same color) positive, and positive for one or more of WT or SA RBD, 
NTD (both variants on a single color) or S-2P. Longitudinal timepoints from each study participant were 
analyzed as a unit to mitigate batch effects and allow internal normalization to each individual’s baseline 
sample. Median percentages of antigen specific B-cells along with min, max, median fold rise, and min and 
max of fold rise will be presented by probe (starting with Table 415 and ending with Table 450). Distributions 
of B cell percentages will be graphically displayed (starting with Figure 758 and ending with Figure 1009. 
Individual B-cell responses are shown in Listing 10. 
8.3.3. 
Breakthrough Infections 
Confirmed SARS-CoV-2 infection at any time during the study, defined as a positive RT-PCR test performed 
by the site or using a non-site testing method (RT-PCR or antigen test) or N-antibody positive at a visit, will 
be documented as an exploratory efficacy assessment. Kaplan-Meier curves and 95% confidence intervals of 
infection free survival will be calculated (starting with Figure 1010 and ending with Figure 1018). Time to 
infection restricted mean survival time analyses will also be reported (starting with Table 451 and ending with 
Table 459). 


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8.3.4. 
Sequencing Results of Breakthrough Infections 
The Simon and Bakel labs at the Icahn School of Medicine at Mount Sinai  will analyze nasopharyngeal swab 
specimens collected from participants who experienced a SARS-CoV-2 breakthrough infection. The analysis 
aims to provide data on SARS-CoV-2 copy numbers and SARS-CoV-2 genotype/lineage. 
The SARS-CoV-2 breakthrough positive nasopharyngeal specimens will be provided either as a dry swab or 
resuspended in viral transport media (both specimen types cryo-preserved at –80C). Biospecimen will be 
accessioned and processed according to the SOPs developed in collaboration with Dr. Greninger [42]. Briefly, 
each specimen undergoesRNA extraction, Reverse Transcriptase quantitative real time PCR (RT qPCR) and 
cDNA synthesis, whole-genome amplification followed by library preparation and next generation Illumina 
sequencing if the amount of SARS-CoV-2 passes the minimum requirements (e.g., less than threshold cycle 
32). SARS-CoV-2 genomes will be assembled and subjected to quality control using the lab’s custom 
vRAPID pipeline [43]. Genomes with at least 95% coverage and 100X depth across all regions will be 
considered complete. Genotypic analysis and clade/lineage assignment of complete genomes will be 
performed using the Nextclade CLI (v2.13.1), pangolin (v2.4) and pangoLEARN (v1.19) pipelines.  Samples 
will be traced to their ancestral lineage assignments by obtaining the first letter and first numerical character 
of the lineage aliases provided by Nextclade. 
A summary of variant PANGO calls are provided starting at Table 460 and ending at Table 468. A visual 
summary is provided starting at Figure 1019 and ending at Figure 1024. 
Individual sequencing results are shown in Listing 11. 
Further details on the analyses of exploratory endpoints will be described in an addendum to the Statistical 
Analysis Plan. 


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9. 
SAFETY EVALUATION 
Summaries and analysis of safety data will be presented for the Safety Analysis Population. 
Solicited non serious AEs will be collected from the time of each vaccination until 7 days after. Solicited AEs 
will be summarized by severity for each day post each vaccination and as the maximum severity over all 8 
days. Additionally, solicited AEs will be analyzed using standard techniques, such as 95% CIs (using the 
Clopper-Pearson method), to summarize the proportion of subjects reporting each symptom, any application 
site symptom, and any systemic symptom.  
Unsolicited non-serious AEs will be collected from the time of first vaccination through 28 days after each 
vaccination. Unsolicited AEs will be coded by MedDRA for preferred term and system organ class (SOC). 
SAEs, MAAEs, NOCMCs, AESIs, and AEs leading to withdrawal from the study will be collected from the 
time of first vaccination through 12 months after the last vaccine dose. The numbers of SAEs, MAAEs, 
NOCMCS, AESIs, and AEs leading to withdrawal from the study will be reported by detailed listings 
showing the event description, MedDRA preferred term and SOC, relevant dates (vaccinations and AEs), 
severity, relatedness, and outcome for each event. Non-serious unsolicited AEs will be summarized as number 
and percentage of subjects reporting at least one event in each MedDRA preferred term and SOC, cross 
tabulated by severity and relationship to study product. Additionally, the proportion of subjects and 95% CIs 
of AEs in aggregate and by MedDRA categories will be computed.  
9.1. 
Demographic and Other Baseline Characteristics 
Summaries of age, sex, ethnicity, race, time from first booster, time since covid infection, time since 1st 
booster or covid infection, and prior infection status (by self-report, N-Protein, either) will be presented by 
vaccination group (Table 12 and Table 13). Ethnicity is categorized as Hispanic or LatinX, or not Hispanic 
and not LatinX. In accordance with NIH reporting policy, subjects may self-designate as belonging to more 
than one race or may refuse to identify a race, the latter reflected in the CRF as “No” to each racial option. 
Individual subject listings (Appendix 3) will be presented for all demographics (Listing 6). 
9.1.1. 
Prior and Concurrent Medical Conditions 
All current illnesses and past pre-existing medical conditions will be MedDRA® coded using MedDRA 
dictionary version 23.0 or higher. 
Summaries of subjects’ pre-existing medical conditions will be presented by vaccination group (Table 14). 
Individual subject listings will be presented for all medical conditions (Listing 7). 
9.1.2. 
Prior and Concomitant Medications  
Summaries of medications that were started prior to dosing and continuing at the time of dosing will be 
presented by WHO Drug Terms 2 and 3 and treatment group (Table 486). 
Individual subject listings will be presented for all concomitant medications (Listing 17). 
9.2. 
Measurements of Treatment Compliance 
All subjects are to receive one or two  doses of study product administered in the clinic. The number of 
subjects receiving each dose will be summarized as part of the subject disposition table (Table 9). 


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9.3. 
Adverse Events 
When calculating the incidence of adverse events (i.e., on a per subject basis), each subject will only be 
counted once and any repetitions of adverse events within a subject will be ignored; the denominator will be 
the total population size. All adverse events reported will be included in the summaries and analyses. 
9.3.1. 
Solicited Events and Symptoms 
Systemic solicited adverse events were collected pre-vaccination, and systemic and local solicited adverse 
events were collected 30 minutes post-vaccination and then daily for 7 days after each vaccination and graded 
on a scale of 0 (absent), 1 (mild), 2 (moderate) and 3 (severe). Systemic events include fatigue, headache, 
myalgia, and fever. Local events include pain at injection site, erythema, and induration. 
The proportion of subjects reporting at least one solicited adverse event will be summarized for each solicited 
adverse event, any systemic symptom, any local symptom, and any symptoms. The 95% CI will be calculated 
using the Clopper-Pearson method (Table 470, Table 471, Table 472, Figure 1025, and Figure 1026). 
For each systemic and local event, any systemic event, any local event, and any solicited event, the maximum 
severity over 7 days after each vaccination will be summarized for the Safety population. The number and 
percentage of subjects reporting each event will be summarized by the maximum severity and treatment 
group, separately for each vaccination and over all vaccinations. For each event the denominator is the 
number of subjects with non-missing data for the specific event (Table 471, Table 472, Figure 1025, and 
Figure 1026).  
The number of subjects reporting a solicited adverse event will be summarized for each day post vaccination 
for each vaccination and for all vaccinations combined both in a summary table (Table 473, Table 474, 
Table 475, Table 476, Table 477, Table 478) and graphically in a bar chart (Figure 1027 and Figure 1028). 
The mean, standard deviation, median, minimum, and maximum duration of solicited events will be 
summarized (Table 479). Day of solicited symptom onset will be summarized graphically (Figure 1029, 
Figure 1030, Figure 1031, Figure 1032) 
Solicited adverse events by subject will be presented in Listing 9 and Listing 10, and graphically starting with 
Figure 1033 and ending with Figure 1044. 
9.3.2. 
Unsolicited Adverse Events 
Unsolicited AEs will be collected until 28 days after each vaccination. The proportion of subjects reporting at 
least one unsolicited adverse event will be summarized by MedDRA system organ class and preferred term 
for each vaccination and over all vaccinations. Denominators for percentages are the number of subjects who 
received the vaccination being summarized.  
Adverse events by subject will be presented in Listing 14. 
The following summaries for unsolicited adverse events will be presented by MedDRA system organ class, 
preferred term, vaccination, and treatment group: 
• Summary of severity and relationship to study product (Table 480, Table 481, and Table 482); 
• Subject listing of non-serious adverse events of moderate or greater severity (Table 484); 
• Bar charts of incidence and frequency of adverse events by severity and MedDRA system organ 
class (Figure 1045 and Figure 1046). 


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9.4. 
Deaths, Serious Adverse Events and other Significant Adverse Events 
The following listings will be presented including Subject ID, Age (years) Adverse Event Description, 
Adverse Event Onset Date/End Date, Last Dose Received/Days Post Dose, Reason Reported as an SAE, 
Relationship to Treatment, Alternate Etiology if not Related, Outcome, and Duration of Event (days): 
• Deaths and Serious Adverse Events (Table 483); 
• Adverse Events of Special Interest (Table 485); 
• New Onset Chronic Medical Conditions and Medically Attended Adverse Events (Table 485). 
9.5. 
Pregnancies 
For any subjects in the Safety population who became pregnant during the study, every attempt was made to 
follow these subjects to completion of pregnancy to document the outcome, including information regarding 
any complications with pregnancy and/or delivery. In addition, a listing of pregnancies and outcomes will be 
presented (Listing 18, Listing 19, Listing 20, Listing 21, and Listing 22). 
9.6. 
Clinical Laboratory Evaluations 
Not applicable. 
9.7. 
Vital Signs and Physical Evaluations 
Vital sign measurements included systolic blood pressure, diastolic blood pressure and oral temperature. Vital 
signs were assessed at screening visit and Day 1 (Listing 15). 
Physical Examinations performed at screening visit and Day 1 (Listing 16). 
There are no planned vital sign measurements or physical examinations for follow-up visits. No tabulations 
will be made. 
9.8. 
Concomitant Medications 
Concomitant medications will be coded to the Anatomical Therapeutic Classification using the WHO Drug 
Dictionary. The use of prior and concomitant medications taken during the study will be recorded on the 
CRFs. A by-subject listing of concomitant medication use will be presented (Listing 17). The use of 
concomitant medications during the study will be summarized by ATC1, ATC2 code and treatment group for 
the Safety population (Table 486). 
9.9. 
Other Safety Measures 
Not applicable. 


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10. 
PHARMACOKINETICS 
Not applicable. 


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11. 
IMMUNOGENICITY 
See Section 8. 


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12. 
OTHER ANALYSES 
Not applicable. 


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13. 
REPORTING CONVENTIONS 
The mean, standard deviation, and other statistics will be reported to 1 decimal place greater than the original 
data. The minimum and maximum will use the same number of decimal places as the original data. 
Proportions will be presented as 2 decimal places; values greater than zero but <0.01 will be presented as 
“<0.01”. Percentages will be reported to the nearest whole number; values greater than zero but < 1% will be 
presented as “<1”; values greater than 99% but less than 100% will be reported as >99%. Estimated 
parameters, not on the same scale as raw observations (e.g. regression coefficients) will be reported to 3 
significant figures. 


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14. 
TECHNICAL DETAILS 
SAS version 9.4 and R 3.6.2 or above will be used to generate all tables, figures, and listings. 


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15. 
SUMMARY OF CHANGES IN THE CONDUCT OF THE STUDY OR 
PLANNED ANALYSES 
ANCOVA models were added to compare vaccination groups to prototype. 
An analysis of breakthrough infections was also added that includes Kaplan-Meier Curves and restricted mean 
survival time. 
An analysis of geometric mean fold drop was added. 


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16. 
REFERENCES 
1. WHO. World Health Organization, Weekly Operational Update on COVID-19.  
2. JHU. JHU. -19 Dashboard, Center for Systems Science and Engineering (CCSE) at Johns Hopkins 
University (JHU).  
3. Corbett KS, Edwards DK, Leist SR, et al. SARS-CoV-2 mRNA vaccine design enabled by prototype 
pathogen preparedness. Nature 2020;586:567-71. 
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vaccine for preventing severe outcomes in Israel: an observational study. Lancet 2021;398:2093-100. 
17. Bar-On YM, Goldberg Y, Mandel M, et al. Protection against Covid-19 by BNT162b2 Booster across 
Age Groups. N Engl J Med 2021;385:2421-30. 


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18. Patalon T, Gazit S, Pitzer VE, Prunas O, Warren JL, Weinberger DM. Odds of Testing Positive for 
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36. Jones JM, Stone M, Sulaeman H, et al. Estimated US Infection- and Vaccine-Induced SARSCoV-2 
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17. 
LISTING OF TABLES, FIGURES, AND LISTINGS  
Table, figure, and listing shells are presented in Appendices 1, 2, and 3. Note, shells are shown only for  
stage 1 as examples. Tables, figures and listings will be presented for each stage in the CSRs. 
 


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APPENDICES 


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APPENDIX 1. TABLE MOCK-UPS 
 
 


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LIST OF TABLES 
Table 1: 
Objectives and Endpoints (Outcome Measures) .........................................................13 
Table 2: 
Study Design ...............................................................................................................81 
Table 3: 
Schedule of Study Procedures - Single Dose .............................................................82 
Table 4: 
Schedule of Study Procedures - 2 Doses ....................................................................84 
Table 5: 
Probability of observing one or more Adverse Events for various event rates 
in one vaccine group (or strata) ..................................................................................87 
Table 6: 
Two-sided 95% confidence intervals based on observing a particular average 
loge-antibody titer in subjects’ vaccine groups and potential strata sizes ...................87 
Table 7: 
Distribution of Protocol Deviations by Category, Type, and Treatment 
Group ..........................................................................................................................89 
Table 8: 
Distribution of Major Protocol Deviations by Category, Type, and Treatment 
Group ..........................................................................................................................90 
Table 9: 
Subject Disposition by Treatment Group ...................................................................93 
Table 10: Analysis Populations by Treatment Group .................................................................94 
Table 11: Ineligibility Summary of Screen Failures ...................................................................95 
Table 12: Summary of Categorical Demographic and Baseline Characteristics by 
Treatment Group, All Enrolled Subjects ....................................................................96 
Table 13: Summary of Continuous Demographic and Baseline Characteristics by 
Treatment Group, All Enrolled Subjects ....................................................................98 
Table 14: Summary of Subjects with Pre-Existing Medical Conditions by MedDRA 
System Organ Class and Treatment Group ..............................................................100 
Table 15: Serum IgG Binding Assay Area Under the Curve  Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Prototype, Overall – 
mITT Population .......................................................................................................101 
Table 16: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Prototype, Overall – Per 
Protocol Population ..................................................................................................103 
Table 17: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Prototype, Younger 
Cohort – mITT Population ........................................................................................103 
Table 18: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Prototype, Younger 
Cohort – Per Protocol Population .............................................................................103 
Table 19: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Prototype, Older Cohort 
– mITT Population ....................................................................................................103 


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Table 20: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Prototype, Older Cohort 
– Per Protocol Population .........................................................................................103 
Table 21: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Prototype, Infected (by 
Self-Report or N-protein) Cohort – mITT Population ..............................................103 
Table 22: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Prototype, Infected (by 
Self-Report or N-protein) Cohort – Per Protocol Population ...................................103 
Table 23: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Prototype, Uninfected (by 
Self-Report or N-protein) Cohort – mITT Population ..............................................104 
Table 24: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Prototype, Uninfected (by 
Self-Report or N-protein) Cohort – Per Protocol Population ...................................104 
Table 25: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Prototype, Younger 
Infected (by Self-Report or N-protein) Cohort – mITT Population .........................104 
Table 26: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Prototype, Younger 
Infected (by Self-Report or N-protein) Cohort – Per Protocol Population ...............104 
Table 27: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Prototype, Younger 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population .....................104 
Table 28: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Prototype, Younger 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population ..........104 
Table 29: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Prototype, Older Infected 
(by Self-Report or N-protein) Cohort – mITT Population .......................................104 
Table 30: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Prototype, Older Infected 
(by Self-Report or N-protein) Cohort – Per Protocol Population .............................104 
Table 31: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Prototype, Older 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population .....................104 
Table 32: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Prototype, Older 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population ..........104 


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Table 33: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 1 Dose Beta + Omicron, 
Overall – mITT Population .......................................................................................104 
Table 34: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 1 Dose Beta + Omicron, 
Overall – Per Protocol Population ............................................................................104 
Table 35: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 1 Dose Beta + Omicron, 
Younger Cohort – mITT Population .........................................................................104 
Table 36: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 1 Dose Beta + Omicron, 
Younger Cohort – Per Protocol Population ..............................................................104 
Table 37: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 1 Dose Beta + Omicron, 
Older Cohort – mITT Population .............................................................................105 
Table 38: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 1 Dose Beta + Omicron, 
Older Cohort – Per Protocol Population ...................................................................105 
Table 39: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 1 Dose Beta + Omicron, 
Infected (by Self-Report or N-protein) Cohort – mITT Population .........................105 
Table 40: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 1 Dose Beta + Omicron, 
Infected (by Self-Report or N-protein) Cohort – Per Protocol Population ...............105 
Table 41: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 1 Dose Beta + Omicron, 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population .....................105 
Table 42: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 1 Dose Beta + Omicron, 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population ..........105 
Table 43: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 1 Dose Beta + Omicron, 
Younger Infected (by Self-Report or N-protein) Cohort – mITT Population ..........105 
Table 44: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 1 Dose Beta + Omicron, 
Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................105 
Table 45: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 1 Dose Beta + Omicron, 
Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................105 


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Table 46: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 1 Dose Beta + Omicron, 
Younger Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................105 
Table 47: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 1 Dose Beta + Omicron, 
Older Infected (by Self-Report or N-protein) Cohort – mITT Population ...............105 
Table 48: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 1 Dose Beta + Omicron, 
Older Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................105 
Table 49: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 1 Dose Beta + Omicron, 
Older Uninfected (by Self-Report or N-protein) Cohort – mITT Population ..........105 
Table 50: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 1 Dose Beta + Omicron, 
Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................106 
Table 51: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Delta + Omicron, Overall 
– mITT Population ....................................................................................................106 
Table 52: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Delta + Omicron, Overall 
– Per Protocol Population .........................................................................................106 
Table 53: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Delta + Omicron, 
Younger Cohort – mITT Population .........................................................................106 
Table 54: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Delta + Omicron, 
Younger Cohort – Per Protocol Population ..............................................................106 
Table 55: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Delta + Omicron, Older 
Cohort – mITT Population ........................................................................................106 
Table 56: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Delta + Omicron, Older 
Cohort – Per Protocol Population .............................................................................106 
Table 57: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Delta + Omicron, 
Infected (by Self-Report or N-protein) Cohort – mITT Population .........................106 


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Table 58: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Delta + Omicron, 
Infected (by Self-Report or N-protein) Cohort – Per Protocol Population ...............106 
Table 59: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Delta + Omicron, 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population .....................106 
Table 60: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Delta + Omicron, 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population ..........106 
Table 61: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Delta + Omicron, 
Younger Infected (by Self-Report or N-protein) Cohort – mITT Population ..........106 
Table 62: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Delta + Omicron, 
Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................106 
Table 63: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Delta + Omicron, 
Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................106 
Table 64: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Delta + Omicron, 
Younger Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................107 
Table 65: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Delta + Omicron, Older 
Infected (by Self-Report or N-protein) Cohort – mITT Population .........................107 
Table 66: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Delta + Omicron, Older 
Infected (by Self-Report or N-protein) Cohort – Per Protocol Population ...............107 
Table 67: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Delta + Omicron, Older 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population .....................107 
Table 68: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Delta + Omicron, Older 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population ..........107 
Table 69: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron, Overall– mITT 
Population .................................................................................................................107 


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Table 70: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron, Overall – Per 
Protocol Population ..................................................................................................107 
Table 71: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron, Younger 
Cohort – mITT Population ........................................................................................107 
Table 72: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron, Younger 
Cohort – Per Protocol Population .............................................................................107 
Table 73: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron, Older Cohort – 
mITT Population .......................................................................................................107 
Table 74: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron, Older Cohort – 
Per Protocol Population ............................................................................................107 
Table 75: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron, Infected (by 
Self-Report or N-protein) Cohort – mITT Population ..............................................107 
Table 76: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron, Infected (by 
Self-Report or N-protein) Cohort – Per Protocol Population ...................................107 
Table 77: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron, Uninfected (by 
Self-Report or N-protein) Cohort – mITT Population ..............................................107 
Table 78: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron, Uninfected (by 
Self-Report or N-protein) Cohort – Per Protocol Population ...................................107 
Table 79: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron, Younger 
Infected (by Self-Report or N-protein) Cohort – mITT Population .........................108 
Table 80: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron, Younger 
Infected (by Self-Report or N-protein) Cohort – Per Protocol Population ...............108 
Table 81: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron, Younger 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population .....................108 
Table 82: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron, Younger 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population ..........108 


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Table 83: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron, Older Infected 
(by Self-Report or N-protein) Cohort – mITT Population .......................................108 
Table 84: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron, Older Infected 
(by Self-Report or N-protein) Cohort – Per Protocol Population .............................108 
Table 85: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron, Older 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population .....................108 
Table 86: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron, Older 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population ..........108 
Table 87: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron + Prototype, 
Overall– mITT Population ........................................................................................108 
Table 88: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron + Prototype, 
Overall– Per Protocol Population .............................................................................108 
Table 89: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron + Prototype, 
Younger Cohort – mITT Population .........................................................................108 
Table 90: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron + Prototype, 
Younger Cohort – Per Protocol Population ..............................................................108 
Table 91: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron + Prototype, 
Older Cohort – mITT Population .............................................................................108 
Table 92: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron + Prototype, 
Older Cohort – Per Protocol Population ...................................................................108 
Table 93: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron + Prototype, 
Infected (by Self-Report or N-protein) Cohort – mITT Population .........................109 
Table 94: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron + Prototype, 
Infected (by Self-Report or N-protein) Cohort – Per Protocol Population ...............109 
Table 95: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron + Prototype, 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population .....................109 


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Table 96: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron + Prototype, 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population ..........109 
Table 97: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron + Prototype, 
Younger Infected (by Self-Report or N-protein) Cohort – mITT Population ..........109 
Table 98: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron + Prototype, 
Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................109 
Table 99: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron + Prototype, 
Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................109 
Table 100: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron + Prototype, 
Younger Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................109 
Table 101: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron + Prototype, 
Older Infected (by Self-Report or N-protein) Cohort – mITT Population ...............109 
Table 102: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron + Prototype, 
Older Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................109 
Table 103: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron + Prototype, 
Older Uninfected (by Self-Report or N-protein) Cohort – mITT Population ..........109 
Table 104: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, Omicron + Prototype, 
Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................109 
Table 105: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 2 Dose Beta + Omicron, 
Overall – mITT Population .......................................................................................110 
Table 106: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 2 Dose Beta + Omicron, 
Overall– Per Protocol Population .............................................................................113 
Table 107: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 2 Dose Beta + Omicron, 
Younger Cohort – mITT Population .........................................................................113 


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Table 108: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 2 Dose Beta + Omicron, 
Younger Cohort – Per Protocol Population ..............................................................113 
Table 109: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 2 Dose Beta + Omicron, 
Older Cohort – mITT Population .............................................................................113 
Table 110: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 2 Dose Beta + Omicron, 
Older Cohort – Per Protocol Population ...................................................................113 
Table 111: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 2 Dose Beta + Omicron, 
Infected (by Self-Report or N-protein) Cohort – mITT Population .........................113 
Table 112: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 2 Dose Beta + Omicron, 
Infected (by Self-Report or N-protein) Cohort – Per Protocol Population ...............113 
Table 113: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 2 Dose Beta + Omicron, 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population .....................114 
Table 114: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 2 Dose Beta + Omicron, 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population ..........114 
Table 115: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 2 Dose Beta + Omicron, 
Younger Infected (by Self-Report or N-protein) Cohort – mITT Population ..........114 
Table 116: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 2 Dose Beta + Omicron, 
Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................114 
Table 117: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 2 Dose Beta + Omicron, 
Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................114 
Table 118: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 2 Dose Beta + Omicron, 
Younger Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................114 
Table 119: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 2 Dose Beta + Omicron, 
Older Infected (by Self-Report or N-protein) Cohort – mITT Population ...............114 
Table 120: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 2 Dose Beta + Omicron, 


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Older Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................114 
Table 121: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 2 Dose Beta + Omicron, 
Older Uninfected (by Self-Report or N-protein) Cohort – mITT Population ..........114 
Table 122: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Summary Results by Time Point and Variant, 2 Dose Beta + Omicron, 
Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................114 
Table 123: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Prototype, Overall – mITT Population .......................................................115 
Table 124: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Prototype, Overall – Per Protocol Population.............................................117 
Table 125: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Prototype, Younger Cohort – mITT Population .........................................117 
Table 126: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Prototype, Younger Cohort – Per Protocol Population ..............................117 
Table 127: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Prototype, Older Cohort – mITT Population ..............................................117 
Table 128: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Prototype, Older Cohort – Per Protocol Population ...................................117 
Table 129: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Prototype, Infected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................117 
Table 130: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Prototype, Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population ..................................................................................................117 
Table 131: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Prototype, Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................118 
Table 132: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Prototype, Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population ..................................................................................................118 
Table 133: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Prototype, Younger Infected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................118 
Table 134: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Prototype, Younger Infected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................118 


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Table 135: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Prototype, Younger Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................118 
Table 136: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Prototype, Younger Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................118 
Table 137: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Prototype, Older Infected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................118 
Table 138: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Prototype, Older Infected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................118 
Table 139: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................118 
Table 140: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................118 
Table 141: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 1 Dose Beta + Omicron, Overall– mITT Population ..................................118 
Table 142: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 1 Dose Beta + Omicron, Overall– Per Protocol Population .......................118 
Table 143: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 1 Dose Beta + Omicron, Younger Cohort – mITT Population...................118 
Table 144: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 1 Dose Beta + Omicron, Younger Cohort – Per Protocol Population ........118 
Table 145: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 1 Dose Beta + Omicron, Older Cohort – mITT Population .......................118 
Table 146: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 1 Dose Beta + Omicron, Older Cohort – Per Protocol Population .............118 
Table 147: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 1 Dose Beta + Omicron, Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................118 
Table 148: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 1 Dose Beta + Omicron, Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................119 
Table 149: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 1 Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................119 


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Table 150: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 1 Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................119 
Table 151: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 1 Dose Beta + Omicron, Younger Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................119 
Table 152: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 1 Dose Beta + Omicron, Younger Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................119 
Table 153: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 1 Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................119 
Table 154: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 1 Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................119 
Table 155: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 1 Dose Beta + Omicron, Older Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................119 
Table 156: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 1 Dose Beta + Omicron, Older Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................119 
Table 157: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 1 Dose Beta + Omicron, Older Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................119 
Table 158: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 1 Dose Beta + Omicron, Older Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................119 
Table 159: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Delta + Omicron, Overall– mITT Population.............................................119 
Table 160: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Delta + Omicron, Overall – Per Protocol Population .................................119 
Table 161: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Delta + Omicron, Younger Cohort – mITT Population .............................119 
Table 162: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Delta + Omicron, Younger Cohort – Per Protocol Population ...................119 
Table 163: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Delta + Omicron, Older Cohort – mITT Population ..................................120 
Table 164: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Delta + Omicron, Older Cohort – Per Protocol Population ........................120 


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Table 165: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Delta + Omicron, Infected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................120 
Table 166: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Delta + Omicron, Infected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................120 
Table 167: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Delta + Omicron, Uninfected (by Self-Report or N-protein) Cohort 
– mITT Population ....................................................................................................120 
Table 168: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Delta + Omicron, Uninfected (by Self-Report or N-protein) Cohort 
– Per Protocol Population .........................................................................................120 
Table 169: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Delta + Omicron, Younger Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................120 
Table 170: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Delta + Omicron, Younger Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................120 
Table 171: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Delta + Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................120 
Table 172: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Delta + Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................120 
Table 173: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Delta + Omicron, Older Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................120 
Table 174: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Delta + Omicron, Older Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................120 
Table 175: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Delta + Omicron, Older Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................120 
Table 176: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Delta + Omicron, Older Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................120 
Table 177: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron, Overall– mITT Population .........................................................120 
Table 178: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron, Overall – Per Protocol Population ..............................................121 


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Table 179: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron, Younger Cohort – mITT Population ..........................................121 
Table 180: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron, Younger Cohort – Per Protocol Population ................................121 
Table 181: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron, Older Cohort – mITT Population ...............................................121 
Table 182: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron, Older Cohort – Per Protocol Population .....................................121 
Table 183: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron, Infected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................121 
Table 184: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron, Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population ..................................................................................................121 
Table 185: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron, Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................121 
Table 186: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron, Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population ..................................................................................................121 
Table 187: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron, Younger Infected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................121 
Table 188: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron, Younger Infected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................121 
Table 189: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort 
– mITT Population ....................................................................................................121 
Table 190: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort 
– Per Protocol Population .........................................................................................121 
Table 191: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron, Older Infected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................121 
Table 192: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron, Older Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population ..................................................................................................121 


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Table 193: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................121 
Table 194: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................121 
Table 195: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron + Prototype, Overall – mITT Population .....................................121 
Table 196: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron + Prototype, Overall – Per Protocol Population ..........................122 
Table 197: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron + Prototype, Younger Cohort – mITT Population.......................122 
Table 198: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron + Prototype, Younger Cohort – Per Protocol Population ............122 
Table 199: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron + Prototype, Older Cohort – mITT Population ...........................122 
Table 200: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron + Prototype, Older Cohort – Per Protocol Population .................122 
Table 201: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron + Prototype, Infected (by Self-Report or N-protein) Cohort 
– mITT Population ....................................................................................................122 
Table 202: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron + Prototype, Infected (by Self-Report or N-protein) Cohort 
– Per Protocol Population .........................................................................................122 
Table 203: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron + Prototype, Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................122 
Table 204: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron + Prototype, Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................122 
Table 205: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron + Prototype, Younger Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................122 
Table 206: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron + Prototype, Younger Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................122 
Table 207: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron + Prototype, Younger Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................122 


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Table 208: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron + Prototype, Younger Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................122 
Table 209: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron + Prototype, Older Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................122 
Table 210: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron + Prototype, Older Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................122 
Table 211: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron + Prototype, Older Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................123 
Table 212: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, Omicron + Prototype, Older Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................123 
Table 213: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant,  2 Dose Beta + Omicron, Overall – mITT Population ................................124 
Table 214: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 2 Dose Beta + Omicron, Overall – Per Protocol Population ......................127 
Table 215: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 2 Dose Beta + Omicron, Younger Cohort – mITT Population...................127 
Table 216: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 2 Dose Beta + Omicron, Younger Cohort – Per Protocol Population ........127 
Table 217: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 2 Dose Beta + Omicron, Older Cohort – mITT Population .......................127 
Table 218: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 2 Dose Beta + Omicron, Older Cohort – Per Protocol Population .............127 
Table 219: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 2 Dose Beta + Omicron, Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................127 
Table 220: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 2 Dose Beta + Omicron, Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................127 
Table 221: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 2 Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................128 
Table 222: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 2 Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................128 


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Table 223: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 2 Dose Beta + Omicron, Younger Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................128 
Table 224: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 2 Dose Beta + Omicron, Younger Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................128 
Table 225: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 2 Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................128 
Table 226: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 2 Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................128 
Table 227: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 2 Dose Beta + Omicron, Older Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................128 
Table 228: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 2 Dose Beta + Omicron, Older Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................128 
Table 229: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 2 Dose Beta + Omicron, Older Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................128 
Table 230: Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and 
Variant, 2 Dose Beta + Omicron, Older Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................128 
Table 231: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Prototype, Overall – mITT Population ................................................129 
Table 232: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Prototype, Overall– Per Protocol Population .......................................131 
Table 233: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Prototype, Younger Cohort – mITT Population ..................................131 
Table 234: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Prototype, Younger Cohort – Per Protocol Population ........................131 
Table 235: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Prototype, Older Cohort – mITT Population .......................................131 
Table 236: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Prototype, Older Cohort – Per Protocol Population.............................131 
Table 237: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Prototype, Infected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................131 


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Table 238: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Prototype, Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population ..................................................................................................131 
Table 239: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Prototype, Uninfected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................131 
Table 240: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Prototype, Uninfected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................131 
Table 241: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Prototype, Younger Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................131 
Table 242: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Prototype, Younger Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................132 
Table 243: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Prototype, Younger Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................132 
Table 244: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Prototype, Younger Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................132 
Table 245: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Prototype, Older Infected (by Self-Report or N-protein) Cohort 
– mITT Population ....................................................................................................132 
Table 246: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Prototype, Older Infected (by Self-Report or N-protein) Cohort 
– Per Protocol Population .........................................................................................132 
Table 247: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Prototype, Older Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................132 
Table 248: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Prototype, Older Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................132 
Table 249: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 1 Dose Beta + Omicron, Overall – mITT Population ..........................132 
Table 250: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 1 Dose Beta + Omicron, Overall – Per Protocol Population ...............132 
Table 251: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 1 Dose Beta + Omicron, Younger Cohort – mITT Population ............132 


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Table 252: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 1 Dose Beta + Omicron, Younger Cohort – Per Protocol 
Population .................................................................................................................132 
Table 253: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 1 Dose Beta + Omicron, Older Cohort – mITT Population .................132 
Table 254: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 1 Dose Beta + Omicron, Older Cohort – Per Protocol 
Population .................................................................................................................132 
Table 255: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 1 Dose Beta + Omicron, Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................132 
Table 256: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 1 Dose Beta + Omicron, Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................132 
Table 257: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 1 Dose Beta + Omicron, Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................132 
Table 258: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 1 Dose Beta + Omicron, Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................133 
Table 259: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 1 Dose Beta + Omicron, Younger Infected (by Self-Report or 
N-protein) Cohort – mITT Population ......................................................................133 
Table 260: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 1 Dose Beta + Omicron, Younger Infected (by Self-Report or 
N-protein) Cohort – Per Protocol Population ...........................................................133 
Table 261: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 1 Dose Beta + Omicron, Younger Uninfected (by Self-Report 
or N-protein) Cohort – mITT Population .................................................................133 
Table 262: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 1 Dose Beta + Omicron, Younger Uninfected (by Self-Report 
or N-protein) Cohort – Per Protocol Population .......................................................133 
Table 263: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 1 Dose Beta + Omicron, Older Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................133 
Table 264: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 1 Dose Beta + Omicron, Older Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................133 


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Table 265: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 1 Dose Beta + Omicron, Older Uninfected (by Self-Report or 
N-protein) Cohort – mITT Population ......................................................................133 
Table 266: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 1 Dose Beta + Omicron, Older Uninfected (by Self-Report or 
N-protein) Cohort – Per Protocol Population ...........................................................133 
Table 267: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Delta + Omicron, Overall – mITT Population .....................................133 
Table 268: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Delta + Omicron, Overall – Per Protocol Population ..........................133 
Table 269: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Delta + Omicron, Younger Cohort – mITT Population .......................133 
Table 270: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Delta + Omicron, Younger Cohort – Per Protocol Population ............133 
Table 271: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Delta + Omicron, Older Cohort – mITT Population............................133 
Table 272: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Delta + Omicron, Older Cohort – Per Protocol Population .................133 
Table 273: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Delta + Omicron, Infected (by Self-Report or N-protein) Cohort 
– mITT Population ....................................................................................................134 
Table 274: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Delta + Omicron, Infected (by Self-Report or N-protein) Cohort 
– Per Protocol Population .........................................................................................134 
Table 275: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Delta + Omicron, Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................134 
Table 276: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Delta + Omicron, Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................134 
Table 277: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Delta + Omicron, Younger Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................134 
Table 278: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Delta + Omicron, Younger Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................134 
Table 279: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Delta + Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................134 


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Table 280: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Delta + Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................134 
Table 281: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Delta + Omicron, Older Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................134 
Table 282: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Delta + Omicron, Older Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................134 
Table 283: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Delta + Omicron, Older Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................134 
Table 284: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Delta + Omicron, Older Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................134 
Table 285: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron, Overall – mITT Population ..................................................134 
Table 286: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron, Overall – Per Protocol Population .......................................134 
Table 287: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron, Younger Cohort – mITT Population ....................................134 
Table 288: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron, Younger Cohort – Per Protocol Population .........................135 
Table 289: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron, Older Cohort – mITT Population ........................................135 
Table 290: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron, Older Cohort – Per Protocol Population ..............................135 
Table 291: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron, Infected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................135 
Table 292: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron, Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population ..................................................................................................135 
Table 293: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron, Uninfected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................135 
Table 294: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron, Uninfected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................135 


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Table 295: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron, Younger Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................135 
Table 296: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron, Younger Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................135 
Table 297: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron, Younger Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................135 
Table 298: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron, Younger Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................135 
Table 299: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron, Older Infected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................135 
Table 300: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron, Older Infected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................135 
Table 301: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron, Older Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................135 
Table 302: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron, Older Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................135 
Table 303: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron + Prototype, Overall – mITT Population ..............................135 
Table 304: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron + Prototype, Overall – Per Protocol Population ...................135 
Table 305: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron + Prototype, Younger Cohort – mITT Population ................135 
Table 306: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron + Prototype, Younger Cohort – Per Protocol 
Population .................................................................................................................136 
Table 307: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron + Prototype, Older Cohort – mITT Population .....................136 
Table 308: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron + Prototype, Older Cohort – Per Protocol Population ..........136 
Table 309: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron + Prototype, Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................136 


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Table 310: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron + Prototype, Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................136 
Table 311: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron + Prototype, Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................136 
Table 312: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron + Prototype, Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................136 
Table 313: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron + Prototype, Younger Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................136 
Table 314: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron + Prototype, Younger Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................136 
Table 315: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron + Prototype, Younger Uninfected (by Self-Report or 
N-protein) Cohort – mITT Population ......................................................................136 
Table 316: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron + Prototype, Younger Uninfected (by Self-Report or 
N-protein) Cohort – Per Protocol Population ...........................................................136 
Table 317: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron + Prototype, Older Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................136 
Table 318: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron + Prototype, Older Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................136 
Table 319: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron + Prototype, Older Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................136 
Table 320: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, Omicron + Prototype, Older Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................136 
Table 321: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 2 Dose Beta + Omicron, Overall – mITT Population ..........................137 
Table 322: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 2 Dose Beta + Omicron, Overall – Per Protocol Population ...............140 
Table 323: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 2 Dose Beta + Omicron, Younger Cohort – mITT Population ............140 


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Table 324: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 2 Dose Beta + Omicron, Younger Cohort – Per Protocol 
Population .................................................................................................................140 
Table 325: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 2 Dose Beta + Omicron, Older Cohort – mITT Population .................140 
Table 326: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 2 Dose Beta + Omicron, Older Cohort – Per Protocol 
Population .................................................................................................................140 
Table 327: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 2 Dose Beta + Omicron, Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................140 
Table 328: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 2 Dose Beta + Omicron, Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................140 
Table 329: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 2 Dose Beta + Omicron, Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................140 
Table 330: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 2 Dose Beta + Omicron, Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................141 
Table 331: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 2 Dose Beta + Omicron, Younger Infected (by Self-Report or 
N-protein) Cohort – mITT Population ......................................................................141 
Table 332: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 2 Dose Beta + Omicron, Younger Infected (by Self-Report or 
N-protein) Cohort – Per Protocol Population ...........................................................141 
Table 333: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 2 Dose Beta + Omicron, Younger Uninfected (by Self-Report 
or N-protein) Cohort – mITT Population .................................................................141 
Table 334: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 2 Dose Beta + Omicron, Younger Uninfected (by Self-Report 
or N-protein) Cohort – Per Protocol Population .......................................................141 
Table 335: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 2 Dose Beta + Omicron, Older Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................141 
Table 336: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 2 Dose Beta + Omicron, Older Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................141 


Statistical Analysis Plan - DMID Protocol: 22-0004  
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Table 337: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 2 Dose Beta + Omicron, Older Uninfected (by Self-Report or 
N-protein) Cohort – mITT Population ......................................................................141 
Table 338: Focus Reduction Neutralization Test ID50 Summary Results by Time Point 
and Variant, 2 Dose Beta + Omicron, Older Uninfected (by Self-Report or 
N-protein) Cohort – Per Protocol Population ...........................................................141 
Table 339: Pseudovirus Neutralization Treatment Group Effects as Ratios Relative 
to the Prototype Arm from ANCOVA model, Overall – mITT 
Population ................................................................................................................142 
Table 340: Pseudovirus Neutralization Treatment Group Effects as Ratios Relative 
to the Prototype Arm from ANCOVA model, Overall – Per Protocol 
Population ................................................................................................................143 
Table 341: Pseudovirus Neutralization Treatment Group Effects as Ratios Relative 
to the Prototype Arm from ANCOVA model, Uninfected (by Self-
Report or N-Protein) Cohort – mITT Population ...............................................143 
Table 342: Pseudovirus Neutralization Treatment Group Effects as Ratios Relative 
to the Prototype Arm from ANCOVA model, Uninfected (by Self-
Report or N-Protein) Cohort – Per Protocol Population ....................................143 
Table 343: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Overall – mITT Population ................................................................144 
Table 344: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Overall – Per Protocol Population .....................................................152 
Table 345: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Older Cohort – mITT Population ......................................................152 
Table 346: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Older Cohort – Per Protocol Population ............................................152 
Table 347: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Younger Cohort – mITT Population..................................................152 
Table 348: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Younger Cohort – Per Protocol Population .......................................152 
Table 349: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Infected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................153 
Table 350: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................153 
Table 351: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................153 


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Table 352: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population ..................................................................................................153 
Table 353: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Older Infected (by Self-Report or  N-protein) Cohort – mITT 
Population .................................................................................................................153 
Table 354: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Older Infected (by Self-Report or  N-protein) Cohort – Per 
Protocol Population ..................................................................................................153 
Table 355: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Older Uninfected (by Self-Report or  N-protein) Cohort – 
mITT Population .......................................................................................................153 
Table 356: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Older Uninfected (by Self-Report or  N-protein) Cohort – Per 
Protocol Population ..................................................................................................153 
Table 357: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Younger Infected (by Self-Report or  N-protein) Cohort – 
mITT Population .......................................................................................................153 
Table 358: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Younger Infected (by Self-Report or  N-protein) Cohort – Per 
Protocol Population ..................................................................................................153 
Table 359: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Younger Uninfected (by Self-Report or  N-protein) Cohort – 
mITT Population .......................................................................................................153 
Table 360: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Younger Uninfected (by Self-Report or  N-protein) Cohort – 
Per Protocol Population ............................................................................................153 
Table 361: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Overall – mITT Population .................................................................154 
Table 362: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Overall – Per Protocol Population .......................................................161 
Table 363: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Older Cohort – mITT Population ........................................................161 
Table 364: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Older Cohort – Per Protocol Population .............................................161 
Table 365: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Younger Cohort – mITT Population ...................................................161 
Table 366: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Younger Cohort – Per Protocol Population.........................................161 


Statistical Analysis Plan - DMID Protocol: 22-0004  
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Table 367: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Infected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................161 
Table 368: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................161 
Table 369: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................161 
Table 370: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................161 
Table 371: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Older Infected (by Self-Report or  N-protein) Cohort – mITT 
Population .................................................................................................................162 
Table 372: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Older Infected (by Self-Report or  N-protein) Cohort – Per 
Protocol Population ..................................................................................................162 
Table 373: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Older Uninfected (by Self-Report or  N-protein) Cohort – 
mITT Population .......................................................................................................162 
Table 374: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Older Uninfected (by Self-Report or  N-protein) Cohort – Per 
Protocol Population ..................................................................................................162 
Table 375: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Younger Infected (by Self-Report or  N-protein) Cohort – 
mITT Population .......................................................................................................162 
Table 376: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Younger Infected (by Self-Report or  N-protein) Cohort – Per 
Protocol Population ..................................................................................................162 
Table 377: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Younger Uninfected (by Self-Report or  N-protein) Cohort – 
mITT Population .......................................................................................................162 
Table 378: Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Younger Uninfected (by Self-Report or  N-protein) Cohort – 
Per Protocol Population ............................................................................................162 
Table 379: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Overall – mITT Population ................................................................163 
Table 380: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Overall – Per Protocol Population .....................................................170 


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Table 381: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Older Cohort – mITT Population ......................................................170 
Table 382: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Older Cohort – Per Protocol Population ............................................170 
Table 383: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Younger Cohort – mITT Population..................................................170 
Table 384: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Younger Cohort – Per Protocol Population .......................................170 
Table 385: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Infected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................170 
Table 386: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................170 
Table 387: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................170 
Table 388: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population ..................................................................................................170 
Table 389: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Older Infected (by Self-Report or  N-protein) Cohort – mITT 
Population .................................................................................................................170 
Table 390: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Older Infected (by Self-Report or  N-protein) Cohort – Per 
Protocol Population ..................................................................................................170 
Table 391: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Older Uninfected (by Self-Report or  N-protein) Cohort – 
mITT Population .......................................................................................................170 
Table 392: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Older Uninfected (by Self-Report or  N-protein) Cohort – Per 
Protocol Population ..................................................................................................170 
Table 393: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Younger Infected (by Self-Report)  Cohort – mITT Population .......170 
Table 394: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Younger Infected (by Self-Report or  N-protein) Cohort – Per 
Protocol Population ..................................................................................................170 
Table 395: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Younger Uninfected (by Self-Report or  N-protein) Cohort – 
mITT Population .......................................................................................................171 


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Table 396: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 
Dose Groups, Younger Uninfected (by Self-Report or  N-protein) Cohort – 
Per Protocol Population ............................................................................................171 
Table 397: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Overall – mITT Population .................................................................172 
Table 398: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Overall – Per Protocol Population .......................................................178 
Table 399: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Older Cohort – mITT Population ........................................................178 
Table 400: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Older Cohort – Per Protocol Population .............................................178 
Table 401: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Younger Cohort – mITT Population ...................................................178 
Table 402: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Younger Cohort – Per Protocol Population.........................................178 
Table 403: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Infected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................178 
Table 404: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................178 
Table 405: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................178 
Table 406: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................178 
Table 407: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Older Infected (by Self-Report or  N-protein) Cohort – mITT 
Population .................................................................................................................178 
Table 408: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Older Infected (by Self-Report or  N-protein) Cohort – Per 
Protocol Population ..................................................................................................178 
Table 409: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Older Uninfected (by Self-Report or  N-protein) Cohort – 
mITT Population .......................................................................................................178 
Table 410: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Older Uninfected (by Self-Report or  N-protein) Cohort – Per 
Protocol Population ..................................................................................................178 


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Table 411: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Younger Infected (by Self-Report or  N-protein) Cohort – 
mITT Population .......................................................................................................178 
Table 412: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Younger Infected (by Self-Report or  N-protein) Cohort – Per 
Protocol Population ..................................................................................................178 
Table 413: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Younger Uninfected (by Self-Report or  N-protein) Cohort – 
mITT Population .......................................................................................................179 
Table 414: Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 
Dose Group, Younger Uninfected (by Self-Report or  N-protein) Cohort – 
Per Protocol Population ............................................................................................179 
Table 415: Percent of Total B-cells by timepoint and Vaccination arm, Overall – mITT 
Population .................................................................................................................180 
Table 416: Percent of Total B-cells by timepoint and Vaccination arm, Overall – Per 
Protocol Population ..................................................................................................180 
Table 417: Percent of Total B-cells by timepoint and Vaccination arm, Older Cohort – 
mITT Population .......................................................................................................180 
Table 418: Percent of Total B-cells by timepoint and Vaccination arm, Older Cohort – 
Per Protocol Population ............................................................................................180 
Table 419: Percent of Total B-cells by timepoint and Vaccination arm, Younger Cohort 
– mITT Population ....................................................................................................180 
Table 420: Percent of Total B-cells by timepoint and Vaccination arm, Younger Cohort 
– Per Protocol Population .........................................................................................180 
Table 421: Percent of Total B-cells by timepoint and Vaccination arm, Infected (by 
Self-Report or N-protein) Cohort – mITT Population ..............................................180 
Table 422: Percent of Total B-cells by timepoint and Vaccination arm, Infected (by 
Self-Report or N-protein) Cohort – Per Protocol Population ...................................180 
Table 423: Percent of Total B-cells by timepoint and Vaccination arm, Uninfected (by 
Self-Report or N-protein) Cohort – mITT Population ..............................................181 
Table 424: Percent of Total B-cells by timepoint and Vaccination arm, Uninfected (by 
Self-Report or N-protein) Cohort – Per Protocol Population ...................................181 
Table 425: Percent of Total B-cells by timepoint and Vaccination arm, Older Infected 
(by Self-Report or  N-protein) Cohort – mITT Population ......................................181 
Table 426: Percent of Total B-cells by timepoint and Vaccination arm, Older Infected 
(by Self-Report or  N-protein) Cohort – Per Protocol Population ............................181 
Table 427: Percent of Total B-cells by timepoint and Vaccination arm, Older 
Uninfected (by Self-Report or  N-protein) Cohort – mITT Population ....................181 


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Table 428: Percent of Total B-cells by timepoint and Vaccination arm, Older 
Uninfected (by Self-Report or  N-protein) Cohort – Per Protocol Population .........181 
Table 429: Percent of Total B-cells by timepoint and Vaccination arm, Younger 
Infected (by Self-Report or  N-protein) Cohort – mITT Population ........................181 
Table 430: Percent of Total B-cells by timepoint and Vaccination arm, Younger 
Infected (by Self-Report or  N-protein) Cohort – Per Protocol Population ..............181 
Table 431: Percent of Total B-cells by timepoint and Vaccination arm, Younger 
Uninfected (by Self-Report or  N-protein) Cohort – mITT Population ....................181 
Table 432: Percent of Total B-cells by timepoint and Vaccination arm, Younger 
Uninfected (by Self-Report or  N-protein) Cohort – Per Protocol Population .........181 
Table 433: Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, 
Overall – mITT Population .......................................................................................182 
Table 434: Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, 
Overall – Per Protocol Population ............................................................................182 
Table 435: Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, 
Older Cohort – mITT Population .............................................................................182 
Table 436: Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, 
Older Cohort – Per Protocol Population ...................................................................182 
Table 437: Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, 
Younger Cohort – mITT Population .........................................................................182 
Table 438: Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, 
Younger Cohort – Per Protocol Population ..............................................................182 
Table 439: Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, 
Infected (by Self-Report or N-protein) Cohort – mITT Population .........................182 
Table 440: Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, 
Infected (by Self-Report or N-protein) Cohort – Per Protocol Population ...............182 
Table 441: Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population .....................182 
Table 442: Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population ..........183 
Table 443: Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, 
Older Infected (by Self-Report or  N-protein) Cohort – mITT Population ..............183 
Table 444: Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, 
Older Infected (by Self-Report or  N-protein) Cohort – Per Protocol 
Population .................................................................................................................183 
Table 445: Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, 
Older Uninfected (by Self-Report or  N-protein) Cohort – mITT Population .........183 


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Table 446: Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, 
Older Uninfected (by Self-Report or  N-protein) Cohort – Per Protocol 
Population .................................................................................................................183 
Table 447: Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, 
Younger Infected (by Self-Report or  N-protein) Cohort – mITT Population .........183 
Table 448: Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, 
Younger Infected (by Self-Report or  N-protein) Cohort – Per Protocol 
Population .................................................................................................................183 
Table 449: Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, 
Younger Uninfected (by Self-Report or  N-protein) Cohort – mITT 
Population .................................................................................................................183 
Table 450: Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, 
Younger Uninfected (by Self-Report or  N-protein) Cohort – Per Protocol 
Population .................................................................................................................183 
Table 451: Time to Infection Restricted Mean Survival Analysis by Vaccination Group, 
Overall – mITT Population .......................................................................................184 
Table 452: Time to Infection Restricted Mean Survival Analysis by Vaccination Group, 
Younger Cohort– mITT Population ..........................................................................184 
Table 453: Time to Infection Restricted Mean Survival Analysis by Vaccination Group, 
Older Cohort – mITT Population .............................................................................184 
Table 454: Time to Infection Restricted Mean Survival Analysis by Vaccination Group, 
Infected Cohort (By Self-Report or N-protein) – mITT Population .........................184 
Table 455: Time to Infection Restricted Mean Survival Analysis by Vaccination Group, 
Uninfected Cohort (By Self Report or N-protein) – mITT Population ....................185 
Table 456: Time to Infection Restricted Mean Survival Analysis by Vaccination Group, 
Younger Infected Cohort (By Self-Report or  N-protein)– mITT Population ..........185 
Table 457: Time to Infection Restricted Mean Survival Analysis by Vaccination Group, 
Younger Uninfected Cohort (By Self-Report or  N-protein)– mITT 
Population .................................................................................................................185 
Table 458: Time to Infection Restricted Mean Survival Analysis by Vaccination Group, 
Older Infected Cohort (By Self-Report or  N-protein)– mITT Population ..............185 
Table 459: Time to Infection Restricted Mean Survival Analysis by Vaccination Group, 
Older Uninfected Cohort (By Self-Report or  N-protein)– mITT Population ..........185 
Table 460: Number of Breakthrough Infections by PANGO Call and Treatment Group, 
Overall – Safety Population ......................................................................................186 
Table 461: Breakthrough Infections by PANGO Call and Treatment Group, Older 
Cohort – Safety Population .......................................................................................188 
Table 462: Breakthrough Infections by PANGO Call and Treatment Group, Younger 
Cohort – Safety Population .......................................................................................188 


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Table 463: Breakthrough Infections by PANGO Call and Treatment Group, Infected (by 
Self-Report or N-protein) Cohort – Safety Population .............................................188 
Table 464: Breakthrough Infections by PANGO Call and Treatment Group, Uninfected 
(by Self-Report or N-protein) Cohort – Safety Population ......................................188 
Table 465: Breakthrough Infections by PANGO Call and Treatment Group, Older 
Infected (by Self-Report or N-protein) Cohort – Safety Population ........................188 
Table 466: Breakthrough Infections by PANGO Call and Treatment Group, Older 
Uninfected (by Self-Report or N-protein) Cohort – Safety Population ....................188 
Table 467: Breakthrough Infections by PANGO Call and Treatment Group, Younger 
Infected (by Self-Report) Cohort – Safety Population .............................................188 
Table 468: Breakthrough Infections by PANGO Call and Treatment Group, Younger 
Uninfected (by Self-Report or N-protein) Cohort – Safety Population ....................188 
Table 469: Overall Summary of Adverse Events by Treatment Group – All Subjects ..............189 
Table 470: Serious Adverse Events and Non-Serious Adverse Events Occurring in 5% 
of Subjects in Any Treatment Group by MedDRA System Organ Class and 
Preferred Term, and Treatment Group – Safety Population .....................................191 
Table 471: Number and Percentage of Subjects Experiencing Solicited Events with 95% 
Confidence Intervals by Symptom, Dose, and Treatment Group – Post Dose 
1 ................................................................................................................................192 
Table 472: Number and Percentage of Subjects Experiencing Solicited Events with 95% 
Confidence Intervals by Symptom, Dose, and Treatment Group – Two Dose 
Treatment Group .......................................................................................................195 
Table 473: Summary of Solicited Events by Days Post Treatment, Symptom, and 
Treatment Group – Prototype ...................................................................................198 
Table 474: Summary of Solicited Events by Days Post Treatment, Symptom, and 
Treatment Group – Beta + Omicron .........................................................................201 
Table 475: Summary of Solicited Events by Days Post Treatment, Symptom, and 
Treatment Group – Delta + Omicron........................................................................201 
Table 476: Summary of Solicited Events by Days Post Treatment, Symptom, and 
Treatment Group – Omicron ....................................................................................201 
Table 477: Summary of Solicited Events by Days Post Treatment, Symptom, and 
Treatment Group – Omicron + Prototype .................................................................201 
Table 478: Summary of Solicited Events by Days Post Treatment, Symptom, and 
Treatment Group – Beta+Omicron ...........................................................................202 
Table 479: Summary of Duration of Solicited Symptoms by Treatment Group - All 
Subjects .....................................................................................................................208 
Table 480: All Adverse Events Cross-Classified by MedDRA System Organ Class, 
Severity, Relationship to Study Treatment, and Treatment Group ..........................212 


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Table 481: Summary of All Unsolicited Adverse Events by MedDRA System Organ 
Class and Preferred Term, Severity, Relationship, and Treatment Group ...............215 
Table 482: Number and Percentage of Subjects Experiencing Unsolicited Adverse 
Events by MedDRA® System Organ Class and Preferred Term, Severity, 
Relationship, and Treatment Group ..........................................................................217 
Table 483: Listing of Serious Adverse Events ...........................................................................219 
Table 484: Listing of Non-Serious, Unsolicited, Moderate or Severe Adverse Events .............220 
Table 485: Listing of AESIs, MAAEs and NOCMCs ................................................................221 
Table 486: Number and Percentage of Subjects with Prior and Concurrent Medications 
by WHO Drug Classification and Treatment Group ................................................226 
 


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9.1 
Overall Study Design and Plan Description 
Table 2: 
Study Design 
 
Arms Vaccine 
Platform 
Samp
le 
Size 
Vaccine Candidate 
Interval 
(weeks)* 
Timing 
of First 
Dose  
Timing of 
Second Dose 
Stage 1 
1 
Moderna 
mRNA-1273 
100 
Prototype 
≥16 
D1 
NA 
2 
100 
Beta + Omicron  
≥16 
D1 
NA 
3 
100 
Beta + Omicron  
≥16 
D1 
D57 
4 
100 
Delta + Omicron  
≥16 
D1 
NA 
5 
100 
Omicron  
≥16 
D1 
NA 
6 
100 
Omicron + Prototype  
≥16 
D1 
NA 
 
Stage 2 
7 
Pfizer/ 
BioNTech 
BNT162b2 
50 
Wildtype (Prototype) 
≥16 
D1 
NA 
8 
50 
Beta + Omicron  
≥16 
D1 
NA 
9 
50 
Omicron  
≥16 
D1 
NA 
10 
50 
Beta  
≥16 
D1 
NA 
11 
50 
Beta + Wildtype  
≥16 
D1 
NA 
12 
50 
Omicron + Wildtype  
≥16 
D1 
NA 
 
Stage 3 
13 
Sanofi 
CoV2 preS 
dTM-AS03 
50 
Prototype 
≥16 
D1 
NA 
14 
50 
Beta  
≥16 
D1 
NA 
15 
50 
Beta+ Prototype 
≥16 
D1 
NA 
 
Stage 4 
16^ 
Pfizer/ 
BioNTech 
BNT162b2 
bivalent 
100 
Omicron BA.1 + 
Wildtype (Prototype) 
≥16 
D1 
NA 
17^ 
100 
Omicron BA.4/BA.5 + 
Wildtype (Prototype) 
≥16 
D1 
NA 
Two age strata:  
• 
18-64 years 
• 
≥ 65 years (~45% in ≥ 65 years). 
^For arms 16 and 17 or stage 4, only participants between the ages of 18 to 49 years will be enrolled. 
 
Two infection strata:  
• 
Confirmed prior SARS-CoV-2 infection (~20%) 
• 
No known history of prior infection.   
*interval (in weeks) since last exposure to SARS-CoV-2 infection or vaccination 
 


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9.5.1 Immunogenicity and Safety Measurements Assessed and Flow Chart 
Table 3: 
Schedule of Study Procedures - Single Dose 
Study Day 
D-28 
to 
D-1 
1 
4 
8
b 
15 
29 
91 
181 
271 
366 
Illness/ 
Unscheduled 
Visitk,m 
Early 
Termination 
Visit 
Visit Number 
00
a 
1 
1A 
2 
3 
4 
5 
6 
7 
8 
 
 
Window (+/-) 
 
0 
1 
1 
2 
2 
7m 
14m 
14m 
28m 
 
 
Informed Consent
a 
X 
 
 
 
 
 
 
 
 
 
 
 
Eligibility Criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
Vaccination 
 
X 
 
 
 
 
 
 
 
 
 
 
Concomitant Meds 
X 
X 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Interim History 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical Examc - Targeted 
X 
X 
 
 
 
 
 
 
 
 
(X) 
 
Vital Signs
c 
X 
X 
 
 
 
 
 
 
 
 
(X) 
 
Height/Weight (BMI)
a 
X 
 
 
 
 
 
 
 
 
 
 
 
Urine β-HCG
d 
X 
X 
 
 
 
 
 
 
 
 
 
 
Memory Aide 
 
X 
X 
X 
 
 
 
 
 
 
 
 
Solicited AEs 
 
X 
X 
X 
 
 
 
 
 
 
 
 
Unsolicited AEs 
 
X 
X 
X 
X 
X 
 
 
 
 
 
 
MAAEs, SAEs, NOCMCs, AEs leading to 
withdrawal from the study and AESIs 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Nasal swab for PCR & Sequencingf 
 
 
 
 
 
 
 
 
 
 
(X) 
 
Assays 
Serum for Serological Immunogenicity 
Assaysg and Biomarker Testingl 
 
34l 
 
4l 
 
34 
34 
34 
34 
34 
34 
4l-34m 
34 
PBMC Cellular Assays & Plasmag,h 
(select sites only) 
 
64-70 
 
 
64-70 
 
64-70 64-70 64-70 
 
64-70m 
64-70 
Daily Volume (mL)g,i 
 
98-
104 
4 
 
98-
104 
34 
98-
104 
98-
104 
98-
104 
34 
4-104 
98-104 


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Cumulative Volume (mL) over 56 day-
periodg,i 
 
98-
104 
102-
108 
 
200-
212 
234-
246 
132-
138 
98-
104 
98-
104 
132-
138 
 
 
Total Cumulative Volume (mL)g,i 
 
98-
104 
102-
108 
 
200-
212 
234-
246 
332-
350 
430-
454 
528-
558 
562-
592 
 
 
a Optional screening visit – informed consent and screening activities can be a separate visit or combined with Day 1. 
b Telephone visit 
c Vital signs and targeted physical exam will be performed on screening and before vaccination otherwise, only as clinically indicated or based on interim medical history. 
d For subjects of childbearing potential, a urine pregnancy will be performed at screening. If enrollment occurs on a separate day, a repeat urine pregnancy test will be done within 24 
hours of study vaccine administration and negative results confirmed prior to dosing.  
e  The memory aid will be distributed at the Day 1 visit, queried for completion at the Day 8 telephone call and reviewed during an interview with the subject at the D15 visit and confirmed 
data recorded on the DCF. 
fCollect nasal swab for PCR (1-2). Swabs can be self-collected and visit done by phone. Sequencing will be performed on all Illness visit-confirmed SARS-CoV-2 specimens. 
g Inability (e.g., failure of venipuncture) to collect all baseline samples on Day 1 will not exclude the subject from further participation in this study as long as a minimum of baseline 
blood volume is collected (refer to the MOP for the protocol defined minimum number of required aliquots). Blood volume for PBMC varies depending on the type of tubes used for 
blood collection (refer to the MOP). 
h Selected sites will perform PBMC separation on selected subjects (refer to MOP for more guidance). 
i Blood volumes for early termination visit are not included in the blood volume totals. 
j After vaccination on Day 1, immunosuppressant drugs, COVID-19 related prophylaxis and therapies as well as vaccines will be recorded. For any SAE occurring at any time during the 
study, all medications will be recorded. 
k If an unscheduled visit is performed to evaluate an adverse event, vital signs and targeted physical exam will be performed, as indicated. If, in the judgement of the site investigator, the 
event, occurring within 4 weeks after vaccination, is a case of suspected myocarditis and/or pericarditis, the site will coordinate an appropriate diagnostic workup to make a determination 
of probable or confirmed myocarditis and/or pericarditis which may include, but is not limited to, an ECG, cardiac troponin testing and referral to a cardiologist (directly, or through the 
emergency department or primary care clinic). The suspected myocarditis and/or pericarditis case should be reported to the DMID Medical Monitor within 24 hours of site awareness.  
lSerum for biomarker testing will be collected on Day 4 and stored for potential biomarker testing at a central laboratory and compared to testing of an aliquot from serum obtained on 
Day 1.  If an unscheduled visit is related to a concern for myocarditis and/or pericarditis within 4 weeks after vaccination, a 4 mL SST will be collected and stored for potential biomarker 
testing at a central laboratory.  
mIf a participant is planning to receive a COVID-19 booster outside the study, an unscheduled visit will be performed where safety and immunogenicity (collection of sera, plasma and 
PBMC) assessments will be performed. However, if that planned visit falls within twice the window for an upcoming visit ( e.g +/- 14 days for D 91, +/-28 days for D 181 and D 271, 
+/- 56 days for D 366) then it will occur  and be documented as out of window for the planned upcoming scheduled visit (refer to MOP for more guidance).  
 
 


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Table 4: 
Schedule of Study Procedures - 2 Doses 
Study Day 
D-
28 
to 
D-
1 
1 
4 
8b 
15 
29 
57 
60 
64b 
71 
85 
147 
237 
327 
422 
Illness/ 
Unscheduled 
Visitk,m 
Early 
Termination 
Visit 
Visit Number 
00a 
1 
1A 
2 
3 
4 
5 
5A 
6 
7 
8 
9 
10 
11 
12 
  
  
Window (+/-) 
  
0 
1 
1 
2 
2 
3 
1 
1 
2 
2 
7m 
14m 
14m 
28m 
  
  
Informed Consenta 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility Criteria 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Vaccination 
 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Concomitant Meds 
X 
X 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Interim History 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical Examc – 
Targeted 
X 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
(X) 
 
Vital Signsc 
X 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
(X) 
 
Height/Weight (BMI)a 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine β-HCG
d 
X 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Memory Aide 
 
X 
X 
X 
 
 
X 
X 
X 
 
 
 
 
 
 
 
 
Solicited AEs 
 
X 
X 
X 
 
 
X 
X 
X 
 
 
 
 
 
 
 
 
Unsolicited AEs 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
MAAEs, SAEs, 
NOCMCs, AEs leading 
to withdrawal from the 
study and AESIs 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Nasal swab for PCR & 
Sequencingf 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(X) 
 
Assays 
Serum for Serological 
Immunogenicity 
 
34l 
 
4l 
 
34 
34 
34l 
 
4l 
 
34 
34 
34 
34 
34 
34 
4l-34m 
34 


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Study Day 
D-
28 
to 
D-
1 
1 
4 
8b 
15 
29 
57 
60 
64b 
71 
85 
147 
237 
327 
422 
Illness/ 
Unscheduled 
Visitk,m 
Early 
Termination 
Visit 
Visit Number 
00a 
1 
1A 
2 
3 
4 
5 
5A 
6 
7 
8 
9 
10 
11 
12 
  
  
Window (+/-) 
  
0 
1 
1 
2 
2 
3 
1 
1 
2 
2 
7m 
14m 
14m 
28m 
  
  
Assaysg and Biomarker 
Testingl 
PBMC Cellular Assays 
& Plasmag,h 
(select sites only) 
 
64-
70 
 
 
64-
70 
 
64-
70 
 
 
64-
70 
 
64-
70 
64-
70 
64-
70 
 
64-70m 
64-70 
Daily Volume (mL)g,i 
 
98-
104 
4 
 
98-
104 
34 
98-
104 
4 
 
98-
104 
34 
98-
104 
98-
104 
98-
104 
34 
4-104 
98-104 
Cumulative Volume 
(mL) over 56 day-
periodg.i 
 
98-
104 
102-
108 
 
200-
212 
234-
246 
332-
350 
238-
250 
 
336-
354 
268-
280 
132-
138 
98-
104 
98-
104 
132-
138 
 
 
Total Cumulative 
Volume (mL)g,i 
 
98-
104 
102-
108 
 
200-
212 
234-
246 
332-
350 
336-
354 
 
434-
458 
468-
492 
566-
596 
664-
700 
762-
804 
796-
838 
 
 
a Optional screening visit – informed consent and screening activities can be a separate visit or combined with Day 1. 
b Telephone visit 
c Vital signs and targeted physical exam will be performed on screening and before vaccination otherwise, only as clinically indicated or based on interim medical history.  
d For subjects of childbearing potential, a urine pregnancy test will be performed at screening. If enrollment occurs on a separate day as screening, a repeat urine pregnancy test will be 
done within 24 hours of first study vaccine administration and repeated on day 57 prior to second study vaccine administration. Negative results must be confirmed prior to each dosing.    
e The memory aid will be distributed at the Day 1 and Day 57 visits, queried for completion at the Day 8 and Day 64 telephone calls and reviewed during an interview with the subject at 
the D15 and Day 71 visits and confirmed data recorded on the DCF. 
f Collect nasal swab for PCR (1-2). Swabs can be self-collected and visit done by phone. Sequencing will be performed on all Illness visit-confirmed SARS-CoV-2 specimens. 
g Inability (e.g., failure of venipuncture) to collect all baseline samples on Day 1 will not exclude the subject from further participation in this study as long as a minimum of baseline 
blood volume is collected (refer to the MOP for the protocol defined minimum number of required aliquots). Blood volume for PBMC varies depending on the type of tubes used for the 
blood collection (refer to the MOP). 
h Selected sites will perform PBMC separation on selected subjects (refer to MOP for more guidance). 
i Blood volumes for early termination visit are not included in the blood volume totals. 
j After vaccination on Day 1, immunosuppressant drugs, COVID-19 related prophylaxis and therapies as well as vaccines will be recorded. For any SAE occurring at any time during the 
study, all medications will be recorded. 


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k If an unscheduled visit is performed to evaluate an adverse event, vital signs and targeted physical exam will be performed, as indicated. If, in the judgement of the site investigator, the 
event, occurring within 4 weeks after each vaccination, is a case of suspected myocarditis and/or pericarditis, the site will coordinate an appropriate diagnostic workup to make a 
determination of probable or confirmed myocarditis and/or pericarditis which may include, but is not limited to, an ECG, cardiac troponin testing and referral to a cardiologist (directly, 
or through the emergency department or primary care clinic). The suspected myocarditis and/or pericarditis case should be reported to the DMID Medical Monitor within 24 hours of 
site awareness. 
lSerum for biomarker testing will be collected on Days 4 and 60 and stored for potential biomarker testing at a central laboratory and compared to testing of an aliquot of serum obtained 
on Days 1 and 57, respectively.  If an unscheduled visit is related to a concern for myocarditis and/or pericarditis within 4 weeks after vaccination, a 4 mL SST will be collected and 
stored for potential biomarker testing at a central laboratory. 
mIf a participant is planning to receive a COVID-19 booster outside the study, an unscheduled visit will be performed where safety and immunogenicity (collection of sera, plasma and 
PBMC) assessments will be performed. However, if that planned visit falls within twice the window for an upcoming visit ( e.g +/- 14 days for D 147, +/-28 days for D 237 and D 327, 
+/- 56 days for D 422) then it will occur and be documented as out of window for the planned upcoming scheduled visit (refer to MOP for more guidance).  
 
Note Windows for subsequent visits should be based off the preceding vaccination visit. 
If intercurrent SARS- CoV-2 infection occurs between the first and prior to the planned second study dose or if a COVID-19 vaccine is given outside the study between the first and prior 
to the planned second study dose, no second vaccination will be given. Participants who do not receive a second dose will revert to the schedule of activities for single dose participants. 
 
 


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9.7.1 Sample Size 
Table 5: 
Probability of observing one or more Adverse Events for various event rates in one 
vaccine group (or strata) 
N 
“True” Event 
Rate 
Probability of Observing ≥ 1 
events (%) 
N 
“True” Event 
Rate 
Probability of Observing ≥ 1 
events (%) 
100 
0.1% 
9.5 
50 
0.1% 
4.9 
0.5% 
39.4 
0.5% 
22.2 
1.0% 
63.4 
1.0% 
39.5 
2.0% 
86.7 
2.0% 
63.6 
3.0% 
95.2 
3.0% 
78.2 
4.0% 
98.3 
4.0% 
87 
5.0% 
99.4 
5.0% 
92.3 
10.0% 
>99.9 
10.0% 
99.5 
15.0% 
>99.9 
15.0% 
>99.9 
20.0% 
>99.9 
20.0% 
>99.9 
30.0% 
>99.9 
30.0% 
>99.9 
25 
0.1% 
2.5 
15 
0.1% 
1.5 
0.5% 
11.8 
0.5% 
7.2 
1.0% 
22.2 
1.0% 
14 
2.0% 
39.7 
2.0% 
26.1 
3.0% 
53.3 
3.0% 
36.7 
4.0% 
64.0 
4.0% 
45.8 
5.0% 
72.3 
5.0% 
53.7 
10.0% 
92.8 
10.0% 
79.4 
15.0% 
98.3 
15.0% 
91.3 
20.0% 
99.6 
20.0% 
96.5 
30.0% 
>99.9 
30.0% 
99.5 
Table 6: 
Two-sided 95% confidence intervals based on observing a particular average loge-
antibody titer in subjects’ vaccine groups and potential strata sizes 
Observed 
average loge 
antibody titer 
SD of loge 
antibody 
titer 
95% confidence interval of  
GMT in vaccine groups and strata 
N = 100 
N = 50 
N = 25 
N = 15 
loge (5) 
0.5 
(4.5, 5.5) 
(4.3, 5.8) 
(4.1, 6.1) 
(3.8, 6.6) 
loge (20) 
(18.1, 22.1) 
(17.4, 23.1) 
(16.3, 24.6) 
(15.2, 26.4) 
loge (50) 
(45.3, 55.2) 
(43.4, 57.6) 
(40.7, 61.5) 
(37.9, 66) 
loge (100) 
(90.6, 110.4) 
(86.8, 115.3) 
(81.4, 122.9) 
(75.8, 131.9) 


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Observed 
average loge 
antibody titer 
SD of loge 
antibody 
titer 
95% confidence interval of  
GMT in vaccine groups and strata 
N = 100 
N = 50 
N = 25 
N = 15 
loge (250) 
(226.4, 276.1) 
(216.9, 288.2) 
(203.4, 307.3) 
(189.5, 329.8) 
loge (500) 
(452.8, 552.1) 
(433.8, 576.3) 
(406.8, 614.6) 
(379.1, 659.5) 
loge (1000) 
(905.6, 1104.3) 
(867.5, 1152.7) 
(813.5, 1229.2) 
(758.1, 1319) 
loge (5) 
1.0 
(4.1, 6.1) 
(3.8, 6.6) 
(3.3, 7.6) 
(2.9, 8.7) 
loge (20) 
(16.4, 24.4) 
(15.1, 26.6) 
(13.2, 30.2) 
(11.5, 34.8) 
loge (50) 
(41, 61) 
(37.6, 66.4) 
(33.1, 75.6) 
(28.7, 87) 
loge (100) 
(82, 121.9) 
(75.3, 132.9) 
(66.2, 151.1) 
(57.5, 174) 
loge (250) 
(205, 304.9) 
(188.2, 332.2) 
(165.5, 377.8) 
(143.7, 435) 
loge (500) 
(410, 609.7) 
(376.3, 664.3) 
(330.9, 755.5) 
(287.4, 869.9) 
loge (1000) 
(820, 1219.5) 
(752.6, 1328.7) 
(661.8, 1511) 
(574.8, 1739.8) 
 
 


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10.2 
Protocol Deviations 
Table 7: 
Distribution of Protocol Deviations by Category, Type, and Treatment Group 
[Implementation Note: Only display deviations that have occurred in at least one treatment group.] 
Category 
Deviation Type 
Prototype  
(N=X) 
Beta 
(B.1.351) + 
Omicron 
(B.1.1.529) 
(N=X) 
Beta 
(B.1.351) + 
Omicron 
(B.1.1.529) 
[two doses] 
(N=X) 
Delta 
(B.1.617.2) 
+ Omicron 
(B.1.1.529) 
(N=X) 
Omicron 
(B.1.1.529) 
(N=X) 
Omicron 
(B.1.1.529) 
+ 
Prototype 
(N=X) 
All 
Subjects 
(N=X) 
No. 
of 
Subj 
No. 
of 
Dev. 
No. 
of 
Subj 
No. 
of 
Dev. 
No. 
of 
Subj 
No. 
of 
Dev. 
No. 
of 
Subj 
No. 
of 
Dev. 
No. 
of 
Subj 
No. 
of 
Dev. 
No. 
of 
Subj 
No. 
of 
Dev. 
No. 
of 
Subj 
No. 
of 
Dev. 
Eligibility/enrollment Any type 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Did not meet inclusion 
criterion 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Met exclusion 
criterion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ICF not signed prior to 
study procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment 
administration 
schedule 
Any type 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Out of window visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Missed visit/visit not 
conducted 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Missed treatment 
administration 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Delayed treatment 
administration 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Follow-up visit 
schedule 
Any type 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Out of window visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Missed visit/visit not 
conducted 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol 
procedure/assessment Any type 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Incorrect version of 
ICF signed 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood not collected 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COVID-19 test swab 
not collected 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other specimen not 
collected 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Category 
Deviation Type 
Prototype  
(N=X) 
Beta 
(B.1.351) + 
Omicron 
(B.1.1.529) 
(N=X) 
Beta 
(B.1.351) + 
Omicron 
(B.1.1.529) 
[two doses] 
(N=X) 
Delta 
(B.1.617.2) 
+ Omicron 
(B.1.1.529) 
(N=X) 
Omicron 
(B.1.1.529) 
(N=X) 
Omicron 
(B.1.1.529) 
+ 
Prototype 
(N=X) 
All 
Subjects 
(N=X) 
No. 
of 
Subj 
No. 
of 
Dev. 
No. 
of 
Subj 
No. 
of 
Dev. 
No. 
of 
Subj 
No. 
of 
Dev. 
No. 
of 
Subj 
No. 
of 
Dev. 
No. 
of 
Subj 
No. 
of 
Dev. 
No. 
of 
Subj 
No. 
of 
Dev. 
No. 
of 
Subj 
No. 
of 
Dev. 
 
Too few aliquots 
obtained 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Specimen result not 
obtained 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Required procedure 
not conducted 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Required procedure 
done incorrectly 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study product 
temperature excursion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Specimen temperature 
excursion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment 
administration 
Any type 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Required procedure 
done incorrectly 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study product 
temperature excursion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: N=Number of subjects in the Safety Population. 
 
Table with similar format: 
Table 8: 
Distribution of Major Protocol Deviations by Category, Type, and Treatment Group 
 


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12.2.2 Displays of Adverse Events 
The toxicity grading scales in the FDA “Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers 
Enrolled in Preventive Vaccine Clinical Trials” will be used. 
 


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12.4.1 Individual Laboratory Measurements and Abnormal Laboratory Values 
Not applicable. 
 


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14.1 
Description of Study Subjects 
14.1.1 Disposition of Subjects 
Table 9: 
Subject Disposition by Treatment Group 
Subject 
Disposition  
Prototype  
(N=X) 
Beta 
(B.1.351) + 
Omicron 
(B.1.1.529) 
(N=X) 
Beta 
(B.1.351) + 
Omicron 
(B.1.1.529) 
(2 Doses) 
(N=X) 
Delta 
(B.1.617.2) + 
Omicron 
(B.1.1.529) 
(N=X) 
Omicron 
(B.1.1.529) 
(N=X) 
Omicron 
(B.1.1.529) + 
Prototype 
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Screened 
-- 
-- 
-- 
-- 
-- 
-- 
-- 
-- 
-- 
-- 
-- 
-- 
x 
-- 
Enrolled/Randomized 
x 
100 
x 
100 
x 
100 
x 
100 
x 
100 
x 
100 
x 
100 
Received First 
Vaccination 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Received Second 
Vaccination 
NA 
NA 
x 
xx 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
Completed Final 
Blood Draw  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Completed Follow-
upa 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Completed Per 
Protocolb 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: N=Number of subjects enrolled in the study. 
a Refer to Listing 2 for reasons subjects discontinued or terminated early. 
b Refer to Listing 5 for reasons subjects are excluded from the Analysis populations. 
 
 


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Table 10: 
Analysis Populations by Treatment Group 
Analysis 
Populations 
Reason Subjects 
Excluded 
Prototype  
(N=X) 
Beta 
(B.1.351) 
+ 
Omicron 
(B.1.1.529) 
(N=X) 
Beta 
(B.1.351) 
+ 
Omicron 
(B.1.1.529) 
(2 Doses) 
(N=X) 
Delta 
(B.1.617.2) 
+ 
Omicron 
(B.1.1.529) 
(N=X) 
Omicron 
(B.1.1.529) 
(N=X) 
Omicron 
(B.1.1.529) 
+ 
Prototype 
(N=X) 
All 
Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
% 
n 
mITT Population 
Any Reason 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
[Reason 1, for 
example: Did not meet 
eligibility criteria] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[Reason 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[Reason 3] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[Reason 4] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Per Protocol 
Population 
Any Reason 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[Reason 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[Reason 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Safety 
Population 
Any Reason 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[Reason 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[Reason 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: N=Number of subjects enrolled in the study. 
 
 


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Table 11: 
Ineligibility Summary of Screen Failures 
[Implementation Note: See section 4.3 for inclusion and exclusion criteria.] 
Inclusion/Exclusion Category 
Inclusion/Exclusion Criterion 
na 
%b 
Inclusion and Exclusion 
Number of subjects failing any eligibility criterion 
x 
100 
Inclusion 
Any inclusion criterion 
x 
xx 
 
[inclusion criterion 1] 
x 
xx 
 
[inclusion criterion 2] 
x 
xx 
 
[inclusion criterion 3] 
x 
xx 
Exclusion 
Any exclusion criterion 
x 
xx 
 
[exclusion criterion 1] 
x 
xx 
 
[exclusion criterion 2] 
x 
xx 
 
[exclusion criterion 3] 
x 
xx 
a More than one criterion may be marked per subject. 
b Denominator for percentages is the total number of screen failures. 
 
 


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14.1.2 Demographic Data by Study Group 
Table 12: 
Summary of Categorical Demographic and Baseline Characteristics by Treatment Group, All Enrolled Subjects 
Variable 
Characteristic 
Prototype  
(N=X) 
Beta (B.1.351) + 
Omicron 
(B.1.1.529) 
(N=X) 
Beta (B.1.351) + 
Omicron 
(B.1.1.529) 
(2 Doses) 
(N=X) 
Delta (B.1.617.2) 
+ Omicron 
(B.1.1.529) 
(N=X) 
Omicron 
(B.1.1.529) 
(N=X) 
Omicron 
(B.1.1.529) + 
Prototype 
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Sex  
Male 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Female 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ethnicity  
Not Hispanic or LatinX 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Hispanic or LatinX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Not Reported 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unknown 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Race  
American Indian or Alaska 
Native 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Asian 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Native Hawaiian or Other 
Pacific Islander 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Black or African American 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
White 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Multi-Racial 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unknown 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Age Group 
18-64 years 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
>= 65 years 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior Infection 
(Self Report) 
Yes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Variable 
Characteristic 
Prototype  
(N=X) 
Beta (B.1.351) + 
Omicron 
(B.1.1.529) 
(N=X) 
Beta (B.1.351) + 
Omicron 
(B.1.1.529) 
(2 Doses) 
(N=X) 
Delta (B.1.617.2) 
+ Omicron 
(B.1.1.529) 
(N=X) 
Omicron 
(B.1.1.529) 
(N=X) 
Omicron 
(B.1.1.529) + 
Prototype 
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Prior Infection 
(Positive 
Nuclear 
Protein Antibody 
or Self-Report) 
Yes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SARS-COV-2 
Vaccination 
Regimen 
mRNA Primary, mRNA 
Boost 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ad26 Primary, mRNA 
Boost 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ad26 Primary, Ad26 Boost 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: N=Number of subjects in the Safety Population. 
 


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Table 13: 
Summary of Continuous Demographic and Baseline Characteristics by Treatment 
Group, All Enrolled Subjects 
Variable 
Statistic 
Prototype  
(N=X) 
Beta (B.1.351) 
+ Omicron 
(B.1.1.529) 
(N=X) 
Beta 
(B.1.351) + 
Omicron 
(B.1.1.529) 
(2 Doses) 
(N=X) 
Delta 
(B.1.617.2) 
+ Omicron 
(B.1.1.529) 
(N=X) 
Omicron 
(B.1.1.529) 
(N=X) 
Omicron 
(B.1.1.529) 
+ 
Prototype 
(N=X) 
All 
Subjects 
(N=X) 
Age (Years) 
Mean 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
Standard 
Deviation 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
Median 
x 
x 
x 
x 
x 
x 
x 
Minimum 
x 
x 
x 
x 
x 
x 
x 
Maximum 
x 
x 
x 
x 
x 
x 
x 
Height (cm) 
Mean 
 
 
 
 
 
 
 
Standard 
Deviation 
 
 
 
 
 
 
 
Median 
 
 
 
 
 
 
 
Minimum 
 
 
 
 
 
 
 
Maximum 
 
 
 
 
 
 
 
Weight (kg) 
Mean 
 
 
 
 
 
 
 
Standard 
Deviation 
 
 
 
 
 
 
 
Median 
 
 
 
 
 
 
 
Minimum 
 
 
 
 
 
 
 
Maximum 
 
 
 
 
 
 
 
BMI (kg/m2) 
Mean 
 
 
 
 
 
 
 
Standard 
Deviation 
 
 
 
 
 
 
 
Median 
 
 
 
 
 
 
 
Minimum 
 
 
 
 
 
 
 
Maximum 
 
 
 
 
 
 
 
Days since 
most recent 
COVID19 
Vaccine 
Mean 
 
 
 
 
 
 
 
Standard 
Deviation 
 
 
 
 
 
 
 
Median 
 
 
 
 
 
 
 
Minimum 
 
 
 
 
 
 
 
Maximum 
 
 
 
 
 
 
 
Days since 
most recent 
self-reported 
COVID19 
infection 
n 
 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
 
Standard 
Deviation 
 
 
 
 
 
 
 


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Variable 
Statistic 
Prototype  
(N=X) 
Beta (B.1.351) 
+ Omicron 
(B.1.1.529) 
(N=X) 
Beta 
(B.1.351) + 
Omicron 
(B.1.1.529) 
(2 Doses) 
(N=X) 
Delta 
(B.1.617.2) 
+ Omicron 
(B.1.1.529) 
(N=X) 
Omicron 
(B.1.1.529) 
(N=X) 
Omicron 
(B.1.1.529) 
+ 
Prototype 
(N=X) 
All 
Subjects 
(N=X) 
Median 
 
 
 
 
 
 
 
Minimum 
 
 
 
 
 
 
 
Maximum 
 
 
 
 
 
 
 
Days since 
most recent 
self-reported 
COVID19 
infection or 
COVID19 
Vaccination 
Mean 
 
 
 
 
 
 
 
Standard 
Deviation 
 
 
 
 
 
 
 
Median 
 
 
 
 
 
 
 
Minimum 
 
 
 
 
 
 
 
Maximum 
 
 
 
 
 
 
 
Note: N=Number of subjects in the Safety Population 
 
 


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14.1.3 Prior and Concurrent Medical Conditions 
Table 14: 
Summary of Subjects with Pre-Existing Medical Conditions by MedDRA System Organ Class and Treatment Group 
MedDRA System Organ Class 
Prototype  
(N=X) 
Beta (B.1.351) + 
Omicron 
(B.1.1.529) 
(N=X) 
Beta (B.1.351) + 
Omicron 
(B.1.1.529) 
(2 Doses) 
(N=X) 
Delta (B.1.617.2) 
+ Omicron 
(B.1.1.529) 
(N=X) 
Omicron 
(B.1.1.529) 
(N=X) 
Omicron 
(B.1.1.529) + 
Prototype 
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Any SOC 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
[SOC 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[SOC 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: N=Number of subjects in the Safety Population; n = Number of subjects reporting medical history within the specified SOC.  
A subject is only counted once per SOC. 
 
 


Statistical Analysis Plan - DMID Protocol: 22-0004  
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14.2 
Immunogenicity Data 
Table 15: 
Serum IgG Binding Assay Area Under the Curve  Measured by ECLIA 10-plex 
Summary Results by Time Point and Variant, Prototype, Overall – mITT Population 
Time Point 
Statistic 
D614G 
(N=X) 
B.1.351 
(N=X) 
B.1.617.2 
(N=X) 
BA.1 (N=X) 
BA.2.12.1 
(N=X) 
BA.5/BA.5 
(N=X) 
Day 1  
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 15 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 29 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 91 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
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Time Point 
Statistic 
D614G 
(N=X) 
B.1.351 
(N=X) 
B.1.617.2 
(N=X) 
BA.1 (N=X) 
BA.2.12.1 
(N=X) 
BA.5/BA.5 
(N=X) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 181 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 271 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 366 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
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Time Point 
Statistic 
D614G 
(N=X) 
B.1.351 
(N=X) 
B.1.617.2 
(N=X) 
BA.1 (N=X) 
BA.2.12.1 
(N=X) 
BA.5/BA.5 
(N=X) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Note: N=Number of subjects in the mITT Population. 
n=Number of subjects with results available at time point. 
GM=Geometric Mean, GMRD614G=Geometric Mean Ratio to D614G variant, GMFR=Geometric Mean Fold Rise, 
GMFD=Geometric Mean Fold Drop. 
Confidence intervals of the GM, GMR, GMFR, and GMFD were calculated with the Student’s t distribution on log-transformed 
data. Confidence intervals of the Seropositive rate were calculated with the Clopper-Pearson method. 
 
Implementation notes:  
Extra variant columns may be added for additional variants. 
For tables using the PP population, update footnote to read: “Notes: N=Number of subjects in the Per Protocol 
population.” 
Add a note to indicate the lower limit of detection for the assay used to calculate the seropositive rate. 
 
Tables with Similar Format: 
Table 16: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Prototype, Overall – Per Protocol Population 
Table 17: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Prototype, Younger Cohort – mITT Population 
Table 18: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Prototype, Younger Cohort – Per Protocol 
Population 
Table 19: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Prototype, Older Cohort – mITT Population 
Table 20: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Prototype, Older Cohort – Per Protocol Population 
Table 21: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Prototype, Infected (by Self-Report or N-protein) 
Cohort – mITT Population 
Table 22: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Prototype, Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
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Table 23: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Prototype, Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population 
Table 24: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Prototype, Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population 
Table 25: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Prototype, Younger Infected (by Self-Report or N-
protein) Cohort – mITT Population 
Table 26: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Prototype, Younger Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population 
Table 27: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Prototype, Younger Uninfected (by Self-Report or N-
protein) Cohort – mITT Population 
Table 28: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Prototype, Younger Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population 
Table 29: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Prototype, Older Infected (by Self-Report or N-
protein) Cohort – mITT Population 
Table 30: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Prototype, Older Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population 
Table 31: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Prototype, Older Uninfected (by Self-Report or N-
protein) Cohort – mITT Population 
Table 32: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Prototype, Older Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population 
Table 33: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 1 Dose Beta + Omicron, Overall – mITT Population 
Table 34: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 1 Dose Beta + Omicron, Overall – Per Protocol 
Population 
Table 35: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 1 Dose Beta + Omicron, Younger Cohort – mITT 
Population 
Table 36: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 1 Dose Beta + Omicron, Younger Cohort – Per 
Protocol Population 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
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Table 37: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 1 Dose Beta + Omicron, Older Cohort – mITT 
Population 
Table 38: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 1 Dose Beta + Omicron, Older Cohort – Per Protocol 
Population 
Table 39: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 1 Dose Beta + Omicron, Infected (by Self-Report or 
N-protein) Cohort – mITT Population 
Table 40: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 1 Dose Beta + Omicron, Infected (by Self-Report or 
N-protein) Cohort – Per Protocol Population 
Table 41: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 1 Dose Beta + Omicron, Uninfected (by Self-Report 
or N-protein) Cohort – mITT Population 
Table 42: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 1 Dose Beta + Omicron, Uninfected (by Self-Report 
or N-protein) Cohort – Per Protocol Population 
Table 43: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 1 Dose Beta + Omicron, Younger Infected (by Self-
Report or N-protein) Cohort – mITT Population 
Table 44: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 1 Dose Beta + Omicron, Younger Infected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
Table 45: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 1 Dose Beta + Omicron, Younger Uninfected (by 
Self-Report or N-protein) Cohort – mITT Population 
Table 46: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 1 Dose Beta + Omicron, Younger Uninfected (by 
Self-Report or N-protein) Cohort – Per Protocol Population 
Table 47: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 1 Dose Beta + Omicron, Older Infected (by Self-
Report or N-protein) Cohort – mITT Population 
Table 48: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 1 Dose Beta + Omicron, Older Infected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
Table 49: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 1 Dose Beta + Omicron, Older Uninfected (by Self-
Report or N-protein) Cohort – mITT Population 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
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Table 50: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 1 Dose Beta + Omicron, Older Uninfected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
Table 51: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Delta + Omicron, Overall – mITT Population 
Table 52: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Delta + Omicron, Overall – Per Protocol Population 
Table 53: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Delta + Omicron, Younger Cohort – mITT 
Population 
Table 54: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Delta + Omicron, Younger Cohort – Per Protocol 
Population 
Table 55: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Delta + Omicron, Older Cohort – mITT Population 
Table 56: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Delta + Omicron, Older Cohort – Per Protocol 
Population 
Table 57: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Delta + Omicron, Infected (by Self-Report or N-
protein) Cohort – mITT Population 
Table 58: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Delta + Omicron, Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population 
Table 59: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Delta + Omicron, Uninfected (by Self-Report or N-
protein) Cohort – mITT Population 
Table 60: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Delta + Omicron, Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population 
Table 61: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Delta + Omicron, Younger Infected (by Self-Report 
or N-protein) Cohort – mITT Population 
Table 62: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Delta + Omicron, Younger Infected (by Self-Report 
or N-protein) Cohort – Per Protocol Population 
Table 63: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Delta + Omicron, Younger Uninfected (by Self-
Report or N-protein) Cohort – mITT Population 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
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Table 64: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Delta + Omicron, Younger Uninfected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
Table 65: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Delta + Omicron, Older Infected (by Self-Report or 
N-protein) Cohort – mITT Population 
Table 66: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Delta + Omicron, Older Infected (by Self-Report or 
N-protein) Cohort – Per Protocol Population 
Table 67: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Delta + Omicron, Older Uninfected (by Self-Report 
or N-protein) Cohort – mITT Population 
Table 68: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Delta + Omicron, Older Uninfected (by Self-Report 
or N-protein) Cohort – Per Protocol Population 
Table 69: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron, Overall– mITT Population 
Table 70: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron, Overall – Per Protocol Population 
Table 71: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron, Younger Cohort – mITT Population 
Table 72: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron, Younger Cohort – Per Protocol Population 
Table 73: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron, Older Cohort – mITT Population 
Table 74: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron, Older Cohort – Per Protocol Population 
Table 75: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron, Infected (by Self-Report or N-protein) 
Cohort – mITT Population 
Table 76: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron, Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population 
Table 77: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron, Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population 
Table 78: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron, Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
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Table 79: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron, Younger Infected (by Self-Report or N-
protein) Cohort – mITT Population 
Table 80: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron, Younger Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population 
Table 81: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – mITT Population 
Table 82: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population 
Table 83: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron, Older Infected (by Self-Report or N-
protein) Cohort – mITT Population 
Table 84: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron, Older Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population 
Table 85: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron, Older Uninfected (by Self-Report or N-
protein) Cohort – mITT Population 
Table 86: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron, Older Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population 
Table 87: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron + Prototype, Overall– mITT Population 
Table 88: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron + Prototype, Overall– Per Protocol 
Population 
Table 89: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron + Prototype, Younger Cohort – mITT 
Population 
Table 90: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron + Prototype, Younger Cohort – Per 
Protocol Population 
Table 91: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron + Prototype, Older Cohort – mITT 
Population 
Table 92: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron + Prototype, Older Cohort – Per Protocol 
Population 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
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Table 93: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron + Prototype, Infected (by Self-Report or N-
protein) Cohort – mITT Population 
Table 94: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron + Prototype, Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population 
Table 95: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron + Prototype, Uninfected (by Self-Report or 
N-protein) Cohort – mITT Population 
Table 96: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron + Prototype, Uninfected (by Self-Report or 
N-protein) Cohort – Per Protocol Population 
Table 97: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron + Prototype, Younger Infected (by Self-
Report or N-protein) Cohort – mITT Population 
Table 98: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron + Prototype, Younger Infected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
Table 99: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron + Prototype, Younger Uninfected (by Self-
Report or N-protein) Cohort – mITT Population 
Table 100: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron + Prototype, Younger Uninfected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
Table 101: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron + Prototype, Older Infected (by Self-Report 
or N-protein) Cohort – mITT Population 
Table 102: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron + Prototype, Older Infected (by Self-Report 
or N-protein) Cohort – Per Protocol Population 
Table 103: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron + Prototype, Older Uninfected (by Self-
Report or N-protein) Cohort – mITT Population 
Table 104: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, Omicron + Prototype, Older Uninfected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
 
 


Statistical Analysis Plan - DMID Protocol: 22-0004  
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Table 105: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 2 Dose Beta + Omicron, Overall – mITT Population 
Time Point 
Statistic 
D614G 
(N=X) 
B.1.351 
(N=X) 
B.1.617.2 
(N=X) 
BA.1 (N=X) 
BA.2.12.1 
(N=X) 
BA.4/BA.5 
(N=X) 
Day 1  
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 15 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 29 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 57 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
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Time Point 
Statistic 
D614G 
(N=X) 
B.1.351 
(N=X) 
B.1.617.2 
(N=X) 
BA.1 (N=X) 
BA.2.12.1 
(N=X) 
BA.4/BA.5 
(N=X) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 71 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 85 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 147 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
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Time Point 
Statistic 
D614G 
(N=X) 
B.1.351 
(N=X) 
B.1.617.2 
(N=X) 
BA.1 (N=X) 
BA.2.12.1 
(N=X) 
BA.4/BA.5 
(N=X) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 237 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 327 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 422 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
Version 1.0 
10 October 2023 
- 113 - 
RESTRICTED 
Time Point 
Statistic 
D614G 
(N=X) 
B.1.351 
(N=X) 
B.1.617.2 
(N=X) 
BA.1 (N=X) 
BA.2.12.1 
(N=X) 
BA.4/BA.5 
(N=X) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Note: N=Number of subjects in the mITT Population. 
n=Number of subjects with results available at time point. 
GM=Geometric Mean, GMRD614G=Geometric Mean Ratio to D614G variant, GMFR=Geometric Mean Fold Rise, 
GMFD=Geometric Mean Fold Drop. 
Confidence intervals of the GM, GMR, GMFR, and GMFD were calculated with the Student’s t distribution on log-transformed 
data. Confidence intervals of the Seropositive rate were calculated with the Clopper-Pearson method. 
Implementation notes:  
Extra variant columns may be added for additional variants. 
For tables using the PP population, update footnote to read: “Notes: N=Number of subjects in the Per Protocol 
population.” 
Add a note to indicate the lower limit of detection for the assay used to calculate the seropositive rate. 
 
Tables with Similar Format: 
Table 106: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 2 Dose Beta + Omicron, Overall– Per Protocol 
Population 
Table 107: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 2 Dose Beta + Omicron, Younger Cohort – mITT 
Population 
Table 108: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 2 Dose Beta + Omicron, Younger Cohort – Per 
Protocol Population 
Table 109: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 2 Dose Beta + Omicron, Older Cohort – mITT 
Population 
Table 110: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 2 Dose Beta + Omicron, Older Cohort – Per Protocol 
Population 
Table 111: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 2 Dose Beta + Omicron, Infected (by Self-Report or 
N-protein) Cohort – mITT Population 
Table 112: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 2 Dose Beta + Omicron, Infected (by Self-Report or 
N-protein) Cohort – Per Protocol Population 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
Version 1.0 
10 October 2023 
- 114 - 
RESTRICTED 
Table 113: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 2 Dose Beta + Omicron, Uninfected (by Self-Report 
or N-protein) Cohort – mITT Population 
Table 114: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 2 Dose Beta + Omicron, Uninfected (by Self-Report 
or N-protein) Cohort – Per Protocol Population 
Table 115: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 2 Dose Beta + Omicron, Younger Infected (by Self-
Report or N-protein) Cohort – mITT Population 
Table 116: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 2 Dose Beta + Omicron, Younger Infected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
Table 117: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 2 Dose Beta + Omicron, Younger Uninfected (by 
Self-Report or N-protein) Cohort – mITT Population 
Table 118: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 2 Dose Beta + Omicron, Younger Uninfected (by 
Self-Report or N-protein) Cohort – Per Protocol Population 
Table 119: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 2 Dose Beta + Omicron, Older Infected (by Self-
Report or N-protein) Cohort – mITT Population 
Table 120: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 2 Dose Beta + Omicron, Older Infected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
Table 121: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 2 Dose Beta + Omicron, Older Uninfected (by Self-
Report or N-protein) Cohort – mITT Population 
Table 122: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex Summary 
Results by Time Point and Variant, 2 Dose Beta + Omicron, Older Uninfected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
 
 


Statistical Analysis Plan - DMID Protocol: 22-0004  
Version 1.0 
10 October 2023 
- 115 - 
RESTRICTED 
Table 123: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Prototype, Overall – mITT Population 
Time Point 
Statistic 
D614G 
(N=X) 
B.1.351 
(N=X) 
B.1.617.2 
(N=X) 
BA.1 (N=X) 
BA.2.12.1 
(N=X) 
BA.4/BA.5 
(N=X) 
Day 1  
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 15 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 29 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 91 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
Version 1.0 
10 October 2023 
- 116 - 
RESTRICTED 
Time Point 
Statistic 
D614G 
(N=X) 
B.1.351 
(N=X) 
B.1.617.2 
(N=X) 
BA.1 (N=X) 
BA.2.12.1 
(N=X) 
BA.4/BA.5 
(N=X) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 181 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 271 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 366 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
Version 1.0 
10 October 2023 
- 117 - 
RESTRICTED 
Time Point 
Statistic 
D614G 
(N=X) 
B.1.351 
(N=X) 
B.1.617.2 
(N=X) 
BA.1 (N=X) 
BA.2.12.1 
(N=X) 
BA.4/BA.5 
(N=X) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Note: N=Number of subjects in the mITT Population. 
n=Number of subjects with results available at time point. 
GM=Geometric Mean, GMRD614G=Geometric Mean Ratio to D614G variant, GMFR=Geometric Mean Fold Rise, 
GMFD=Geometric Mean Fold Drop. 
Confidence intervals of the GM, GMR, GMFR, and GMFD were calculated with the Student’s t distribution on log-transformed 
data. Confidence intervals of the Seropositive rate were calculated with the Clopper-Pearson method. 
 
Implementation notes:  
Extra variant columns included as placeholders may not be needed. 
For tables using the PP population, update footnote to read: “Notes: N=Number of subjects in the Per Protocol 
population.” 
Add a note to indicate the lower limit of detection for the assay used to calculate the seropositive rate. 
 
Tables with Similar Format: 
Table 124: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Prototype, Overall – Per Protocol Population 
Table 125: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Prototype, Younger Cohort – mITT Population 
Table 126: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Prototype, Younger Cohort – Per Protocol Population 
Table 127: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Prototype, Older Cohort – mITT Population 
Table 128: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Prototype, Older Cohort – Per Protocol Population 
Table 129: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Prototype, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Table 130: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Prototype, Infected (by Self-Report or N-protein) Cohort – Per Protocol Population 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
Version 1.0 
10 October 2023 
- 118 - 
RESTRICTED 
Table 131: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Prototype, Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Table 132: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Prototype, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Table 133: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Prototype, Younger Infected (by Self-Report or N-protein) Cohort – mITT Population 
Table 134: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Prototype, Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 135: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Prototype, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Table 136: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Prototype, Younger Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 137: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Prototype, Older Infected (by Self-Report or N-protein) Cohort – mITT Population 
Table 138: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Prototype, Older Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 139: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Table 140: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 141: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 1 
Dose Beta + Omicron, Overall– mITT Population 
Table 142: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 1 
Dose Beta + Omicron, Overall– Per Protocol Population 
Table 143: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 1 
Dose Beta + Omicron, Younger Cohort – mITT Population 
Table 144: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 1 
Dose Beta + Omicron, Younger Cohort – Per Protocol Population 
Table 145: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 1 
Dose Beta + Omicron, Older Cohort – mITT Population 
Table 146: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 1 
Dose Beta + Omicron, Older Cohort – Per Protocol Population 
Table 147: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 1 
Dose Beta + Omicron, Infected (by Self-Report or N-protein) Cohort – mITT Population 


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Table 148: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 1 
Dose Beta + Omicron, Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 149: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 1 
Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 150: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 1 
Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 151: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 1 
Dose Beta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 152: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 1 
Dose Beta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Table 153: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 1 
Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 154: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 1 
Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Table 155: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 1 
Dose Beta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 156: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 1 
Dose Beta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Table 157: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 1 
Dose Beta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 158: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 1 
Dose Beta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Table 159: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Overall– mITT Population 
Table 160: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Overall – Per Protocol Population 
Table 161: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Younger Cohort – mITT Population 
Table 162: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Younger Cohort – Per Protocol Population 


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Table 163: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Older Cohort – mITT Population 
Table 164: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Older Cohort – Per Protocol Population 
Table 165: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Table 166: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 167: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Table 168: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 169: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 170: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 171: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 172: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Table 173: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 174: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 175: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 176: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 177: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron, Overall– mITT Population 


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Table 178: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron, Overall – Per Protocol Population 
Table 179: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron, Younger Cohort – mITT Population 
Table 180: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron, Younger Cohort – Per Protocol Population 
Table 181: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron, Older Cohort – mITT Population 
Table 182: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron, Older Cohort – Per Protocol Population 
Table 183: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Table 184: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron, Infected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Table 185: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron, Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Table 186: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Table 187: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron, Younger Infected (by Self-Report or N-protein) Cohort – mITT Population 
Table 188: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron, Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 189: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Table 190: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 191: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron, Older Infected (by Self-Report or N-protein) Cohort – mITT Population 
Table 192: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron, Older Infected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Table 193: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Table 194: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 195: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Overall – mITT Population 


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Table 196: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Overall – Per Protocol Population 
Table 197: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Younger Cohort – mITT Population 
Table 198: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Younger Cohort – Per Protocol Population 
Table 199: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Older Cohort – mITT Population 
Table 200: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Older Cohort – Per Protocol Population 
Table 201: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Table 202: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 203: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 204: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 205: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Younger Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 206: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Younger Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Table 207: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 208: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Younger Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Table 209: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Older Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 210: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Older Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 


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Table 211: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 212: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
 


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Table 213: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant,  
2 Dose Beta + Omicron, Overall – mITT Population 
Time Point 
Statistic 
D614G 
(N=X) 
B.1.351 
(N=X) 
B.1.617.2 
(N=X) 
BA.1 (N=X) 
BA.2.12.1 
(N=X) 
BA.4/BA.5 
(N=X) 
Day 1  
 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 15 
 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 29 
 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 57 
 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 


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Time Point 
Statistic 
D614G 
(N=X) 
B.1.351 
(N=X) 
B.1.617.2 
(N=X) 
BA.1 (N=X) 
BA.2.12.1 
(N=X) 
BA.4/BA.5 
(N=X) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 71 
 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 85 
 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 147 
 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
Version 1.0 
10 October 2023 
- 126 - 
RESTRICTED 
Time Point 
Statistic 
D614G 
(N=X) 
B.1.351 
(N=X) 
B.1.617.2 
(N=X) 
BA.1 (N=X) 
BA.2.12.1 
(N=X) 
BA.4/BA.5 
(N=X) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 237 
 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 327 
 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 422 
 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
Version 1.0 
10 October 2023 
- 127 - 
RESTRICTED 
Time Point 
Statistic 
D614G 
(N=X) 
B.1.351 
(N=X) 
B.1.617.2 
(N=X) 
BA.1 (N=X) 
BA.2.12.1 
(N=X) 
BA.4/BA.5 
(N=X) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Note: N=Number of subjects in the mITT Population. 
n=Number of subjects with results available at time point. 
GM=Geometric Mean, GMRD614G=Geometric Mean Ratio to D614G variant, GMFR=Geometric Mean Fold Rise, 
GMFD=Geometric Mean Fold Drop. 
Confidence intervals of the GM, GMR, GMFR, and GMFD were calculated with the Student’s t distribution on log-transformed 
data. Confidence intervals of the Seropositive rate were calculated with the Clopper-Pearson method. 
Implementation notes:  
Extra variant columns may be added for additional variants. 
For tables using the PP population, update footnote to read: “Notes: N=Number of subjects in the Per Protocol 
population.” 
Add a note to indicate the lower limit of detection for the assay used to calculate the seropositive rate. 
 
Tables with Similar Format: 
Table 214: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 2 
Dose Beta + Omicron, Overall – Per Protocol Population 
Table 215: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 2 
Dose Beta + Omicron, Younger Cohort – mITT Population 
Table 216: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 2 
Dose Beta + Omicron, Younger Cohort – Per Protocol Population 
Table 217: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 2 
Dose Beta + Omicron, Older Cohort – mITT Population 
Table 218: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 2 
Dose Beta + Omicron, Older Cohort – Per Protocol Population 
Table 219: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 2 
Dose Beta + Omicron, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Table 220: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 2 
Dose Beta + Omicron, Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
Version 1.0 
10 October 2023 
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RESTRICTED 
Table 221: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 2 
Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 222: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 2 
Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 223: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 2 
Dose Beta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 224: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 2 
Dose Beta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Table 225: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 2 
Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 226: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 2 
Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Table 227: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 2 
Dose Beta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 228: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 2 
Dose Beta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Table 229: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 2 
Dose Beta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 230: 
Pseudovirus Neutralization Assay ID50 Summary Results by Time Point and Variant, 2 
Dose Beta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
 
 


Statistical Analysis Plan - DMID Protocol: 22-0004  
Version 1.0 
10 October 2023 
- 129 - 
RESTRICTED 
Table 231: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Prototype, Overall – mITT Population 
Time Point 
Statistic 
D614G 
(N=X) 
B.1.351 
(N=X) 
B.1.617.2 
(N=X) 
BA.1 
(N=X) 
BA.2.12.1(N=X) 
BA.4/BA.5 
(N=X) 
Day 1  
 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 15 
 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 29 
 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 91 
 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
Version 1.0 
10 October 2023 
- 130 - 
RESTRICTED 
Time Point 
Statistic 
D614G 
(N=X) 
B.1.351 
(N=X) 
B.1.617.2 
(N=X) 
BA.1 
(N=X) 
BA.2.12.1(N=X) 
BA.4/BA.5 
(N=X) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 181 
 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 271 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
 
Day 366 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 


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Time Point 
Statistic 
D614G 
(N=X) 
B.1.351 
(N=X) 
B.1.617.2 
(N=X) 
BA.1 
(N=X) 
BA.2.12.1(N=X) 
BA.4/BA.5 
(N=X) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Note: N=Number of subjects in the mITT Population. 
n=Number of subjects with results available at time point. 
GM=Geometric Mean, GMRD614G=Geometric Mean Ratio to D614G variant, GMFR=Geometric Mean Fold Rise, 
GMFD=Geometric Mean Fold Drop. 
Confidence intervals of the GM, GMR, GMFR, and GMFD were calculated with the Student’s t distribution on log-transformed 
data. Confidence intervals of the Seropositive rate were calculated with the Clopper-Pearson method. 
 
Implementation notes:  
Extra variant columns may be added for additional variants. 
For tables using the PP population, update footnote to read: “Notes: N=Number of subjects in the Per Protocol 
population.” 
 
Tables with Similar Format: 
Table 232: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Prototype, Overall– Per Protocol Population 
Table 233: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Prototype, Younger Cohort – mITT Population 
Table 234: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Prototype, Younger Cohort – Per Protocol Population 
Table 235: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Prototype, Older Cohort – mITT Population 
Table 236: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Prototype, Older Cohort – Per Protocol Population 
Table 237: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Prototype, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Table 238: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Prototype, Infected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Table 239: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Prototype, Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Table 240: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Prototype, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Table 241: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Prototype, Younger Infected (by Self-Report or N-protein) Cohort – mITT Population 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
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Table 242: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Prototype, Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 243: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Prototype, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Table 244: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Prototype, Younger Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 245: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Prototype, Older Infected (by Self-Report or N-protein) Cohort – mITT Population 
Table 246: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Prototype, Older Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 247: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Table 248: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 249: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
1 Dose Beta + Omicron, Overall – mITT Population 
Table 250: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
1 Dose Beta + Omicron, Overall – Per Protocol Population 
Table 251: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
1 Dose Beta + Omicron, Younger Cohort – mITT Population 
Table 252: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
1 Dose Beta + Omicron, Younger Cohort – Per Protocol Population 
Table 253: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
1 Dose Beta + Omicron, Older Cohort – mITT Population 
Table 254: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
1 Dose Beta + Omicron, Older Cohort – Per Protocol Population 
Table 255: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
1 Dose Beta + Omicron, Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 256: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
1 Dose Beta + Omicron, Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 257: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
1 Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
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Table 258: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
1 Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 259: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
1 Dose Beta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 260: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
1 Dose Beta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Table 261: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
1 Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – 
mITT Population 
Table 262: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
1 Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Table 263: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
1 Dose Beta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 264: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
1 Dose Beta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Table 265: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
1 Dose Beta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 266: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
1 Dose Beta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Table 267: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Overall – mITT Population 
Table 268: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Overall – Per Protocol Population 
Table 269: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Younger Cohort – mITT Population 
Table 270: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Younger Cohort – Per Protocol Population 
Table 271: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Older Cohort – mITT Population 
Table 272: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Older Cohort – Per Protocol Population 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
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Table 273: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Table 274: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 275: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Table 276: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 277: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 278: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 279: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 280: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Table 281: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 282: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 283: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 284: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Delta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 285: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron, Overall – mITT Population 
Table 286: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron, Overall – Per Protocol Population 
Table 287: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron, Younger Cohort – mITT Population 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
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Table 288: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron, Younger Cohort – Per Protocol Population 
Table 289: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron, Older Cohort – mITT Population 
Table 290: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron, Older Cohort – Per Protocol Population 
Table 291: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Table 292: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron, Infected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Table 293: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron, Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Table 294: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Table 295: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron, Younger Infected (by Self-Report or N-protein) Cohort – mITT Population 
Table 296: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron, Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 297: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Table 298: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 299: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron, Older Infected (by Self-Report or N-protein) Cohort – mITT Population 
Table 300: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron, Older Infected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Table 301: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Table 302: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 303: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Overall – mITT Population 
Table 304: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Overall – Per Protocol Population 
Table 305: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Younger Cohort – mITT Population 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
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Table 306: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Younger Cohort – Per Protocol Population 
Table 307: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Older Cohort – mITT Population 
Table 308: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Older Cohort – Per Protocol Population 
Table 309: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Table 310: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 311: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 312: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 313: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Younger Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 314: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Younger Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Table 315: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 316: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Younger Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Table 317: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Older Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 318: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Older Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Table 319: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 320: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
Omicron + Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 


Statistical Analysis Plan - DMID Protocol: 22-0004  
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Table 321: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
2 Dose Beta + Omicron, Overall – mITT Population 
Time Point 
Statistic 
D614G 
(N=X) 
B.1.351 
(N=X) 
B.1.617.2 
(N=X) 
BA.1 (N=X) 
BA.2.12.1 
(N=X) 
BA.4/BA.5 
(N=X) 
Day 1  
 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 15 
 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 29 
 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 57 
 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
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Time Point 
Statistic 
D614G 
(N=X) 
B.1.351 
(N=X) 
B.1.617.2 
(N=X) 
BA.1 (N=X) 
BA.2.12.1 
(N=X) 
BA.4/BA.5 
(N=X) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 71 
 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 85 
 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 147 
 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
Version 1.0 
10 October 2023 
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RESTRICTED 
Time Point 
Statistic 
D614G 
(N=X) 
B.1.351 
(N=X) 
B.1.617.2 
(N=X) 
BA.1 (N=X) 
BA.2.12.1 
(N=X) 
BA.4/BA.5 
(N=X) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 237 
 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 327 
 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Day 422 
 
n 
x 
x 
x 
x 
x 
x 
GMT (95% 
CI) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
x.x  
(x.x, x.x) 
Median 
(Min,Max) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMRD614G 
(95% CI) 
NA 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
GMFR 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
Version 1.0 
10 October 2023 
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Time Point 
Statistic 
D614G 
(N=X) 
B.1.351 
(N=X) 
B.1.617.2 
(N=X) 
BA.1 (N=X) 
BA.2.12.1 
(N=X) 
BA.4/BA.5 
(N=X) 
GMFD 
(95% CI) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
x.x 
(x.x, x.x) 
Seropositive 
(95% CI) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
0.0X 
(0.xx,0.xx) 
Note: N=Number of subjects in the mITT Population. 
n=Number of subjects with results available at time point. 
GM=Geometric Mean, GMRD614G=Geometric Mean Ratio to D614G variant, GMFR=Geometric Mean Fold Rise, 
GMFD=Geometric Mean Fold Drop. 
Confidence intervals of the GM, GMR, GMFR, and GMFD were calculated with the Student’s t distribution on log-transformed 
data. Confidence intervals of the Seropositive rate were calculated with the Clopper-Pearson method. 
Implementation notes:  
Extra variant columns may be added for additional variants. 
For tables using the PP population, update footnote to read: “Notes: N=Number of subjects in the Per Protocol 
population.” 
Add a note to indicate the lower limit of detection for the assay used to calculate the seropositive rate. 
 
Tables with Similar Format: 
Table 322: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
2 Dose Beta + Omicron, Overall – Per Protocol Population 
Table 323: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
2 Dose Beta + Omicron, Younger Cohort – mITT Population 
Table 324: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
2 Dose Beta + Omicron, Younger Cohort – Per Protocol Population 
Table 325: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
2 Dose Beta + Omicron, Older Cohort – mITT Population 
Table 326: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
2 Dose Beta + Omicron, Older Cohort – Per Protocol Population 
Table 327: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
2 Dose Beta + Omicron, Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 328: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
2 Dose Beta + Omicron, Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 329: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
2 Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
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Table 330: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
2 Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 331: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
2 Dose Beta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 332: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
2 Dose Beta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Table 333: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
2 Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – 
mITT Population 
Table 334: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
2 Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Table 335: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
2 Dose Beta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 336: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
2 Dose Beta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Table 337: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
2 Dose Beta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 338: 
Focus Reduction Neutralization Test ID50 Summary Results by Time Point and Variant, 
2 Dose Beta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
 
 


Statistical Analysis Plan - DMID Protocol: 22-0004  
Version 1.0 
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Table 339: 
Pseudovirus Neutralization Treatment Group Effects as Ratios Relative to the Prototype 
Arm from ANCOVA model, Overall – mITT Population 
Study Day 
Treatment 
Group 
D614G (N=X) 
B.1.351 
(N=X) 
B.1.617.2 
(N=X) 
B.1.1.529 
(N=X) 
BA.2.12.1 
(N=X) 
BA.4/BA.5 
(N=X) 
Day 15 
Beta + 
Omicron 
 
 
 
 
 
 
Delta + 
Omicron 
 
 
 
 
 
 
Omicron 
 
 
 
 
 
 
Omicron + 
Prototype 
 
 
 
 
 
 
Day 29 
Beta + 
Omicron 
 
 
 
 
 
 
Delta + 
Omicron 
 
 
 
 
 
 
Omicron 
 
 
 
 
 
 
Omicron + 
Prototype 
 
 
 
 
 
 
Day 91 
Beta + 
Omicron 
 
 
 
 
 
 
Delta + 
Omicron 
 
 
 
 
 
 
Omicron 
 
 
 
 
 
 
Omicron + 
Prototype 
 
 
 
 
 
 
Day 181 
Beta + 
Omicron 
 
 
 
 
 
 
Delta + 
Omicron 
 
 
 
 
 
 
Omicron 
 
 
 
 
 
 
Omicron + 
Prototype 
 
 
 
 
 
 
Day 271 
Beta + 
Omicron 
 
 
 
 
 
 
Delta + 
Omicron 
 
 
 
 
 
 
Omicron 
 
 
 
 
 
 
Omicron + 
Prototype 
 
 
 
 
 
 
Day 366 
Beta + 
Omicron 
 
 
 
 
 
 
Delta + 
Omicron 
 
 
 
 
 
 
Omicron 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
Version 1.0 
10 October 2023 
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RESTRICTED 
Study Day 
Treatment 
Group 
D614G (N=X) 
B.1.351 
(N=X) 
B.1.617.2 
(N=X) 
B.1.1.529 
(N=X) 
BA.2.12.1 
(N=X) 
BA.4/BA.5 
(N=X) 
Omicron + 
Prototype 
 
 
 
 
 
 
Note: N=Number of subjects in the mITT Population. 
Effect estimates are ratios relative to the Prototype treatment group. Effect estimates and CIs are from 
an ANCOVA model adjusted for prior infection, log10 of baseline antibody titers, age group, and 
previous vaccination regimen. A Bonferroni adjustment is applied to the CIs. 
 
 
 
Tables with Similar Format: 
Table 340: 
Pseudovirus Neutralization Treatment Group Effects as Ratios Relative to the Prototype 
Arm from ANCOVA model, Overall – Per Protocol Population 
Table 341: 
Pseudovirus Neutralization Treatment Group Effects as Ratios Relative to the Prototype 
Arm from ANCOVA model, Uninfected (by Self-Report or N-Protein) Cohort – mITT 
Population 
Table 342: 
Pseudovirus Neutralization Treatment Group Effects as Ratios Relative to the Prototype 
Arm from ANCOVA model, Uninfected (by Self-Report or N-Protein) Cohort – Per 
Protocol Population 
 
 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
Version 1.0 
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Table 343: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Overall – mITT Population 
[Implementation Note: Tables should include rows for median, min, max, GMFR and 95% CI of GMFR. Column order should be Peptide Pool, 
Cytokine and Time Point.] 
Time Point 
Peptide Pool 
Cytokine 
Statistic 
Prototype 
(N=X) 
1 Dose Beta 
+ Omicron 
(N=X) 
Delta + 
Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All 1 Dose 
Subjects  
(N=X) 
Day 1, Pre-Booster Dose 
Beta Mutations 
IFNγ 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/CM 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/EM 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
Version 1.0 
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Time Point 
Peptide Pool 
Cytokine 
Statistic 
Prototype 
(N=X) 
1 Dose Beta 
+ Omicron 
(N=X) 
Delta + 
Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All 1 Dose 
Subjects  
(N=X) 
IFNγ or IL-2/N 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/TD 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2 and 
154 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2 or 154 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2 or 
154/C 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
Version 1.0 
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Time Point 
Peptide Pool 
Cytokine 
Statistic 
Prototype 
(N=X) 
1 Dose Beta 
+ Omicron 
(N=X) 
Delta + 
Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All 1 Dose 
Subjects  
(N=X) 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2 or 
154/E 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2 or 
154/N 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2 or 
154/T 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IL-17a 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
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Time Point 
Peptide Pool 
Cytokine 
Statistic 
Prototype 
(N=X) 
1 Dose Beta 
+ Omicron 
(N=X) 
Delta + 
Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All 1 Dose 
Subjects  
(N=X) 
IL-2 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IL-4 and 154  
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IL-4 IL-5 IL-13 and 
154 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
TNFα 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
Beta S 
IFNγ 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
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Time Point 
Peptide Pool 
Cytokine 
Statistic 
Prototype 
(N=X) 
1 Dose Beta 
+ Omicron 
(N=X) 
Delta + 
Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All 1 Dose 
Subjects  
(N=X) 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/CM 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/EM 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
Repeat for all cytokines 
Conserved S1 
IFNγ 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
Version 1.0 
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Time Point 
Peptide Pool 
Cytokine 
Statistic 
Prototype 
(N=X) 
1 Dose Beta 
+ Omicron 
(N=X) 
Delta + 
Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All 1 Dose 
Subjects  
(N=X) 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/CM 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/EM 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
Repeat for all cytokines 
Conserved S2 
IFNγ 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2 
n 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
Version 1.0 
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Time Point 
Peptide Pool 
Cytokine 
Statistic 
Prototype 
(N=X) 
1 Dose Beta 
+ Omicron 
(N=X) 
Delta + 
Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All 1 Dose 
Subjects  
(N=X) 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/CM 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/EM 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
Repeat for all cytokines 
Original 
Matched 
IFNγ 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 


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Time Point 
Peptide Pool 
Cytokine 
Statistic 
Prototype 
(N=X) 
1 Dose Beta 
+ Omicron 
(N=X) 
Delta + 
Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All 1 Dose 
Subjects  
(N=X) 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/CM 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/EM 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
Repeat for all cytokines 
Original S 
IFNγ 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 


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Time Point 
Peptide Pool 
Cytokine 
Statistic 
Prototype 
(N=X) 
1 Dose Beta 
+ Omicron 
(N=X) 
Delta + 
Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All 1 Dose 
Subjects  
(N=X) 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/CM 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/EM 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
Repeat for all cytokines 
Repeat for all study days 
Note: N=Number of Subjects. 
n=Number of subjects with results available at time point. 
NE=Not Estimable 
a Confidence interval calculated based on the Student’s t-distribution 
b Exact binomial confidence interval calculated using the Clopper-Pearson methodology. 
Tables with Similar Format: 
Table 344: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Overall – Per Protocol Population 
Table 345: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Older Cohort – mITT Population 
Table 346: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Older Cohort – Per Protocol Population 
Table 347: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Younger Cohort – mITT Population 
Table 348: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Younger Cohort – Per Protocol Population 


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Table 349: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Infected (by Self-Report or N-protein) 
Cohort – mITT Population 
Table 350: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population 
Table 351: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population 
Table 352: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population 
Table 353: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Older Infected (by Self-Report or  
N-protein) Cohort – mITT Population 
Table 354: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Older Infected (by Self-Report or  
N-protein) Cohort – Per Protocol Population 
Table 355: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Older Uninfected (by Self-Report or  
N-protein) Cohort – mITT Population 
Table 356: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Older Uninfected (by Self-Report or  
N-protein) Cohort – Per Protocol Population 
Table 357: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Younger Infected (by Self-Report or  
N-protein) Cohort – mITT Population 
Table 358: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Younger Infected (by Self-Report or  
N-protein) Cohort – Per Protocol Population 
Table 359: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Younger Uninfected (by Self-Report or  
N-protein) Cohort – mITT Population 
Table 360: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Younger Uninfected (by Self-Report or  
N-protein) Cohort – Per Protocol Population 
 
 


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Table 361: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Overall – mITT Population 
[Implementation Note: Tables should include rows for median, min, max, GMFR and 95% CI of GMFR. Column order should be Peptide Pool, 
Cytokine and Time Point.] 
Time Point 
Peptide Pool 
Cytokine 
Statistic 
2 Dose Beta + Omicron 
(N=X) 
Day 1, Pre-Booster Dose 
Beta Mutations 
IFNγ 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/CM 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/EM 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/N 
n 
 
Mean 
 
95% CIa 
 


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Time Point 
Peptide Pool 
Cytokine 
Statistic 
2 Dose Beta + Omicron 
(N=X) 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/TD 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2 and 154 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2 or 154 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2 or 154/C 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2 or 154/E 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 


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Time Point 
Peptide Pool 
Cytokine 
Statistic 
2 Dose Beta + Omicron 
(N=X) 
95% CIb 
 
IFNγ or IL-2 or 154/N 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2 or 154/T 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IL-17a 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IL-2 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IL-4 and 154  
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 


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Time Point 
Peptide Pool 
Cytokine 
Statistic 
2 Dose Beta + Omicron 
(N=X) 
IL-4 IL-5 IL-13 and 154 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
TNFα 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
Beta S 
IFNγ 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/CM 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/EM 
n 
 


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Time Point 
Peptide Pool 
Cytokine 
Statistic 
2 Dose Beta + Omicron 
(N=X) 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
Conserved S1 
IFNγ 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/CM 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/EM 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 


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Time Point 
Peptide Pool 
Cytokine 
Statistic 
2 Dose Beta + Omicron 
(N=X) 
Conserved S2 
IFNγ 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/CM 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/EM 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
Original Matched 
IFNγ 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 


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Time Point 
Peptide Pool 
Cytokine 
Statistic 
2 Dose Beta + Omicron 
(N=X) 
IFNγ or IL-2 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/CM 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/EM 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
Original S 
IFNγ 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 


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Time Point 
Peptide Pool 
Cytokine 
Statistic 
2 Dose Beta + Omicron 
(N=X) 
IFNγ or IL-2/CM 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/EM 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
Tables with Similar Format: 
Table 362: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Overall – Per Protocol Population 
Table 363: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Older Cohort – mITT Population 
Table 364: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Older Cohort – Per Protocol Population 
Table 365: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Younger Cohort – mITT Population 
Table 366: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Younger Cohort – Per Protocol Population 
Table 367: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Infected (by Self-Report or N-protein) 
Cohort – mITT Population 
Table 368: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population 
Table 369: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population 
Table 370: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population 


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Table 371: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Older Infected (by Self-Report or  
N-protein) Cohort – mITT Population 
Table 372: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Older Infected (by Self-Report or  
N-protein) Cohort – Per Protocol Population 
Table 373: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Older Uninfected (by Self-Report or  
N-protein) Cohort – mITT Population 
Table 374: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Older Uninfected (by Self-Report or  
N-protein) Cohort – Per Protocol Population 
Table 375: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Younger Infected (by Self-Report or  
N-protein) Cohort – mITT Population 
Table 376: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Younger Infected (by Self-Report or  
N-protein) Cohort – Per Protocol Population 
Table 377: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Younger Uninfected (by Self-Report or  
N-protein) Cohort – mITT Population 
Table 378: 
Mean Percentages of CD4 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Younger Uninfected (by Self-Report or  
N-protein) Cohort – Per Protocol Population 
 


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Table 379: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Overall – mITT Population 
[Implementation Note: Tables should include rows for median, min, max, GMFR and 95% CI of GMFR.  Column order should be Peptide Pool, 
Cytokine and Time Point.] 
Time Point 
Peptide Pool 
Cytokine 
Statistic 
Prototype 
(N=X) 
1 Dose Beta + 
Omicron 
(N=X) 
Delta + 
Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All 1 Dose 
Subjects  
(N=X) 
Day 1, Pre-Booster Dose 
 
Beta Mutations 
IFNγ or IL-2 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/CM 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/EM 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/N 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 


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Time Point 
Peptide Pool 
Cytokine 
Statistic 
Prototype 
(N=X) 
1 Dose Beta + 
Omicron 
(N=X) 
Delta + 
Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All 1 Dose 
Subjects  
(N=X) 
IFNγ or IL-2/TD 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
Beta S 
IFNγ or IL-2 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/CM 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/EM 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/N 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 


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Time Point 
Peptide Pool 
Cytokine 
Statistic 
Prototype 
(N=X) 
1 Dose Beta + 
Omicron 
(N=X) 
Delta + 
Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All 1 Dose 
Subjects  
(N=X) 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/TD 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
Conserved S1 
IFNγ or IL-2 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/CM 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/EM 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 


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Time Point 
Peptide Pool 
Cytokine 
Statistic 
Prototype 
(N=X) 
1 Dose Beta + 
Omicron 
(N=X) 
Delta + 
Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All 1 Dose 
Subjects  
(N=X) 
IFNγ or IL-2/N 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/TD 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
Conserved S2 
IFNγ or IL-2 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/CM 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/EM 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 


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Time Point 
Peptide Pool 
Cytokine 
Statistic 
Prototype 
(N=X) 
1 Dose Beta + 
Omicron 
(N=X) 
Delta + 
Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All 1 Dose 
Subjects  
(N=X) 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/N 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/TD 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
Original 
Matched 
IFNγ or IL-2 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/CM 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 


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Time Point 
Peptide Pool 
Cytokine 
Statistic 
Prototype 
(N=X) 
1 Dose Beta + 
Omicron 
(N=X) 
Delta + 
Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All 1 Dose 
Subjects  
(N=X) 
IFNγ or IL-2/EM 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/N 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/TD 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
Original S 
IFNγ or IL-2 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/CM 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 


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Time Point 
Peptide Pool 
Cytokine 
Statistic 
Prototype 
(N=X) 
1 Dose Beta + 
Omicron 
(N=X) 
Delta + 
Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All 1 Dose 
Subjects  
(N=X) 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/EM 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/N 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
IFNγ or IL-2/TD 
n 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
95% CIa 
 
 
 
 
 
 
Response 
Rate 
 
 
 
 
 
 
95% CIb 
 
 
 
 
 
 
Repeat for all study days 
Note: N=Number of Subjects. 
n=Number of subjects with results available at time point. 
NE=Not Estimable 
a Confidence interval calculated based on the Student’s t-distribution 
b Exact binomial confidence interval calculated using the Clopper-Pearson methodology. 
 


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Tables with Similar Format: 
Table 380: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Overall – Per Protocol Population 
Table 381: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Older Cohort – mITT Population 
Table 382: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Older Cohort – Per Protocol Population 
Table 383: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Younger Cohort – mITT Population 
Table 384: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Younger Cohort – Per Protocol Population 
Table 385: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Infected (by Self-Report or N-protein) 
Cohort – mITT Population 
Table 386: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population 
Table 387: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population 
Table 388: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population 
Table 389: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Older Infected (by Self-Report or  
N-protein) Cohort – mITT Population 
Table 390: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Older Infected (by Self-Report or  
N-protein) Cohort – Per Protocol Population 
Table 391: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Older Uninfected (by Self-Report or  
N-protein) Cohort – mITT Population 
Table 392: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Older Uninfected (by Self-Report or  
N-protein) Cohort – Per Protocol Population 
Table 393: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Younger Infected (by Self-Report)  
Cohort – mITT Population 
Table 394: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Younger Infected (by Self-Report or  
N-protein) Cohort – Per Protocol Population 


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Table 395: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Younger Uninfected (by Self-Report or  
N-protein) Cohort – mITT Population 
Table 396: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 1 Dose Groups, Younger Uninfected (by Self-Report or  
N-protein) Cohort – Per Protocol Population 
 
 


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Table 397: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Overall – mITT Population 
[Implementation Note: Tables should include rows for median, min, max, GMFR and 95% CI of GMFR.  Column order should be Peptide Pool, 
Cytokine and Time Point.] 
Time Point 
Peptide Pool 
Cytokine 
Statistic 
2 Dose Beta + Omicron 
(N=X) 
Day 1, Pre-Booster Dose 
 
Beta Mutations 
IFNγ or IL-2 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/CM 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/EM 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/N 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/TD 
n 
 
Mean 
 
95% CIa 
 


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Time Point 
Peptide Pool 
Cytokine 
Statistic 
2 Dose Beta + Omicron 
(N=X) 
Response Rate 
 
95% CIb 
 
Beta S 
IFNγ or IL-2 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/CM 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/EM 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/N 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/TD 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
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Time Point 
Peptide Pool 
Cytokine 
Statistic 
2 Dose Beta + Omicron 
(N=X) 
95% CIb 
 
Conserved S1 
IFNγ or IL-2 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/CM 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/EM 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/N 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/TD 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 


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Time Point 
Peptide Pool 
Cytokine 
Statistic 
2 Dose Beta + Omicron 
(N=X) 
Conserved S2 
IFNγ or IL-2 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/CM 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/EM 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/N 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/TD 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
Original Matched 
IFNγ or IL-2 
n 
 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
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Time Point 
Peptide Pool 
Cytokine 
Statistic 
2 Dose Beta + Omicron 
(N=X) 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/CM 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/EM 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/N 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/TD 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
Original S 
IFNγ or IL-2 
n 
 
Mean 
 


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Time Point 
Peptide Pool 
Cytokine 
Statistic 
2 Dose Beta + Omicron 
(N=X) 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/CM 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/EM 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/N 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
IFNγ or IL-2/TD 
n 
 
Mean 
 
95% CIa 
 
Response Rate 
 
95% CIb 
 
 
 
 


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Tables with Similar Format: 
Table 398: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Overall – Per Protocol Population 
Table 399: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Older Cohort – mITT Population 
Table 400: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Older Cohort – Per Protocol Population 
Table 401: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Younger Cohort – mITT Population 
Table 402: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Younger Cohort – Per Protocol Population 
Table 403: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Infected (by Self-Report or N-protein) 
Cohort – mITT Population 
Table 404: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population 
Table 405: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population 
Table 406: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population 
Table 407: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Older Infected (by Self-Report or  
N-protein) Cohort – mITT Population 
Table 408: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Older Infected (by Self-Report or  
N-protein) Cohort – Per Protocol Population 
Table 409: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Older Uninfected (by Self-Report or  
N-protein) Cohort – mITT Population 
Table 410: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Older Uninfected (by Self-Report or  
N-protein) Cohort – Per Protocol Population 
Table 411: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Younger Infected (by Self-Report or  
N-protein) Cohort – mITT Population 
Table 412: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Younger Infected (by Self-Report or  
N-protein) Cohort – Per Protocol Population 


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Table 413: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Younger Uninfected (by Self-Report or  
N-protein) Cohort – mITT Population 
Table 414: 
Mean Percentages of CD8 T Cells Expressing Cytokines with 95% CI, 2 Dose Group, Younger Uninfected (by Self-Report or  
N-protein) Cohort – Per Protocol Population 
 


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Table 415: 
Percent of Total B-cells by timepoint and Vaccination arm, Overall – mITT Population 
Probe 
Time Point 
Statistic 
Prototype 
(N=X) 
1 Dose Beta + 
Omicron 
(N=X) 
Delta + Omicron 
(N=X) 
Omicron (N=X) 
Omicron + 
Prototype (N=X) 
All 1 Dose 
Subjects  
(N=X) 
NTD WT_SA+ 
Day 1 
n 
xx 
xx 
xx 
xx 
xx 
xx 
Median (%) 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min, Max (%) 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
Day 15 
n 
xx 
xx 
xx 
xx 
xx 
xx 
Median (%) 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min, Max (%) 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
Median Fold 
Rise 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min, Max Fold 
Rise 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
Repeat for probes for RBD WT+, RBD WT+ SA+, S2P SA+, S2P WT+, S2P WT+ SA+, Any probe. Include all available time points.  
N=number of subjects in group. 
n=number of subjects with data available at visit. 
Tables with Similar Format: 
Table 416: 
Percent of Total B-cells by timepoint and Vaccination arm, Overall – Per Protocol Population 
Table 417: 
Percent of Total B-cells by timepoint and Vaccination arm, Older Cohort – mITT Population 
Table 418: 
Percent of Total B-cells by timepoint and Vaccination arm, Older Cohort – Per Protocol Population 
Table 419: 
Percent of Total B-cells by timepoint and Vaccination arm, Younger Cohort – mITT Population 
Table 420: 
Percent of Total B-cells by timepoint and Vaccination arm, Younger Cohort – Per Protocol Population 
Table 421: 
Percent of Total B-cells by timepoint and Vaccination arm, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Table 422: 
Percent of Total B-cells by timepoint and Vaccination arm, Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 


Statistical Analysis Plan - DMID Protocol: 22-0004  
 
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Table 423: 
Percent of Total B-cells by timepoint and Vaccination arm, Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Table 424: 
Percent of Total B-cells by timepoint and Vaccination arm, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Table 425: 
Percent of Total B-cells by timepoint and Vaccination arm, Older Infected (by Self-Report or  
N-protein) Cohort – mITT Population 
Table 426: 
Percent of Total B-cells by timepoint and Vaccination arm, Older Infected (by Self-Report or  
N-protein) Cohort – Per Protocol Population 
Table 427: 
Percent of Total B-cells by timepoint and Vaccination arm, Older Uninfected (by Self-Report or  
N-protein) Cohort – mITT Population 
Table 428: 
Percent of Total B-cells by timepoint and Vaccination arm, Older Uninfected (by Self-Report or  
N-protein) Cohort – Per Protocol Population 
Table 429: 
Percent of Total B-cells by timepoint and Vaccination arm, Younger Infected (by Self-Report or  
N-protein) Cohort – mITT Population 
Table 430: 
Percent of Total B-cells by timepoint and Vaccination arm, Younger Infected (by Self-Report or  
N-protein) Cohort – Per Protocol Population 
Table 431: 
Percent of Total B-cells by timepoint and Vaccination arm, Younger Uninfected (by Self-Report or  
N-protein) Cohort – mITT Population 
Table 432: 
Percent of Total B-cells by timepoint and Vaccination arm, Younger Uninfected (by Self-Report or  
N-protein) Cohort – Per Protocol Population 


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Table 433: 
Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, Overall – mITT Population 
Probe 
Time Point 
Statistic 
2 Dose Beta + Omicron 
(N=X) 
NTD WT_SA+ 
Day 1 
n 
xx 
Median (%) 
xx.x 
Min, Max (%) 
xx.x, xx.x 
Day 15 
n 
xx 
Median (%) 
xx.x 
Min, Max (%) 
xx.x, xx.x 
Median Fold Rise 
xx.x 
Min, Max Fold Rise 
xx.x, xx.x 
Repeat for probes for RBD WT+, RBD WT+ SA+, S2P SA+, S2P WT+, S2P WT+ SA+, Any probe. Include all available time points.  
N=number of subjects in group. 
n=number of subjects with data available at visit. 
Tables with Similar Format: 
Table 434: 
Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, Overall – Per Protocol Population 
Table 435: 
Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, Older Cohort – mITT Population 
Table 436: 
Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, Older Cohort – Per Protocol Population 
Table 437: 
Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, Younger Cohort – mITT Population 
Table 438: 
Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, Younger Cohort – Per Protocol Population 
Table 439: 
Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Table 440: 
Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Table 441: 
Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, Uninfected (by Self-Report or N-protein) Cohort – 
mITT Population 


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Table 442: 
Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Table 443: 
Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, Older Infected (by Self-Report or  
N-protein) Cohort – mITT Population 
Table 444: 
Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, Older Infected (by Self-Report or  
N-protein) Cohort – Per Protocol Population 
Table 445: 
Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, Older Uninfected (by Self-Report or  
N-protein) Cohort – mITT Population 
Table 446: 
Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, Older Uninfected (by Self-Report or  
N-protein) Cohort – Per Protocol Population 
Table 447: 
Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, Younger Infected (by Self-Report or  
N-protein) Cohort – mITT Population 
Table 448: 
Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, Younger Infected (by Self-Report or  
N-protein) Cohort – Per Protocol Population 
Table 449: 
Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, Younger Uninfected (by Self-Report or  
N-protein) Cohort – mITT Population 
Table 450: 
Percent of Total B-cells by timepoint and Vaccination arm, 2 Dose Group, Younger Uninfected (by Self-Report or  
N-protein) Cohort – Per Protocol Population 


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Table 451: 
Time to Infection Restricted Mean Survival Analysis by Vaccination Group, Overall – mITT Population 
Vaccination Group 
Total Number 
Subjects with 
COVID-19 Infection 
Proportion 
Infected at Day 29 
(95% CI)b  
Proportion 
Infected at Day 
91 (95% CI)b,c 
Proportion 
Infected at Day 
181 (95% CI)b,c 
Taua 
Restricted Mean Infection Time (Days) 
Estimate 
95% CI 
Prototype 
x 
 
 
 
 
x.x 
x.x, x.x 
1 Dose 
Beta+Omicron 
x 
 
 
 
 
x.x 
x.x, x.x 
2 Dose 
Beta+Omicron 
x 
 
 
 
 
x.x 
x.x, x.x 
Delta+Omicron 
x 
 
 
 
 
x.x 
x.x, x.x 
Omicron 
x 
 
 
 
 
x.x 
x.x, x.x 
Omicron+Prototype 
x 
 
 
 
 
x.x 
x.x, x.x 
N= Number of subjects in the specified vaccination group.  
a Tau is the truncation time point for the Restricted Mean Survival Time analysis and is equal to the minimum of the largest observed times in each group 
bKaplan-Meier Estimate and 95% confidence interval. 
c91/181 days after last vaccination. 
Programming Notes: 
Within a subgroup: 
proc lifetest data=dat plots=(rmst) method=breslow rmst(cl); 
by subgroup; 
time infday * Censor(1); 
strata trtcode /diff=all; 
ods output  rmst=rmst; 
run; 
Tables with Similar Formatting: 
Table 452: 
Time to Infection Restricted Mean Survival Analysis by Vaccination Group, Younger Cohort– mITT Population 
Table 453: 
Time to Infection Restricted Mean Survival Analysis by Vaccination Group, Older Cohort – mITT Population 
Table 454: 
Time to Infection Restricted Mean Survival Analysis by Vaccination Group, Infected Cohort (By Self-Report or N-protein) – 
mITT Population 


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Table 455: 
Time to Infection Restricted Mean Survival Analysis by Vaccination Group, Uninfected Cohort (By Self Report or N-protein) – 
mITT Population 
Table 456: 
Time to Infection Restricted Mean Survival Analysis by Vaccination Group, Younger Infected Cohort (By Self-Report or  
N-protein)– mITT Population 
Table 457: 
Time to Infection Restricted Mean Survival Analysis by Vaccination Group, Younger Uninfected Cohort (By Self-Report or  
N-protein)– mITT Population 
Table 458: 
Time to Infection Restricted Mean Survival Analysis by Vaccination Group, Older Infected Cohort (By Self-Report or  
N-protein)– mITT Population 
Table 459: 
Time to Infection Restricted Mean Survival Analysis by Vaccination Group, Older Uninfected Cohort (By Self-Report or  
N-protein)– mITT Population 
 


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Table 460: 
Number of Breakthrough Infections by PANGO Call and Treatment Group, Overall – Safety Population 
[Implementation Note: Listed variants are examples only, the sequenced variants will be included in the table.  Percentages are based on the number of 
sequenced samples available during the interval.] 
Interval 
Variant 
Prototype 
(N=X) 
Beta + 
Omicron 
(N=X) 
Beta + 
Omicron 
(Second 
Dose) 
(N=X) 
Delta + 
Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All Subjects 
(N=X) 
Day 1 to Day 8 (n=x) 
D614G 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Beta 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Delta 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
BA.1 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
BA.4/5 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
XBB.1 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Day 9 to Day 15 (n=x) 
D614G 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Beta 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Delta 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
BA.1 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
BA.4/5 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
XBB.1 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Day 16 to Day 29 (n=x) 
D614G 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Beta 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Delta 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
BA.1 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
BA.4/5 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
XBB.1 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Day 30 to Day 91 (n=x) 
D614G 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Beta 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Delta 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 


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Interval 
Variant 
Prototype 
(N=X) 
Beta + 
Omicron 
(N=X) 
Beta + 
Omicron 
(Second 
Dose) 
(N=X) 
Delta + 
Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All Subjects 
(N=X) 
BA.1 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
BA.4/5 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
XBB.1 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Day 92 to Day 181 (n=x) 
D614G 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Beta 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Delta 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
BA.1 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
BA.4/5 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
XBB.1 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Day 182 to Day 271 (n=x) 
D614G 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Beta 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Delta 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
BA.1 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
BA.4/5 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
XBB.1 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Day 272 to Day 366 (n=x) 
D614G 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Beta 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Delta 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
BA.1 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
BA.4/5 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
XBB.1 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Any Time Point (n=x) 
D614G 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Beta 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Delta 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 


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Interval 
Variant 
Prototype 
(N=X) 
Beta + 
Omicron 
(N=X) 
Beta + 
Omicron 
(Second 
Dose) 
(N=X) 
Delta + 
Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All Subjects 
(N=X) 
BA.1 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
BA.4/5 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
XBB.1 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Note: N=Number of subjects in Safety Population with sequencing done. 
n=number of subjects with reported infections and sequencing available at a given visit. 
 
 
 
Tables with Similar Format: 
Table 461: 
Breakthrough Infections by PANGO Call and Treatment Group, Older Cohort – Safety Population 
Table 462: 
Breakthrough Infections by PANGO Call and Treatment Group, Younger Cohort – Safety Population 
Table 463: 
Breakthrough Infections by PANGO Call and Treatment Group, Infected (by Self-Report or N-protein) Cohort – Safety 
Population 
Table 464: 
Breakthrough Infections by PANGO Call and Treatment Group, Uninfected (by Self-Report or N-protein) Cohort – Safety 
Population 
Table 465: 
Breakthrough Infections by PANGO Call and Treatment Group, Older Infected (by Self-Report or N-protein) Cohort – Safety 
Population 
Table 466: 
Breakthrough Infections by PANGO Call and Treatment Group, Older Uninfected (by Self-Report or N-protein) Cohort – Safety 
Population 
Table 467: 
Breakthrough Infections by PANGO Call and Treatment Group, Younger Infected (by Self-Report) Cohort – Safety Population 
Table 468: 
Breakthrough Infections by PANGO Call and Treatment Group, Younger Uninfected (by Self-Report or N-protein) Cohort – 
Safety Population 
 


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14.3 
Safety Data 
14.3.1 Displays of Adverse Events 
Table 469: 
Overall Summary of Adverse Events by Treatment Group – All Subjects 
Subjectsa with 
Prototype 
(N=X) 
Beta + Omicron 
(N=X) 
Beta + Omicron  
(2 Doses) 
(N=X) 
Delta + 
Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All Subjects 
(N=X) 
Category 1 
Category 2 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
At least one local 
solicited adverse event 
NA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
At least one systemic 
solicited adverse event 
NA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
At least one 
unsolicited adverse 
event 
NA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
At least one related 
unsolicited adverse 
event 
Any Grade 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild (Grade 1) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate (Grade 
2) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe (Grade 3) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
At least one severe 
(Grade 3) unsolicited 
adverse event 
Any relationship 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Related 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unrelated 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
At least one serious 
adverse eventb 
Any relationship 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Related 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unrelated 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Subjectsa with 
Prototype 
(N=X) 
Beta + Omicron 
(N=X) 
Beta + Omicron  
(2 Doses) 
(N=X) 
Delta + 
Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All Subjects 
(N=X) 
Category 1 
Category 2 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
At least one adverse 
event leading to early 
terminationc 
NA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
At least one Adverse 
Event of Special 
Interest 
NA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
At least one medically 
attended adverse event 
NA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
At least one new onset 
chronic medical 
condition 
NA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N = Number of subjects in the Safety Population 
aSubjects are counted once for each category regardless of the number of events. 
bA listing of Serious Adverse Events is included in Table 483. 
cAs reported on the Adverse Event eCRF. 
 
 


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Table 470: 
Serious Adverse Events and Non-Serious Adverse Events Occurring in 5% of Subjects in Any Treatment Group by MedDRA 
System Organ Class and Preferred Term, and Treatment Group – Safety Population 
Preferred Term 
MedDRA 
System Organ 
Class 
Prototype 
(N=X) 
Beta + Omicron 
(N=X) 
Beta + Omicron 
(2 Doses) 
(N=X) 
Delta + Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All Subjects 
(N=X) 
 
 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
Serious Adverse Events 
All  
All 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
 
 
 
 
 
 
 
x 
x 
x 
PT1 
SOC1 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
 
 
 
 
 
 
 
x 
x 
x 
Etc. 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other (Non-serious) Adverse Events 
All  
All 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
 
 
 
 
 
 
 
x 
x 
x 
PT1 
SOC1 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
 
 
 
 
 
 
 
x 
x 
x 
Etc 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N = number of subjects in the Safety Population (number of subjects at risk). 
n = number of subjects reporting event. 
Events = total frequency of events reported. 
 


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14.3.1.1 
Solicited Adverse Events 
Table 471: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% Confidence Intervals by Symptom, Dose, and 
Treatment Group – Post Dose 1 
 
Prototype 
(N=X) 
Beta + Omicron 
(N=X) 
Delta + Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All Subjects 
(N=X) 
Symptom 
Severity 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Any Symptom 
None 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
Any Systemic 
Symptom 
None 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
Arthralgia 
None 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
Fatigue 
None 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
Fevera 
None 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 


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Prototype 
(N=X) 
Beta + Omicron 
(N=X) 
Delta + Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All Subjects 
(N=X) 
Symptom 
Severity 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
Feverishness 
None 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
Headache 
None 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
Myalgia 
None 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
Nausea 
None 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
Any Local Symptom 
None 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
Erythema/Redness 
None 
 
 
 
 
 
 
 
 
 
 
 
 


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Prototype 
(N=X) 
Beta + Omicron 
(N=X) 
Delta + Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All Subjects 
(N=X) 
Symptom 
Severity 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
Erythema/Redness 
Measurement (mm) 
None 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
Induration/Swelling 
None 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
Induration/Swelling 
Measurement (mm) 
None 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
Pain 
None 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
Severity is the maximum severity reported over all solicited symptoms post dosing for each subject. 
N=All subjects receiving vaccination with any solicited event data recorded in the database. 


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Table 472: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% Confidence Intervals by Symptom, Dose, and 
Treatment Group – Two Dose Treatment Group 
 
Beta + Omicron (2 Doses) 
Post Dose 2 
(N=X) 
Beta + Omicron (2 Doses) 
Post Either Dose 
(N=X) 
Symptom 
Severity 
n 
% 
n 
% 
Any Symptom 
None 
 
 
 
 
Mild 
 
 
 
 
Moderate 
 
 
 
 
Severe 
 
 
 
 
Any Systemic Symptom 
None 
 
 
 
 
Mild 
 
 
 
 
Moderate 
 
 
 
 
Severe 
 
 
 
 
Arthralgia 
None 
 
 
 
 
Mild 
 
 
 
 
Moderate 
 
 
 
 
Severe 
 
 
 
 
Fatigue 
None 
 
 
 
 
Mild 
 
 
 
 
Moderate 
 
 
 
 
Severe 
 
 
 
 
Fevera 
None 
 
 
 
 
Mild 
 
 
 
 
Moderate 
 
 
 
 
Severe 
 
 
 
 


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Beta + Omicron (2 Doses) 
Post Dose 2 
(N=X) 
Beta + Omicron (2 Doses) 
Post Either Dose 
(N=X) 
Symptom 
Severity 
n 
% 
n 
% 
Feverishness 
None 
 
 
 
 
Mild 
 
 
 
 
Moderate 
 
 
 
 
Severe 
 
 
 
 
Headache 
None 
 
 
 
 
Mild 
 
 
 
 
Moderate 
 
 
 
 
Severe 
 
 
 
 
Myalgia 
None 
 
 
 
 
Mild 
 
 
 
 
Moderate 
 
 
 
 
Severe 
 
 
 
 
Nausea 
None 
 
 
 
 
Mild 
 
 
 
 
Moderate 
 
 
 
 
Severe 
 
 
 
 
Any Local Symptom 
None 
 
 
 
 
Mild 
 
 
 
 
Moderate 
 
 
 
 
Severe 
 
 
 
 
Erythema/Redness 
None 
 
 
 
 
Mild 
 
 
 
 


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Beta + Omicron (2 Doses) 
Post Dose 2 
(N=X) 
Beta + Omicron (2 Doses) 
Post Either Dose 
(N=X) 
Symptom 
Severity 
n 
% 
n 
% 
Moderate 
 
 
 
 
Severe 
 
 
 
 
Erythema/Redness 
Measurement (mm) 
None 
 
 
 
 
Mild 
 
 
 
 
Moderate 
 
 
 
 
Severe 
 
 
 
 
Induration/Swelling 
None 
 
 
 
 
Mild 
 
 
 
 
Moderate 
 
 
 
 
Severe 
 
 
 
 
Induration/Swelling 
Measurement (mm) 
None 
 
 
 
 
Mild 
 
 
 
 
Moderate 
 
 
 
 
Severe 
 
 
 
 
Pain 
None 
 
 
 
 
Mild 
 
 
 
 
Moderate 
 
 
 
 
Severe 
 
 
 
 
 
 


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Table 473: 
Summary of Solicited Events by Days Post Treatment, Symptom, and Treatment Group – Prototype  
 
Pre-Dose  
( N=X) 
Post-Dose 
(N=X) 
Day 1 
(N=X) 
Day 2 
(N=X) 
Day 3 
(N=X) 
Day 4 
(N=X) 
Day 5 
(N=X) 
Day 6 
(N=X) 
Day 7 
(N=X) 
Day 8+ 1 
(N=X) 
Any  
Post-Dose2 
Symptom 
Severity 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Any  
Symptom 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Any  
Systemic  
Symptom 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Arthralgia 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fatigue 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fever 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Feverishness 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Pre-Dose  
( N=X) 
Post-Dose 
(N=X) 
Day 1 
(N=X) 
Day 2 
(N=X) 
Day 3 
(N=X) 
Day 4 
(N=X) 
Day 5 
(N=X) 
Day 6 
(N=X) 
Day 7 
(N=X) 
Day 8+ 1 
(N=X) 
Any  
Post-Dose2 
Symptom 
Severity 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Headache 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Myalgia 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Nausea 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Any Local 
Symptom 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Erythema/Redness 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Pre-Dose  
( N=X) 
Post-Dose 
(N=X) 
Day 1 
(N=X) 
Day 2 
(N=X) 
Day 3 
(N=X) 
Day 4 
(N=X) 
Day 5 
(N=X) 
Day 6 
(N=X) 
Day 7 
(N=X) 
Day 8+ 1 
(N=X) 
Any  
Post-Dose2 
Symptom 
Severity 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Erythema/Redness 
Measurement (mm) 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Induration/Swelling 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Induration/Swelling 
Measurement (mm) 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pain 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes: N=Number of subjects in the Safety Population.  
Severity is the maximum severity reported post dosing for each subject for each day. 
1 Day 8+ includes the maximum severity of each symptom reported on or after Day 8 (includes ongoing symptoms) 
2 Indicates how many subjects had “None”, “Mild”, “Moderate”, or “Severe” as their maximum severity for any day. A subject may be counted in more than one of these categories. 
 
 


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Tables with Similar Format: 
Implementation note: For any symptoms or days with missing data, add a “Not Reported” row. 
Table 474: 
Summary of Solicited Events by Days Post Treatment, Symptom, and Treatment Group – Beta + Omicron 
Table 475: 
Summary of Solicited Events by Days Post Treatment, Symptom, and Treatment Group – Delta + Omicron 
Table 476: 
Summary of Solicited Events by Days Post Treatment, Symptom, and Treatment Group – Omicron 
Table 477: 
Summary of Solicited Events by Days Post Treatment, Symptom, and Treatment Group – Omicron + Prototype 
 
 


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Table 478: 
Summary of Solicited Events by Days Post Treatment, Symptom, and Treatment Group – Beta+Omicron  
 
Pre-Dose  
( N=X) 
Post-Dose 
(N=X) 
Day 1 
(N=X) 
Day 2 
(N=X) 
Day 3 
(N=X) 
Day 4 
(N=X) 
Day 5 
(N=X) 
Day 6 
(N=X) 
Day 7 
(N=X) 
Day 8+ 1 
(N=X) 
Any  
Post-Dose2 
Symptom 
Severity 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Dose 2 
Any  
Symptom 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Any  
Systemic  
Symptom 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Arthralgia 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fatigue 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fever 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Feverishness 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Pre-Dose  
( N=X) 
Post-Dose 
(N=X) 
Day 1 
(N=X) 
Day 2 
(N=X) 
Day 3 
(N=X) 
Day 4 
(N=X) 
Day 5 
(N=X) 
Day 6 
(N=X) 
Day 7 
(N=X) 
Day 8+ 1 
(N=X) 
Any  
Post-Dose2 
Symptom 
Severity 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Headache 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Myalgia 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Nausea 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Any Local 
Symptom 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Erythema/Redness 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Pre-Dose  
( N=X) 
Post-Dose 
(N=X) 
Day 1 
(N=X) 
Day 2 
(N=X) 
Day 3 
(N=X) 
Day 4 
(N=X) 
Day 5 
(N=X) 
Day 6 
(N=X) 
Day 7 
(N=X) 
Day 8+ 1 
(N=X) 
Any  
Post-Dose2 
Symptom 
Severity 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Erythema/Redness 
Measurement (mm) 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Induration/Swelling 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Induration/Swelling 
Measurement (mm) 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pain 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Any Dose 
Any  
Symptom 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Pre-Dose  
( N=X) 
Post-Dose 
(N=X) 
Day 1 
(N=X) 
Day 2 
(N=X) 
Day 3 
(N=X) 
Day 4 
(N=X) 
Day 5 
(N=X) 
Day 6 
(N=X) 
Day 7 
(N=X) 
Day 8+ 1 
(N=X) 
Any  
Post-Dose2 
Symptom 
Severity 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Any  
Systemic  
Symptom 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Arthralgia 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fatigue 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fever 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Feverishness 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Headache 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Myalgia 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Pre-Dose  
( N=X) 
Post-Dose 
(N=X) 
Day 1 
(N=X) 
Day 2 
(N=X) 
Day 3 
(N=X) 
Day 4 
(N=X) 
Day 5 
(N=X) 
Day 6 
(N=X) 
Day 7 
(N=X) 
Day 8+ 1 
(N=X) 
Any  
Post-Dose2 
Symptom 
Severity 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Nausea 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Any Local 
Symptom 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Erythema/Redness 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Erythema/Redness 
Measurement (mm) 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Induration/Swelling 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Pre-Dose  
( N=X) 
Post-Dose 
(N=X) 
Day 1 
(N=X) 
Day 2 
(N=X) 
Day 3 
(N=X) 
Day 4 
(N=X) 
Day 5 
(N=X) 
Day 6 
(N=X) 
Day 7 
(N=X) 
Day 8+ 1 
(N=X) 
Any  
Post-Dose2 
Symptom 
Severity 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Induration/Swelling 
Measurement (mm) 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pain 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes: N=Number of subjects in the Safety Population.  
Severity is the maximum severity reported post dosing for each subject for each day. 
1 Day 8+ includes the maximum severity of each symptom reported on or after Day 8 (includes ongoing symptoms) 
2 Indicates how many subjects had “None”, “Mild”, “Moderate”, or “Severe” as their maximum severity for any day. A subject may be counted in more than one of these categories. 
 
 


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Table 479: 
Summary of Duration of Solicited Symptoms by Treatment Group - All Subjects 
Variable 
Statistic 
Prototype 
(N=X) 
Beta + Omicron 
(N=X) 
Beta + Omicron 
(Second Dose) 
(N=X) 
Delta + 
Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All Subjects 
(N=X) 
Any Symptom 
n 
 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
 
Standard 
Deviation 
 
 
 
 
 
 
 
Median 
 
 
 
 
 
 
 
Minimum 
 
 
 
 
 
 
 
Maximum 
 
 
 
 
 
 
 
Any Systemic 
Symptom 
n 
 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
 
Standard 
Deviation 
 
 
 
 
 
 
 
Median 
 
 
 
 
 
 
 
Minimum 
 
 
 
 
 
 
 
Maximum 
 
 
 
 
 
 
 
Arthralgia 
n 
 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
 
Standard 
Deviation 
 
 
 
 
 
 
 
Median 
 
 
 
 
 
 
 
Minimum 
 
 
 
 
 
 
 
Maximum 
 
 
 
 
 
 
 
Fatigue 
n 
 
 
 
 
 
 
 


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Variable 
Statistic 
Prototype 
(N=X) 
Beta + Omicron 
(N=X) 
Beta + Omicron 
(Second Dose) 
(N=X) 
Delta + 
Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All Subjects 
(N=X) 
Mean 
 
 
 
 
 
 
 
Standard 
Deviation 
 
 
 
 
 
 
 
Median 
 
 
 
 
 
 
 
Minimum 
 
 
 
 
 
 
 
Maximum 
 
 
 
 
 
 
 
Fever 
n 
 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
 
Standard 
Deviation 
 
 
 
 
 
 
 
Median 
 
 
 
 
 
 
 
Minimum 
 
 
 
 
 
 
 
Maximum 
 
 
 
 
 
 
 
Feverishness 
n 
 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
 
Standard 
Deviation 
 
 
 
 
 
 
 
Median 
 
 
 
 
 
 
 
Minimum 
 
 
 
 
 
 
 
Maximum 
 
 
 
 
 
 
 
Headache 
n 
 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
 
Standard 
Deviation 
 
 
 
 
 
 
 


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Variable 
Statistic 
Prototype 
(N=X) 
Beta + Omicron 
(N=X) 
Beta + Omicron 
(Second Dose) 
(N=X) 
Delta + 
Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All Subjects 
(N=X) 
Median 
 
 
 
 
 
 
 
Minimum 
 
 
 
 
 
 
 
Maximum 
 
 
 
 
 
 
 
Myalgia 
n 
 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
 
Standard 
Deviation 
 
 
 
 
 
 
 
Median 
 
 
 
 
 
 
 
Minimum 
 
 
 
 
 
 
 
Maximum 
 
 
 
 
 
 
 
Nausea 
n 
 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
 
Standard 
Deviation 
 
 
 
 
 
 
 
Median 
 
 
 
 
 
 
 
Minimum 
 
 
 
 
 
 
 
Maximum 
 
 
 
 
 
 
 
Any Local 
Symptom 
n 
 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
 
Standard 
Deviation 
 
 
 
 
 
 
 
Median 
 
 
 
 
 
 
 
Minimum 
 
 
 
 
 
 
 
Maximum 
 
 
 
 
 
 
 


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Variable 
Statistic 
Prototype 
(N=X) 
Beta + Omicron 
(N=X) 
Beta + Omicron 
(Second Dose) 
(N=X) 
Delta + 
Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All Subjects 
(N=X) 
Erythema/redness 
n 
 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
 
Standard 
Deviation 
 
 
 
 
 
 
 
Median 
 
 
 
 
 
 
 
Minimum 
 
 
 
 
 
 
 
Maximum 
 
 
 
 
 
 
 
Induration/swelling 
n 
 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
 
Standard 
Deviation 
 
 
 
 
 
 
 
Median 
 
 
 
 
 
 
 
Minimum 
 
 
 
 
 
 
 
Maximum 
 
 
 
 
 
 
 
Pain 
n 
 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
 
Standard 
Deviation 
 
 
 
 
 
 
 
Median 
 
 
 
 
 
 
 
Minimum 
 
 
 
 
 
 
 
Maximum 
 
 
 
 
 
 
 
Notes: N=Number of subjects in the Safety Population. 
n=Number of solicited adverse events. 
 


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14.3.1.2 
Unsolicited Adverse Events 
Table 480: 
All Adverse Events Cross-Classified by MedDRA System Organ Class, Severity, Relationship to Study Treatment, and Treatment 
Group  
 
Relationship to Vaccination 
Treatment Group 
MedDRA System Organ Class 
Severity 
Not Related 
(n) 
Related 
(n) 
Not Yet Determined 
(n) 
Prototype 
(N=X) 
Any SOC 
Mild 
 
 
 
Moderate 
 
 
 
Severe 
 
 
 
[Repeat for all reported SOC] 
Mild 
 
 
 
Moderate 
 
 
 
Severe 
 
 
 
Beta + Omicron 
(N=X) 
Any SOC 
Mild 
 
 
 
Moderate 
 
 
 
Severe 
 
 
 
[Repeat for all reported SOC] 
Mild 
 
 
 
Moderate 
 
 
 
Severe 
 
 
 
Beta + Omicron (Post Second 
Dose) 
(N=X) 
Any SOC 
Mild 
 
 
 
Moderate 
 
 
 
Severe 
 
 
 
[Repeat for all reported SOC] 
Mild 
 
 
 
Moderate 
 
 
 
Severe 
 
 
 
Delta + Omicron 
(N=X) 
Any SOC 
Mild 
 
 
 
Moderate 
 
 
 


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Relationship to Vaccination 
Treatment Group 
MedDRA System Organ Class 
Severity 
Not Related 
(n) 
Related 
(n) 
Not Yet Determined 
(n) 
Severe 
 
 
 
[Repeat for all reported SOC] 
Mild 
 
 
 
Moderate 
 
 
 
Severe 
 
 
 
Omicron 
(N=X) 
Any SOC 
Mild 
 
 
 
Moderate 
 
 
 
Severe 
 
 
 
[Repeat for all reported SOC] 
Mild 
 
 
 
Moderate 
 
 
 
Severe 
 
 
 
Omicron + Prototype 
(N=X) 
Any SOC 
Mild 
 
 
 
Moderate 
 
 
 
Severe 
 
 
 
[Repeat for all reported SOC] 
Mild 
 
 
 
Moderate 
 
 
 
Severe 
 
 
 
All Subjects 
(N=X) 
Any SOC 
Mild 
 
 
 
Moderate 
 
 
 
Severe 
 
 
 
[Repeat for all reported SOC] 
Mild 
 
 
 
Moderate 
 
 
 
Severe 
 
 
 


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Relationship to Vaccination 
Treatment Group 
MedDRA System Organ Class 
Severity 
Not Related 
(n) 
Related 
(n) 
Not Yet Determined 
(n) 
Notes: N=Number of subjects in the Safety Population. 
n=Number of events. 
 


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Table 481: 
Summary of All Unsolicited Adverse Events by MedDRA System Organ Class and Preferred Term, Severity, Relationship, and 
Treatment Group  
 
Severity 
Relationship to Study Vaccination 
Treatment Group 
System Organ Class (SOC) 
Preferred Term (PT) 
Total 
Events 
(n) 
Mild 
(n) 
Moderate 
(n) 
Severe 
(n) 
Not 
Related 
(n) 
Related 
(n) 
Not Yet 
Determined 
(n) 
Prototype 
(N=X) 
Any SOC 
Any PT 
 
 
 
 
 
 
 
Gastrointestinal disorders 
Any PT 
 
 
 
 
 
 
 
Flatulence 
 
 
 
 
 
 
 
Vomiting 
 
 
 
 
 
 
 
[Repeat for all reported 
SOC] 
Any PT 
 
 
 
 
 
 
 
[Repeat for all reported 
PT] 
 
 
 
 
 
 
 
Beta + Omicron 
(N=X) 
Any SOC 
Any PT 
 
 
 
 
 
 
 
[Repeat for all reported 
SOC] 
Any PT 
 
 
 
 
 
 
 
[Repeat for all reported 
PT] 
 
 
 
 
 
 
 
Beta + Omicron (Post 
Second Dose) 
(N=X) 
Any SOC 
Any PT 
 
 
 
 
 
 
 
[Repeat for all reported 
SOC] 
Any PT 
 
 
 
 
 
 
 
[Repeat for all reported 
PT] 
 
 
 
 
 
 
 
Delta + Omicron 
(N=X) 
Any SOC 
Any PT 
 
 
 
 
 
 
 
[Repeat for all reported 
SOC] 
Any PT 
 
 
 
 
 
 
 
[Repeat for all reported 
PT] 
 
 
 
 
 
 
 
Omicron 
(N=X) 
Any SOC 
Any PT 
 
 
 
 
 
 
 
Any PT 
 
 
 
 
 
 
 


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Severity 
Relationship to Study Vaccination 
Treatment Group 
System Organ Class (SOC) 
Preferred Term (PT) 
Total 
Events 
(n) 
Mild 
(n) 
Moderate 
(n) 
Severe 
(n) 
Not 
Related 
(n) 
Related 
(n) 
Not Yet 
Determined 
(n) 
[Repeat for all reported 
SOC] 
[Repeat for all reported 
PT] 
 
 
 
 
 
 
 
Omicron + Prototype 
(N=X) 
Any SOC 
Any PT 
 
 
 
 
 
 
 
[Repeat for all reported 
SOC] 
Any PT 
 
 
 
 
 
 
 
[Repeat for all reported 
PT] 
 
 
 
 
 
 
 
All Subjects 
(N=X) 
Any SOC 
Any PT 
 
 
 
 
 
 
 
[Repeat for all reported 
SOC] 
Any PT 
 
 
 
 
 
 
 
[Repeat for all reported 
PT] 
 
 
 
 
 
 
 
Notes: N=Number of subjects in the Safety Population. 
n=Number of events. 


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Table 482: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events by MedDRA® System Organ Class and Preferred 
Term, Severity, Relationship, and Treatment Group  
 
Severity 
Relationship to Study 
Vaccination 
 
Any 
Incidence 
Mild 
Moderate 
Severe 
Not 
Related 
Related 
Treatment Group 
MedDRA System Organ Class 
MedDRA Preferred 
Term 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Prototype 
(N=X) 
Any SOC 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for all reported SOC] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for all reported 
PT] 
 
 
 
 
 
 
 
 
 
 
 
 
Beta + Omicron 
(N=X) 
Any SOC 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for all reported SOC] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for all reported 
PT] 
 
 
 
 
 
 
 
 
 
 
 
 
Beta + Omicron (Post 
Second Dose) 
(N=X) 
Any SOC 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for all reported SOC] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for all reported 
PT] 
 
 
 
 
 
 
 
 
 
 
 
 
Delta + Omicron 
(N=X) 
Any SOC 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for all reported SOC] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for all reported 
PT] 
 
 
 
 
 
 
 
 
 
 
 
 
Omicron 
(N=X) 
Any SOC 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for all reported SOC] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for all reported 
PT] 
 
 
 
 
 
 
 
 
 
 
 
 


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Severity 
Relationship to Study 
Vaccination 
 
Any 
Incidence 
Mild 
Moderate 
Severe 
Not 
Related 
Related 
Treatment Group 
MedDRA System Organ Class 
MedDRA Preferred 
Term 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Omicron + Prototype 
(N=X) 
Any SOC 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for all reported SOC] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for all reported 
PT] 
 
 
 
 
 
 
 
 
 
 
 
 
All Subjects 
(N=X) 
Any SOC 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for all reported SOC] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for all reported 
PT] 
 
 
 
 
 
 
 
 
 
 
 
 
Note: N=Number of subjects in the Safety Population. 
n=Number of subjects reporting event with the specified SOC. 
This table presents number and percentage of subjects. A subject is only counted once per PT and is summarized according to their highest severity and closest relationship. 
 


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14.3.2 Listing of Deaths, Other Serious and Significant Adverse Events 
Table 483: 
Listing of Serious Adverse Events 
Adverse 
Event 
Associated 
with Dose 
No. 
No. of Days 
Post 
Associated 
Dose 
(Duration) 
No. of Days 
Post Dose 
the Event 
Became 
Serious 
Reason 
Reported 
as an SAE 
Severity 
Relationship 
to Study 
Treatment 
If Not 
Related, 
Alternative 
Etiology 
Action 
Taken with 
Study 
Treatment 
Subject 
Discontinued 
Due to AE 
Outcome 
MedDRA 
System 
Organ 
Class 
MedDRA 
Preferred 
Term 
Subject ID: , Treatment Group: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
 
 
Comments: 
 
Subject ID: , Treatment Group: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
 
 
Comments: 
 
 


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Table 484: 
Listing of Non-Serious, Unsolicited, Moderate or Severe Adverse Events 
Adverse 
Event 
Associated 
with Dose No. 
No. of Days 
Post 
Associated 
Dose 
(Duration) 
Severity 
Relationship 
to Study 
Treatment 
If Not 
Related, 
Alternative 
Etiology 
Action Taken 
with Study 
Treatment 
Subject 
Discontinued 
Due to AE 
Outcome 
MedDRA 
System Organ 
Class 
MedDRA 
Preferred 
Term 
Subject ID: , Treatment Group: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
Comments: 
 
Subject ID: , Treatment Group: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
Comments: 
 


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Table 485: 
Listing of AESIs, MAAEs and NOCMCs 
Subject ID 
Treatment 
Group 
Event 
Description 
Date of Product 
Administrationa 
Duration 
of Event 
Date of 
Onset 
MedDRA®  
Sytem Organ 
Class 
MAAEs 
NOCMCs 
AESI 
Relationshipb 
Outcome 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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14.3.3 Narratives of Deaths, Other Serious and Significant Adverse Events 
(not included in SAP, but this is a placeholder for the CSR) 
 


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14.3.4 Abnormal Laboratory Value Listings (by Subject) 
Not Applicable. 
 


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14.3.5 Displays of Laboratory Results 
Not Applicable. 
 
 


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14.3.6 Displays of Vital Signs 
Not Applicable. 
 


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14.4 
Summary of Concomitant Medications 
Table 486: 
Number and Percentage of Subjects with Prior and Concurrent Medications by WHO 
Drug Classification and Treatment Group 
WHO 
Drug 
Code 
Level 1, 
Anatomic 
Group 
WHO Drug 
Code 
Level 2, 
Therapeutic 
Subgroup 
Prototype 
(N=X) 
Beta + 
Omicron 
(N=X) 
Beta + 
Omicron 
(Second 
Dose) 
(N=X) 
Delta + 
Omicron 
(N=X) 
Omicron 
(N=X) 
Omicron + 
Prototype 
(N=X) 
All 
Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Any Level 
1 Codes 
Any Level 2 
Codes 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
[ATC 
Level 1 - 
1] 
Any [ATC 1 
– 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[ATC 2 - 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[ATC 2 - 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[ATC 2 - 3] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[ATC 
Level 1 – 
2] 
[ATC 2 - 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[ATC 2 - 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[ATC 2 - 3] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N = [define the population for this table, e.g., Number of subjects in the Safety Population].  
n=Number of subjects reporting taking at least one medication in the specific WHO Drug Class. 
 
 
 


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APPENDIX 2.  FIGURE MOCK-UPS 
 
 


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LIST OF FIGURES 
Figure 1: 
CONSORT Flow Diagram .......................................................................................301 
Figure 2: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Prototype, Overall – mITT 
Population .................................................................................................................302 
Figure 3: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Prototype, Overall – Per 
Protocol Population ..................................................................................................303 
Figure 4: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Prototype, Younger 
Cohort – mITT Population ........................................................................................303 
Figure 5: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Prototype, Younger 
Cohort – Per Protocol Population .............................................................................303 
Figure 6: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Prototype, Older Cohort – 
mITT Population .......................................................................................................303 
Figure 7: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Prototype, Older Cohort – 
Per Protocol Population ............................................................................................303 
Figure 8: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Prototype, Infected (by 
Self-Report or N-protein) Cohort – mITT Population ..............................................303 
Figure 9: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Prototype, Infected (by 
Self-Report or N-protein) Cohort – Per Protocol Population ...................................303 
Figure 10: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Prototype, Uninfected (by 
Self-Report or N-protein) Cohort – mITT Population ..............................................303 
Figure 11: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Prototype, Uninfected (by 
Self-Report or N-protein) Cohort – Per Protocol Population ...................................303 
Figure 12: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Prototype, Younger 
Infected (by Self-Report or N-protein) Cohort – mITT Population .........................303 
Figure 13: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Prototype, Younger 
Infected (by Self-Report or N-protein) Cohort – Per Protocol Population ...............303 


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Figure 14: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Prototype, Younger 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population .....................303 
Figure 15: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Prototype, Younger 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population ..........303 
Figure 16: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Prototype, Older Infected 
(by Self-Report or N-protein) Cohort – mITT Population .......................................304 
Figure 17: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Prototype, Older Infected 
(by Self-Report or N-protein) Cohort – Per Protocol Population .............................304 
Figure 18: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Prototype, Older 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population .....................304 
Figure 19: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Prototype, Older 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population ..........304 
Figure 20: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, 
Overall – mITT Population .......................................................................................304 
Figure 21: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, 
Overall– Per Protocol Population .............................................................................304 
Figure 22: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, 
Younger Cohort – mITT Population .........................................................................304 
Figure 23: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, 
Younger Cohort – Per Protocol Population ..............................................................304 
Figure 24: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, 
Older Cohort – mITT Population .............................................................................304 
Figure 25: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, 
Older Cohort – Per Protocol Population ...................................................................304 
Figure 26: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, 
Infected (by Self-Report or N-protein) Cohort – mITT Population .........................304 


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Figure 27: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, 
Infected (by Self-Report or N-protein) Cohort – Per Protocol Population ...............304 
Figure 28: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, 
Uninfected (by Self-Report) Cohort – mITT Population .........................................304 
Figure 29: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population ..........305 
Figure 30: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, 
Younger Infected (by Self-Report or N-protein) Cohort – mITT Population ..........305 
Figure 31: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, 
Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................305 
Figure 32: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, 
Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................305 
Figure 33: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, 
Younger Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................305 
Figure 34: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, 
Older Infected (by Self-Report or N-protein) Cohort – mITT Population ...............305 
Figure 35: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, 
Older Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................305 
Figure 36: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, 
Older Uninfected (by Self-Report or N-protein) Cohort – mITT Population ..........305 
Figure 37: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, 
Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................305 
Figure 38: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Delta + Omicron, Overall 
– mITT Population ....................................................................................................305 


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Figure 39: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Delta + Omicron, Overall 
– Per Protocol Population .........................................................................................305 
Figure 40: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Delta + Omicron, 
Younger Cohort – mITT Population .........................................................................305 
Figure 41: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Delta + Omicron, 
Younger Cohort – Per Protocol Population ..............................................................305 
Figure 42: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Delta + Omicron, Older 
Cohort – mITT Population ........................................................................................306 
Figure 43: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Delta + Omicron, Older 
Cohort – Per Protocol Population .............................................................................306 
Figure 44: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Delta + Omicron, Infected 
(by Self-Report or N-protein) Cohort – mITT Population .......................................306 
Figure 45: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Delta + Omicron, Infected 
(by Self-Report or N-protein) Cohort – Per Protocol Population .............................306 
Figure 46: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Delta + Omicron, 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population .....................306 
Figure 47: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Delta + Omicron, 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population ..........306 
Figure 48: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Delta + Omicron, 
Younger Infected (by Self-Report or N-protein) Cohort – mITT Population ..........306 
Figure 49: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Delta + Omicron, 
Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................306 
Figure 50: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Delta + Omicron, 
Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................306 
Figure 51: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Delta + Omicron, 


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Younger Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................306 
Figure 52: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Delta + Omicron, Older 
Infected (by Self-Report or N-protein) Cohort – mITT Population .........................306 
Figure 53: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Delta + Omicron, Older 
Infected (by Self-Report or N-protein) Cohort – Per Protocol Population ...............306 
Figure 54: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Delta + Omicron, Older 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population .....................306 
Figure 55: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Delta + Omicron, Older 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population ..........307 
Figure 56: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron, Overall– mITT 
Population .................................................................................................................307 
Figure 57: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron, Overall – Per 
Protocol Population ..................................................................................................307 
Figure 58: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron, Younger Cohort 
– mITT Population ....................................................................................................307 
Figure 59: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron, Younger Cohort 
– Per Protocol Population .........................................................................................307 
Figure 60: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron, Older Cohort – 
mITT Population .......................................................................................................307 
Figure 61: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron, Older Cohort – 
Per Protocol Population ............................................................................................307 
Figure 62: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron, Infected (by 
Self-Report or N-protein) Cohort – mITT Population ..............................................307 
Figure 63: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron, Infected (by 
Self-Report or N-protein) Cohort – Per Protocol Population ...................................307 


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Figure 64: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron, Uninfected (by 
Self-Report or N-protein) Cohort – mITT Population ..............................................307 
Figure 65: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron, Uninfected (by 
Self-Report or N-protein) Cohort – Per Protocol Population ...................................307 
Figure 66: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron, Younger 
Infected (by Self-Report or N-protein) Cohort – mITT Population .........................307 
Figure 67: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron, Younger 
Infected (by Self-Report or N-protein) Cohort – Per Protocol Population ...............307 
Figure 68: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron, Younger 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population .....................307 
Figure 69: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron, Younger 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population ..........308 
Figure 70: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron, Older Infected 
(by Self-Report or N-protein) Cohort – mITT Population .......................................308 
Figure 71: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron, Older Infected 
(by Self-Report or N-protein) Cohort – Per Protocol Population .............................308 
Figure 72: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron, Older 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population .....................308 
Figure 73: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron, Older 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population ..........308 
Figure 74: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron + Prototype, 
Overall– mITT Population ........................................................................................308 
Figure 75: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron + Prototype, 
Overall– Per Protocol Population .............................................................................308 
Figure 76: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron + Prototype, 
Younger Cohort – mITT Population .........................................................................308 


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Figure 77: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron + Prototype, 
Younger Cohort – Per Protocol Population ..............................................................308 
Figure 78: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron + Prototype, 
Older Cohort – mITT Population .............................................................................308 
Figure 79: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron + Prototype, 
Older Cohort – Per Protocol Population ...................................................................308 
Figure 80: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron + Prototype, 
Infected (by Self-Report or N-protein) Cohort – mITT Population .........................308 
Figure 81: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron + Prototype, 
Infected (by Self-Report or N-protein) Cohort – Per Protocol Population ...............308 
Figure 82: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron + Prototype, 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population .....................309 
Figure 83: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron + Prototype, 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population ..........309 
Figure 84: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron + Prototype, 
Younger Infected (by Self-Report or N-protein) Cohort – mITT Population ..........309 
Figure 85: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron + Prototype, 
Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................309 
Figure 86: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron + Prototype, 
Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................309 
Figure 87: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron + Prototype, 
Younger Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................309 
Figure 88: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron + Prototype, 
Older Infected (by Self-Report or N-protein) Cohort – mITT Population ...............309 
Figure 89: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron + Prototype, 


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Older Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................309 
Figure 90: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron + Prototype, 
Older Uninfected (by Self-Report or N-protein) Cohort – mITT Population ..........309 
Figure 91: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, Omicron + Prototype, 
Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................309 
Figure 92: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, 
Overall– mITT Population ........................................................................................309 
Figure 93: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, 
Overall– Per Protocol Population .............................................................................309 
Figure 94: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, 
Younger Cohort – mITT Population .........................................................................309 
Figure 95: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, 
Younger Cohort – Per Protocol Population ..............................................................310 
Figure 96: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, 
Older Cohort – mITT Population .............................................................................310 
Figure 97: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, 
Older Cohort – Per Protocol Population ...................................................................310 
Figure 98: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, 
Infected (by Self-Report or N-protein) Cohort – mITT Population .........................310 
Figure 99: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, 
Infected (by Self-Report or N-protein) Cohort – Per Protocol Population ...............310 
Figure 100: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population .....................310 
Figure 101: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population ..........310 


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Figure 102: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, 
Younger Infected (by Self-Report or N-protein) Cohort – mITT Population ..........310 
Figure 103: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, 
Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................310 
Figure 104: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, 
Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................310 
Figure 105: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, 
Younger Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................310 
Figure 106: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, 
Older Infected (by Self-Report or N-protein) Cohort – mITT Population ...............310 
Figure 107: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, 
Older Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................310 
Figure 108: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, 
Older Uninfected (by Self-Report or N-protein) Cohort – mITT Population ..........311 
Figure 109: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, 
Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................311 
Figure 110: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Prototype, Overall – mITT Population .......................................................311 
Figure 111: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Prototype, Overall – Per Protocol Population.............................................311 
Figure 112: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Prototype, Younger Cohort – mITT Population .........................................311 
Figure 113: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Prototype, Younger Cohort – Per Protocol Population ..............................311 
Figure 114: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Prototype, Older Cohort – mITT Population ..............................................311 


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Figure 115: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Prototype, Older Cohort – Per Protocol Population ...................................311 
Figure 116: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Prototype, Infected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................311 
Figure 117: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Prototype, Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population ..................................................................................................311 
Figure 118: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Prototype, Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................311 
Figure 119: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Prototype, Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population ..................................................................................................311 
Figure 120: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Prototype, Younger Infected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................311 
Figure 121: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Prototype, Younger Infected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................311 
Figure 122: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Prototype, Younger Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................311 
Figure 123: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Prototype, Younger Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................311 
Figure 124: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Prototype, Older Infected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................311 
Figure 125: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Prototype, Older Infected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................312 
Figure 126: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................312 
Figure 127: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................312 
Figure 128: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 1 Dose Beta + Omicron, Overall– mITT Population ..................................312 


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Figure 129: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 1 Dose Beta + Omicron, Overall– Per Protocol Population .......................312 
Figure 130: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 1 Dose Beta + Omicron, Younger Cohort – mITT Population...................312 
Figure 131: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 1 Dose Beta + Omicron, Younger Cohort – Per Protocol Population ........312 
Figure 132: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 1 Dose Beta + Omicron, Older Cohort – mITT Population .......................312 
Figure 133: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 1 Dose Beta + Omicron, Older Cohort – Per Protocol Population .............312 
Figure 134: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 1 Dose Beta + Omicron, Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................312 
Figure 135: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 1 Dose Beta + Omicron, Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................312 
Figure 136: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 1 Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................312 
Figure 137: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 1 Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................312 
Figure 138: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 1 Dose Beta + Omicron, Younger Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................312 
Figure 139: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 1 Dose Beta + Omicron, Younger Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................312 
Figure 140: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 1 Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................312 
Figure 141: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 1 Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................313 
Figure 142: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 1 Dose Beta + Omicron, Older Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................313 
Figure 143: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 1 Dose Beta + Omicron, Older Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................313 


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Figure 144: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 1 Dose Beta + Omicron, Older Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................313 
Figure 145: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 1 Dose Beta + Omicron, Older Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................313 
Figure 146: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Delta + Omicron, Overall– mITT Population.............................................313 
Figure 147: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Delta + Omicron, Overall – Per Protocol Population .................................313 
Figure 148: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Delta + Omicron, Younger Cohort – mITT Population .............................313 
Figure 149: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Delta + Omicron, Younger Cohort – Per Protocol Population ...................313 
Figure 150: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Delta + Omicron, Older Cohort – mITT Population ..................................313 
Figure 151: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Delta + Omicron, Older Cohort – Per Protocol Population ........................313 
Figure 152: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Delta + Omicron, Infected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................313 
Figure 153: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Delta + Omicron, Infected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................313 
Figure 154: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Delta + Omicron, Uninfected (by Self-Report or N-protein) Cohort 
– mITT Population ....................................................................................................313 
Figure 155: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Delta + Omicron, Uninfected (by Self-Report or N-protein) Cohort 
– Per Protocol Population .........................................................................................313 
Figure 156: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Delta + Omicron, Younger Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................313 
Figure 157: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Delta + Omicron, Younger Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................314 
Figure 158: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Delta + Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................314 


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Figure 159: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Delta + Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................314 
Figure 160: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Delta + Omicron, Older Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................314 
Figure 161: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Delta + Omicron, Older Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................314 
Figure 162: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Delta + Omicron, Older Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................314 
Figure 163: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Delta + Omicron, Older Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................314 
Figure 164: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron, Overall– mITT Population .........................................................314 
Figure 165: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron, Overall – Per Protocol Population ..............................................314 
Figure 166: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron, Younger Cohort – mITT Population ..........................................314 
Figure 167: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron, Younger Cohort – Per Protocol Population ................................314 
Figure 168: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron, Older Cohort – mITT Population ...............................................314 
Figure 169: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron, Older Cohort – Per Protocol Population .....................................314 
Figure 170: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron, Infected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................314 
Figure 171: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron, Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population ..................................................................................................314 
Figure 172: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron, Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................314 
Figure 173: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron, Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population ..................................................................................................315 


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Figure 174: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron, Younger Infected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................315 
Figure 175: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron, Younger Infected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................315 
Figure 176: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort 
– mITT Population ....................................................................................................315 
Figure 177: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort 
– Per Protocol Population .........................................................................................315 
Figure 178: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron, Older Infected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................315 
Figure 179: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron, Older Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population ..................................................................................................315 
Figure 180: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................315 
Figure 181: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................315 
Figure 182: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron + Prototype, Overall – mITT Population .....................................315 
Figure 183: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron + Prototype, Overall – Per Protocol Population ..........................315 
Figure 184: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron + Prototype, Younger Cohort – mITT Population.......................315 
Figure 185: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron + Prototype, Younger Cohort – Per Protocol Population ............315 
Figure 186: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron + Prototype, Older Cohort – mITT Population ...........................315 
Figure 187: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron + Prototype, Older Cohort – Per Protocol Population .................315 
Figure 188: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron + Prototype, Infected (by Self-Report or N-protein) Cohort 
– mITT Population ....................................................................................................315 


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Figure 189: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron + Prototype, Infected (by Self-Report or N-protein) Cohort 
– Per Protocol Population .........................................................................................315 
Figure 190: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron + Prototype, Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................316 
Figure 191: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron + Prototype, Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................316 
Figure 192: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron + Prototype, Younger Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................316 
Figure 193: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron + Prototype, Younger Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................316 
Figure 194: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron + Prototype, Younger Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................316 
Figure 195: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron + Prototype, Younger Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................316 
Figure 196: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron + Prototype, Older Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................316 
Figure 197: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron + Prototype, Older Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................316 
Figure 198: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron + Prototype, Older Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................316 
Figure 199: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, Omicron + Prototype, Older Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................316 
Figure 200: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 2 Dose Beta + Omicron, Overall – mITT Population .................................316 
Figure 201: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 2 Dose Beta + Omicron, Overall – Per Protocol Population ......................316 
Figure 202: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 2 Dose Beta + Omicron, Younger Cohort – mITT Population...................316 


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Figure 203: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 2 Dose Beta + Omicron, Younger Cohort – Per Protocol Population ........316 
Figure 204: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 2 Dose Beta + Omicron, Older Cohort – mITT Population .......................316 
Figure 205: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 2 Dose Beta + Omicron, Older Cohort – Per Protocol Population .............316 
Figure 206: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 2 Dose Beta + Omicron, Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................317 
Figure 207: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 2 Dose Beta + Omicron, Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................317 
Figure 208: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 2 Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................317 
Figure 209: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 2 Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................317 
Figure 210: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 2 Dose Beta + Omicron, Younger Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................317 
Figure 211: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 2 Dose Beta + Omicron, Younger Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................317 
Figure 212: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 2 Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................317 
Figure 213: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 2 Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................317 
Figure 214: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 2 Dose Beta + Omicron, Older Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................317 
Figure 215: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 2 Dose Beta + Omicron, Older Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................317 
Figure 216: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 2 Dose Beta + Omicron, Older Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................317 


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Figure 217: Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and 
Variant, 2 Dose Beta + Omicron, Older Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................317 
Figure 218: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Prototype, Overall– mITT Population .................................................317 
Figure 219: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Prototype, Overall– Per Protocol Population .......................................318 
Figure 220: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Prototype, Younger Cohort – mITT Population ..................................318 
Figure 221: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Prototype, Younger Cohort – Per Protocol Population ........................318 
Figure 222: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Prototype, Older Cohort – mITT Population .......................................318 
Figure 223: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Prototype, Older Cohort – Per Protocol Population.............................318 
Figure 224: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Prototype, Infected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................318 
Figure 225: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Prototype, Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population ..................................................................................................318 
Figure 226: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Prototype, Uninfected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................318 
Figure 227: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Prototype, Uninfected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................318 
Figure 228: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Prototype, Younger Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................318 
Figure 229: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Prototype, Younger Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................318 
Figure 230: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Prototype, Younger Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................318 
Figure 231: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Prototype, Younger Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................318 


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Figure 232: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Prototype, Older Infected (by Self-Report or N-protein) Cohort 
– mITT Population ....................................................................................................318 
Figure 233: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Prototype, Older Infected (by Self-Report or N-protein) Cohort 
– Per Protocol Population .........................................................................................318 
Figure 234: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Prototype, Older Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................318 
Figure 235: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Prototype, Older Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................318 
Figure 236: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 1 Dose Beta + Omicron, Overall – mITT Population ..........................319 
Figure 237: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 1 Dose Beta + Omicron, Overall – Per Protocol Population ...............319 
Figure 238: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 1 Dose Beta + Omicron, Younger Cohort – mITT Population ............319 
Figure 239: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 1 Dose Beta + Omicron, Younger Cohort – Per Protocol 
Population .................................................................................................................319 
Figure 240: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 1 Dose Beta + Omicron, Older Cohort – mITT Population .................319 
Figure 241: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 1 Dose Beta + Omicron, Older Cohort – Per Protocol 
Population .................................................................................................................319 
Figure 242: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 1 Dose Beta + Omicron, Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................319 
Figure 243: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 1 Dose Beta + Omicron, Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................319 
Figure 244: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 1 Dose Beta + Omicron, Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................319 
Figure 245: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 1 Dose Beta + Omicron, Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................319 


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Figure 246: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 1 Dose Beta + Omicron, Younger Infected (by Self-Report or 
N-protein) Cohort – mITT Population ......................................................................319 
Figure 247: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 1 Dose Beta + Omicron, Younger Infected (by Self-Report or 
N-protein) Cohort – Per Protocol Population ...........................................................319 
Figure 248: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 1 Dose Beta + Omicron, Younger Uninfected (by Self-Report 
or N-protein) Cohort – mITT Population .................................................................319 
Figure 249: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 1 Dose Beta + Omicron, Younger Uninfected (by Self-Report 
or N-protein) Cohort – Per Protocol Population .......................................................319 
Figure 250: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 1 Dose Beta + Omicron, Older Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................319 
Figure 251: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 1 Dose Beta + Omicron, Older Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................320 
Figure 252: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 1 Dose Beta + Omicron, Older Uninfected (by Self-Report or 
N-protein) Cohort – mITT Population ......................................................................320 
Figure 253: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 1 Dose Beta + Omicron, Older Uninfected (by Self-Report or 
N-protein) Cohort – Per Protocol Population ...........................................................320 
Figure 254: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Delta + Omicron, Overall – mITT Population .....................................320 
Figure 255: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Delta + Omicron, Overall – Per Protocol Population ..........................320 
Figure 256: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Delta + Omicron, Younger Cohort – mITT Population .......................320 
Figure 257: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Delta + Omicron, Younger Cohort – Per Protocol Population ............320 
Figure 258: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Delta + Omicron, Older Cohort – mITT Population............................320 
Figure 259: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Delta + Omicron, Older Cohort – Per Protocol Population .................320 
Figure 260: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Delta + Omicron, Infected (by Self-Report or N-protein) Cohort 
– mITT Population ....................................................................................................320 


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Figure 261: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Delta + Omicron, Infected (by Self-Report or N-protein) Cohort 
– Per Protocol Population .........................................................................................320 
Figure 262: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Delta + Omicron, Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................320 
Figure 263: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Delta + Omicron, Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................320 
Figure 264: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Delta + Omicron, Younger Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................320 
Figure 265: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Delta + Omicron, Younger Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................320 
Figure 266: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Delta + Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................320 
Figure 267: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Delta + Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................321 
Figure 268: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Delta + Omicron, Older Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................321 
Figure 269: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Delta + Omicron, Older Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................321 
Figure 270: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Delta + Omicron, Older Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................321 
Figure 271: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Delta + Omicron, Older Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................321 
Figure 272: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron, Overall – mITT Population ..................................................321 
Figure 273: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron, Overall – Per Protocol Population .......................................321 
Figure 274: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron, Younger Cohort – mITT Population ....................................321 


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Figure 275: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron, Younger Cohort – Per Protocol Population .........................321 
Figure 276: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron, Older Cohort – mITT Population ........................................321 
Figure 277: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron, Older Cohort – Per Protocol Population ..............................321 
Figure 278: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron, Infected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................321 
Figure 279: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron, Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population ..................................................................................................321 
Figure 280: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron, Uninfected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................321 
Figure 281: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron, Uninfected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................321 
Figure 282: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron, Younger Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................321 
Figure 283: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron, Younger Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................322 
Figure 284: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron, Younger Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................322 
Figure 285: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron, Younger Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................322 
Figure 286: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron, Older Infected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................322 
Figure 287: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron, Older Infected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................322 
Figure 288: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron, Older Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................322 


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Figure 289: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron, Older Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................322 
Figure 290: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron + Prototype, Overall – mITT Population ..............................322 
Figure 291: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron + Prototype, Overall – Per Protocol Population ...................322 
Figure 292: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron + Prototype, Younger Cohort – mITT Population ................322 
Figure 293: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron + Prototype, Younger Cohort – Per Protocol 
Population .................................................................................................................322 
Figure 294: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron + Prototype, Older Cohort – mITT Population .....................322 
Figure 295: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron + Prototype, Older Cohort – Per Protocol Population ..........322 
Figure 296: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron + Prototype, Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................322 
Figure 297: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron + Prototype, Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................322 
Figure 298: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron + Prototype, Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................322 
Figure 299: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron + Prototype, Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................323 
Figure 300: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron + Prototype, Younger Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................323 
Figure 301: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron + Prototype, Younger Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................323 
Figure 302: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron + Prototype, Younger Uninfected (by Self-Report or 
N-protein) Cohort – mITT Population ......................................................................323 
Figure 303: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron + Prototype, Younger Uninfected (by Self-Report or 
N-protein) Cohort – Per Protocol Population ...........................................................323 


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Figure 304: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron + Prototype, Older Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................323 
Figure 305: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron + Prototype, Older Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................323 
Figure 306: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron + Prototype, Older Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................323 
Figure 307: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, Omicron + Prototype, Older Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................323 
Figure 308: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 2 Dose Beta + Omicron, Overall – mITT Population ..........................323 
Figure 309: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 2 Dose Beta + Omicron, Overall – Per Protocol Population ...............323 
Figure 310: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 2 Dose Beta + Omicron, Younger Cohort – mITT Population ............323 
Figure 311: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 2 Dose Beta + Omicron, Younger Cohort – Per Protocol 
Population .................................................................................................................323 
Figure 312: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 2 Dose Beta + Omicron, Older Cohort – mITT Population .................323 
Figure 313: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 2 Dose Beta + Omicron, Older Cohort – Per Protocol 
Population .................................................................................................................323 
Figure 314: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 2 Dose Beta + Omicron, Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................324 
Figure 315: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 2 Dose Beta + Omicron, Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................324 
Figure 316: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 2 Dose Beta + Omicron, Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................324 
Figure 317: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 2 Dose Beta + Omicron, Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................324 


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Figure 318: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 2 Dose Beta + Omicron, Younger Infected (by Self-Report or 
N-protein) Cohort – mITT Population ......................................................................324 
Figure 319: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 2 Dose Beta + Omicron, Younger Infected (by Self-Report or 
N-protein) Cohort – Per Protocol Population ...........................................................324 
Figure 320: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 2 Dose Beta + Omicron, Younger Uninfected (by Self-Report 
or N-protein) Cohort – mITT Population .................................................................324 
Figure 321: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 2 Dose Beta + Omicron, Younger Uninfected (by Self-Report 
or N-protein) Cohort – Per Protocol Population .......................................................324 
Figure 322: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 2 Dose Beta + Omicron, Older Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................324 
Figure 323: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 2 Dose Beta + Omicron, Older Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................324 
Figure 324: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 2 Dose Beta + Omicron, Older Uninfected (by Self-Report or 
N-protein) Cohort – mITT Population ......................................................................324 
Figure 325: Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point 
and Variant, 2 Dose Beta + Omicron, Older Uninfected (by Self-Report or 
N-protein) Cohort – Per Protocol Population ...........................................................324 
Figure 326: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Prototype, Overall – mITT 
Population .................................................................................................................325 
Figure 327: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Prototype, Overall – Per 
Protocol Population ..................................................................................................325 
Figure 328: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Prototype, Younger Cohort – 
mITT Population .......................................................................................................325 
Figure 329: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Prototype, Younger Cohort – 
Per Protocol Population ............................................................................................325 
Figure 330: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Prototype, Older Cohort – 
mITT Population .......................................................................................................325 


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Figure 331: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Prototype, Older Cohort – Per 
Protocol Population ..................................................................................................326 
Figure 332: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Prototype, Infected (by Self-
Report or N-protein) Cohort – mITT Population .....................................................326 
Figure 333: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Prototype, Infected (by Self-
Report or N-protein) Cohort – Per Protocol Population ...........................................326 
Figure 334: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Prototype, Uninfected (by Self-
Report or N-protein) Cohort – mITT Population .....................................................326 
Figure 335: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Prototype, Uninfected (by Self-
Report or N-protein) Cohort – Per Protocol Population ...........................................326 
Figure 336: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Prototype, Younger Infected 
(by Self-Report or N-protein) Cohort – mITT Population .......................................326 
Figure 337: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Prototype, Younger Infected 
(by Self-Report or N-protein) Cohort – Per Protocol Population .............................326 
Figure 338: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Prototype, Younger Uninfected 
(by Self-Report or N-protein) Cohort – mITT Population .......................................326 
Figure 339: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Prototype, Younger Uninfected 
(by Self-Report or N-protein) Cohort – Per Protocol Population .............................326 
Figure 340: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Prototype, Older Infected (by 
Self-Report or N-protein) Cohort – mITT Population ..............................................326 
Figure 341: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Prototype, Older Infected (by 
Self-Report or N-protein) Cohort – Per Protocol Population ...................................326 
Figure 342: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Prototype, Older Uninfected 
(by Self-Report or N-protein) Cohort – mITT Population .......................................326 
Figure 343: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Prototype, Older Uninfected 
(by Self-Report or N-protein) Cohort – Per Protocol Population .............................326 


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Figure 344: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 1 Dose Beta + Omicron, 
Overall – mITT Population .......................................................................................327 
Figure 345: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 1 Dose Beta + Omicron, 
Overall– Per Protocol Population .............................................................................327 
Figure 346: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 1 Dose Beta + Omicron, 
Younger Cohort – mITT Population .........................................................................327 
Figure 347: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 1 Dose Beta + Omicron, 
Younger Cohort – Per Protocol Population ..............................................................327 
Figure 348: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 1 Dose Beta + Omicron, Older 
Cohort – mITT Population ........................................................................................327 
Figure 349: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 1 Dose Beta + Omicron, Older 
Cohort – Per Protocol Population .............................................................................327 
Figure 350: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 1 Dose Beta + Omicron, 
Infected (by Self-Report or N-protein) Cohort – mITT Population .........................327 
Figure 351: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 1 Dose Beta + Omicron, 
Infected (by Self-Report or N-protein) Cohort – Per Protocol Population ...............327 
Figure 352: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 1 Dose Beta + Omicron, 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population .....................327 
Figure 353: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 1 Dose Beta + Omicron, 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population ..........327 
Figure 354: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 1 Dose Beta + Omicron, 
Younger Infected (by Self-Report or N-protein) Cohort – mITT Population ..........327 
Figure 355: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 1 Dose Beta + Omicron, 
Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................327 
Figure 356: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 1 Dose Beta + Omicron, 
Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................327 


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Figure 357: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 1 Dose Beta + Omicron, 
Younger Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................328 
Figure 358: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 1 Dose Beta + Omicron, Older 
Infected (by Self-Report or N-protein) Cohort – mITT Population .........................328 
Figure 359: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 1 Dose Beta + Omicron, Older 
Infected (by Self-Report or N-protein) Cohort – Per Protocol Population ...............328 
Figure 360: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 1 Dose Beta + Omicron, Older 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population .....................328 
Figure 361: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 1 Dose Beta + Omicron, Older 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population ..........328 
Figure 362: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Delta + Omicron, Overall – 
mITT Population .......................................................................................................328 
Figure 363: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Delta + Omicron, Overall – Per 
Protocol Population ..................................................................................................328 
Figure 364: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Delta + Omicron, Younger 
Cohort – mITT Population ........................................................................................328 
Figure 365: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Delta + Omicron, Younger 
Cohort – Per Protocol Population .............................................................................328 
Figure 366: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Delta + Omicron, Older Cohort 
– mITT Population ....................................................................................................328 
Figure 367: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Delta + Omicron, Older Cohort 
– Per Protocol Population .........................................................................................328 
Figure 368: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Delta + Omicron, Infected (by 
Self-Report or N-protein) Cohort – mITT Population ..............................................328 
Figure 369: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Delta + Omicron, Infected (by 
Self-Report or N-protein) Cohort – Per Protocol Population ...................................328 


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Figure 370: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Delta + Omicron, Uninfected 
(by Self-Report or N-protein) Cohort – mITT Population .......................................328 
Figure 371: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Delta + Omicron, Uninfected 
(by Self-Report or N-protein) Cohort – Per Protocol Population .............................329 
Figure 372: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Delta + Omicron, Younger 
Infected (by Self-Report or N-protein) Cohort – mITT Population .........................329 
Figure 373: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Delta + Omicron, Younger 
Infected (by Self-Report or N-protein) Cohort – Per Protocol Population ...............329 
Figure 374: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Delta + Omicron, Younger 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population .....................329 
Figure 375: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Delta + Omicron, Younger 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population ..........329 
Figure 376: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Delta + Omicron, Older 
Infected (by Self-Report or N-protein) Cohort – mITT Population .........................329 
Figure 377: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Delta + Omicron, Older 
Infected (by Self-Report or N-protein) Cohort – Per Protocol Population ...............329 
Figure 378: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Delta + Omicron, Older 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population .....................329 
Figure 379: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Delta + Omicron, Older 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population ..........329 
Figure 380: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron, Overall– mITT 
Population .................................................................................................................329 
Figure 381: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron, Overall – Per 
Protocol Population ..................................................................................................329 
Figure 382: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron, Younger Cohort – 
mITT Population .......................................................................................................329 


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Figure 383: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron, Younger Cohort – 
Per Protocol Population ............................................................................................329 
Figure 384: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron, Older Cohort – 
mITT Population .......................................................................................................329 
Figure 385: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron, Older Cohort – Per 
Protocol Population ..................................................................................................329 
Figure 386: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron, Infected (by Self-
Report or N-protein) Cohort – mITT Population .....................................................330 
Figure 387: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron, Infected (by Self-
Report or N-protein) Cohort – Per Protocol Population ...........................................330 
Figure 388: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron, Uninfected (by Self-
Report or N-protein) Cohort – mITT Population .....................................................330 
Figure 389: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron, Uninfected (by Self-
Report or N-protein) Cohort – Per Protocol Population ...........................................330 
Figure 390: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron, Younger Infected (by 
Self-Report or N-protein) Cohort – mITT Population ..............................................330 
Figure 391: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron, Younger Infected (by 
Self-Report or N-protein) Cohort – Per Protocol Population ...................................330 
Figure 392: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron, Younger Uninfected 
(by Self-Report or N-protein) Cohort – mITT Population .......................................330 
Figure 393: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron, Younger Uninfected 
(by Self-Report or N-protein) Cohort – Per Protocol Population .............................330 
Figure 394: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron, Older Infected (by 
Self-Report or N-protein) Cohort – mITT Population ..............................................330 
Figure 395: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron, Older Infected (by 
Self-Report or N-protein) Cohort – Per Protocol Population ...................................330 


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Figure 396: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron, Older Uninfected (by 
Self-Report or N-protein) Cohort – mITT Population ..............................................330 
Figure 397: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron, Older Uninfected (by 
Self-Report or N-protein) Cohort – Per Protocol Population ...................................330 
Figure 398: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron + Prototype, Overall– 
mITT Population .......................................................................................................330 
Figure 399: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron + Prototype, Overall– 
Per Protocol Population ............................................................................................331 
Figure 400: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron + Prototype, Younger 
Cohort – mITT Population ........................................................................................331 
Figure 401: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron + Prototype, Younger 
Cohort – Per Protocol Population .............................................................................331 
Figure 402: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron + Prototype, Older 
Cohort – mITT Population ........................................................................................331 
Figure 403: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron + Prototype, Older 
Cohort – Per Protocol Population .............................................................................331 
Figure 404: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron + Prototype, Infected 
(by Self-Report or N-protein) Cohort – mITT Population .......................................331 
Figure 405: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron + Prototype, Infected 
(by Self-Report or N-protein) Cohort – Per Protocol Population .............................331 
Figure 406: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron + Prototype, 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population .....................331 
Figure 407: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron + Prototype, 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population ..........331 
Figure 408: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron + Prototype, Younger 
Infected (by Self-Report or N-protein) Cohort – mITT Population .........................331 


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Figure 409: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron + Prototype, Younger 
Infected (by Self-Report or N-protein) Cohort – Per Protocol Population ...............331 
Figure 410: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron + Prototype, Younger 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population .....................331 
Figure 411: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron + Prototype, Younger 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population ..........331 
Figure 412: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron + Prototype, Older 
Infected (by Self-Report or N-protein) Cohort – mITT Population .........................332 
Figure 413: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron + Prototype, Older 
Infected (by Self-Report or N-protein) Cohort – Per Protocol Population ...............332 
Figure 414: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron + Prototype, Older 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population .....................332 
Figure 415: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, Omicron + Prototype, Older 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population ..........332 
Figure 416: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 2 Dose Beta + Omicron, 
Overall– mITT Population ........................................................................................332 
Figure 417: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 2 Dose Beta + Omicron, 
Overall– Per Protocol Population .............................................................................332 
Figure 418: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 2 Dose Beta + Omicron, 
Younger Cohort – mITT Population .........................................................................332 
Figure 419: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 2 Dose Beta + Omicron, 
Younger Cohort – Per Protocol Population ..............................................................332 
Figure 420: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 2 Dose Beta + Omicron, Older 
Cohort – mITT Population ........................................................................................332 
Figure 421: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 2 Dose Beta + Omicron, Older 
Cohort – Per Protocol Population .............................................................................332 


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Figure 422: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 2 Dose Beta + Omicron, 
Infected (by Self-Report or N-protein) Cohort – mITT Population .........................332 
Figure 423: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 2 Dose Beta + Omicron, 
Infected (by Self-Report or N-protein) Cohort – Per Protocol Population ...............332 
Figure 424: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 2 Dose Beta + Omicron, 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population .....................332 
Figure 425: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 2 Dose Beta + Omicron, 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population ..........333 
Figure 426: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 2 Dose Beta + Omicron, 
Younger Infected (by Self-Report or N-protein) Cohort – mITT Population ..........333 
Figure 427: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 2 Dose Beta + Omicron, 
Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................333 
Figure 428: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 2 Dose Beta + Omicron, 
Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................333 
Figure 429: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 2 Dose Beta + Omicron, 
Younger Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population .................................................................................................................333 
Figure 430: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 2 Dose Beta + Omicron, Older 
Infected (by Self-Report or N-protein) Cohort – mITT Population .........................333 
Figure 431: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 2 Dose Beta + Omicron, Older 
Infected (by Self-Report or N-protein) Cohort – Per Protocol Population ...............333 
Figure 432: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 2 Dose Beta + Omicron, Older 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population .....................333 
Figure 433: Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-
plex Distribution by Time Point and Variant, 2 Dose Beta + Omicron, Older 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population ..........333 
Figure 434: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Prototype, Overall – mITT Population .......................................................333 


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Figure 435: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Prototype, Overall – Per Protocol Population.............................................333 
Figure 436: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Prototype, Younger Cohort – mITT Population .........................................333 
Figure 437: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Prototype, Younger Cohort – Per Protocol Population ..............................333 
Figure 438: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Prototype, Older Cohort – mITT Population ..............................................333 
Figure 439: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Prototype, Older Cohort – Per Protocol Population ...................................333 
Figure 440: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Prototype, Infected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................334 
Figure 441: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Prototype, Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population ..................................................................................................334 
Figure 442: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Prototype, Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................334 
Figure 443: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Prototype, Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population ..................................................................................................334 
Figure 444: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Prototype, Younger Infected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................334 
Figure 445: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Prototype, Younger Infected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................334 
Figure 446: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Prototype, Younger Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................334 
Figure 447: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Prototype, Younger Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................334 
Figure 448: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Prototype, Older Infected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................334 
Figure 449: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Prototype, Older Infected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................334 


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Figure 450: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................334 
Figure 451: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................334 
Figure 452: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Overall– mITT Population ..................................334 
Figure 453: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Overall– Per Protocol Population .......................334 
Figure 454: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Younger Cohort – mITT Population...................334 
Figure 455: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Younger Cohort – Per Protocol Population ........334 
Figure 456: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Older Cohort – mITT Population .......................334 
Figure 457: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Older Cohort – Per Protocol Population .............335 
Figure 458: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................335 
Figure 459: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................335 
Figure 460: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................335 
Figure 461: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................335 
Figure 462: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Younger Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................335 
Figure 463: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Younger Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................335 
Figure 464: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................335 


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Figure 465: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................335 
Figure 466: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Older Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................335 
Figure 467: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Older Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................335 
Figure 468: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Older Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................335 
Figure 469: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Older Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................335 
Figure 470: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Overall– mITT Population.............................................335 
Figure 471: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Overall – Per Protocol Population .................................335 
Figure 472: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Younger Cohort – mITT Population .............................335 
Figure 473: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Younger Cohort – Per Protocol Population ...................336 
Figure 474: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Older Cohort – mITT Population ..................................336 
Figure 475: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Older Cohort – Per Protocol Population ........................336 
Figure 476: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Infected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................336 
Figure 477: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Infected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................336 
Figure 478: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Uninfected (by Self-Report or N-protein) Cohort 
– mITT Population ....................................................................................................336 
Figure 479: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Uninfected (by Self-Report or N-protein) Cohort 
– Per Protocol Population .........................................................................................336 


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Figure 480: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Younger Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................336 
Figure 481: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Younger Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................336 
Figure 482: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................336 
Figure 483: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................336 
Figure 484: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Older Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................336 
Figure 485: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Older Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................336 
Figure 486: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Older Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................336 
Figure 487: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Older Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................336 
Figure 488: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron, Overall– mITT Population .........................................................336 
Figure 489: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron, Overall – Per Protocol Population ..............................................336 
Figure 490: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron, Younger Cohort – mITT Population ..........................................336 
Figure 491: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron, Younger Cohort – Per Protocol Population ................................337 
Figure 492: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron, Older Cohort – mITT Population ...............................................337 
Figure 493: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron, Older Cohort – Per Protocol Population .....................................337 
Figure 494: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron, Infected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................337 


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Figure 495: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron, Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population ..................................................................................................337 
Figure 496: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron, Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................337 
Figure 497: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron, Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population ..................................................................................................337 
Figure 498: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron, Younger Infected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................337 
Figure 499: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron, Younger Infected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................337 
Figure 500: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort 
– mITT Population ....................................................................................................337 
Figure 501: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort 
– Per Protocol Population .........................................................................................337 
Figure 502: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron, Older Infected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................337 
Figure 503: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron, Older Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population ..................................................................................................337 
Figure 504: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................337 
Figure 505: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................337 
Figure 506: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Overall – mITT Population .....................................337 
Figure 507: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Overall – Per Protocol Population ..........................337 
Figure 508: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Younger Cohort – mITT Population.......................337 


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Figure 509: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Younger Cohort – Per Protocol Population ............338 
Figure 510: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Older Cohort – mITT Population ...........................338 
Figure 511: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Older Cohort – Per Protocol Population .................338 
Figure 512: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Infected (by Self-Report or N-protein) Cohort 
– mITT Population ....................................................................................................338 
Figure 513: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Infected (by Self-Report or N-protein) Cohort 
– Per Protocol Population .........................................................................................338 
Figure 514: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................338 
Figure 515: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................338 
Figure 516: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Younger Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................338 
Figure 517: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Younger Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................338 
Figure 518: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Younger Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................338 
Figure 519: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Younger Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................338 
Figure 520: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Older Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................338 
Figure 521: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Older Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................338 
Figure 522: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Older Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................338 


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Figure 523: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Older Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................338 
Figure 524: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Overall – mITT Population .................................338 
Figure 525: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Overall – Per Protocol Population ......................338 
Figure 526: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Younger Cohort – mITT Population...................339 
Figure 527: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Younger Cohort – Per Protocol Population ........339 
Figure 528: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Older Cohort – mITT Population .......................339 
Figure 529: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Older Cohort – Per Protocol Population .............339 
Figure 530: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................339 
Figure 531: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................339 
Figure 532: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................339 
Figure 533: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................339 
Figure 534: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Younger Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................339 
Figure 535: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Younger Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................339 
Figure 536: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................339 
Figure 537: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................339 


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Figure 538: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Older Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................339 
Figure 539: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Older Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................339 
Figure 540: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Older Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................339 
Figure 541: Pseudovirus Neutralization Assay ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Older Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................339 
Figure 542: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Prototype, Overall– mITT Population ........................................................340 
Figure 543: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Prototype, Overall– Per Protocol Population..............................................340 
Figure 544: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Prototype, Younger Cohort – mITT Population .........................................340 
Figure 545: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Prototype, Younger Cohort – Per Protocol Population ..............................340 
Figure 546: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Prototype, Older Cohort – mITT Population ..............................................340 
Figure 547: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Prototype, Older Cohort – Per Protocol Population ...................................340 
Figure 548: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Prototype, Infected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................340 
Figure 549: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Prototype, Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population ..................................................................................................340 
Figure 550: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Prototype, Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................340 
Figure 551: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Prototype, Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population ..................................................................................................340 
Figure 552: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Prototype, Younger Infected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................340 


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Figure 553: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Prototype, Younger Infected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................340 
Figure 554: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Prototype, Younger Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................340 
Figure 555: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Prototype, Younger Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................340 
Figure 556: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Prototype, Older Infected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................340 
Figure 557: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Prototype, Older Infected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................340 
Figure 558: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................340 
Figure 559: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................341 
Figure 560: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Overall – mITT Population .................................341 
Figure 561: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Overall – Per Protocol Population ......................341 
Figure 562: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Younger Cohort – mITT Population...................341 
Figure 563: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Younger Cohort – Per Protocol Population ........341 
Figure 564: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Older Cohort – mITT Population .......................341 
Figure 565: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Older Cohort – Per Protocol Population .............341 
Figure 566: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................341 
Figure 567: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................341 


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Figure 568: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................341 
Figure 569: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................341 
Figure 570: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Younger Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................341 
Figure 571: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Younger Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................341 
Figure 572: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................341 
Figure 573: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................341 
Figure 574: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Older Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................341 
Figure 575: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Older Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................342 
Figure 576: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Older Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................342 
Figure 577: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 1 Dose Beta + Omicron, Older Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................342 
Figure 578: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Overall – mITT Population............................................342 
Figure 579: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Overall – Per Protocol Population .................................342 
Figure 580: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Younger Cohort – mITT Population .............................342 
Figure 581: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Younger Cohort – Per Protocol Population ...................342 
Figure 582: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Older Cohort – mITT Population ..................................342 


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Figure 583: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Older Cohort – Per Protocol Population ........................342 
Figure 584: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Infected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................342 
Figure 585: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Infected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................342 
Figure 586: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Uninfected (by Self-Report or N-protein) Cohort 
– mITT Population ....................................................................................................342 
Figure 587: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Uninfected (by Self-Report or N-protein) Cohort 
– Per Protocol Population .........................................................................................342 
Figure 588: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Younger Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................342 
Figure 589: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Younger Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................342 
Figure 590: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................342 
Figure 591: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................342 
Figure 592: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Older Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................343 
Figure 593: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Older Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................343 
Figure 594: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Older Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................343 
Figure 595: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Delta + Omicron, Older Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................343 
Figure 596: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron, Overall – mITT Population ........................................................343 


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Figure 597: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron, Overall – Per Protocol Population ..............................................343 
Figure 598: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron, Younger Cohort – mITT Population ..........................................343 
Figure 599: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron, Younger Cohort – Per Protocol Population ................................343 
Figure 600: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron, Older Cohort – mITT Population ...............................................343 
Figure 601: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron, Older Cohort – Per Protocol Population .....................................343 
Figure 602: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron, Infected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................343 
Figure 603: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron, Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population ..................................................................................................343 
Figure 604: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron, Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population .................................................................................................................343 
Figure 605: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron, Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population ..................................................................................................343 
Figure 606: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron, Younger Infected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................343 
Figure 607: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron, Younger Infected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................343 
Figure 608: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort 
– mITT Population ....................................................................................................343 
Figure 609: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort 
– Per Protocol Population .........................................................................................344 
Figure 610: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron, Older Infected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................344 
Figure 611: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron, Older Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population ..................................................................................................344 


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Figure 612: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – 
mITT Population .......................................................................................................344 
Figure 613: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – 
Per Protocol Population ............................................................................................344 
Figure 614: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Overall – mITT Population .....................................344 
Figure 615: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Overall – Per Protocol Population ..........................344 
Figure 616: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Younger Cohort – mITT Population.......................344 
Figure 617: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Younger Cohort – Per Protocol Population ............344 
Figure 618: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Older Cohort – mITT Population ...........................344 
Figure 619: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Older Cohort – Per Protocol Population .................344 
Figure 620: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Infected (by Self-Report or N-protein) Cohort 
– mITT Population ....................................................................................................344 
Figure 621: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Infected (by Self-Report or N-protein) Cohort 
– Per Protocol Population .........................................................................................344 
Figure 622: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................344 
Figure 623: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................344 
Figure 624: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Younger Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................344 
Figure 625: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Younger Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................345 
Figure 626: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Younger Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................345 


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Figure 627: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Younger Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................345 
Figure 628: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Older Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................345 
Figure 629: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Older Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................345 
Figure 630: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Older Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................345 
Figure 631: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, Omicron + Prototype, Older Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................345 
Figure 632: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Overall – mITT Population .................................345 
Figure 633: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Overall – Per Protocol Population ......................345 
Figure 634: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Younger Cohort – mITT Population...................345 
Figure 635: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Younger Cohort – Per Protocol Population ........345 
Figure 636: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Older Cohort – mITT Population .......................345 
Figure 637: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Older Cohort – Per Protocol Population .............345 
Figure 638: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Infected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................345 
Figure 639: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................345 
Figure 640: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) 
Cohort – mITT Population ........................................................................................345 
Figure 641: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) 
Cohort – Per Protocol Population .............................................................................346 


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Figure 642: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Younger Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................346 
Figure 643: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Younger Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................346 
Figure 644: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................346 
Figure 645: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................346 
Figure 646: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Older Infected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................346 
Figure 647: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Older Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................346 
Figure 648: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Older Uninfected (by Self-Report or N-
protein) Cohort – mITT Population ..........................................................................346 
Figure 649: Focus Reduction Neutralization Test ID50 Distribution by Time Point and 
Variant, 2 Dose Beta + Omicron, Older Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population ...............................................................346 
Figure 650: Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, 
Overall - mITT Population .......................................................................................347 
Figure 651: Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, 
Overall - Per Protocol Population .............................................................................347 
Figure 652: Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, 
Overall - mITT Population .......................................................................................347 
Figure 653: Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, 
Overall - Per Protocol Population .............................................................................347 
Figure 654: Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, 
Overall - mITT Population .......................................................................................347 
Figure 655: Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, 
Overall - Per Protocol Population .............................................................................347 
Figure 656: Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, 
Overall - mITT Population .......................................................................................347 


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Figure 657: Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, 
Overall - Per Protocol Population .............................................................................347 
Figure 658: Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Overall - 
mITT Population .......................................................................................................348 
Figure 659: Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Overall - 
Per Protocol Population ............................................................................................348 
Figure 660: Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Overall - 
mITT Population .......................................................................................................348 
Figure 661: Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Overall - 
Per Protocol Population ............................................................................................348 
Figure 662: Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, 
Younger Cohort - mITT Population .........................................................................348 
Figure 663: Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, 
Younger Cohort - Per Protocol Population ...............................................................348 
Figure 664: Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, 
Younger Cohort - mITT Population .........................................................................348 
Figure 665: Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, 
Younger Cohort - Per Protocol Population ...............................................................348 
Figure 666: Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, 
Younger Cohort - mITT Population .........................................................................348 
Figure 667: Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, 
Younger Cohort - Per Protocol Population ...............................................................348 
Figure 668: Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, 
Younger Cohort - mITT Population .........................................................................348 
Figure 669: Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, 
Younger Cohort - Per Protocol Population ...............................................................348 
Figure 670: Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Younger 
Cohort - mITT Population ........................................................................................348 
Figure 671: Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Younger 
Cohort - Per Protocol Population ..............................................................................348 
Figure 672: Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Younger 
Cohort - mITT Population ........................................................................................348 
Figure 673: Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Younger 
Cohort - Per Protocol Population ..............................................................................348 
Figure 674: Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, 
Older Cohort - mITT Population ..............................................................................348 
Figure 675: Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, 
Older Cohort - Per Protocol Population....................................................................348 


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Figure 676: Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, 
Older Cohort - mITT Population ..............................................................................348 
Figure 677: Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, 
Older Cohort - Per Protocol Population....................................................................349 
Figure 678: Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, 
Older Cohort - mITT Population ..............................................................................349 
Figure 679: Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, 
Older Cohort - Per Protocol Population....................................................................349 
Figure 680: Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, 
Older Cohort - mITT Population ..............................................................................349 
Figure 681: Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, 
Older Cohort - Per Protocol Population....................................................................349 
Figure 682: Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Older 
Cohort - mITT Population ........................................................................................349 
Figure 683: Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Older 
Cohort - Per Protocol Population ..............................................................................349 
Figure 684: Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Older 
Cohort - mITT Population ........................................................................................349 
Figure 685: Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Older 
Cohort - Per Protocol Population ..............................................................................349 
Figure 686: Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, 
Infected (by Self-Report and N-protein) Cohort - mITT Population .......................349 
Figure 687: Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, 
Infected (by Self-Report and N-protein) Cohort - Per Protocol Population .............349 
Figure 688: Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, 
Infected (by Self-Report and N-protein) Cohort - mITT Population .......................349 
Figure 689: Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, 
Infected (by Self-Report and N-protein) Cohort - Per Protocol Population .............349 
Figure 690: Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, 
Infected (by Self-Report and N-protein) Cohort - mITT Population .......................349 
Figure 691: Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, 
Infected (by Self-Report and N-protein) Cohort - Per Protocol Population .............349 
Figure 692: Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, 
Infected (by Self-Report and N-protein) Cohort - mITT Population .......................349 
Figure 693: Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, 
Infected (by Self-Report and N-protein) Cohort - Per Protocol Population .............349 
Figure 694: Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Infected 
(by Self-Report and N-protein) Cohort - mITT Population ......................................349 


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Figure 695: Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Infected 
(by Self-Report and N-protein) Cohort - Per Protocol Population ...........................349 
Figure 696: Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Infected 
(by Self-Report and N-protein) Cohort - mITT Population ......................................350 
Figure 697: Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Infected 
(by Self-Report and N-protein) Cohort - Per Protocol Population ...........................350 
Figure 698: Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, 
Uninfected (by Self-Report and N-protein) Cohort - mITT Population ...................350 
Figure 699: Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, 
Uninfected (by Self-Report and N-protein) Cohort - Per Protocol Population ........350 
Figure 700: Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, 
Uninfected (by Self-Report and N-protein) Cohort - mITT Population ...................350 
Figure 701: Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, 
Uninfected (by Self-Report and N-protein) Cohort - Per Protocol Population ........350 
Figure 702: Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, 
Uninfected (by Self-Report and N-protein) Cohort - mITT Population ...................350 
Figure 703: Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, 
Uninfected (by Self-Report and N-protein) Cohort - Per Protocol Population ........350 
Figure 704: Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, 
Uninfected (by Self-Report and N-protein) Cohort - mITT Population ...................350 
Figure 705: Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, 
Uninfected (by Self-Report and N-protein) Cohort - Per Protocol Population ........350 
Figure 706: Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, 
Uninfected (by Self-Report and N-protein) Cohort - mITT Population ...................350 
Figure 707: Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, 
Uninfected (by Self-Report and N-protein) Cohort - Per Protocol Population ........350 
Figure 708: Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, 
Uninfected (by Self-Report and N-protein) Cohort - mITT Population ...................350 
Figure 709: Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, 
Uninfected (by Self-Report and N-protein) Cohort - Per Protocol Population ........350 
Figure 710: Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, 
Younger Infected (by Self-Report and N-protein) Cohort - mITT Population ........350 
Figure 711: Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, 
Younger Infected (by Self-Report and N-protein) Cohort - Per Protocol 
Population .................................................................................................................350 
Figure 712: Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, 
Younger Infected (by Self-Report and N-protein) Cohort - mITT Population ........350 


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Figure 713: Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, 
Younger Infected (by Self-Report and N-protein) Cohort - Per Protocol 
Population .................................................................................................................350 
Figure 714: Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, 
Younger Infected (by Self-Report and N-protein) Cohort - mITT Population ........350 
Figure 715: Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, 
Younger Infected (by Self-Report and N-protein) Cohort - Per Protocol 
Population .................................................................................................................351 
Figure 716: Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, 
Younger Infected (by Self-Report and N-protein) Cohort - mITT Population ........351 
Figure 717: Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, 
Younger Infected (by Self-Report and N-protein) Cohort - Per Protocol 
Population .................................................................................................................351 
Figure 718: Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Younger 
Infected (by Self-Report and N-protein) Cohort - mITT Population .......................351 
Figure 719: Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Younger 
Infected (by Self-Report and N-protein) Cohort - Per Protocol Population .............351 
Figure 720: Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Younger 
Infected (by Self-Report and N-protein) Cohort - mITT Population .......................351 
Figure 721: Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Younger 
Infected (by Self-Report and N-protein) Cohort - Per Protocol Population .............351 
Figure 722: Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, 
Older Infected (by Self-Report and N-protein) Cohort - mITT Population .............351 
Figure 723: Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, 
Older Infected (by Self-Report and N-protein) Cohort - Per Protocol 
Population .................................................................................................................351 
Figure 724: Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, 
Older Infected (by Self-Report and N-protein) Cohort - mITT Population .............351 
Figure 725: Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, 
Older Infected (by Self-Report and N-protein) Cohort - Per Protocol 
Population .................................................................................................................351 
Figure 726: Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, 
Older Infected (by Self-Report and N-protein) Cohort - mITT Population .............351 
Figure 727: Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, 
Older Infected (by Self-Report and N-protein) Cohort - Per Protocol 
Population .................................................................................................................351 
Figure 728: Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, 
Older Infected (by Self-Report and N-protein) Cohort - mITT Population .............351 


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Figure 729: Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, 
Older Infected (by Self-Report and N-protein) Cohort - Per Protocol 
Population .................................................................................................................351 
Figure 730: Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Older 
Infected (by Self-Report and N-protein) Cohort - mITT Population .......................351 
Figure 731: Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Older 
Infected (by Self-Report and N-protein) Cohort - Per Protocol Population .............351 
Figure 732: Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Older 
Infected (by Self-Report and N-protein) Cohort - mITT Population .......................351 
Figure 733: Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Older 
Infected (by Self-Report and N-protein) Cohort - Per Protocol Population .............351 
Figure 734: Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, 
Younger Uninfected (by Self-Report and N-protein) Cohort - mITT 
Population .................................................................................................................352 
Figure 735: Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, 
Younger Uninfected (by Self-Report and N-protein) Cohort - Per Protocol 
Population .................................................................................................................352 
Figure 736: Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, 
Younger Uninfected (by Self-Report and N-protein) Cohort - mITT 
Population .................................................................................................................352 
Figure 737: Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, 
Younger Uninfected (by Self-Report and N-protein) Cohort - Per Protocol 
Population .................................................................................................................352 
Figure 738: Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, 
Younger Uninfected (by Self-Report and N-protein) Cohort - mITT 
Population .................................................................................................................352 
Figure 739: Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, 
Younger Uninfected (by Self-Report and N-protein) Cohort - Per Protocol 
Population .................................................................................................................352 
Figure 740: Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, 
Younger Uninfected (by Self-Report and N-protein) Cohort - mITT 
Population .................................................................................................................352 
Figure 741: Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, 
Younger Uninfected (by Self-Report and N-protein) Cohort - Per Protocol 
Population .................................................................................................................352 
Figure 742: Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Younger 
Uninfected (by Self-Report and N-protein) Cohort - mITT Population ...................352 
Figure 743: Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Younger 
Uninfected (by Self-Report and N-protein) Cohort - Per Protocol Population ........352 


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Figure 744: Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Younger 
Uninfected (by Self-Report and N-protein) Cohort - mITT Population ...................352 
Figure 745: Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Younger 
Uninfected (by Self-Report and N-protein) Cohort - Per Protocol Population ........352 
Figure 746: Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, 
Older Uninfected (by Self-Report and N-protein) Cohort - mITT Population .........352 
Figure 747: Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, 
Older Uninfected (by Self-Report and N-protein) Cohort - Per Protocol 
Population .................................................................................................................352 
Figure 748: Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, 
Older Uninfected (by Self-Report and N-protein) Cohort - mITT Population .........352 
Figure 749: Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, 
Older Uninfected (by Self-Report and N-protein) Cohort - Per Protocol 
Population .................................................................................................................352 
Figure 750: Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, 
Older Uninfected (by Self-Report and N-protein) Cohort - mITT Population .........352 
Figure 751: Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, 
Older Uninfected (by Self-Report and N-protein) Cohort - Per Protocol 
Population .................................................................................................................352 
Figure 752: Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, 
Older Uninfected (by Self-Report and N-protein) Cohort - mITT Population .........352 
Figure 753: Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, 
Older Uninfected (by Self-Report and N-protein) Cohort - Per Protocol 
Population .................................................................................................................353 
Figure 754: Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Older 
Uninfected (by Self-Report and N-protein) Cohort - mITT Population ...................353 
Figure 755: Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Older 
Uninfected (by Self-Report and N-protein) Cohort - Per Protocol Population ........353 
Figure 756: Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Older 
Uninfected (by Self-Report and N-protein) Cohort - mITT Population ...................353 
Figure 757: Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Older 
Uninfected (by Self-Report and N-protein) Cohort - Per Protocol Population ........353 
Figure 758: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by 
timepoint and Vaccination arm, Overall - mITT Population ....................................354 
Figure 759: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by 
timepoint and Vaccination arm, Overall – Per Protocol Population ........................354 
Figure 760: Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by 
timepoint and Vaccination arm, Overall – mITT Population ...................................354 


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Figure 761: Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by 
timepoint and Vaccination arm, Overall – Per Protocol Population ........................354 
Figure 762: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta 
by timepoint and Vaccination arm, Overall – mITT Population ..............................354 
Figure 763: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta 
by timepoint and Vaccination arm, Overall – Per Protocol Population ...................354 
Figure 764: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron 
by timepoint and Vaccination arm, Overall – mITT Population ..............................354 
Figure 765: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron 
by timepoint and Vaccination arm, Overall – Per Protocol Population ...................354 
Figure 766: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Beta by timepoint and Vaccination arm, Overall – mITT Population ......................354 
Figure 767: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Beta by timepoint and Vaccination arm, Overall – Per Protocol Population ...........354 
Figure 768: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta-Beta by timepoint and Vaccination arm, Overall – mITT Population ............354 
Figure 769: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta-Beta by timepoint and Vaccination arm, Overall – Per Protocol 
Population .................................................................................................................355 
Figure 770: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta by timepoint and Vaccination arm, Overall – mITT Population ....................355 
Figure 771: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta by timepoint and Vaccination arm, Overall – Per Protocol Population ..........355 
Figure 772: Distribution of Percent of IgG B-cells expressing RBD Omicron by 
timepoint and Vaccination arm, Overall – mITT Population ...................................355 
Figure 773: Distribution of Percent of IgG B-cells expressing RBD Omicron by 
timepoint and Vaccination arm, Overall – Per Protocol Population ........................355 
Figure 774: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by 
timepoint and Vaccination arm, Overall – mITT Population ...................................355 
Figure 775: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by 
timepoint and Vaccination arm, Overall – Per Protocol Population ........................355 
Figure 776: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta 
by timepoint and Vaccination arm, Overall – mITT Population ..............................355 
Figure 777: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta 
by timepoint and Vaccination arm, Overall – Per Protocol Population ...................355 
Figure 778: Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by 
timepoint and Vaccination arm, Overall – mITT Population ...................................355 


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Figure 779: Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by 
timepoint and Vaccination arm, Overall – Per Protocol Population ........................355 
Figure 780: Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint 
and Vaccination arm, Overall – mITT Population ...................................................355 
Figure 781: Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint 
and Vaccination arm, Overall – Per Protocol Population .........................................355 
Figure 782: Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint 
and Vaccination arm, Overall – mITT Population ...................................................355 
Figure 783: Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint 
and Vaccination arm, Overall – Per Protocol Population .........................................355 
Figure 784: Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by 
timepoint and Vaccination arm, Overall – mITT Population ...................................355 
Figure 785: Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by 
timepoint and Vaccination arm, Overall – Per Protocol Population ........................355 
Figure 786: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by 
timepoint and Vaccination arm, Younger Cohort - mITT Population......................355 
Figure 787: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by 
timepoint and Vaccination arm, Younger Cohort – Per Protocol Population ..........355 
Figure 788: Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by 
timepoint and Vaccination arm, Younger Cohort – mITT Population .....................356 
Figure 789: Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by 
timepoint and Vaccination arm, Younger Cohort – Per Protocol Population ..........356 
Figure 790: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta 
by timepoint and Vaccination arm, Younger Cohort – mITT Population ................356 
Figure 791: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta 
by timepoint and Vaccination arm, Younger Cohort – Per Protocol 
Population .................................................................................................................356 
Figure 792: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron 
by timepoint and Vaccination arm, Younger Cohort – mITT Population ................356 
Figure 793: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron 
by timepoint and Vaccination arm, Younger Cohort – Per Protocol 
Population .................................................................................................................356 
Figure 794: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Beta by timepoint and Vaccination arm, Younger Cohort – mITT Population ........356 
Figure 795: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Beta by timepoint and Vaccination arm, Younger Cohort – Per Protocol 
Population .................................................................................................................356 


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Figure 796: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta-Beta by timepoint and Vaccination arm, Younger Cohort – mITT 
Population .................................................................................................................356 
Figure 797: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta-Beta by timepoint and Vaccination arm, Younger Cohort – Per 
Protocol Population ..................................................................................................356 
Figure 798: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta by timepoint and Vaccination arm, Younger Cohort – mITT 
Population .................................................................................................................356 
Figure 799: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta by timepoint and Vaccination arm, Younger Cohort – Per Protocol 
Population .................................................................................................................356 
Figure 800: Distribution of Percent of IgG B-cells expressing RBD Omicron by 
timepoint and Vaccination arm, Younger Cohort – mITT Population .....................356 
Figure 801: Distribution of Percent of IgG B-cells expressing RBD Omicron by 
timepoint and Vaccination arm, Younger Cohort – Per Protocol Population ..........356 
Figure 802: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by 
timepoint and Vaccination arm, Younger Cohort – mITT Population .....................356 
Figure 803: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by 
timepoint and Vaccination arm, Younger Cohort – Per Protocol Population ..........356 
Figure 804: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta 
by timepoint and Vaccination arm, Younger Cohort – mITT Population ................356 
Figure 805: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta 
by timepoint and Vaccination arm, Younger Cohort – Per Protocol 
Population .................................................................................................................356 
Figure 806: Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by 
timepoint and Vaccination arm, Younger Cohort – mITT Population .....................356 
Figure 807: Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by 
timepoint and Vaccination arm, Younger Cohort – Per Protocol Population ..........357 
Figure 808: Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint 
and Vaccination arm, Younger Cohort – mITT Population .....................................357 
Figure 809: Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint 
and Vaccination arm, Younger Cohort – Per Protocol Population ...........................357 
Figure 810: Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint 
and Vaccination arm, Younger Cohort – mITT Population .....................................357 
Figure 811: Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint 
and Vaccination arm, Younger Cohort – Per Protocol Population ...........................357 
Figure 812: Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by 
timepoint and Vaccination arm, Younger Cohort – mITT Population .....................357 


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Figure 813: Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by 
timepoint and Vaccination arm, Younger Cohort – Per Protocol Population ..........357 
Figure 814: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by 
timepoint and Vaccination arm, Older Cohort - mITT Population ..........................357 
Figure 815: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by 
timepoint and Vaccination arm, Older Cohort – Per Protocol Population ...............357 
Figure 816: Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by 
timepoint and Vaccination arm, Older Cohort – mITT Population ..........................357 
Figure 817: Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by 
timepoint and Vaccination arm, Older Cohort – Per Protocol Population ...............357 
Figure 818: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta 
by timepoint and Vaccination arm, Older Cohort – mITT Population .....................357 
Figure 819: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta 
by timepoint and Vaccination arm, Older Cohort – Per Protocol Population ..........357 
Figure 820: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron 
by timepoint and Vaccination arm, Older Cohort – mITT Population .....................357 
Figure 821: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron 
by timepoint and Vaccination arm, Older Cohort – Per Protocol Population ..........357 
Figure 822: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Beta by timepoint and Vaccination arm, Older Cohort – mITT Population ............357 
Figure 823: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Beta by timepoint and Vaccination arm, Older Cohort – Per Protocol 
Population .................................................................................................................357 
Figure 824: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta-Beta by timepoint and Vaccination arm, Older Cohort – mITT 
Population .................................................................................................................357 
Figure 825: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta-Beta by timepoint and Vaccination arm, Older Cohort – Per Protocol 
Population .................................................................................................................358 
Figure 826: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta by timepoint and Vaccination arm, Older Cohort – mITT Population ...........358 
Figure 827: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta by timepoint and Vaccination arm, Older Cohort – Per Protocol 
Population .................................................................................................................358 
Figure 828: Distribution of Percent of IgG B-cells expressing RBD Omicron by 
timepoint and Vaccination arm, Older Cohort – mITT Population ..........................358 
Figure 829: Distribution of Percent of IgG B-cells expressing RBD Omicron by 
timepoint and Vaccination arm, Older Cohort – Per Protocol Population ...............358 


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Figure 830: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by 
timepoint and Vaccination arm, Older Cohort – mITT Population ..........................358 
Figure 831: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by 
timepoint and Vaccination arm, Older Cohort – Per Protocol Population ...............358 
Figure 832: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta 
by timepoint and Vaccination arm, Older Cohort – mITT Population .....................358 
Figure 833: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta 
by timepoint and Vaccination arm, Older Cohort – Per Protocol Population ..........358 
Figure 834: Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by 
timepoint and Vaccination arm, Older Cohort – mITT Population ..........................358 
Figure 835: Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by 
timepoint and Vaccination arm, Older Cohort – Per Protocol Population ...............358 
Figure 836: Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint 
and Vaccination arm, Older Cohort – mITT Population ..........................................358 
Figure 837: Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint 
and Vaccination arm, Older Cohort – Per Protocol Population ................................358 
Figure 838: Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint 
and Vaccination arm, Older Cohort – mITT Population ..........................................358 
Figure 839: Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint 
and Vaccination arm, Older Cohort – Per Protocol Population ................................358 
Figure 840: Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by 
timepoint and Vaccination arm, Older Cohort – mITT Population ..........................358 
Figure 841: Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by 
timepoint and Vaccination arm, Older Cohort – Per Protocol Population ...............358 
Figure 842: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by 
timepoint and Vaccination arm, Infected (by Self-Report and N-protein) 
Cohort - mITT Population ........................................................................................358 
Figure 843: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by 
timepoint and Vaccination arm, Infected (by Self-Report and N-protein) 
Cohort – Per Protocol Population .............................................................................358 
Figure 844: Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by 
timepoint and Vaccination arm, Infected (by Self-Report and N-protein) 
Cohort – mITT Population ........................................................................................359 
Figure 845: Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by 
timepoint and Vaccination arm, Infected (by Self-Report and N-protein) 
Cohort – Per Protocol Population .............................................................................359 
Figure 846: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta 
by timepoint and Vaccination arm, Infected (by Self-Report and N-protein) 
Cohort – mITT Population ........................................................................................359 


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Figure 847: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta 
by timepoint and Vaccination arm, Infected (by Self-Report and N-protein) 
Cohort – Per Protocol Population .............................................................................359 
Figure 848: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron 
by timepoint and Vaccination arm, Infected (by Self-Report and N-protein) 
Cohort – mITT Population ........................................................................................359 
Figure 849: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron 
by timepoint and Vaccination arm, Infected (by Self-Report and N-protein) 
Cohort – Per Protocol Population .............................................................................359 
Figure 850: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Beta by timepoint and Vaccination arm, Infected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................359 
Figure 851: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Beta by timepoint and Vaccination arm, Infected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................359 
Figure 852: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta-Beta by timepoint and Vaccination arm, Infected (by Self-Report and 
N-protein) Cohort – mITT Population ......................................................................359 
Figure 853: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta-Beta by timepoint and Vaccination arm, Infected (by Self-Report and 
N-protein) Cohort – Per Protocol Population ...........................................................359 
Figure 854: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta by timepoint and Vaccination arm, Infected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................359 
Figure 855: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta by timepoint and Vaccination arm, Infected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................359 
Figure 856: Distribution of Percent of IgG B-cells expressing RBD Omicron by 
timepoint and Vaccination arm, Infected (by Self-Report and N-protein) 
Cohort – mITT Population ........................................................................................359 
Figure 857: Distribution of Percent of IgG B-cells expressing RBD Omicron by 
timepoint and Vaccination arm, Infected (by Self-Report and N-protein) 
Cohort – Per Protocol Population .............................................................................359 
Figure 858: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by 
timepoint and Vaccination arm, Infected (by Self-Report and N-protein) 
Cohort – mITT Population ........................................................................................360 
Figure 859: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by 
timepoint and Vaccination arm, Infected (by Self-Report and N-protein) 
Cohort – Per Protocol Population .............................................................................360 


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Figure 860: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta 
by timepoint and Vaccination arm, Infected (by Self-Report and N-protein) 
Cohort – mITT Population ........................................................................................360 
Figure 861: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta 
by timepoint and Vaccination arm, Infected (by Self-Report and N-protein) 
Cohort – Per Protocol Population .............................................................................360 
Figure 862: Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by 
timepoint and Vaccination arm, Infected (by Self-Report and N-protein) 
Cohort – mITT Population ........................................................................................360 
Figure 863: Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by 
timepoint and Vaccination arm, Infected (by Self-Report and N-protein) 
Cohort – Per Protocol Population .............................................................................360 
Figure 864: Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint 
and Vaccination arm, Infected (by Self-Report and N-protein) Cohort – 
mITT Population .......................................................................................................360 
Figure 865: Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint 
and Vaccination arm, Infected (by Self-Report and N-protein) Cohort – Per 
Protocol Population ..................................................................................................360 
Figure 866: Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint 
and Vaccination arm, Infected (by Self-Report and N-protein) Cohort – 
mITT Population .......................................................................................................360 
Figure 867: Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint 
and Vaccination arm, Infected (by Self-Report and N-protein) Cohort – Per 
Protocol Population ..................................................................................................360 
Figure 868: Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by 
timepoint and Vaccination arm, Infected (by Self-Report and N-protein) 
Cohort – mITT Population ........................................................................................360 
Figure 869: Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by 
timepoint and Vaccination arm, Infected (by Self-Report and N-protein) 
Cohort – Per Protocol Population .............................................................................360 
Figure 870: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by 
timepoint and Vaccination arm, Uninfected (by Self-Report and N-protein) 
Cohort - mITT Population ........................................................................................360 
Figure 871: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by 
timepoint and Vaccination arm, Uninfected (by Self-Report and N-protein) 
Cohort – Per Protocol Population .............................................................................360 
Figure 872: Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by 
timepoint and Vaccination arm, Uninfected (by Self-Report and N-protein) 
Cohort – mITT Population ........................................................................................360 


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Figure 873: Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by 
timepoint and Vaccination arm, Uninfected (by Self-Report and N-protein) 
Cohort – Per Protocol Population .............................................................................360 
Figure 874: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta 
by timepoint and Vaccination arm, Uninfected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................361 
Figure 875: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta 
by timepoint and Vaccination arm, Uninfected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................361 
Figure 876: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron 
by timepoint and Vaccination arm, Uninfected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................361 
Figure 877: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron 
by timepoint and Vaccination arm, Uninfected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................361 
Figure 878: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Beta by timepoint and Vaccination arm, Uninfected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................361 
Figure 879: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Beta by timepoint and Vaccination arm, Uninfected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................361 
Figure 880: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta-Beta by timepoint and Vaccination arm, Uninfected (by Self-Report 
and N-protein) Cohort – mITT Population ...............................................................361 
Figure 881: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta-Beta by timepoint and Vaccination arm, Uninfected (by Self-Report 
and N-protein) Cohort – Per Protocol Population ....................................................361 
Figure 882: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta by timepoint and Vaccination arm, Uninfected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................361 
Figure 883: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta by timepoint and Vaccination arm, Uninfected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................361 
Figure 884: Distribution of Percent of IgG B-cells expressing RBD Omicron by 
timepoint and Vaccination arm, Uninfected (by Self-Report and N-protein) 
Cohort – mITT Population ........................................................................................361 
Figure 885: Distribution of Percent of IgG B-cells expressing RBD Omicron by 
timepoint and Vaccination arm, Uninfected (by Self-Report and N-protein) 
Cohort – Per Protocol Population .............................................................................361 


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Figure 886: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by 
timepoint and Vaccination arm, Uninfected (by Self-Report and N-protein) 
Cohort – mITT Population ........................................................................................361 
Figure 887: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by 
timepoint and Vaccination arm, Uninfected (by Self-Report and N-protein) 
Cohort – Per Protocol Population .............................................................................361 
Figure 888: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta 
by timepoint and Vaccination arm, Uninfected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................362 
Figure 889: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta 
by timepoint and Vaccination arm, Uninfected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................362 
Figure 890: Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by 
timepoint and Vaccination arm, Uninfected (by Self-Report and N-protein) 
Cohort – mITT Population ........................................................................................362 
Figure 891: Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by 
timepoint and Vaccination arm, Uninfected (by Self-Report and N-protein) 
Cohort – Per Protocol Population .............................................................................362 
Figure 892: Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint 
and Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – 
mITT Population .......................................................................................................362 
Figure 893: Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint 
and Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – 
Per Protocol Population ............................................................................................362 
Figure 894: Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint 
and Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – 
mITT Population .......................................................................................................362 
Figure 895: Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint 
and Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – 
Per Protocol Population ............................................................................................362 
Figure 896: Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by 
timepoint and Vaccination arm, Uninfected (by Self-Report and N-protein) 
Cohort – mITT Population ........................................................................................362 
Figure 897: Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by 
timepoint and Vaccination arm, Uninfected (by Self-Report and N-protein) 
Cohort – Per Protocol Population .............................................................................362 
Figure 898: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by 
timepoint and Vaccination arm, Younger Infected (by Self-Report and N-
protein) Cohort - mITT Population...........................................................................362 


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Figure 899: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by 
timepoint and Vaccination arm, Younger Infected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................362 
Figure 900: Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by 
timepoint and Vaccination arm, Younger Infected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................362 
Figure 901: Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by 
timepoint and Vaccination arm, Younger Infected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................362 
Figure 902: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta 
by timepoint and Vaccination arm, Younger Infected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................362 
Figure 903: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta 
by timepoint and Vaccination arm, Younger Infected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................363 
Figure 904: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron 
by timepoint and Vaccination arm, Younger Infected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................363 
Figure 905: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron 
by timepoint and Vaccination arm, Younger Infected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................363 
Figure 906: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Beta by timepoint and Vaccination arm, Younger Infected (by Self-Report 
and N-protein) Cohort – mITT Population ...............................................................363 
Figure 907: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Beta by timepoint and Vaccination arm, Younger Infected (by Self-Report 
and N-protein) Cohort – Per Protocol Population ....................................................363 
Figure 908: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta-Beta by timepoint and Vaccination arm, Younger Infected (by Self-
Report and N-protein) Cohort – mITT Population ...................................................363 
Figure 909: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta-Beta by timepoint and Vaccination arm, Younger Infected (by Self-
Report and N-protein) Cohort – Per Protocol Population ........................................363 
Figure 910: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta by timepoint and Vaccination arm, Younger Infected (by Self-Report 
and N-protein) Cohort – mITT Population ...............................................................363 
Figure 911: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta by timepoint and Vaccination arm, Younger Infected (by Self-Report 
and N-protein) Cohort – Per Protocol Population ....................................................363 


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Figure 912: Distribution of Percent of IgG B-cells expressing RBD Omicron by 
timepoint and Vaccination arm, Younger Infected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................363 
Figure 913: Distribution of Percent of IgG B-cells expressing RBD Omicron by 
timepoint and Vaccination arm, Younger Infected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................363 
Figure 914: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by 
timepoint and Vaccination arm, Younger Infected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................363 
Figure 915: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by 
timepoint and Vaccination arm, Younger Infected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................363 
Figure 916: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta 
by timepoint and Vaccination arm, Younger Infected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................364 
Figure 917: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta 
by timepoint and Vaccination arm, Younger Infected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................364 
Figure 918: Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by 
timepoint and Vaccination arm, Younger Infected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................364 
Figure 919: Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by 
timepoint and Vaccination arm, Younger Infected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................364 
Figure 920: Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint 
and Vaccination arm, Younger Infected (by Self-Report and N-protein) 
Cohort – mITT Population ........................................................................................364 
Figure 921: Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint 
and Vaccination arm, Younger Infected (by Self-Report and N-protein) 
Cohort – Per Protocol Population .............................................................................364 
Figure 922: Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint 
and Vaccination arm, Younger Infected (by Self-Report and N-protein) 
Cohort – mITT Population ........................................................................................364 
Figure 923: Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint 
and Vaccination arm, Younger Infected (by Self-Report and N-protein) 
Cohort – Per Protocol Population .............................................................................364 
Figure 924: Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by 
timepoint and Vaccination arm, Younger Infected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................364 


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Figure 925: Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by 
timepoint and Vaccination arm, Younger Infected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................364 
Figure 926: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by 
timepoint and Vaccination arm, Younger Uninfected (by Self-Report and N-
protein) Cohort - mITT Population...........................................................................364 
Figure 927: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by 
timepoint and Vaccination arm, Younger Uninfected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................364 
Figure 928: Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by 
timepoint and Vaccination arm, Younger Uninfected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................364 
Figure 929: Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by 
timepoint and Vaccination arm, Younger Uninfected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................364 
Figure 930: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta 
by timepoint and Vaccination arm, Younger Uninfected (by Self-Report and 
N-protein) Cohort – mITT Population ......................................................................365 
Figure 931: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta 
by timepoint and Vaccination arm, Younger Uninfected (by Self-Report and 
N-protein) Cohort – Per Protocol Population ...........................................................365 
Figure 932: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron 
by timepoint and Vaccination arm, Younger Uninfected (by Self-Report and 
N-protein) Cohort – mITT Population ......................................................................365 
Figure 933: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron 
by timepoint and Vaccination arm, Younger Uninfected (by Self-Report and 
N-protein) Cohort – Per Protocol Population ...........................................................365 
Figure 934: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Beta by timepoint and Vaccination arm, Younger Uninfected (by Self-
Report and N-protein) Cohort – mITT Population ...................................................365 
Figure 935: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Beta by timepoint and Vaccination arm, Younger Uninfected (by Self-
Report and N-protein) Cohort – Per Protocol Population ........................................365 
Figure 936: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta-Beta by timepoint and Vaccination arm, Younger Uninfected (by Self-
Report and N-protein) Cohort – mITT Population ...................................................365 
Figure 937: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta-Beta by timepoint and Vaccination arm, Younger Uninfected (by Self-
Report and N-protein) Cohort – Per Protocol Population ........................................365 


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Figure 938: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta by timepoint and Vaccination arm, Younger Uninfected (by Self-
Report and N-protein) Cohort – mITT Population ...................................................365 
Figure 939: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta by timepoint and Vaccination arm, Younger Uninfected (by Self-
Report and N-protein) Cohort – Per Protocol Population ........................................365 
Figure 940: Distribution of Percent of IgG B-cells expressing RBD Omicron by 
timepoint and Vaccination arm, Younger Uninfected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................365 
Figure 941: Distribution of Percent of IgG B-cells expressing RBD Omicron by 
timepoint and Vaccination arm, Younger Uninfected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................365 
Figure 942: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by 
timepoint and Vaccination arm, Younger Uninfected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................365 
Figure 943: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by 
timepoint and Vaccination arm, Younger Uninfected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................366 
Figure 944: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta 
by timepoint and Vaccination arm, Younger Uninfected (by Self-Report and 
N-protein) Cohort – mITT Population ......................................................................366 
Figure 945: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta 
by timepoint and Vaccination arm, Younger Uninfected (by Self-Report and 
N-protein) Cohort – Per Protocol Population ...........................................................366 
Figure 946: Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by 
timepoint and Vaccination arm, Younger Uninfected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................366 
Figure 947: Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by 
timepoint and Vaccination arm, Younger Uninfected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................366 
Figure 948: Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint 
and Vaccination arm, Younger Uninfected (by Self-Report and N-protein) 
Cohort – mITT Population ........................................................................................366 
Figure 949: Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint 
and Vaccination arm, Younger Uninfected (by Self-Report and N-protein) 
Cohort – Per Protocol Population .............................................................................366 
Figure 950: Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint 
and Vaccination arm, Younger Uninfected (by Self-Report and N-protein) 
Cohort – mITT Population ........................................................................................366 


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Figure 951: Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint 
and Vaccination arm, Younger Uninfected (by Self-Report and N-protein) 
Cohort – Per Protocol Population .............................................................................366 
Figure 952: Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by 
timepoint and Vaccination arm, Younger Uninfected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................366 
Figure 953: Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by 
timepoint and Vaccination arm, Younger Uninfected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................366 
Figure 954: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by 
timepoint and Vaccination arm, Older Infected (by Self-Report and N-
protein) Cohort - mITT Population...........................................................................366 
Figure 955: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by 
timepoint and Vaccination arm, Older Infected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................366 
Figure 956: Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by 
timepoint and Vaccination arm, Older Infected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................366 
Figure 957: Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by 
timepoint and Vaccination arm, Older Infected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................367 
Figure 958: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta 
by timepoint and Vaccination arm, Older Infected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................367 
Figure 959: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta 
by timepoint and Vaccination arm, Older Infected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................367 
Figure 960: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron 
by timepoint and Vaccination arm, Older Infected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................367 
Figure 961: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron 
by timepoint and Vaccination arm, Older Infected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................367 
Figure 962: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Beta by timepoint and Vaccination arm, Older Infected (by Self-Report and 
N-protein) Cohort – mITT Population ......................................................................367 
Figure 963: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Beta by timepoint and Vaccination arm, Older Infected (by Self-Report and 
N-protein) Cohort – Per Protocol Population ...........................................................367 


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Figure 964: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta-Beta by timepoint and Vaccination arm, Older Infected (by Self-
Report and N-protein) Cohort – mITT Population ...................................................367 
Figure 965: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta-Beta by timepoint and Vaccination arm, Older Infected (by Self-
Report and N-protein) Cohort – Per Protocol Population ........................................367 
Figure 966: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta by timepoint and Vaccination arm, Older Infected (by Self-Report and 
N-protein) Cohort – mITT Population ......................................................................367 
Figure 967: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta by timepoint and Vaccination arm, Older Infected (by Self-Report and 
N-protein) Cohort – Per Protocol Population ...........................................................367 
Figure 968: Distribution of Percent of IgG B-cells expressing RBD Omicron by 
timepoint and Vaccination arm, Older Infected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................367 
Figure 969: Distribution of Percent of IgG B-cells expressing RBD Omicron by 
timepoint and Vaccination arm, Older Infected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................367 
Figure 970: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by 
timepoint and Vaccination arm, Older Infected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................367 
Figure 971: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by 
timepoint and Vaccination arm, Older Infected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................368 
Figure 972: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta 
by timepoint and Vaccination arm, Older Infected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................368 
Figure 973: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta 
by timepoint and Vaccination arm, Older Infected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................368 
Figure 974: Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by 
timepoint and Vaccination arm, Older Infected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................368 
Figure 975: Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by 
timepoint and Vaccination arm, Older Infected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................368 
Figure 976: Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint 
and Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort 
– mITT Population ....................................................................................................368 


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Figure 977: Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint 
and Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort 
– Per Protocol Population .........................................................................................368 
Figure 978: Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint 
and Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort 
– mITT Population ....................................................................................................368 
Figure 979: Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint 
and Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort 
– Per Protocol Population .........................................................................................368 
Figure 980: Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by 
timepoint and Vaccination arm, Older Infected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................368 
Figure 981: Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by 
timepoint and Vaccination arm, Older Infected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................368 
Figure 982: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by 
timepoint and Vaccination arm, Older Uninfected (by Self-Report and N-
protein) Cohort - mITT Population...........................................................................368 
Figure 983: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by 
timepoint and Vaccination arm, Older Uninfected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................368 
Figure 984: Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by 
timepoint and Vaccination arm, Older Uninfected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................368 
Figure 985: Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by 
timepoint and Vaccination arm, Older Uninfected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................369 
Figure 986: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta 
by timepoint and Vaccination arm, Older Uninfected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................369 
Figure 987: Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta 
by timepoint and Vaccination arm, Older Uninfected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................369 
Figure 988: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron 
by timepoint and Vaccination arm, Older Uninfected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................369 
Figure 989: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron 
by timepoint and Vaccination arm, Older Uninfected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................369 


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Figure 990: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Beta by timepoint and Vaccination arm, Older Uninfected (by Self-Report 
and N-protein) Cohort – mITT Population ...............................................................369 
Figure 991: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Beta by timepoint and Vaccination arm, Older Uninfected (by Self-Report 
and N-protein) Cohort – Per Protocol Population ....................................................369 
Figure 992: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta-Beta by timepoint and Vaccination arm, Older Uninfected (by Self-
Report and N-protein) Cohort – mITT Population ...................................................369 
Figure 993: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta-Beta by timepoint and Vaccination arm, Older Uninfected (by Self-
Report and N-protein) Cohort – Per Protocol Population ........................................369 
Figure 994: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta by timepoint and Vaccination arm, Older Uninfected (by Self-Report 
and N-protein) Cohort – mITT Population ...............................................................369 
Figure 995: Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-
Delta by timepoint and Vaccination arm, Older Uninfected (by Self-Report 
and N-protein) Cohort – Per Protocol Population ....................................................369 
Figure 996: Distribution of Percent of IgG B-cells expressing RBD Omicron by 
timepoint and Vaccination arm, Older Uninfected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................369 
Figure 997: Distribution of Percent of IgG B-cells expressing RBD Omicron by 
timepoint and Vaccination arm, Older Uninfected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................369 
Figure 998: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by 
timepoint and Vaccination arm, Older Uninfected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................370 
Figure 999: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by 
timepoint and Vaccination arm, Older Uninfected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................370 
Figure 1000: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-
Delta by timepoint and Vaccination arm, Older Uninfected (by Self-Report 
and N-protein) Cohort – mITT Population ...............................................................370 
Figure 1001: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-
Delta by timepoint and Vaccination arm, Older Uninfected (by Self-Report 
and N-protein) Cohort – Per Protocol Population ....................................................370 
Figure 1002: Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by 
timepoint and Vaccination arm, Older Uninfected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................370 


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Figure 1003: Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by 
timepoint and Vaccination arm, Older Uninfected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................370 
Figure 1004: Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint 
and Vaccination arm, Older Uninfected (by Self-Report and N-protein) 
Cohort – mITT Population ........................................................................................370 
Figure 1005: Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint 
and Vaccination arm, Older Uninfected (by Self-Report and N-protein) 
Cohort – Per Protocol Population .............................................................................370 
Figure 1006: Distribution of Percent of IgG B-cells expressing RBD Delta by 
timepoint and Vaccination arm, Older Uninfected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................370 
Figure 1007: Distribution of Percent of IgG B-cells expressing RBD Delta by 
timepoint and Vaccination arm, Older Uninfected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................370 
Figure 1008: Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by 
timepoint and Vaccination arm, Older Uninfected (by Self-Report and N-
protein) Cohort – mITT Population ..........................................................................370 
Figure 1009: Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by 
timepoint and Vaccination arm, Older Uninfected (by Self-Report and N-
protein) Cohort – Per Protocol Population ...............................................................370 
Figure 1010: Time to Infection Kaplan-Meier Curve by Vaccination Group, Overall - 
mITT Population .......................................................................................................371 
Figure 1011: Time to Infection Kaplan-Meier Curve by Vaccination Group, Younger 
Cohort- mITT Population .........................................................................................371 
Figure 1012: Time to Infection Kaplan-Meier Curve by Vaccination Group, Older 
Cohort - mITT Population ........................................................................................371 
Figure 1013: Time to Infection Kaplan-Meier Curve by Vaccination Group, Infected 
Cohort (By Self-report or N-protein)- mITT Population ..........................................371 
Figure 1014: Time to Infection Kaplan-Meier Curve by Vaccination Group, Uninfected 
Cohort (By Self-report or N-protein) - mITT Population .........................................371 
Figure 1015: Time to Infection Kaplan-Meier Curve by Vaccination Group, Younger 
Infected Cohort (By Self-report or N-protein) - mITT Population ...........................371 
Figure 1016: Time to Infection Kaplan-Meier Curve by Vaccination Group, Younger 
Uninfected Cohort (By Self-report or N-protein) - mITT Population ......................371 
Figure 1017: Time to Infection Kaplan-Meier Curve by Vaccination Group, Older 
Infected Cohort (By Self-report or N-protein) - mITT Population ...........................372 
Figure 1018: Time to Infection Kaplan-Meier Curve by Vaccination Group, Older 
Uninfected Cohort (By Self-report or N-protein) - mITT Population ......................372 


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Figure 1019: Summary of Breakthrough Infections by PANGO Call and Treatment 
Group, Prototype – Safety Population ......................................................................373 
Figure 1020: Summary of Breakthrough Infections by PANGO Call and Treatment 
Group, 1 Dose Beta + Omicron – Safety Population................................................373 
Figure 1021: Summary of Breakthrough Infections by PANGO Call and Treatment 
Group, 2 Dose Beta + Omicron – Safety Population................................................373 
Figure 1022: Summary of Breakthrough Infections by PANGO Call and Treatment 
Group, Delta + Omicron – Safety Population ..........................................................373 
Figure 1023: Summary of Breakthrough Infections by PANGO Call and Treatment 
Group, Omicron – Safety Population .......................................................................373 
Figure 1024: Summary of Breakthrough Infections by PANGO Call and Treatment 
Group, Omicron + Prototype – Safety Population....................................................373 
Figure 1025: Maximum Severity of Solicited Systemic Symptoms per Subject by Day 
Post Vaccination and Treatment Group – Dose 1 ....................................................374 
Figure 1026: Maximum Severity of Solicited Systemic Symptoms per Subject by Day 
Post Vaccination and Treatment Group – Dose 2 ....................................................374 
Figure 1027: Maximum Severity of Solicited Local Symptoms per Subject by Day Post 
Vaccination and Treatment Group – Dose 1 ............................................................375 
Figure 1028: Maximum Severity of Solicited Local Symptoms per Subject by Day Post 
Vaccination and Treatment Group – Dose 2 ............................................................375 
Figure 1029: Onset of Solicited Systemic Symptoms by Days Post Vaccination and 
Treatment Group – Dose 1 .......................................................................................376 
Figure 1030: Onset of Solicited Systemic Symptoms by Days Post Vaccination and 
Treatment Group – Dose 2 .......................................................................................377 
Figure 1031: Onset of Solicited Local Symptoms by Days Post Vaccination and 
Treatment Group – Dose 1 .......................................................................................377 
Figure 1032: Onset of Solicited Local Symptoms by Days Post Vaccination and 
Treatment Group – Dose 2 .......................................................................................377 
Figure 1033: Solicited Symptoms by Days Post Vaccination and Treatment Group– 
Arthralgia ..................................................................................................................378 
Figure 1034: Solicited Symptoms by Days Post Vaccination and Treatment Group– 
Chills .........................................................................................................................379 
Figure 1035: Solicited Symptoms by Days Post Vaccination and Treatment Group– 
Erythema ...................................................................................................................379 
Figure 1036: Solicited Symptoms by Days Post Vaccination and Treatment Group– 
Erythema (mm) .........................................................................................................379 
Figure 1037: Solicited Symptoms by Days Post Vaccination and Treatment Group– 
Fatigue ......................................................................................................................379 


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Figure 1038: Solicited Symptoms by Days Post Vaccination and Treatment Group– 
Fever .........................................................................................................................379 
Figure 1039: Solicited Symptoms by Days Post Vaccination and Treatment Group– 
Headache ...................................................................................................................379 
Figure 1040: Solicited Symptoms by Days Post Vaccination and Treatment Group– 
Induration ..................................................................................................................379 
Figure 1041: Solicited Symptoms by Days Post Vaccination and Treatment Group– 
Induration (mm) ........................................................................................................379 
Figure 1042: Solicited Symptoms by Days Post Vaccination and Treatment Group– 
Myalgia .....................................................................................................................379 
Figure 1043: Solicited Symptoms by Days Post Vaccination and Treatment Group– 
Nausea .......................................................................................................................379 
Figure 1044: Solicited Symptoms by Days Post Vaccination and Treatment Group– 
Pain ...........................................................................................................................379 
Figure 1045: Frequency of Adverse Events by MedDRA System Organ Class and 
Severity .....................................................................................................................380 
Figure 1046: Incidence of Adverse Events by MedDRA® System Organ Class and 
Maximum Severity ...................................................................................................381 
 


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10.1 
Disposition of Subjects 
Figure 1: 
CONSORT Flow Diagram 
 
 


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14.2.2 
Immunogenicity Response Figures by Measure, Treatment/Vaccination, and Time Point 
Figure 2: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Prototype, Overall – mITT Population  
[Implementation Note: Below is an example figure. Lines will be shown for each variant. Y-axis label will 
say Area Under the Curve (Log10).] 
 
 
 
 
1
15
29
36
43
57
119
Day Post First Vaccination
10²
10⁴
10⁶
10⁸
Reciprocal Endpoint Titer (S-2P) (Log₁₀)
100 μg ≥71 years
50 μg ≥71 years
25 μg ≥71 years
.
100 μg 56-70 years
50 μg 56-70 years
25 μg 56-70 years
250 μg 18-55 years
100 μg 18-55 years
50 μg 18-55 years
25 μg 18-55 years
.


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Figures with Similar Format: 
Figure 3: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Prototype, Overall – Per Protocol 
Population 
Figure 4: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Prototype, Younger Cohort – mITT 
Population 
Figure 5: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Prototype, Younger Cohort – Per Protocol 
Population 
Figure 6: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Prototype, Older Cohort – mITT 
Population 
Figure 7: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Prototype, Older Cohort – Per Protocol 
Population 
Figure 8: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Prototype, Infected (by Self-Report or N-
protein) Cohort – mITT Population 
Figure 9: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Prototype, Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population 
Figure 10: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Prototype, Uninfected (by Self-Report or N-
protein) Cohort – mITT Population 
Figure 11: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Prototype, Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population 
Figure 12: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Prototype, Younger Infected (by Self-
Report or N-protein) Cohort – mITT Population 
Figure 13: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Prototype, Younger Infected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
Figure 14: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Prototype, Younger Uninfected (by Self-
Report or N-protein) Cohort – mITT Population 
Figure 15: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Prototype, Younger Uninfected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
 


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Figure 16: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Prototype, Older Infected (by Self-Report 
or N-protein) Cohort – mITT Population 
Figure 17: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Prototype, Older Infected (by Self-Report 
or N-protein) Cohort – Per Protocol Population 
Figure 18: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Prototype, Older Uninfected (by Self-
Report or N-protein) Cohort – mITT Population 
Figure 19: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Prototype, Older Uninfected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
Figure 20: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, Overall – mITT 
Population 
Figure 21: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, Overall– Per 
Protocol Population 
Figure 22: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, Younger Cohort – 
mITT Population 
Figure 23: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, Younger Cohort – 
Per Protocol Population 
Figure 24: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, Older Cohort – 
mITT Population 
Figure 25: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, Older Cohort – Per 
Protocol Population 
Figure 26: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, Infected (by Self-
Report or N-protein) Cohort – mITT Population 
Figure 27: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, Infected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
Figure 28: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, Uninfected (by 
Self-Report) Cohort – mITT Population 
 
 


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Figure 29: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, Uninfected (by 
Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 30: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, Younger Infected 
(by Self-Report or N-protein) Cohort – mITT Population 
Figure 31: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, Younger Infected 
(by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 32: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, Younger 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 33: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, Younger 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 34: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, Older Infected (by 
Self-Report or N-protein) Cohort – mITT Population 
Figure 35: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, Older Infected (by 
Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 36: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, Older Uninfected 
(by Self-Report or N-protein) Cohort – mITT Population 
Figure 37: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 1 Dose Beta + Omicron, Older Uninfected 
(by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 38: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Delta + Omicron, Overall – mITT 
Population 
Figure 39: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Delta + Omicron, Overall – Per Protocol 
Population 
Figure 40: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Delta + Omicron, Younger Cohort – mITT 
Population 
Figure 41: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Delta + Omicron, Younger Cohort – Per 
Protocol Population 
 
 


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Figure 42: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Delta + Omicron, Older Cohort – mITT 
Population 
Figure 43: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Delta + Omicron, Older Cohort – Per 
Protocol Population 
Figure 44: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Delta + Omicron, Infected (by Self-Report 
or N-protein) Cohort – mITT Population 
Figure 45: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Delta + Omicron, Infected (by Self-Report 
or N-protein) Cohort – Per Protocol Population 
Figure 46: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Delta + Omicron, Uninfected (by Self-
Report or N-protein) Cohort – mITT Population 
Figure 47: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Delta + Omicron, Uninfected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
Figure 48: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Delta + Omicron, Younger Infected (by 
Self-Report or N-protein) Cohort – mITT Population 
Figure 49: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Delta + Omicron, Younger Infected (by 
Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 50: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Delta + Omicron, Younger Uninfected (by 
Self-Report or N-protein) Cohort – mITT Population 
Figure 51: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Delta + Omicron, Younger Uninfected (by 
Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 52: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Delta + Omicron, Older Infected (by Self-
Report or N-protein) Cohort – mITT Population 
Figure 53: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Delta + Omicron, Older Infected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
Figure 54: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Delta + Omicron, Older Uninfected (by 
Self-Report or N-protein) Cohort – mITT Population 
 
 


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Figure 55: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Delta + Omicron, Older Uninfected (by 
Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 56: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron, Overall– mITT Population 
Figure 57: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron, Overall – Per Protocol 
Population 
Figure 58: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron, Younger Cohort – mITT 
Population 
Figure 59: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron, Younger Cohort – Per Protocol 
Population 
Figure 60: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron, Older Cohort – mITT Population 
Figure 61: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron, Older Cohort – Per Protocol 
Population 
Figure 62: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron, Infected (by Self-Report or N-
protein) Cohort – mITT Population 
Figure 63: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron, Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population 
Figure 64: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron, Uninfected (by Self-Report or N-
protein) Cohort – mITT Population 
Figure 65: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron, Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population 
Figure 66: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron, Younger Infected (by Self-Report 
or N-protein) Cohort – mITT Population 
Figure 67: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron, Younger Infected (by Self-Report 
or N-protein) Cohort – Per Protocol Population 
Figure 68: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron, Younger Uninfected (by Self-
Report or N-protein) Cohort – mITT Population 
 


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Figure 69: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron, Younger Uninfected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
Figure 70: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron, Older Infected (by Self-Report or 
N-protein) Cohort – mITT Population 
Figure 71: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron, Older Infected (by Self-Report or 
N-protein) Cohort – Per Protocol Population 
Figure 72: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron, Older Uninfected (by Self-Report 
or N-protein) Cohort – mITT Population 
Figure 73: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron, Older Uninfected (by Self-Report 
or N-protein) Cohort – Per Protocol Population 
Figure 74: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron + Prototype, Overall– mITT 
Population 
Figure 75: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron + Prototype, Overall– Per 
Protocol Population 
Figure 76: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron + Prototype, Younger Cohort – 
mITT Population 
Figure 77: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron + Prototype, Younger Cohort – 
Per Protocol Population 
Figure 78: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron + Prototype, Older Cohort – 
mITT Population 
Figure 79: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron + Prototype, Older Cohort – Per 
Protocol Population 
Figure 80: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron + Prototype, Infected (by Self-
Report or N-protein) Cohort – mITT Population 
Figure 81: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron + Prototype, Infected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
 
 


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Figure 82: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron + Prototype, Uninfected (by Self-
Report or N-protein) Cohort – mITT Population 
Figure 83: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron + Prototype, Uninfected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
Figure 84: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron + Prototype, Younger Infected (by 
Self-Report or N-protein) Cohort – mITT Population 
Figure 85: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron + Prototype, Younger Infected (by 
Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 86: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron + Prototype, Younger Uninfected 
(by Self-Report or N-protein) Cohort – mITT Population 
Figure 87: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron + Prototype, Younger Uninfected 
(by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 88: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron + Prototype, Older Infected (by 
Self-Report or N-protein) Cohort – mITT Population 
Figure 89: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron + Prototype, Older Infected (by 
Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 90: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron + Prototype, Older Uninfected (by 
Self-Report or N-protein) Cohort – mITT Population 
Figure 91: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, Omicron + Prototype, Older Uninfected (by 
Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 92: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, Overall– mITT 
Population 
Figure 93: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, Overall– Per 
Protocol Population 
Figure 94: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, Younger Cohort – 
mITT Population 
 
 


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Figure 95: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, Younger Cohort – 
Per Protocol Population 
Figure 96: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, Older Cohort – 
mITT Population 
Figure 97: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, Older Cohort – Per 
Protocol Population 
Figure 98: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, Infected (by Self-
Report or N-protein) Cohort – mITT Population 
Figure 99: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, Infected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
Figure 100: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, Uninfected (by 
Self-Report or N-protein) Cohort – mITT Population 
Figure 101: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, Uninfected (by 
Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 102: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, Younger Infected 
(by Self-Report or N-protein) Cohort – mITT Population 
Figure 103: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, Younger Infected 
(by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 104: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, Younger 
Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 105: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, Younger 
Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 106: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, Older Infected (by 
Self-Report or N-protein) Cohort – mITT Population 
Figure 107: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, Older Infected (by 
Self-Report or N-protein) Cohort – Per Protocol Population 
 
 


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Figure 108: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, Older Uninfected 
(by Self-Report or N-protein) Cohort – mITT Population 
Figure 109: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Geometric Mean by Time Point and Variant, 2 Dose Beta + Omicron, Older Uninfected 
(by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 110: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Prototype, Overall – mITT Population 
Figure 111: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Prototype, Overall – Per Protocol Population 
Figure 112: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Prototype, Younger Cohort – mITT Population 
Figure 113: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Prototype, Younger Cohort – Per Protocol Population 
Figure 114: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Prototype, Older Cohort – mITT Population 
Figure 115: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Prototype, Older Cohort – Per Protocol Population 
Figure 116: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Prototype, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 117: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Prototype, Infected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 118: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Prototype, Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 119: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Prototype, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 120: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Prototype, Younger Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 121: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Prototype, Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 122: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Prototype, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 123: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Prototype, Younger Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 124: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Prototype, Older Infected (by Self-Report or N-protein) Cohort – mITT Population 
 
 


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Figure 125: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Prototype, Older Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 126: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 127: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 128: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Overall– mITT Population 
Figure 129: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Overall– Per Protocol Population 
Figure 130: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Younger Cohort – mITT Population 
Figure 131: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Younger Cohort – Per Protocol Population 
Figure 132: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Older Cohort – mITT Population 
Figure 133: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Older Cohort – Per Protocol Population 
Figure 134: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 135: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 136: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 137: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 138: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 139: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 140: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 


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Figure 141: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 142: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 143: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 144: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 145: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 146: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Overall– mITT Population 
Figure 147: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Overall – Per Protocol Population 
Figure 148: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Younger Cohort – mITT Population 
Figure 149: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Younger Cohort – Per Protocol Population 
Figure 150: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Older Cohort – mITT Population 
Figure 151: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Older Cohort – Per Protocol Population 
Figure 152: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 153: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 154: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 155: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 156: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – mITT 
Population 


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Figure 157: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 158: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 159: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 160: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 161: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 162: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 163: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 164: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron, Overall– mITT Population 
Figure 165: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron, Overall – Per Protocol Population 
Figure 166: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron, Younger Cohort – mITT Population 
Figure 167: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron, Younger Cohort – Per Protocol Population 
Figure 168: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron, Older Cohort – mITT Population 
Figure 169: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron, Older Cohort – Per Protocol Population 
Figure 170: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 171: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron, Infected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 172: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron, Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
 


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Figure 173: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 174: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron, Younger Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 175: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron, Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 176: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 177: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 178: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron, Older Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 179: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron, Older Infected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 180: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 181: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 182: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Overall – mITT Population 
Figure 183: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Overall – Per Protocol Population 
Figure 184: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Younger Cohort – mITT Population 
Figure 185: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Younger Cohort – Per Protocol Population 
Figure 186: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Older Cohort – mITT Population 
Figure 187: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Older Cohort – Per Protocol Population 
Figure 188: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 189: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
 
 


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Figure 190: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 191: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 192: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Younger Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 193: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Younger Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 194: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 195: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Younger Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 196: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Older Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 197: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Older Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 198: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 199: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 200: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Overall – mITT PopulationFigure 201: Pseudovirus 
Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 2 Dose Beta + 
Omicron, Overall – Per Protocol Population 
Figure 202: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Younger Cohort – mITT Population 
Figure 203: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Younger Cohort – Per Protocol Population 
Figure 204: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Older Cohort – mITT Population 
Figure 205: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 2 


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Dose Beta + Omicron, Older Cohort – Per Protocol Population 
Figure 206: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 207: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 208: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 209: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 210: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 211: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 212: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 213: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 214: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 215: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 216: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 217: 
Pseudovirus Neutralization Assay ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 218: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Prototype, Overall– mITT Population 
 
 


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Figure 219: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Prototype, Overall– Per Protocol Population 
Figure 220: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Prototype, Younger Cohort – mITT Population 
Figure 221: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Prototype, Younger Cohort – Per Protocol Population 
Figure 222: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Prototype, Older Cohort – mITT Population 
Figure 223: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Prototype, Older Cohort – Per Protocol Population 
Figure 224: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Prototype, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 225: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Prototype, Infected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 226: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Prototype, Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 227: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Prototype, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 228: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Prototype, Younger Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 229: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Prototype, Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 230: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Prototype, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 231: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Prototype, Younger Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 232: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Prototype, Older Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 233: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Prototype, Older Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 234: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 235: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
 
 


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Figure 236: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Overall – mITT Population 
Figure 237: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Overall – Per Protocol Population 
Figure 238: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Younger Cohort – mITT Population 
Figure 239: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Younger Cohort – Per Protocol Population 
Figure 240: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Older Cohort – mITT Population 
Figure 241: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Older Cohort – Per Protocol Population 
Figure 242: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 243: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 244: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 245: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 246: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 247: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 248: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 249: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 250: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
 
 


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Figure 251: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 252: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 253: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 1 
Dose Beta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 254: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Overall – mITT Population 
Figure 255: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Overall – Per Protocol Population 
Figure 256: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Younger Cohort – mITT Population 
Figure 257: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Younger Cohort – Per Protocol Population 
Figure 258: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Older Cohort – mITT Population 
Figure 259: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Older Cohort – Per Protocol Population 
Figure 260: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 261: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 262: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 263: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 264: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 265: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 266: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 


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Figure 267: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 268: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 269: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 270: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 271: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Delta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 272: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron, Overall – mITT Population 
Figure 273: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron, Overall – Per Protocol Population 
Figure 274: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron, Younger Cohort – mITT Population 
Figure 275: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron, Younger Cohort – Per Protocol Population 
Figure 276: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron, Older Cohort – mITT Population 
Figure 277: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron, Older Cohort – Per Protocol Population 
Figure 278: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 279: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron, Infected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 280: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron, Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 281: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 282: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron, Younger Infected (by Self-Report or N-protein) Cohort – mITT Population 
 
 


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Figure 283: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron, Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 284: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 285: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 286: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron, Older Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 287: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron, Older Infected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 288: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 289: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 290: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Overall – mITT Population 
Figure 291: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Overall – Per Protocol Population 
Figure 292: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Younger Cohort – mITT Population 
Figure 293: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Younger Cohort – Per Protocol Population 
Figure 294: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Older Cohort – mITT Population 
Figure 295: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Older Cohort – Per Protocol Population 
Figure 296: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 297: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 298: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
 
 


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Figure 299: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 300: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Younger Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 301: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Younger Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 302: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 303: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Younger Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 304: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Older Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 305: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Older Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 306: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 307: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 
Omicron + Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 308: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Overall – mITT Population 
Figure 309: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Overall – Per Protocol Population 
Figure 310: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Younger Cohort – mITT Population 
Figure 311: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Younger Cohort – Per Protocol Population 
Figure 312: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Older Cohort – mITT Population 
Figure 313: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Older Cohort – Per Protocol Population 
 
 


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Figure 314: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 315: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 316: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 317: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 318: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 319: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 320: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 321: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 322: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 323: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 324: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 325: 
Focus Reduction Neutralization Test ID50 Geometric Mean by Time Point and Variant, 2 
Dose Beta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
 
 


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Figure 326: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Prototype, Overall – mITT Population  
[Implementation Note: Below is an example figure. Group boxplots by variant instead of by treatment arm as 
in the example figure. Y-axis label will say Area Under the Curve (Log10). Include lines to connect points 
between each box plot over time (the lines will connect the points for a subject).] 
 
 
Figures with Similar Format: 
Figure 327: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Prototype, Overall – Per Protocol Population 
Figure 328: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Prototype, Younger Cohort – mITT Population 
Figure 329: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Prototype, Younger Cohort – Per Protocol 
Population 
Figure 330: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Prototype, Older Cohort – mITT Population 
0
10
10²
10³
10⁴
10⁵
10⁶
10⁷
10⁸
Reciprocal Endpoint Titer (S-2P)
1
15
29
36
43
57
119
1
15
29
36
43
57
1
15
29
36
43
57
119
1
15
29
36
43
57
119
Convalescent
25 μg
(18-55 years)
50 μg
(18-55 years)
100 μg
(18-55 years)
250 μg
(18-55 years)
Study Day


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Figure 331: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Prototype, Older Cohort – Per Protocol 
Population 
Figure 332: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Prototype, Infected (by Self-Report or N-
protein) Cohort – mITT Population 
Figure 333: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Prototype, Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population 
Figure 334: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Prototype, Uninfected (by Self-Report or N-
protein) Cohort – mITT Population 
Figure 335: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Prototype, Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population 
Figure 336: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Prototype, Younger Infected (by Self-Report or 
N-protein) Cohort – mITT Population 
Figure 337: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Prototype, Younger Infected (by Self-Report or 
N-protein) Cohort – Per Protocol Population 
Figure 338: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Prototype, Younger Uninfected (by Self-Report 
or N-protein) Cohort – mITT Population 
Figure 339: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Prototype, Younger Uninfected (by Self-Report 
or N-protein) Cohort – Per Protocol Population 
Figure 340: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Prototype, Older Infected (by Self-Report or N-
protein) Cohort – mITT Population 
Figure 341: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Prototype, Older Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population 
Figure 342: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Prototype, Older Uninfected (by Self-Report or 
N-protein) Cohort – mITT Population 
Figure 343: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Prototype, Older Uninfected (by Self-Report or 
N-protein) Cohort – Per Protocol Population 


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Figure 344: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 1 Dose Beta + Omicron, Overall – mITT 
Population 
Figure 345: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 1 Dose Beta + Omicron, Overall– Per Protocol 
Population 
Figure 346: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 1 Dose Beta + Omicron, Younger Cohort – 
mITT Population 
Figure 347: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 1 Dose Beta + Omicron, Younger Cohort – Per 
Protocol Population 
Figure 348: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 1 Dose Beta + Omicron, Older Cohort – mITT 
Population 
Figure 349: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 1 Dose Beta + Omicron, Older Cohort – Per 
Protocol Population 
Figure 350: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 1 Dose Beta + Omicron, Infected (by Self-Report 
or N-protein) Cohort – mITT Population 
Figure 351: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 1 Dose Beta + Omicron, Infected (by Self-Report 
or N-protein) Cohort – Per Protocol Population 
Figure 352: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 1 Dose Beta + Omicron, Uninfected (by Self-
Report or N-protein) Cohort – mITT Population 
Figure 353: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 1 Dose Beta + Omicron, Uninfected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
Figure 354: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 1 Dose Beta + Omicron, Younger Infected (by 
Self-Report or N-protein) Cohort – mITT Population 
Figure 355: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 1 Dose Beta + Omicron, Younger Infected (by 
Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 356: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 1 Dose Beta + Omicron, Younger Uninfected (by 
Self-Report or N-protein) Cohort – mITT Population 


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Figure 357: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 1 Dose Beta + Omicron, Younger Uninfected (by 
Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 358: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 1 Dose Beta + Omicron, Older Infected (by Self-
Report or N-protein) Cohort – mITT Population 
Figure 359: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 1 Dose Beta + Omicron, Older Infected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
Figure 360: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 1 Dose Beta + Omicron, Older Uninfected (by 
Self-Report or N-protein) Cohort – mITT Population 
Figure 361: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 1 Dose Beta + Omicron, Older Uninfected (by 
Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 362: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Delta + Omicron, Overall – mITT Population 
Figure 363: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Delta + Omicron, Overall – Per Protocol 
Population 
Figure 364: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Delta + Omicron, Younger Cohort – mITT 
Population 
Figure 365: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Delta + Omicron, Younger Cohort – Per 
Protocol Population 
Figure 366: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Delta + Omicron, Older Cohort – mITT 
Population 
Figure 367: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Delta + Omicron, Older Cohort – Per Protocol 
Population 
Figure 368: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Delta + Omicron, Infected (by Self-Report or N-
protein) Cohort – mITT Population 
Figure 369: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Delta + Omicron, Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population 
Figure 370: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Delta + Omicron, Uninfected (by Self-Report or 
N-protein) Cohort – mITT Population 


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Figure 371: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Delta + Omicron, Uninfected (by Self-Report or 
N-protein) Cohort – Per Protocol Population 
Figure 372: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Delta + Omicron, Younger Infected (by Self-
Report or N-protein) Cohort – mITT Population 
Figure 373: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Delta + Omicron, Younger Infected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
Figure 374: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Delta + Omicron, Younger Uninfected (by Self-
Report or N-protein) Cohort – mITT Population 
Figure 375: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Delta + Omicron, Younger Uninfected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
Figure 376: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Delta + Omicron, Older Infected (by Self-
Report or N-protein) Cohort – mITT Population 
Figure 377: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Delta + Omicron, Older Infected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
Figure 378: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Delta + Omicron, Older Uninfected (by Self-
Report or N-protein) Cohort – mITT Population 
Figure 379: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Delta + Omicron, Older Uninfected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
Figure 380: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron, Overall– mITT Population 
Figure 381: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron, Overall – Per Protocol Population 
Figure 382: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron, Younger Cohort – mITT Population 
Figure 383: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron, Younger Cohort – Per Protocol 
Population 
Figure 384: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron, Older Cohort – mITT Population 
Figure 385: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron, Older Cohort – Per Protocol 
Population 


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Figure 386: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron, Infected (by Self-Report or N-protein) 
Cohort – mITT Population 
Figure 387: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron, Infected (by Self-Report or N-protein) 
Cohort – Per Protocol Population 
Figure 388: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron, Uninfected (by Self-Report or N-
protein) Cohort – mITT Population 
Figure 389: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron, Uninfected (by Self-Report or N-
protein) Cohort – Per Protocol Population 
Figure 390: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron, Younger Infected (by Self-Report or 
N-protein) Cohort – mITT Population 
Figure 391: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron, Younger Infected (by Self-Report or 
N-protein) Cohort – Per Protocol Population 
Figure 392: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron, Younger Uninfected (by Self-Report 
or N-protein) Cohort – mITT Population 
Figure 393: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron, Younger Uninfected (by Self-Report 
or N-protein) Cohort – Per Protocol Population 
Figure 394: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron, Older Infected (by Self-Report or N-
protein) Cohort – mITT Population 
Figure 395: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron, Older Infected (by Self-Report or N-
protein) Cohort – Per Protocol Population 
Figure 396: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron, Older Uninfected (by Self-Report or 
N-protein) Cohort – mITT Population 
Figure 397: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron, Older Uninfected (by Self-Report or 
N-protein) Cohort – Per Protocol Population 
Figure 398: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron + Prototype, Overall– mITT 
Population 


Statistical Analysis Plan - DMID Protocol: 22-0004  
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Figure 399: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron + Prototype, Overall– Per Protocol 
Population 
Figure 400: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron + Prototype, Younger Cohort – mITT 
Population 
Figure 401: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron + Prototype, Younger Cohort – Per 
Protocol Population 
Figure 402: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron + Prototype, Older Cohort – mITT 
Population 
Figure 403: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron + Prototype, Older Cohort – Per 
Protocol Population 
Figure 404: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron + Prototype, Infected (by Self-Report 
or N-protein) Cohort – mITT Population 
Figure 405: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron + Prototype, Infected (by Self-Report 
or N-protein) Cohort – Per Protocol Population 
Figure 406: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron + Prototype, Uninfected (by Self-
Report or N-protein) Cohort – mITT Population 
Figure 407: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron + Prototype, Uninfected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
Figure 408: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron + Prototype, Younger Infected (by 
Self-Report or N-protein) Cohort – mITT Population 
Figure 409: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron + Prototype, Younger Infected (by 
Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 410: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron + Prototype, Younger Uninfected (by 
Self-Report or N-protein) Cohort – mITT Population 
Figure 411: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron + Prototype, Younger Uninfected (by 
Self-Report or N-protein) Cohort – Per Protocol Population 


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Figure 412: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron + Prototype, Older Infected (by Self-
Report or N-protein) Cohort – mITT Population 
Figure 413: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron + Prototype, Older Infected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
Figure 414: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron + Prototype, Older Uninfected (by 
Self-Report or N-protein) Cohort – mITT Population 
Figure 415: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, Omicron + Prototype, Older Uninfected (by 
Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 416: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 2 Dose Beta + Omicron, Overall– mITT 
Population 
Figure 417: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 2 Dose Beta + Omicron, Overall– Per Protocol 
Population 
Figure 418: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 2 Dose Beta + Omicron, Younger Cohort – 
mITT Population 
Figure 419: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 2 Dose Beta + Omicron, Younger Cohort – Per 
Protocol Population 
Figure 420: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 2 Dose Beta + Omicron, Older Cohort – mITT 
Population 
Figure 421: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 2 Dose Beta + Omicron, Older Cohort – Per 
Protocol Population 
Figure 422: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 2 Dose Beta + Omicron, Infected (by Self-Report 
or N-protein) Cohort – mITT Population 
Figure 423: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 2 Dose Beta + Omicron, Infected (by Self-Report 
or N-protein) Cohort – Per Protocol Population 
Figure 424: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 2 Dose Beta + Omicron, Uninfected (by Self-
Report or N-protein) Cohort – mITT Population 


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Figure 425: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 2 Dose Beta + Omicron, Uninfected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
Figure 426: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 2 Dose Beta + Omicron, Younger Infected (by 
Self-Report or N-protein) Cohort – mITT Population 
Figure 427: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 2 Dose Beta + Omicron, Younger Infected (by 
Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 428: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 2 Dose Beta + Omicron, Younger Uninfected (by 
Self-Report or N-protein) Cohort – mITT Population 
Figure 429: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 2 Dose Beta + Omicron, Younger Uninfected (by 
Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 430: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 2 Dose Beta + Omicron, Older Infected (by Self-
Report or N-protein) Cohort – mITT Population 
Figure 431: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 2 Dose Beta + Omicron, Older Infected (by Self-
Report or N-protein) Cohort – Per Protocol Population 
Figure 432: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 2 Dose Beta + Omicron, Older Uninfected (by 
Self-Report or N-protein) Cohort – mITT Population 
Figure 433: 
Serum IgG Binding Assay Area Under the Curve Measured by ECLIA 10-plex 
Distribution by Time Point and Variant, 2 Dose Beta + Omicron, Older Uninfected (by 
Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 434: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Prototype, Overall – mITT Population 
Figure 435: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Prototype, Overall – Per Protocol Population 
Figure 436: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Prototype, Younger Cohort – mITT Population 
Figure 437: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Prototype, Younger Cohort – Per Protocol Population 
Figure 438: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Prototype, Older Cohort – mITT Population 
Figure 439: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Prototype, Older Cohort – Per Protocol Population 


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Figure 440: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Prototype, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 441: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Prototype, Infected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 442: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Prototype, Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 443: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Prototype, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 444: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Prototype, Younger Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 445: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Prototype, Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 446: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Prototype, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 447: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Prototype, Younger Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 448: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Prototype, Older Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 449: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Prototype, Older Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 450: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 451: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 452: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Overall– mITT Population 
Figure 453: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Overall– Per Protocol Population 
Figure 454: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Younger Cohort – mITT Population 
Figure 455: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Younger Cohort – Per Protocol Population 
Figure 456: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Older Cohort – mITT Population 


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Figure 457: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Older Cohort – Per Protocol Population 
Figure 458: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 459: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Infected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 460: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 461: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 462: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 463: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 464: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 465: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 466: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 467: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 468: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 469: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 470: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Delta + 
Omicron, Overall– mITT Population 
Figure 471: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Delta + 
Omicron, Overall – Per Protocol Population 
Figure 472: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Delta + 
Omicron, Younger Cohort – mITT Population 


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Figure 473: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Delta + 
Omicron, Younger Cohort – Per Protocol Population 
Figure 474: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Delta + 
Omicron, Older Cohort – mITT Population 
Figure 475: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Delta + 
Omicron, Older Cohort – Per Protocol Population 
Figure 476: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Delta + 
Omicron, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 477: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Delta + 
Omicron, Infected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 478: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Delta + 
Omicron, Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 479: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Delta + 
Omicron, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 480: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Delta + 
Omicron, Younger Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 481: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Delta + 
Omicron, Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 482: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Delta + 
Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 483: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Delta + 
Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 484: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Delta + 
Omicron, Older Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 485: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Delta + 
Omicron, Older Infected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 486: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Delta + 
Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 487: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Delta + 
Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 488: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Omicron, Overall– mITT Population 
Figure 489: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Omicron, Overall – Per Protocol Population 
Figure 490: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Omicron, Younger Cohort – mITT Population 


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Figure 491: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Omicron, Younger Cohort – Per Protocol Population 
Figure 492: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Omicron, Older Cohort – mITT Population 
Figure 493: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Omicron, Older Cohort – Per Protocol Population 
Figure 494: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Omicron, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 495: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Omicron, Infected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 496: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Omicron, Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 497: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Omicron, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 498: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Omicron, Younger Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 499: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Omicron, Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 500: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 501: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 502: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Omicron, Older Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 503: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Omicron, Older Infected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 504: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 505: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 
Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 506: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Omicron 
+ Prototype, Overall – mITT Population 
Figure 507: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Omicron 
+ Prototype, Overall – Per Protocol Population 
Figure 508: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Omicron 
+ Prototype, Younger Cohort – mITT Population 


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Figure 509: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Omicron 
+ Prototype, Younger Cohort – Per Protocol Population 
Figure 510: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Omicron 
+ Prototype, Older Cohort – mITT Population 
Figure 511: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Omicron 
+ Prototype, Older Cohort – Per Protocol Population 
Figure 512: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Omicron 
+ Prototype, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 513: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Omicron 
+ Prototype, Infected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 514: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Omicron 
+ Prototype, Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 515: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Omicron 
+ Prototype, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 516: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Omicron 
+ Prototype, Younger Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 517: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Omicron 
+ Prototype, Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 518: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Omicron 
+ Prototype, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 519: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Omicron 
+ Prototype, Younger Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 520: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Omicron 
+ Prototype, Older Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 521: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Omicron 
+ Prototype, Older Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 522: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Omicron 
+ Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 523: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, Omicron 
+ Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 524: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Overall – mITT PopulationFigure 525: Pseudovirus Neutralization 
Assay ID50 Distribution by Time Point and Variant, 2 Dose Beta + Omicron, Overall – 
Per Protocol Population 


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Figure 526: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Younger Cohort – mITT Population 
Figure 527: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Younger Cohort – Per Protocol Population 
Figure 528: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Older Cohort – mITT Population 
Figure 529: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Older Cohort – Per Protocol Population 
Figure 530: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 531: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Infected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 532: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 533: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 534: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 535: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 536: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 537: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 538: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 539: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 540: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 541: 
Pseudovirus Neutralization Assay ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 


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Figure 542: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Prototype, Overall– mITT Population 
Figure 543: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Prototype, Overall– Per Protocol Population 
Figure 544: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Prototype, Younger Cohort – mITT Population 
Figure 545: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Prototype, Younger Cohort – Per Protocol Population 
Figure 546: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Prototype, Older Cohort – mITT Population 
Figure 547: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Prototype, Older Cohort – Per Protocol Population 
Figure 548: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Prototype, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 549: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Prototype, Infected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 550: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Prototype, Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 551: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Prototype, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 552: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Prototype, Younger Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 553: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Prototype, Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 554: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Prototype, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 555: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Prototype, Younger Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 556: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Prototype, Older Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 557: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Prototype, Older Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 558: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – mITT Population 


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Figure 559: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 560: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Overall – mITT Population 
Figure 561: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Overall – Per Protocol Population 
Figure 562: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Younger Cohort – mITT Population 
Figure 563: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Younger Cohort – Per Protocol Population 
Figure 564: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Older Cohort – mITT Population 
Figure 565: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Older Cohort – Per Protocol Population 
Figure 566: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 567: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Infected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 568: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 569: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 570: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 571: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 572: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 573: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 574: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – mITT Population 


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Figure 575: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 576: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 577: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 1 Dose 
Beta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 578: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, Delta 
+ Omicron, Overall – mITT Population 
Figure 579: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, Delta 
+ Omicron, Overall – Per Protocol Population 
Figure 580: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, Delta 
+ Omicron, Younger Cohort – mITT Population 
Figure 581: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, Delta 
+ Omicron, Younger Cohort – Per Protocol Population 
Figure 582: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, Delta 
+ Omicron, Older Cohort – mITT Population 
Figure 583: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, Delta 
+ Omicron, Older Cohort – Per Protocol Population 
Figure 584: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, Delta 
+ Omicron, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 585: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, Delta 
+ Omicron, Infected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 586: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, Delta 
+ Omicron, Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 587: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, Delta 
+ Omicron, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 588: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, Delta 
+ Omicron, Younger Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 589: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, Delta 
+ Omicron, Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 590: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, Delta 
+ Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 591: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, Delta 
+ Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 


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Figure 592: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, Delta 
+ Omicron, Older Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 593: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, Delta 
+ Omicron, Older Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 594: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, Delta 
+ Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 595: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, Delta 
+ Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 596: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron, Overall – mITT Population 
Figure 597: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron, Overall – Per Protocol Population 
Figure 598: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron, Younger Cohort – mITT Population 
Figure 599: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron, Younger Cohort – Per Protocol Population 
Figure 600: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron, Older Cohort – mITT Population 
Figure 601: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron, Older Cohort – Per Protocol Population 
Figure 602: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 603: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron, Infected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 604: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron, Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 605: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 606: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron, Younger Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 607: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron, Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 608: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT Population 


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Figure 609: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 610: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron, Older Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 611: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron, Older Infected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 612: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 613: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 614: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron + Prototype, Overall – mITT Population 
Figure 615: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron + Prototype, Overall – Per Protocol Population 
Figure 616: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron + Prototype, Younger Cohort – mITT Population 
Figure 617: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron + Prototype, Younger Cohort – Per Protocol Population 
Figure 618: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron + Prototype, Older Cohort – mITT Population 
Figure 619: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron + Prototype, Older Cohort – Per Protocol Population 
Figure 620: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron + Prototype, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 621: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron + Prototype, Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 622: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron + Prototype, Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 623: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron + Prototype, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 624: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron + Prototype, Younger Infected (by Self-Report or N-protein) Cohort – mITT 
Population 


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Figure 625: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron + Prototype, Younger Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 626: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron + Prototype, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 627: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron + Prototype, Younger Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 628: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron + Prototype, Older Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 629: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron + Prototype, Older Infected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 630: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron + Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 631: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 
Omicron + Prototype, Older Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 632: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Overall – mITT Population 
Figure 633: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Overall – Per Protocol Population 
Figure 634: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Younger Cohort – mITT Population 
Figure 635: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Younger Cohort – Per Protocol Population 
Figure 636: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Older Cohort – mITT Population 
Figure 637: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Older Cohort – Per Protocol Population 
Figure 638: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 639: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Infected (by Self-Report or N-protein) Cohort – Per Protocol Population 
Figure 640: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – mITT Population 


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Figure 641: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 642: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 643: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Younger Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 644: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 645: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Younger Uninfected (by Self-Report or N-protein) Cohort – Per 
Protocol Population 
Figure 646: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – mITT Population 
Figure 647: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Older Infected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
Figure 648: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – mITT 
Population 
Figure 649: 
Focus Reduction Neutralization Test ID50 Distribution by Time Point and Variant, 2 Dose 
Beta + Omicron, Older Uninfected (by Self-Report or N-protein) Cohort – Per Protocol 
Population 
 
 


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Figure 650: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, Overall - mITT 
Population 
 
Implementation Note: 
Figure shown is an example. Have one plot for each of the 6 treatment arms. Along the x-axis should be each 
of the study days (Days 1, 15, 91, 181, and 271 for 1 dose treatment arms and Days 1, 15, 57, 71, 147, 237, 
and 327 for 2 dose treatment arms). 
Figures with Similar Format: 
Figure 651: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, Overall - Per 
Protocol Population 
Figure 652: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, Overall - mITT 
Population 
Figure 653: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, Overall - Per 
Protocol Population 
Figure 654: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, Overall - mITT 
Population 
Figure 655: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, Overall - Per 
Protocol Population 
Figure 656: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, Overall - mITT 
Population 
Figure 657: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, Overall - Per 
Protocol Population 
 
0.0
0.4
0.8
1.2
Day 1
Day 29
Day 43
% CD4 T cells
18-55 years
25 μg
0.0
0.4
0.8
1.2
Day 1
Day 29
Day 43
56-70 years
25 μg
0.0
0.4
0.8
1.2
Day 1
Day 29
Day 43
≥ 71 years
25 μg
0.0
0.4
0.8
1.2
Day 1
Day 29
Day 43
% CD4 T cells
18-55 years
100 μg
0.0
0.4
0.8
1.2
Day 1
Day 29
Day 43
56-70 years
100 μg
0.0
0.4
0.8
1.2
Day 1
Day 29
Day 43
≥ 71 years
100 μg
Any Th1 Response
IFN-γ
IL-2
TNF


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Figure 658: 
Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Overall - mITT 
Population 
Figure 659: 
Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Overall - Per Protocol 
Population 
Figure 660: 
Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Overall - mITT 
Population 
Figure 661: 
Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Overall - Per Protocol 
Population 
Figure 662: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, Younger Cohort - 
mITT Population 
Figure 663: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, Younger Cohort - 
Per Protocol Population 
Figure 664: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, Younger Cohort - 
mITT Population 
Figure 665: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, Younger Cohort - 
Per Protocol Population 
Figure 666: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, Younger Cohort - 
mITT Population 
Figure 667: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, Younger Cohort - 
Per Protocol Population 
Figure 668: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, Younger Cohort - 
mITT Population 
Figure 669: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, Younger Cohort - 
Per Protocol Population 
Figure 670: 
Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Younger Cohort - 
mITT Population 
Figure 671: 
Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Younger Cohort - Per 
Protocol Population 
Figure 672: 
Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Younger Cohort - 
mITT Population 
Figure 673: 
Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Younger Cohort - Per 
Protocol Population 
Figure 674: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, Older Cohort - 
mITT Population 
Figure 675: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, Older Cohort - 
Per Protocol Population 
Figure 676: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, Older Cohort - 
mITT Population 


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Figure 677: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, Older Cohort - 
Per Protocol Population 
Figure 678: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, Older Cohort - 
mITT Population 
Figure 679: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, Older Cohort - 
Per Protocol Population 
Figure 680: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, Older Cohort - 
mITT Population 
Figure 681: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, Older Cohort - 
Per Protocol Population 
Figure 682: 
Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Older Cohort - mITT 
Population 
Figure 683: 
Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Older Cohort - Per 
Protocol Population 
Figure 684: 
Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Older Cohort - mITT 
Population 
Figure 685: 
Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Older Cohort - Per 
Protocol Population 
Figure 686: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, Infected (by Self-
Report and N-protein) Cohort - mITT Population 
Figure 687: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, Infected (by Self-
Report and N-protein) Cohort - Per Protocol Population 
Figure 688: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, Infected (by Self-
Report and N-protein) Cohort - mITT Population 
Figure 689: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, Infected (by Self-
Report and N-protein) Cohort - Per Protocol Population 
Figure 690: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, Infected (by Self-
Report and N-protein) Cohort - mITT Population 
Figure 691: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, Infected (by Self-
Report and N-protein) Cohort - Per Protocol Population 
Figure 692: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, Infected (by Self-
Report and N-protein) Cohort - mITT Population 
Figure 693: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, Infected (by Self-
Report and N-protein) Cohort - Per Protocol Population 
Figure 694: 
Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Infected (by Self-
Report and N-protein) Cohort - mITT Population 
Figure 695: 
Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Infected (by Self-
Report and N-protein) Cohort - Per Protocol Population 


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Figure 696: 
Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Infected (by Self-
Report and N-protein) Cohort - mITT Population 
Figure 697: 
Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Infected (by Self-
Report and N-protein) Cohort - Per Protocol Population 
Figure 698: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, Uninfected (by 
Self-Report and N-protein) Cohort - mITT Population 
Figure 699: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, Uninfected (by 
Self-Report and N-protein) Cohort - Per Protocol Population 
Figure 700: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, Uninfected (by 
Self-Report and N-protein) Cohort - mITT Population 
Figure 701: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, Uninfected (by 
Self-Report and N-protein) Cohort - Per Protocol Population 
Figure 702: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, Uninfected (by 
Self-Report and N-protein) Cohort - mITT Population 
Figure 703: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, Uninfected (by 
Self-Report and N-protein) Cohort - Per Protocol Population 
Figure 704: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, Uninfected (by 
Self-Report and N-protein) Cohort - mITT Population 
Figure 705: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, Uninfected (by 
Self-Report and N-protein) Cohort - Per Protocol Population 
Figure 706: 
Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Uninfected (by Self-
Report and N-protein) Cohort - mITT Population 
Figure 707: 
Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Uninfected (by Self-
Report and N-protein) Cohort - Per Protocol Population 
Figure 708: 
Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Uninfected (by Self-
Report and N-protein) Cohort - mITT Population 
Figure 709: 
Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Uninfected (by Self-
Report and N-protein) Cohort - Per Protocol Population 
Figure 710: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, Younger Infected 
(by Self-Report and N-protein) Cohort - mITT Population 
Figure 711: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, Younger Infected 
(by Self-Report and N-protein) Cohort - Per Protocol Population 
Figure 712: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, Younger Infected 
(by Self-Report and N-protein) Cohort - mITT Population 
Figure 713: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, Younger Infected 
(by Self-Report and N-protein) Cohort - Per Protocol Population 
Figure 714: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, Younger Infected 
(by Self-Report and N-protein) Cohort - mITT Population 


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Figure 715: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, Younger Infected 
(by Self-Report and N-protein) Cohort - Per Protocol Population 
Figure 716: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, Younger Infected 
(by Self-Report and N-protein) Cohort - mITT Population 
Figure 717: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, Younger Infected 
(by Self-Report and N-protein) Cohort - Per Protocol Population 
Figure 718: 
Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Younger Infected (by 
Self-Report and N-protein) Cohort - mITT Population 
Figure 719: 
Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Younger Infected (by 
Self-Report and N-protein) Cohort - Per Protocol Population 
Figure 720: 
Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Younger Infected (by 
Self-Report and N-protein) Cohort - mITT Population 
Figure 721: 
Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Younger Infected (by 
Self-Report and N-protein) Cohort - Per Protocol Population 
Figure 722: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, Older Infected 
(by Self-Report and N-protein) Cohort - mITT Population 
Figure 723: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, Older Infected 
(by Self-Report and N-protein) Cohort - Per Protocol Population 
Figure 724: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, Older Infected 
(by Self-Report and N-protein) Cohort - mITT Population 
Figure 725: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, Older Infected 
(by Self-Report and N-protein) Cohort - Per Protocol Population 
Figure 726: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, Older Infected 
(by Self-Report and N-protein) Cohort - mITT Population 
Figure 727: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, Older Infected 
(by Self-Report and N-protein) Cohort - Per Protocol Population 
Figure 728: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, Older Infected 
(by Self-Report and N-protein) Cohort - mITT Population 
Figure 729: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, Older Infected 
(by Self-Report and N-protein) Cohort - Per Protocol Population 
Figure 730: 
Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Older Infected (by 
Self-Report and N-protein) Cohort - mITT Population 
Figure 731: 
Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Older Infected (by 
Self-Report and N-protein) Cohort - Per Protocol Population 
Figure 732: 
Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Older Infected (by 
Self-Report and N-protein) Cohort - mITT Population 
Figure 733: 
Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Older Infected (by 
Self-Report and N-protein) Cohort - Per Protocol Population 


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Figure 734: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, Younger 
Uninfected (by Self-Report and N-protein) Cohort - mITT Population 
Figure 735: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, Younger 
Uninfected (by Self-Report and N-protein) Cohort - Per Protocol Population 
Figure 736: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, Younger 
Uninfected (by Self-Report and N-protein) Cohort - mITT Population 
Figure 737: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, Younger 
Uninfected (by Self-Report and N-protein) Cohort - Per Protocol Population 
Figure 738: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, Younger 
Uninfected (by Self-Report and N-protein) Cohort - mITT Population 
Figure 739: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, Younger 
Uninfected (by Self-Report and N-protein) Cohort - Per Protocol Population 
Figure 740: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, Younger 
Uninfected (by Self-Report and N-protein) Cohort - mITT Population 
Figure 741: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, Younger 
Uninfected (by Self-Report and N-protein) Cohort - Per Protocol Population 
Figure 742: 
Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Younger Uninfected 
(by Self-Report and N-protein) Cohort - mITT Population 
Figure 743: 
Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Younger Uninfected 
(by Self-Report and N-protein) Cohort - Per Protocol Population 
Figure 744: 
Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Younger Uninfected 
(by Self-Report and N-protein) Cohort - mITT Population 
Figure 745: 
Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Younger Uninfected 
(by Self-Report and N-protein) Cohort - Per Protocol Population 
Figure 746: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, Older Uninfected 
(by Self-Report and N-protein) Cohort - mITT Population 
Figure 747: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S1 Peptide Pool, Older Uninfected 
(by Self-Report and N-protein) Cohort - Per Protocol Population 
Figure 748: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, Older Uninfected 
(by Self-Report and N-protein) Cohort - mITT Population 
Figure 749: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S1 Peptide Pool, Older Uninfected 
(by Self-Report and N-protein) Cohort - Per Protocol Population 
Figure 750: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, Older Uninfected 
(by Self-Report and N-protein) Cohort - mITT Population 
Figure 751: 
Percentages of CD4 T Cells Expressing Th1 Cytokines S2 Peptide Pool, Older Uninfected 
(by Self-Report and N-protein) Cohort - Per Protocol Population 
Figure 752: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, Older Uninfected 
(by Self-Report and N-protein) Cohort - mITT Population 


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Figure 753: 
Percentages of CD4 T Cells Expressing Th2 Cytokines S2 Peptide Pool, Older Uninfected 
(by Self-Report and N-protein) Cohort - Per Protocol Population 
Figure 754: 
Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Older Uninfected (by 
Self-Report and N-protein) Cohort - mITT Population 
Figure 755: 
Percentages of CD8 T Cells Expressing Cytokines S1 Peptide Pool, Older Uninfected (by 
Self-Report and N-protein) Cohort - Per Protocol Population 
Figure 756: 
Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Older Uninfected (by 
Self-Report and N-protein) Cohort - mITT Population 
Figure 757: 
Percentages of CD8 T Cells Expressing Cytokines S2 Peptide Pool, Older Uninfected (by 
Self-Report and N-protein) Cohort - Per Protocol Population 
 
 


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Figure 758: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by timepoint and 
Vaccination arm, Overall - mITT Population 
 
 
Figures with similar format: 
Figure 759: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by timepoint and 
Vaccination arm, Overall – Per Protocol Population 
Figure 760: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by timepoint and 
Vaccination arm, Overall – mITT Population 
Figure 761: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by timepoint and 
Vaccination arm, Overall – Per Protocol Population 
Figure 762: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta by timepoint 
and Vaccination arm, Overall – mITT Population 
Figure 763: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta by timepoint 
and Vaccination arm, Overall – Per Protocol Population 
Figure 764: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron by timepoint 
and Vaccination arm, Overall – mITT Population 
Figure 765: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron by timepoint 
and Vaccination arm, Overall – Per Protocol Population 
Figure 766: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Beta by 
timepoint and Vaccination arm, Overall – mITT Population 
Figure 767: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Beta by 
timepoint and Vaccination arm, Overall – Per Protocol Population 
Figure 768: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta-Beta by 
timepoint and Vaccination arm, Overall – mITT Population 
 
 


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Figure 769: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta-Beta by 
timepoint and Vaccination arm, Overall – Per Protocol Population 
Figure 770: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta by 
timepoint and Vaccination arm, Overall – mITT Population 
Figure 771: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta by 
timepoint and Vaccination arm, Overall – Per Protocol Population 
Figure 772: 
Distribution of Percent of IgG B-cells expressing RBD Omicron by timepoint and 
Vaccination arm, Overall – mITT Population 
Figure 773: 
Distribution of Percent of IgG B-cells expressing RBD Omicron by timepoint and 
Vaccination arm, Overall – Per Protocol Population 
Figure 774: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by timepoint and 
Vaccination arm, Overall – mITT Population 
Figure 775: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by timepoint and 
Vaccination arm, Overall – Per Protocol Population 
Figure 776: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta by timepoint 
and Vaccination arm, Overall – mITT Population 
Figure 777: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta by timepoint 
and Vaccination arm, Overall – Per Protocol Population 
Figure 778: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by timepoint and 
Vaccination arm, Overall – mITT Population 
Figure 779: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by timepoint and 
Vaccination arm, Overall – Per Protocol Population 
Figure 780: 
Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint and Vaccination 
arm, Overall – mITT Population 
Figure 781: 
Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint and Vaccination 
arm, Overall – Per Protocol Population 
Figure 782: 
Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint and 
Vaccination arm, Overall – mITT Population 
Figure 783: 
Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint and 
Vaccination arm, Overall – Per Protocol Population 
Figure 784: 
Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by timepoint and 
Vaccination arm, Overall – mITT Population 
Figure 785: 
Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by timepoint and 
Vaccination arm, Overall – Per Protocol Population 
Figure 786: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by timepoint and 
Vaccination arm, Younger Cohort - mITT Population 
Figure 787: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by timepoint and 
Vaccination arm, Younger Cohort – Per Protocol Population 
 
 


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Figure 788: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by timepoint and 
Vaccination arm, Younger Cohort – mITT Population 
Figure 789: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by timepoint and 
Vaccination arm, Younger Cohort – Per Protocol Population 
Figure 790: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta by timepoint 
and Vaccination arm, Younger Cohort – mITT Population 
Figure 791: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta by timepoint 
and Vaccination arm, Younger Cohort – Per Protocol Population 
Figure 792: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron by timepoint 
and Vaccination arm, Younger Cohort – mITT Population 
Figure 793: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron by timepoint 
and Vaccination arm, Younger Cohort – Per Protocol Population 
Figure 794: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Beta by 
timepoint and Vaccination arm, Younger Cohort – mITT Population 
Figure 795: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Beta by 
timepoint and Vaccination arm, Younger Cohort – Per Protocol Population 
Figure 796: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta-Beta by 
timepoint and Vaccination arm, Younger Cohort – mITT Population 
Figure 797: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta-Beta by 
timepoint and Vaccination arm, Younger Cohort – Per Protocol Population 
Figure 798: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta by 
timepoint and Vaccination arm, Younger Cohort – mITT Population 
Figure 799: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta by 
timepoint and Vaccination arm, Younger Cohort – Per Protocol Population 
Figure 800: 
Distribution of Percent of IgG B-cells expressing RBD Omicron by timepoint and 
Vaccination arm, Younger Cohort – mITT Population 
Figure 801: 
Distribution of Percent of IgG B-cells expressing RBD Omicron by timepoint and 
Vaccination arm, Younger Cohort – Per Protocol Population 
Figure 802: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by timepoint and 
Vaccination arm, Younger Cohort – mITT Population 
Figure 803: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by timepoint and 
Vaccination arm, Younger Cohort – Per Protocol Population 
Figure 804: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta by timepoint 
and Vaccination arm, Younger Cohort – mITT Population 
Figure 805: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta by timepoint 
and Vaccination arm, Younger Cohort – Per Protocol Population 
Figure 806: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by timepoint and 
Vaccination arm, Younger Cohort – mITT Population 
 
 


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Figure 807: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by timepoint and 
Vaccination arm, Younger Cohort – Per Protocol Population 
Figure 808: 
Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint and Vaccination 
arm, Younger Cohort – mITT Population 
Figure 809: 
Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint and Vaccination 
arm, Younger Cohort – Per Protocol Population 
Figure 810: 
Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint and 
Vaccination arm, Younger Cohort – mITT Population 
Figure 811: 
Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint and 
Vaccination arm, Younger Cohort – Per Protocol Population 
Figure 812: 
Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by timepoint and 
Vaccination arm, Younger Cohort – mITT Population 
Figure 813: 
Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by timepoint and 
Vaccination arm, Younger Cohort – Per Protocol Population 
Figure 814: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by timepoint and 
Vaccination arm, Older Cohort - mITT Population 
Figure 815: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by timepoint and 
Vaccination arm, Older Cohort – Per Protocol Population 
Figure 816: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by timepoint and 
Vaccination arm, Older Cohort – mITT Population 
Figure 817: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by timepoint and 
Vaccination arm, Older Cohort – Per Protocol Population 
Figure 818: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta by timepoint 
and Vaccination arm, Older Cohort – mITT Population 
Figure 819: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta by timepoint 
and Vaccination arm, Older Cohort – Per Protocol Population 
Figure 820: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron by timepoint 
and Vaccination arm, Older Cohort – mITT Population 
Figure 821: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron by timepoint 
and Vaccination arm, Older Cohort – Per Protocol Population 
Figure 822: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Beta by 
timepoint and Vaccination arm, Older Cohort – mITT Population 
Figure 823: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Beta by 
timepoint and Vaccination arm, Older Cohort – Per Protocol Population 
Figure 824: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta-Beta by 
timepoint and Vaccination arm, Older Cohort – mITT Population 
 
 


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Figure 825: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta-Beta by 
timepoint and Vaccination arm, Older Cohort – Per Protocol Population 
Figure 826: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta by 
timepoint and Vaccination arm, Older Cohort – mITT Population 
 
Figure 827: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta by 
timepoint and Vaccination arm, Older Cohort – Per Protocol Population 
Figure 828: 
Distribution of Percent of IgG B-cells expressing RBD Omicron by timepoint and 
Vaccination arm, Older Cohort – mITT Population 
Figure 829: 
Distribution of Percent of IgG B-cells expressing RBD Omicron by timepoint and 
Vaccination arm, Older Cohort – Per Protocol Population 
Figure 830: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by timepoint and 
Vaccination arm, Older Cohort – mITT Population 
Figure 831: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by timepoint and 
Vaccination arm, Older Cohort – Per Protocol Population 
Figure 832: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta by timepoint 
and Vaccination arm, Older Cohort – mITT Population 
Figure 833: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta by timepoint 
and Vaccination arm, Older Cohort – Per Protocol Population 
Figure 834: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by timepoint and 
Vaccination arm, Older Cohort – mITT Population 
Figure 835: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by timepoint and 
Vaccination arm, Older Cohort – Per Protocol Population 
Figure 836: 
Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint and Vaccination 
arm, Older Cohort – mITT Population 
Figure 837: 
Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint and Vaccination 
arm, Older Cohort – Per Protocol Population 
Figure 838: 
Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint and 
Vaccination arm, Older Cohort – mITT Population 
Figure 839: 
Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint and 
Vaccination arm, Older Cohort – Per Protocol Population 
Figure 840: 
Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by timepoint and 
Vaccination arm, Older Cohort – mITT Population 
Figure 841: 
Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by timepoint and 
Vaccination arm, Older Cohort – Per Protocol Population 
Figure 842: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by timepoint and 
Vaccination arm, Infected (by Self-Report and N-protein) Cohort - mITT Population 
Figure 843: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by timepoint and 
Vaccination arm, Infected (by Self-Report and N-protein) Cohort – Per Protocol 


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Population 
Figure 844: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by timepoint and 
Vaccination arm, Infected (by Self-Report and N-protein) Cohort – mITT Population 
Figure 845: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by timepoint and 
Vaccination arm, Infected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 846: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta by timepoint 
and Vaccination arm, Infected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 847: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta by timepoint 
and Vaccination arm, Infected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 848: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron by timepoint 
and Vaccination arm, Infected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 849: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron by timepoint 
and Vaccination arm, Infected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 850: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Beta by 
timepoint and Vaccination arm, Infected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 851: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Beta by 
timepoint and Vaccination arm, Infected (by Self-Report and N-protein) Cohort – Per 
Protocol Population 
Figure 852: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta-Beta by 
timepoint and Vaccination arm, Infected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 853: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta-Beta by 
timepoint and Vaccination arm, Infected (by Self-Report and N-protein) Cohort – Per 
Protocol Population 
Figure 854: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta by 
timepoint and Vaccination arm, Infected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 855: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta by 
timepoint and Vaccination arm, Infected (by Self-Report and N-protein) Cohort – Per 
Protocol Population 
Figure 856: 
Distribution of Percent of IgG B-cells expressing RBD Omicron by timepoint and 
Vaccination arm, Infected (by Self-Report and N-protein) Cohort – mITT Population 
Figure 857: 
Distribution of Percent of IgG B-cells expressing RBD Omicron by timepoint and 
Vaccination arm, Infected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 


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Figure 858: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by timepoint and 
Vaccination arm, Infected (by Self-Report and N-protein) Cohort – mITT Population 
 
Figure 859: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by timepoint and 
Vaccination arm, Infected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 860: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta by timepoint 
and Vaccination arm, Infected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 861: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta by timepoint 
and Vaccination arm, Infected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 862: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by timepoint and 
Vaccination arm, Infected (by Self-Report and N-protein) Cohort – mITT Population 
Figure 863: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by timepoint and 
Vaccination arm, Infected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 864: 
Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint and Vaccination 
arm, Infected (by Self-Report and N-protein) Cohort – mITT Population 
Figure 865: 
Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint and Vaccination 
arm, Infected (by Self-Report and N-protein) Cohort – Per Protocol Population 
Figure 866: 
Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint and 
Vaccination arm, Infected (by Self-Report and N-protein) Cohort – mITT Population 
Figure 867: 
Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint and 
Vaccination arm, Infected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 868: 
Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by timepoint and 
Vaccination arm, Infected (by Self-Report and N-protein) Cohort – mITT Population 
Figure 869: 
Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by timepoint and 
Vaccination arm, Infected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 870: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by timepoint and 
Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort - mITT Population 
Figure 871: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by timepoint and 
Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 872: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by timepoint and 
Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – mITT Population 
Figure 873: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by timepoint and 
Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – Per Protocol 


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Population 
Figure 874: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta by timepoint 
and Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 875: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta by timepoint 
and Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 876: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron by timepoint 
and Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 877: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron by timepoint 
and Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 878: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Beta by 
timepoint and Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – 
mITT Population 
Figure 879: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Beta by 
timepoint and Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – Per 
Protocol Population 
Figure 880: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta-Beta by 
timepoint and Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – 
mITT Population 
Figure 881: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta-Beta by 
timepoint and Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – Per 
Protocol Population 
Figure 882: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta by 
timepoint and Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – 
mITT Population 
Figure 883: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta by 
timepoint and Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – Per 
Protocol Population 
Figure 884: 
Distribution of Percent of IgG B-cells expressing RBD Omicron by timepoint and 
Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – mITT Population 
Figure 885: 
Distribution of Percent of IgG B-cells expressing RBD Omicron by timepoint and 
Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 886: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by timepoint and 
Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – mITT Population 
Figure 887: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by timepoint and 
Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 


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Figure 888: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta by timepoint 
and Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 889: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta by timepoint 
and Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 890: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by timepoint and 
Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – mITT Population 
Figure 891: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by timepoint and 
Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 892: 
Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint and Vaccination 
arm, Uninfected (by Self-Report and N-protein) Cohort – mITT Population 
Figure 893: 
Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint and Vaccination 
arm, Uninfected (by Self-Report and N-protein) Cohort – Per Protocol Population 
Figure 894: 
Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint and 
Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – mITT Population 
Figure 895: 
Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint and 
Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 896: 
Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by timepoint and 
Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – mITT Population 
Figure 897: 
Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by timepoint and 
Vaccination arm, Uninfected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 898: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by timepoint and 
Vaccination arm, Younger Infected (by Self-Report and N-protein) Cohort - mITT 
Population 
Figure 899: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by timepoint and 
Vaccination arm, Younger Infected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 900: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by timepoint and 
Vaccination arm, Younger Infected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 901: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by timepoint and 
Vaccination arm, Younger Infected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 902: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta by timepoint 
and Vaccination arm, Younger Infected (by Self-Report and N-protein) Cohort – mITT 


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Population 
 
Figure 903: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta by timepoint 
and Vaccination arm, Younger Infected (by Self-Report and N-protein) Cohort – Per 
Protocol Population 
Figure 904: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron by timepoint 
and Vaccination arm, Younger Infected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 905: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron by timepoint 
and Vaccination arm, Younger Infected (by Self-Report and N-protein) Cohort – Per 
Protocol Population 
Figure 906: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Beta by 
timepoint and Vaccination arm, Younger Infected (by Self-Report and N-protein) Cohort 
– mITT Population 
Figure 907: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Beta by 
timepoint and Vaccination arm, Younger Infected (by Self-Report and N-protein) Cohort 
– Per Protocol Population 
Figure 908: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta-Beta by 
timepoint and Vaccination arm, Younger Infected (by Self-Report and N-protein) Cohort 
– mITT Population 
Figure 909: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta-Beta by 
timepoint and Vaccination arm, Younger Infected (by Self-Report and N-protein) Cohort 
– Per Protocol Population 
Figure 910: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta by 
timepoint and Vaccination arm, Younger Infected (by Self-Report and N-protein) Cohort 
– mITT Population 
Figure 911: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta by 
timepoint and Vaccination arm, Younger Infected (by Self-Report and N-protein) Cohort 
– Per Protocol Population 
Figure 912: 
Distribution of Percent of IgG B-cells expressing RBD Omicron by timepoint and 
Vaccination arm, Younger Infected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 913: 
Distribution of Percent of IgG B-cells expressing RBD Omicron by timepoint and 
Vaccination arm, Younger Infected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 914: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by timepoint and 
Vaccination arm, Younger Infected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 915: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by timepoint and 
Vaccination arm, Younger Infected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 


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Figure 916: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta by timepoint 
and Vaccination arm, Younger Infected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 917: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta by timepoint 
and Vaccination arm, Younger Infected (by Self-Report and N-protein) Cohort – Per 
Protocol Population 
Figure 918: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by timepoint and 
Vaccination arm, Younger Infected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 919: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by timepoint and 
Vaccination arm, Younger Infected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 920: 
Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint and Vaccination 
arm, Younger Infected (by Self-Report and N-protein) Cohort – mITT Population 
Figure 921: 
Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint and Vaccination 
arm, Younger Infected (by Self-Report and N-protein) Cohort – Per Protocol Population 
Figure 922: 
Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint and 
Vaccination arm, Younger Infected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 923: 
Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint and 
Vaccination arm, Younger Infected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 924: 
Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by timepoint and 
Vaccination arm, Younger Infected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 925: 
Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by timepoint and 
Vaccination arm, Younger Infected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 926: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by timepoint and 
Vaccination arm, Younger Uninfected (by Self-Report and N-protein) Cohort - mITT 
Population 
Figure 927: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by timepoint and 
Vaccination arm, Younger Uninfected (by Self-Report and N-protein) Cohort – Per 
Protocol Population 
Figure 928: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by timepoint and 
Vaccination arm, Younger Uninfected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 929: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by timepoint and 
Vaccination arm, Younger Uninfected (by Self-Report and N-protein) Cohort – Per 
Protocol Population 
 


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Figure 930: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta by timepoint 
and Vaccination arm, Younger Uninfected (by Self-Report and N-protein) Cohort – 
mITT Population 
Figure 931: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta by timepoint 
and Vaccination arm, Younger Uninfected (by Self-Report and N-protein) Cohort – Per 
Protocol Population 
Figure 932: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron by timepoint 
and Vaccination arm, Younger Uninfected (by Self-Report and N-protein) Cohort – 
mITT Population 
Figure 933: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron by timepoint 
and Vaccination arm, Younger Uninfected (by Self-Report and N-protein) Cohort – Per 
Protocol Population 
Figure 934: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Beta by 
timepoint and Vaccination arm, Younger Uninfected (by Self-Report and N-protein) 
Cohort – mITT Population 
Figure 935: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Beta by 
timepoint and Vaccination arm, Younger Uninfected (by Self-Report and N-protein) 
Cohort – Per Protocol Population 
Figure 936: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta-Beta by 
timepoint and Vaccination arm, Younger Uninfected (by Self-Report and N-protein) 
Cohort – mITT Population 
Figure 937: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta-Beta by 
timepoint and Vaccination arm, Younger Uninfected (by Self-Report and N-protein) 
Cohort – Per Protocol Population 
Figure 938: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta by 
timepoint and Vaccination arm, Younger Uninfected (by Self-Report and N-protein) 
Cohort – mITT Population 
Figure 939: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta by 
timepoint and Vaccination arm, Younger Uninfected (by Self-Report and N-protein) 
Cohort – Per Protocol Population 
Figure 940: 
Distribution of Percent of IgG B-cells expressing RBD Omicron by timepoint and 
Vaccination arm, Younger Uninfected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 941: 
Distribution of Percent of IgG B-cells expressing RBD Omicron by timepoint and 
Vaccination arm, Younger Uninfected (by Self-Report and N-protein) Cohort – Per 
Protocol Population 
Figure 942: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by timepoint and 
Vaccination arm, Younger Uninfected (by Self-Report and N-protein) Cohort – mITT 
Population 
 
 


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Figure 943: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by timepoint and 
Vaccination arm, Younger Uninfected (by Self-Report and N-protein) Cohort – Per 
Protocol Population 
Figure 944: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta by timepoint 
and Vaccination arm, Younger Uninfected (by Self-Report and N-protein) Cohort – 
mITT Population 
Figure 945: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta by timepoint 
and Vaccination arm, Younger Uninfected (by Self-Report and N-protein) Cohort – Per 
Protocol Population 
Figure 946: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by timepoint and 
Vaccination arm, Younger Uninfected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 947: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by timepoint and 
Vaccination arm, Younger Uninfected (by Self-Report and N-protein) Cohort – Per 
Protocol Population 
Figure 948: 
Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint and Vaccination 
arm, Younger Uninfected (by Self-Report and N-protein) Cohort – mITT Population 
Figure 949: 
Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint and Vaccination 
arm, Younger Uninfected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 950: 
Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint and 
Vaccination arm, Younger Uninfected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 951: 
Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint and 
Vaccination arm, Younger Uninfected (by Self-Report and N-protein) Cohort – Per 
Protocol Population 
Figure 952: 
Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by timepoint and 
Vaccination arm, Younger Uninfected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 953: 
Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by timepoint and 
Vaccination arm, Younger Uninfected (by Self-Report and N-protein) Cohort – Per 
Protocol Population 
Figure 954: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by timepoint and 
Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort - mITT 
Population 
Figure 955: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by timepoint and 
Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 956: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by timepoint and 
Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort – mITT 
Population 


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Figure 957: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by timepoint and 
Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 958: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta by timepoint 
and Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 959: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta by timepoint 
and Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort – Per 
Protocol Population 
Figure 960: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron by timepoint 
and Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 961: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron by timepoint 
and Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort – Per 
Protocol Population 
Figure 962: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Beta by 
timepoint and Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort – 
mITT Population 
Figure 963: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Beta by 
timepoint and Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort – 
Per Protocol Population 
Figure 964: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta-Beta by 
timepoint and Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort – 
mITT Population 
Figure 965: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta-Beta by 
timepoint and Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort – 
Per Protocol Population 
Figure 966: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta by 
timepoint and Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort – 
mITT Population 
Figure 967: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta by 
timepoint and Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort – 
Per Protocol Population 
Figure 968: 
Distribution of Percent of IgG B-cells expressing RBD Omicron by timepoint and 
Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 969: 
Distribution of Percent of IgG B-cells expressing RBD Omicron by timepoint and 
Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 970: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by timepoint and 
Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort – mITT 


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Population 
Figure 971: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by timepoint and 
Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 972: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta by timepoint 
and Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 973: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta by timepoint 
and Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort – Per 
Protocol Population 
Figure 974: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by timepoint and 
Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 975: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by timepoint and 
Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 976: 
Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint and Vaccination 
arm, Older Infected (by Self-Report and N-protein) Cohort – mITT Population 
Figure 977: 
Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint and Vaccination 
arm, Older Infected (by Self-Report and N-protein) Cohort – Per Protocol Population 
Figure 978: 
Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint and 
Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 979: 
Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint and 
Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 980: 
Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by timepoint and 
Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 981: 
Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by timepoint and 
Vaccination arm, Older Infected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 982: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by timepoint and 
Vaccination arm, Older Uninfected (by Self-Report and N-protein) Cohort - mITT 
Population 
Figure 983: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta by timepoint and 
Vaccination arm, Older Uninfected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 984: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by timepoint and 
Vaccination arm, Older Uninfected (by Self-Report and N-protein) Cohort – mITT 
Population 


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Figure 985: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Delta by timepoint and 
Vaccination arm, Older Uninfected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 986: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta by timepoint 
and Vaccination arm, Older Uninfected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 987: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Beta-Delta by timepoint 
and Vaccination arm, Older Uninfected (by Self-Report and N-protein) Cohort – Per 
Protocol Population 
Figure 988: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron by timepoint 
and Vaccination arm, Older Uninfected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 989: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron by timepoint 
and Vaccination arm, Older Uninfected (by Self-Report and N-protein) Cohort – Per 
Protocol Population 
Figure 990: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Beta by 
timepoint and Vaccination arm, Older Uninfected (by Self-Report and N-protein) Cohort 
– mITT Population 
Figure 991: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Beta by 
timepoint and Vaccination arm, Older Uninfected (by Self-Report and N-protein) Cohort 
– Per Protocol Population 
Figure 992: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta-Beta by 
timepoint and Vaccination arm, Older Uninfected (by Self-Report and N-protein) Cohort 
– mITT Population 
Figure 993: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta-Beta by 
timepoint and Vaccination arm, Older Uninfected (by Self-Report and N-protein) Cohort 
– Per Protocol Population 
Figure 994: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta by 
timepoint and Vaccination arm, Older Uninfected (by Self-Report and N-protein) Cohort 
– mITT Population 
Figure 995: 
Distribution of Percent of IgG B-cells expressing RBD Prototype-Omicron-Delta by 
timepoint and Vaccination arm, Older Uninfected (by Self-Report and N-protein) Cohort 
– Per Protocol Population 
Figure 996: 
Distribution of Percent of IgG B-cells expressing RBD Omicron by timepoint and 
Vaccination arm, Older Uninfected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 997: 
Distribution of Percent of IgG B-cells expressing RBD Omicron by timepoint and 
Vaccination arm, Older Uninfected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
 
 


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Figure 998: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by timepoint and 
Vaccination arm, Older Uninfected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 999: 
Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta by timepoint and 
Vaccination arm, Older Uninfected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 1000: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta by timepoint 
and Vaccination arm, Older Uninfected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 1001: Distribution of Percent of IgG B-cells expressing RBD Omicron-Beta-Delta by timepoint 
and Vaccination arm, Older Uninfected (by Self-Report and N-protein) Cohort – Per 
Protocol Population 
Figure 1002: Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by timepoint and 
Vaccination arm, Older Uninfected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 1003: Distribution of Percent of IgG B-cells expressing RBD Omicron-Delta by timepoint and 
Vaccination arm, Older Uninfected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 1004: Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint and Vaccination 
arm, Older Uninfected (by Self-Report and N-protein) Cohort – mITT Population 
Figure 1005: Distribution of Percent of IgG B-cells expressing RBD Beta by timepoint and Vaccination 
arm, Older Uninfected (by Self-Report and N-protein) Cohort – Per Protocol Population 
Figure 1006: Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint and 
Vaccination arm, Older Uninfected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 1007: Distribution of Percent of IgG B-cells expressing RBD Delta by timepoint and 
Vaccination arm, Older Uninfected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 
Figure 1008: Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by timepoint and 
Vaccination arm, Older Uninfected (by Self-Report and N-protein) Cohort – mITT 
Population 
Figure 1009: Distribution of Percent of IgG B-cells expressing RBD Delta-Beta by timepoint and 
Vaccination arm, Older Uninfected (by Self-Report and N-protein) Cohort – Per Protocol 
Population 


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Figure 1010: Time to Infection Kaplan-Meier Curve by Vaccination Group, Overall - mITT 
Population 
 
 
 
Implementation Note:  A separate curve will be shown for each vaccination group. 
 
Figures with Similar Format: 
Figure 1011: Time to Infection Kaplan-Meier Curve by Vaccination Group, Younger Cohort- mITT 
Population 
Figure 1012: Time to Infection Kaplan-Meier Curve by Vaccination Group, Older Cohort - mITT 
Population 
Figure 1013: Time to Infection Kaplan-Meier Curve by Vaccination Group, Infected Cohort (By Self-
report or N-protein)- mITT Population 
Figure 1014: Time to Infection Kaplan-Meier Curve by Vaccination Group, Uninfected Cohort (By 
Self-report or N-protein) - mITT Population 
Figure 1015: Time to Infection Kaplan-Meier Curve by Vaccination Group, Younger Infected Cohort 
(By Self-report or N-protein) - mITT Population 
Figure 1016: Time to Infection Kaplan-Meier Curve by Vaccination Group, Younger Uninfected 
Cohort (By Self-report or N-protein) - mITT Population 


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Figure 1017: Time to Infection Kaplan-Meier Curve by Vaccination Group, Older Infected Cohort (By 
Self-report or N-protein) - mITT Population 
Figure 1018: Time to Infection Kaplan-Meier Curve by Vaccination Group, Older Uninfected Cohort 
(By Self-report or N-protein) - mITT Population 
 


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Figure 1019: Summary of Breakthrough Infections by PANGO Call and Treatment Group, Prototype 
– Safety Population 
[Implementation Note: Figure will be color coded by PANGO Call.] 
 
 
 
Figures with Similar Format: 
 
Figure 1020: Summary of Breakthrough Infections by PANGO Call and Treatment Group, 1 Dose 
Beta + Omicron – Safety Population 
Figure 1021: Summary of Breakthrough Infections by PANGO Call and Treatment Group, 2 Dose 
Beta + Omicron – Safety Population 
Figure 1022: Summary of Breakthrough Infections by PANGO Call and Treatment Group, Delta + 
Omicron – Safety Population 
Figure 1023: Summary of Breakthrough Infections by PANGO Call and Treatment Group, Omicron – 
Safety Population 
Figure 1024: Summary of Breakthrough Infections by PANGO Call and Treatment Group, Omicron + 
Prototype – Safety Population 
 


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14.3.1.1 Solicited Adverse Events 
Figure 1025: Maximum Severity of Solicited Systemic Symptoms per Subject by Day Post Vaccination 
and Treatment Group – Dose 1 
 
Figure with Similar Format: 
Figure 1026: Maximum Severity of Solicited Systemic Symptoms per Subject by Day Post Vaccination 
and Treatment Group – Dose 2 
 


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Figure 1027: Maximum Severity of Solicited Local Symptoms per Subject by Day Post Vaccination 
and Treatment Group – Dose 1 
 
 
Figure with Similar Format: 
Figure 1028: Maximum Severity of Solicited Local Symptoms per Subject by Day Post Vaccination 
and Treatment Group – Dose 2 
 


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Figure 1029: Onset of Solicited Systemic Symptoms by Days Post Vaccination and Treatment Group – Dose 1  
[Implementation Note:  Have a panel for each treatment group.] 
 
 
 
Severe
Moderate
Mild
Percent of Subjects (%)
8/15 Moderate
1/15 Severe
3/15 Mild
1/15 Moderate
2/15 Severe
250 μg 18-55 years (N=15)
1/15 Mild
1/15 Mild
6/15 Moderate
1/15 Mild
6/15 Moderate
100 μg 18-55 years (N=15)
2/15 Mild
4/15 Mild
2/15 Moderate
4/15 Moderate
1/15 Severe
50 μg 18-55 years (N=15)
2/15 Mild
1/15 Moderate
4/15 Moderate
1/15 Mild
25 μg 18-55 years (N=15)
0
10
20
30
40
50
60
0
10
20
30
40
50
60
0
10
20
30
40
50
60
0
10
20
30
40
50
60
Day 8
Day 7
Day 6
Day 5
Day 4
Day 3
Day 2
Day 1
Post-Dose
Pre-Dose
Vaccination Day


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Figures with Similar Format: 
Figure 1030: Onset of Solicited Systemic Symptoms by Days Post Vaccination and Treatment Group – Dose 2  
Figure 1031: Onset of Solicited Local Symptoms by Days Post Vaccination and Treatment Group – Dose 1 
Figure 1032: Onset of Solicited Local Symptoms by Days Post Vaccination and Treatment Group – Dose 2 
 


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Figure 1033: Solicited Symptoms by Days Post Vaccination and Treatment Group– Arthralgia 
 
 
 
Dose 1
18-55 years 25μg
Dose 2
18-55 years 25μg
18-55 years 50μg
18-55 years 50μg
18-55 years 100μg
18-55 years 100μg
0
1
2
3
4
5
6
7
8
Study Day
18-55 years 250μg
0
1
2
3
4
5
6
7
8
Study Day
18-55 years 250μg
None
Mild
Moderate
Severe


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Figures with Similar Format: 
Figure 1034: Solicited Symptoms by Days Post Vaccination and Treatment Group– Chills 
Figure 1035: Solicited Symptoms by Days Post Vaccination and Treatment Group– Erythema 
Figure 1036: Solicited Symptoms by Days Post Vaccination and Treatment Group– Erythema (mm) 
Figure 1037: Solicited Symptoms by Days Post Vaccination and Treatment Group– Fatigue 
Figure 1038: Solicited Symptoms by Days Post Vaccination and Treatment Group– Fever 
Figure 1039: Solicited Symptoms by Days Post Vaccination and Treatment Group– Headache 
Figure 1040: Solicited Symptoms by Days Post Vaccination and Treatment Group– Induration 
Figure 1041: Solicited Symptoms by Days Post Vaccination and Treatment Group– Induration (mm) 
Figure 1042: Solicited Symptoms by Days Post Vaccination and Treatment Group– Myalgia 
Figure 1043: Solicited Symptoms by Days Post Vaccination and Treatment Group– Nausea 
Figure 1044: Solicited Symptoms by Days Post Vaccination and Treatment Group– Pain 
 
 


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14.3.1.2 Unsolicited Adverse Events 
Figure 1045: Frequency of Adverse Events by MedDRA System Organ Class and Severity 
[Implementation Note: Have a panel for each treatment group for Dose 1 and a seventh panel for Dose 2.] 
 
 


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Figure 1046: Incidence of Adverse Events by MedDRA® System Organ Class and Maximum Severity  
[Implementation Note: Have a panel for each treatment group for Dose 1 and a seventh panel for Dose 2] 
 
 


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14.3.5 
Displays of Laboratory Results 
Not Applicable. 


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APPENDIX 3. LISTINGS MOCK-UPS 
 
 


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LISTINGS 
Listing 1: 16.1.6: Listing of Subjects Receiving Investigational Product .................................385 
Listing 2: 16.2.1: Early Terminations or Discontinued Subjects ..............................................386 
Listing 3: 16.2.2.1: Subject-Specific Protocol Deviations ........................................................387 
Listing 4: 16.2.2.2: Non-Subject-Specific Protocol Deviations ................................................388 
Listing 5: 16.2.3: Subjects Excluded from Analysis Populations .............................................389 
Listing 6: 16.2.4.1: Demographic Data .....................................................................................390 
Listing 7: 16.2.4.2: Pre-Existing and Concurrent Medical Conditions .....................................391 
Listing 8: 16.2.6: Individual Immunogenicity Response Data .................................................393 
Listing 9: 16.2.6: Individual T-cell Response Data ..................................................................393 
Listing 10: 16.2.7.1: Solicited Events – Systemic Symptoms ....................................................395 
Listing 11: 16.2.7.2: Solicited Events – Local Symptoms ..........................................................396 
Listing 12: 16.2.7.3: Unsolicited Adverse Events .......................................................................397 
Listing 13: 16.2.9.1: Vital Signs .................................................................................................399 
Listing 14: 16.2.9.2: Physical Exam Findings ............................................................................400 
Listing 15: 16.2.10: Concomitant Medications ...........................................................................401 
Listing 16: 16.2.11.1: Pregnancy Reports – Maternal Information ............................................402 
Listing 17: 16.2.11.2: Pregnancy Reports – Gravida and Para ...................................................402 
Listing 18: 16.2.11.3: Pregnancy Reports – Live Birth Outcomes .............................................403 
Listing 19: 16.2.11.4: Pregnancy Reports – Still Birth Outcomes ..............................................403 
Listing 20: 16.2.11.5: Pregnancy Reports – Spontaneous, Elective, or Therapeutic 
Abortion Outcomes ...................................................................................................403 
 


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Listing 1: 
16.1.6: Listing of Subjects Receiving Investigational Product 
(not included in SAP, but this is a placeholder for the CSR) 


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16.2 
Database Listings by Subject 
16.2.1 Discontinued Subjects 
Listing 2: 
16.2.1: Early Terminations or Discontinued Subjects 
Vaccination Group 
 Subject ID 
Category 
Reason for Early Termination or Treatment Discontinuation 
Study Day 
 
 
 
 
 
 
 
 


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16.2.2 Protocol Deviations 
Listing 3: 
16.2.2.1: Subject-Specific Protocol Deviations 
Vaccination 
Group 
Subject ID 
DV Number 
Deviation 
Deviation 
Category 
Study Day 
Reason for 
Deviation 
Deviation 
Resulted 
in AE? 
Deviation Resulted 
in Subject 
Termination? 
Deviation 
Affected 
Product 
Stability? 
Deviation 
Resolution 
Comments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 4: 
16.2.2.2: Non-Subject-Specific Protocol Deviations 
Site 
Start Date  
Deviation 
End Date 
Reason for 
Deviation 
Deviation 
Resulted in 
Subject 
Termination? 
Deviation 
Affected 
Product 
Stability? 
Deviation 
Category 
Deviation 
Resolution 
Comments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16.2.3 Subjects Excluded from the Efficacy Analysis 
Listing 5: 
16.2.3: Subjects Excluded from Analysis Populations 
Vaccination Group 
Subject ID 
Analyses in which 
Subject is Included 
Analyses from which  
Subject is Excluded 
Results Available? 
Reason Subject Excluded 
 
 
[e.g., Safety, ITT, PP] 
[e.g., Safety, ITT, PP, Day x] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: “Yes” in the “Results available” column indicates that available data were removed from the analysis. “No” indicates that no data were available for inclusion in the analysis. 
 
 


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16.2.4 Demographic Data 
Listing 6: 
16.2.4.1: Demographic Data 
Vaccination 
Group 
 Subject ID 
Sex 
Age at Enrollment (years) 
Ethnicity 
Race 
BMI 
Time Between 
First and 
Second 
Booster (Days) 
Time Between 
Covid 
Infection and 
Second 
Booster (Days) 
Time Between 
Covid 
Infection or 
First Booster 
and Second 
Booster (Days) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 7: 
16.2.4.2: Pre-Existing and Concurrent Medical Conditions 
Vaccination 
Group 
 Subject ID 
MH Number 
Medical History Term 
Condition Start Day  
Condition End Day 
MedDRA System Organ Class 
MedDRA Preferred Term 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16.2.5 Compliance and/or Drug Concentration Data (if available) 
Not Applicable. 
 


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16.2.6 Individual Immunogenicity Response Data 
Listing 8: 
16.2.6: Individual Immunogenicity Response Data 
Vaccination 
Group  
Subject ID  
Planned Time Point 
Actual Study Day 
Assay 
Units 
Results 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listing 9: 
16.2.6: Individual T-cell Response Data 
Vaccination 
Group  
Subject ID  
Planned Time Point 
Actual Study Day 
T-Cell 
Peptide Pool 
Cytokine 
Adjusted Percent 
Responder (Y/N) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 10: 
16.2.6: Individual B-cell Response Data 
Vaccination Group  
Subject ID  
Planned Time Point 
Actual Study Day 
Probe 
Percent 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listing 11: 
16.2.6: Individual Sequencing Data 
Vaccination Group  
Subject ID  
Planned Time Point 
Actual Study Day 
PANGO 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16.2.7 Adverse Events 
Listing 12: 
16.2.7.1: Solicited Events – Systemic Symptoms 
Vaccination 
Group  
Subject ID  
Dose Number 
Post Dose Day 
Assessmenta 
Symptom 
Severity 
Attributed to 
Alternate 
Etiology?b 
Alternate Etiology 
 
 
 
 
MA 
 
 
 
 
 
 
 
 
Clinic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a MA = Data reported by subject on the Memory Aid and reviewed by clinic staff and reported in Solicited Events eCRF. 
b Grade 3 events only.  
Note: Clinic = Data collected by clinic staff during physical exam or symptom assessment (treatment administration record, in-clinic assessment, etc.) 
 
 


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Listing 13: 
16.2.7.2: Solicited Events – Local Symptoms 
Treatment Group  
Subject ID  
Dose Number 
Post Dose Day 
Assessmenta 
Symptom 
Severity 
 
 
 
 
MA 
 
 
 
 
 
 
Clinic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a MA = Data reported by subject on the Memory Aid and reviewed by clinic staff and reported in Solicited Events eCRF. 
Note: Clinic = Data collected by clinic staff during physical exam or symptom assessment (treatment administration record, in-clinic assessment, etc.) 
 
 


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Listing 14: 
16.2.7.3: Unsolicited Adverse Events 
Adverse 
Event 
Associated 
with Dose 
No. 
No. of Days 
Post 
Associated 
Dose 
(Duration) 
Severity 
SAE? 
Relationship 
to Study 
Treatment 
In Not 
Related, 
Alternative 
Etiology 
Action 
Taken with 
Study 
Treatment 
Subject 
Discontinued 
Due to AE 
Outcome 
MedDRA 
System 
Organ Class 
MedDRA 
Preferred 
Term 
Treatment Group: , Subject ID: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
 
Comments: 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment Group: , Subject ID: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
 
Comments: 
Note: For additional details about SAEs, see Figure: xx. 
 
 


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16.2.8 Individual Laboratory Measurements 
Not Applicable. 


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16.2.9 Vital Signs and Physical Exam Findings 
Listing 15: 
16.2.9.1: Vital Signs 
Treatment 
Group 
Subject ID 
Planned Time 
Point 
Actual Study 
Day 
Temperature 
(°C) 
Systolic Blood 
Pressure 
(mmHg) 
Diastolic Blood 
Pressure 
(mmHg) 
Heart Rate 
(beats/min) 
Respiratory Rate 
(breaths/min) 
Weight 
(kg) 
Height 
(cm) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 16: 
16.2.9.2: Physical Exam Findings 
Treatment 
Group 
Subject ID 
Planned Time 
Point 
Actual Study 
Day 
Body System 
Abnormal Finding 
Reported as an AE? 
(AE Description; Number) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16.2.10 Concomitant Medications 
Listing 17: 
16.2.10: Concomitant Medications 
Treatment 
Group 
Subject ID 
CM 
Number 
Medication 
Medication Start 
Day 
Medication End 
Day 
Indication 
Taken for an AE? 
(AE Description; 
Number) 
Taken for a condition 
on Medical History? 
(MH Description; 
Number) 
ATC Level 1  
(ATC Level 2) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16.2.11 Pregnancy Reports 
Listing 18: 
16.2.11.1: Pregnancy Reports – Maternal Information 
Treatment 
Group  
Subject 
ID  
Pregnancy 
Number 
Study Day 
Corresponding 
to Estimated 
Date of 
Conception 
Source of 
Maternal 
Information 
Pregnancy 
Status 
Mother’s 
Pre-
Pregnancy 
BMI 
Mother’s 
Weight 
Gain 
During 
Pregnancy 
Tobacco, 
Alcohol, or 
Drug Use 
During 
Pregnancy? 
Medications 
During 
Pregnancy? 
Maternal 
Complications 
During 
Pregnancy? 
Maternal 
Complications 
During Labor, 
Delivery, or 
Post-Partum? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Maternal Complications are included in the Adverse Event listing. Medications taken during pregnancy are included in the Concomitant Medications Listing. 
Listing 19: 
16.2.11.2: Pregnancy Reports – Gravida and Para 
 
 
 
Live Births 
 
 
 
 
 
Subject 
ID 
Pregnancy 
Number 
Gravida 
Extremely 
PBa 
Very 
Early 
PBa 
Early 
PBa 
Late 
PBa 
Early 
TBb 
Full 
TBb 
Late 
TBb 
Post 
TBb 
Still 
Births 
Spontaneous 
Abortion/ 
Miscarriage 
Elective 
Abortions 
Therapeutic 
Abortions 
Major 
Congenital 
Anomaly 
with 
Previous 
Pregnancy? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Gravida includes the current pregnancy, para events do not. 
a Preterm Birth 
b Term Birth 
 
 


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Listing 20: 
16.2.11.3: Pregnancy Reports – Live Birth Outcomes 
Subject 
ID 
Pregnancy 
Number 
Fetus 
Number 
Pregnancy 
Outcome 
(for this 
Fetus) 
Fetal 
Distress 
During 
Labor and 
Delivery? 
Delivery 
Method 
Gestational 
Age at Live 
Birth  
Size for 
Gestational 
Age 
Apgar 
Score, 1 
minute 
Apgar 
Score, 5 
minutes 
Cord pH 
Congenital 
Anomalies? 
Illnesses/ 
Hospitalizations 
within 1 Month of 
Birth? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Congenital Anomalies are included in the Adverse Event listing. 
Listing 21: 
16.2.11.4: Pregnancy Reports – Still Birth Outcomes 
Subject 
ID 
Date of 
Initial 
Report 
Fetus 
Number 
Pregnancy 
Outcome 
(for this 
Fetus) 
Fetal Distress 
During 
Labor and 
Delivery? 
Delivery 
Method 
Gestational 
Age at Still 
Birth 
Size for 
Gestational 
Age 
Cord pH 
Congenital 
Anomalies? 
Autopsy 
Performed? 
If Autopsy, Etiology 
for Still Birth 
Identified? 
 
 
 
 
 
 
 
 
 
 
 
 
Listing 22: 
16.2.11.5: Pregnancy Reports – Spontaneous, Elective, or Therapeutic Abortion Outcomes 
Subject 
ID 
Date of Initial 
Report 
Fetus Number 
Pregnancy Outcome 
(for this Fetus) 
Gestational Age at 
Termination 
Abnormality in Product of Conception? 
Reason for Therapeutic 
Abortion 
 
 
 
 
 
 
 
 

Prot_001.pdf: 
 
DMID Protocol 22-0004 
Version 5.0 
COVAIL 
 
21 Sep 2022 
 
DMID/NIAID/NIH 
CONFIDENTIAL 
Page 1 of 101 
Phase 2 Clinical Trial to Optimize Immune Coverage of SARS-CoV-2 Existing and 
Emerging Variants 
 
COVID-19 VAriant Immunologic Landscape Trial 
(COVAIL Trial) 
 
DMID Protocol Number: 22-0004 
 
IND Sponsor: Division of Microbiology and Infectious Diseases (DMID) 
 
Version Number: 5.0 
 
21 September 2022 
 
 


 
DMID Protocol 22-0004 
Version 5.0 
COVAIL 
 
21 Sep 2022 
 
DMID/NIAID/NIH 
CONFIDENTIAL 
Page 2 of 101 
STATEMENT OF COMPLIANCE 
Each institution engaged in this research will hold a current Federal wide Assurance (FWA) 
issued by the Office of Human Research Protection (OHRP) for federally funded research. The 
Institutional Review Board (IRB)/Independent or Institutional Ethics Committee (IEC) must be 
registered with OHRP as applicable to the research. 
 
The study will be carried out in accordance with the following as applicable: 
• United States (US) Code of Federal Regulations (CFR) 45 CFR Part 46: Protection of 
Human Subjects 
• Food and Drug Administration (FDA) Regulations: 21 CFR Part 50 (Protection of 
Human Subjects), 21 CFR Part 54 (Financial Disclosure by Clinical Investigators), 21 
CFR Part 56 (IRBs), 21 CFR Part 11, and 21 CFR Part 312 (Investigational New Drug 
Application), and/or 21 CFR 812 (Investigational Device Exemptions) 
• The International Council for Harmonisation (ICH) of Technical Requirements for 
Registration of Pharmaceuticals for Human Use (ICH) E6(R2) Good Clinical Practice 
(GCP), and the Belmont Report: Ethical Principles and Guidelines for the Protection of 
Human Subjects of Research, Report of the National Commission for the Protection of 
Human Subjects of Biomedical and Behavioral Research 
• The policies and procedures of National Institutes of Health (NIH) Office of Extramural 
Research and Division of Microbiology and Infectious Diseases (DMID) 
• The National Institute of Allergy and Infectious Diseases (NIAID) Terms of Award 
• Any additional Federal, State, and Local Regulations and Guidance 
 
The signature below provides the necessary assurance that this study will be conducted 
according to all stipulations of the protocol, including statements regarding confidentiality, and 
according to local legal and regulatory requirements, US federal regulations, and ICH E6(R2) 
GCP guidelines. 
Site Investigator Signature: 
 
Signed: 
 
Date: 
 
 
Name, Credentials 
Title 
 
 
 


 
DMID Protocol 22-0004 
Version 5.0 
COVAIL 
 
21 Sep 2022 
 
DMID/NIAID/NIH 
CONFIDENTIAL 
Page 3 of 101 
TABLE OF CONTENTS 
 
STATEMENT OF COMPLIANCE ................................................................................................ 2 
TABLE OF CONTENTS ................................................................................................................ 3 
LIST OF TABLES .......................................................................................................................... 8 
LIST OF FIGURES ........................................................................................................................ 8 
1. 
PROTOCOL SUMMARY ...................................................................................................... 9 
1.1 
Synopsis .......................................................................................................................... 9 
1.2 
Schedule of Activities (SOA) ....................................................................................... 15 
2. 
INTRODUCTION ................................................................................................................ 20 
2.1 
Background and Study Rationale.................................................................................. 20 
2.1.1 
Public Readiness and Emergency Preparedness Act ............................................ 23 
2.2 
Risk/Benefit Assessment .............................................................................................. 24 
2.2.1 
Known Potential Risks .......................................................................................... 24 
2.2.2 
Known Potential Benefits ..................................................................................... 28 
3. 
OBJECTIVES AND ENDPOINTS ...................................................................................... 30 
4. 
STUDY DESIGN.................................................................................................................. 32 
4.1 
Overall Design .............................................................................................................. 32 
4.2 
Scientific Rationale for Study Design........................................................................... 32 
4.3 
Justification for Doses................................................................................................... 33 
5. 
STUDY POPULATION ....................................................................................................... 34 
5.1 
Inclusion Criteria .......................................................................................................... 34 
5.2 
Exclusion Criteria ......................................................................................................... 34 
5.2.1 
Exclusion of specific populations ......................................................................... 34 
5.3 
Inclusion of Vulnerable Subjects .................................................................................. 34 
5.4 
Lifestyle Considerations ............................................................................................... 34 
5.5 
Screen Failures .............................................................................................................. 35 
5.5.1 
Strategies for Recruitment and Retention ............................................................. 35 
5.5.2 
Retention ............................................................................................................... 35 
5.5.3 
Compensation Plan for Subjects ........................................................................... 35 


 
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5.5.4 
Costs ...................................................................................................................... 35 
6. 
STUDY PRODUCT.............................................................................................................. 36 
6.1 
Study Product(s) and Administration............................................................................ 36 
6.1.1 
Study Product Description .................................................................................... 36 
6.1.2 
Dosing and Administration ................................................................................... 37 
6.1.3 
Dose Modifications ............................................................................................... 38 
6.2 
Accountability/Handling/Storage/Preparation .............................................................. 38 
6.2.1 
Acquisition and Accountability ............................................................................ 38 
6.2.2 
Formulation and Appearance ................................................................................ 39 
6.2.3 
Product Storage and Stability................................................................................ 39 
6.2.4 
Preparation ............................................................................................................ 40 
6.3 
Measures to Minimize Bias: Randomization and Blinding .......................................... 40 
6.3.1 
Treatment Assignment Procedures ....................................................................... 40 
6.3.2 
Randomization and Blinding ................................................................................ 40 
6.3.3 
Blinding and Masking Procedures ........................................................................ 41 
6.4 
Study Intervention Compliance .................................................................................... 41 
6.5 
Concomitant Therapy.................................................................................................... 41 
6.5.1 
Rescue Medicine ................................................................................................... 41 
6.5.2 
Non-Research Standard of Care............................................................................ 41 
7. 
STUDY INTERVENTION DISCONTINUATION AND SUBJECT 
DISCONTINUATION/WITHDRAWAL..................................................................................... 42 
7.1 
Halting Criteria and Discontinuation of Study Intervention ......................................... 42 
7.1.1 
Halting Criteria ..................................................................................................... 42 
7.1.2 
Criteria for Continuation of Dosing and Redosing ............................................... 42 
7.1.3 
Discontinuation of Study Intervention .................................................................. 42 
7.1.3.1 
Delay of Study Vaccination .............................................................................. 43 
7.1.4 
Follow-up for Subjects that Discontinued Study Intervention ............................. 43 
7.1.5 
Follow up for Subjects with a Suspicion for Myocarditis and/or Pericarditis ...... 43 
7.1.5.1 
Probable Case of Acute Myocarditis ................................................................ 44 
7.1.5.2 
Confirmed Case of Acute Myocarditis ............................................................. 44 
7.1.5.3 
Acute Pericarditis Case Definition.................................................................... 44 


 
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21 Sep 2022 
 
DMID/NIAID/NIH 
CONFIDENTIAL 
Page 5 of 101 
7.1.5.4 
Myopericarditis Case Definition ....................................................................... 45 
7.2 
Subject Withdrawal from the Study and Replacement ................................................. 45 
7.3 
Lost to Follow-Up ......................................................................................................... 46 
8. 
STUDY ASSESSMENTS AND PROCEDURES ................................................................ 47 
8.1 
Screening and Immunogenicity Assessments ............................................................... 47 
8.1.1 
Screening or Enrollment/Baseline Procedures...................................................... 47 
8.1.2 
Immunogenicity Evaluations ................................................................................ 48 
8.1.3 
Samples for Suspected SARS-CoV-2 infection .................................................... 49 
8.1.4 
Samples for Genetic/Genomic Analysis ............................................................... 49 
8.1.4.1 
Genetic/Genomic Analysis ............................................................................... 49 
8.1.4.2 
Genetic Privacy and Confidentiality ................................................................. 49 
8.1.4.3 
Management of Results..................................................................................... 49 
8.1.5 
SARS-CoV-2 infection ......................................................................................... 49 
8.1.6. 
Retained Samples for Biomarker Testing ............................................................. 50 
8.2 
Safety and Other Assessments ...................................................................................... 50 
8.3 
Adverse Events and Serious Adverse Events ............................................................... 50 
8.3.1 
Definition of Adverse Event (AE) ........................................................................ 50 
8.3.1.1 
Solicited Adverse Events .................................................................................. 51 
8.3.1.2 
Unsolicited Adverse Events .............................................................................. 52 
8.3.2 
Definition of Serious Adverse Event (SAE) ......................................................... 52 
8.3.3 
Suspected Unexpected Serious Adverse Reactions (SUSAR).............................. 52 
8.3.4 
Classification of an Adverse Event ....................................................................... 53 
8.3.4.1 
Severity of Adverse Events ............................................................................... 53 
8.3.4.2 
Relationship to Study Intervention ................................................................... 53 
8.3.5 
Time Period and Frequency for Event Assessment and Follow-Up ..................... 54 
8.3.6 
Adverse Event Reporting ...................................................................................... 54 
8.3.6.1 
Investigators Reporting of AEs ......................................................................... 54 
8.3.7 
Serious Adverse Event Reporting ......................................................................... 54 
8.3.7.1 
Investigators Reporting of SAEs ...................................................................... 54 
8.3.7.2 
Regulatory Reporting of SAEs ......................................................................... 55 


 
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COVAIL 
 
21 Sep 2022 
 
DMID/NIAID/NIH 
CONFIDENTIAL 
Page 6 of 101 
8.3.8 
Reporting Events to Subjects ................................................................................ 55 
8.3.9 
Adverse Events of Special Interest (AESIs), New Onset of Chronic Medical 
Conditions (NOCMCs) and Medically Attended Adverse Events (MAAEs) ...................... 55 
8.3.10 
Reporting of Pregnancy ........................................................................................ 56 
8.4 
Unanticipated Problems ................................................................................................ 56 
8.4.1 
Definition of Unanticipated Problems (UPs) ........................................................ 56 
8.4.2 
Unanticipated Problem Reporting......................................................................... 57 
8.4.3 
Reporting Unanticipated Problems to Subjects .................................................... 57 
9. 
STATISTICAL CONSIDERATIONS.................................................................................. 58 
9.1 
Statistical Hypotheses ................................................................................................... 58 
9.2 
Sample Size Determination........................................................................................... 58 
9.2.1 
Sample Size Calculation for the Safety Endpoint ................................................. 58 
9.2.2 
Sample Size Calculation for the Immunogenicity Endpoints ............................... 59 
9.3 
Populations for Analyses .............................................................................................. 60 
9.4 
Statistical Analyses ....................................................................................................... 60 
9.4.1 
General Approach ................................................................................................. 60 
9.4.2 
Analysis of the Primary Endpoint(s)..................................................................... 61 
9.4.3 
Analysis of the Secondary Endpoints ................................................................... 61 
9.4.4 
Safety Analyses ..................................................................................................... 61 
9.4.5 
Baseline Descriptive Statistics .............................................................................. 61 
9.4.6 
Planned Interim and Early Analyses ..................................................................... 61 
9.4.6.1 
Interim Safety Analyses .................................................................................... 62 
9.4.6.2 
Interim Immunogenicity Review ...................................................................... 62 
9.4.6.3 
Interim Immunogenicity and Safety Review .................................................... 62 
9.4.7 
Sub-Group Analyses ............................................................................................. 62 
9.4.8 
Tabulation of Individual Subject Data .................................................................. 62 
9.4.9 
Exploratory Analyses ............................................................................................ 62 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ....... 63 
10.1 
Regulatory, Ethical, and Study Oversight Considerations............................................ 63 
10.1.1 
Informed Consent Process .................................................................................... 63 


 
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Version 5.0 
COVAIL 
 
21 Sep 2022 
 
DMID/NIAID/NIH 
CONFIDENTIAL 
Page 7 of 101 
10.1.1.1 
Requirements for Permission by Parents/Guardians and Assent by Children 
(in case of a minor) ........................................................................................................... 64 
10.1.1.2 
Other Informed Consent Procedures ............................................................. 64 
10.1.2 
Study Termination and Closure ............................................................................ 66 
10.1.3 
Confidentiality and Privacy .................................................................................. 66 
10.1.4 
Secondary Use of Stored Specimens and Data ..................................................... 67 
10.1.4.1 
Samples for Secondary Research .................................................................. 68 
10.1.4.2 
Data Sharing for Secondary Research .......................................................... 68 
10.1.5 
Key Roles and Study Governance ........................................................................ 68 
10.1.6 
Safety Oversight.................................................................................................... 68 
10.1.6.1 
Data Safety Monitoring Board (DSMB) ....................................................... 69 
10.1.7 
Clinical Monitoring ............................................................................................... 69 
10.1.8 
Quality Control (QC) and Quality Assurance (QA) ............................................. 69 
10.1.9 
Data Handling and Record Keeping ..................................................................... 70 
10.1.9.1 
Data Collection and Management Responsibilities ...................................... 70 
10.1.9.2 
Study Record Retention ................................................................................ 70 
10.1.9.3 
Source Records ............................................................................................. 71 
10.1.9.4 
Protocol Deviations ....................................................................................... 71 
10.1.9.5 
Data Sharing Plan ......................................................................................... 71 
10.1.9.6 
Genomic Data Sharing (GDS) Plan .............................................................. 71 
10.1.9.7 
Publication .................................................................................................... 72 
10.1.9.8 
Conflict of Interest Policy ............................................................................. 72 
10.2 
Additional Considerations ............................................................................................ 72 
10.2.1 
Research Related Injuries ..................................................................................... 72 
10.3 
Abbreviations ................................................................................................................ 72 
10.4 
Protocol Amendment History ....................................................................................... 78 
11. REFERENCES ..................................................................................................................... 86 
12. APPENDIX A: Adverse Events of Special Interest (AESIs) Terms .................................... 91 
 
 
 


 
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LIST OF TABLES 
Table 1: Study Arms ..................................................................................................................... 11 
Table 2: SOA for single dose ........................................................................................................ 15 
Table 3: SOA for 2 doses .............................................................................................................. 17 
Table 4: Objectives and Endpoints (Outcome Measures)............................................................. 30 
Table 5: Probability of Observing one or more Adverse Event for Various Event Rates in one 
vaccine group (or strata). .............................................................................................................. 58 
Table 6: Two-sided 95% confidence intervals based on observing a particular average loge-
antibody titer in subjects’ vaccine groups and potential strata sizes ............................................ 59 
Table 7: Abbreviations .................................................................................................................. 72 
 
LIST OF FIGURES 
No table of figures entries found. 
 
 


 
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1. 
PROTOCOL SUMMARY 
1.1 
Synopsis 
 
Title:  
Phase 2 Clinical Trial to Optimize Immune Coverage of SARS-CoV-2 Existing 
and Emerging Variants  
 
Short title: 
COVID-19 Adaptive VAriant Immunologic Landscape Trial (COVAIL Trial) 
 
Phase:  
Phase 2 
 
Population:  Approximately 1,500 healthy individuals aged ≥ 18 years  
 
Sites:   
Up to 30 US clinical research sites  
 
Rationale: 
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), causative agent of the 
coronavirus disease of 2019 (COVID-19) pandemic, has infected close to 600 million people 
worldwide and resulted in more than 6 million deaths, including 1 million deaths  in the United 
States (August 18, 2022 WHO; www.who.int). As of September 2022, there are four approved or 
authorized vaccines in the U.S.: two using mRNA-based technology (Pfizer BioNTech 
[BNT162b2] and Moderna [mRNA-1273]), one using a non-replicating viral vector vaccine 
(Johnson and Johnson adenovirus Ad26), and one using protein adjuvanted vaccine (Novavax) all 
encoding the spike protein of the ancestral strain.  A fifth manufacturer Sanofi has another 
adjuvanted protein vaccine that showed efficacy in a phase 3 trial. These and other WHO 
authorized vaccines have been an essential countermeasure against the pandemic.  
However, the emergence of many variants of concern with different degrees of immune escape 
challenge the effectiveness of these vaccines. The persistent evolution of the virus leads to the 
consideration of adapting vaccines to antigenically match circulating variants as well as expanding 
and optimizing immune coverage to existing and emerging antigenic variants. Current efforts are 
directed towards modifying the existing vaccines to include the current circulating variant 
Omicron. However, Omicron may not be the circulating variant during the next wave of COVID-
19. It is important to look beyond Omicron and understand the immunologic landscape and how 
we can use prototype and variant vaccines alone or in combination to address emerging variants.  
This phase 2 clinical trial will evaluate the safety and immunogenicity of additional doses of 
prototype and variant (alone or in combination) vaccine candidates in previously vaccinated 
participants with or without prior SARS-CoV-2 infection, and will evaluate innate, cellular, and 


 
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humoral immune responses to inform on how to shift the immune response to cover new variants 
as they emerge. 
 
Objectives:  
Primary:  
  To evaluate humoral immune responses of candidate SARS-CoV-2 variant vaccines, alone or in 
combination.  
Secondary 
1. To evaluate the safety of candidate SARS-CoV-2 variant vaccines, as assessed by:  
• 
Local and systemic solicited Adverse Events for 7 days following each vaccine dose. 
• 
Unsolicited Adverse Events from Dose 1 to 28 days following each vaccine dose.  
• 
SAEs, MAAEs, AESIs, NOCMCs, and AEs leading to withdrawal from the study  
from Dose 1 to 12 months after last vaccine dose.  
Exploratory:  
1. To assess, in at least a subset of samples, the B cell immune response of candidate SARS-
CoV-2 variant vaccines. 
2. To assess, in at least a subset of samples, the SARS-CoV-2 spike protein-specific T cell 
responses of candidate SARS-CoV-2 variant vaccines. 
3. To assess, in at least a subset of samples, the magnitude, phenotype, and percentage of 
innate immune cells with candidate SARS-CoV-2 variant vaccines. 
4. To assess, in at least a subset of samples, the functional potential of SARS-CoV-2 
specific antibodies to mediate Fc-effector functions across candidate SARS-CoV-2 
variant vaccines.  
5. To evaluate breakthrough SARS-CoV-2 infection by sequencing strains for variant spike 
lineage and assessing anti- nucleocapsid serology.  
 
Study Design:  
This is a Phase 2 randomized open label, non-placebo controlled, multi-site, multi-stage clinical 
trial in individuals, 18 years of age and older, who are in stable state of health, have received a 
complete authorized/approved vaccine series (primary series + a booster either with homologous 
or heterologous vaccine products) ≥ 16 weeks prior to enrollment.  
Subjects will be stratified by i) age (18-64 years and ≥ 65 years of age) (however arms 16 and 17 
or stage 4 will only enroll participants between the ages of 18-49 years) and ii) history of confirmed 
prior SARS-CoV-2 infection, and randomly assigned to receive one of several variant vaccines. 
Enrollment will target a goal of approximately 45% of each of the variant vaccine arms to be in 


 
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older adults (≥ 65 years of age) for stages 1, 2 and 3 and approximately 20% to have had confirmed 
COVID-19 for all 4 stages.  
This is an adaptive design and may add arms of new vaccine platforms and/or variant lineage spike 
vaccines as needed. The study arms will be conducted in different stages (that could overlap) 
depending on public health needs and availability of study products (starting with the available 
mRNA vaccines).  
Table 1: Study Arms 
 
Arms Vaccine 
Platform 
Samp
le 
Size 
Vaccine Candidate 
Interval 
(weeks)* 
Timing 
of First 
Dose  
Timing of 
Second Dose 
Stage 1 
1 
Moderna 
mRNA-1273 
100 
Prototype 
≥16 
D1 
NA 
2 
100 
Beta + Omicron  
≥16 
D1 
NA 
3 
100 
Beta + Omicron  
≥16 
D1 
D57 
4 
100 
Delta + Omicron  
≥16 
D1 
NA 
5 
100 
Omicron  
≥16 
D1 
NA 
6 
100 
Omicron + Prototype  
≥16 
D1 
NA 
 
Stage 2 
7 
Pfizer/ 
BioNTech 
BNT162b2 
50 
Wildtype (Prototype) 
≥16 
D1 
NA 
8 
50 
Beta + Omicron  
≥16 
D1 
NA 
9 
50 
Omicron  
≥16 
D1 
NA 
10 
50 
Beta  
≥16 
D1 
NA 
11 
50 
Beta + Wildtype  
≥16 
D1 
NA 
12 
50 
Omicron + Wildtype  
≥16 
D1 
NA 
 
Stage 3 
13 
Sanofi 
CoV2 preS 
dTM-AS03 
50 
Prototype 
≥16 
D1 
NA 
14 
50 
Beta  
≥16 
D1 
NA 
15 
50 
Beta+ Prototype 
≥16 
D1 
NA 
 
Stage 4 
16^ 
Pfizer/ 
BioNTech 
BNT162b2 
bivalent 
100 
Omicron BA.1 + 
Wildtype (Prototype) 
≥16 
D1 
NA 
17^ 
100 
Omicron BA.4/BA.5 + 
Wildtype (Prototype) 
≥16 
D1 
NA 
 
Two age strata:  
• 
18-64 years 
• 
≥ 65 years (~45% in ≥ 65 years). 
^For arms 16 and 17 or stage 4, only participants between the ages of 18 to 49 years will be enrolled. 
 
Two infection strata:  
• 
Confirmed prior SARS-CoV-2 infection (~20%) 
• 
No known history of prior infection.   


 
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*interval (in weeks) since last exposure to SARS-CoV-2 infection or vaccination 
 
Duration of Study:   Up to 4 years  
 
Duration of participation per subject: Up to 2 years (approximately 12 months after last 
inoculation)  
 
Criteria for Inclusion/Exclusion:  
Inclusion Criteria: 
Participants must meet all of the following criteria to be eligible to participate in this study: 
1. Individuals ≥ 18 years of age at the time of consent (18-49 years for stage 4).  
2. Confirmed receipt of a complete primary and booster COVID-19 vaccine series, either 
homologous or heterologous, with an FDA authorized/approved vaccine at least 16 weeks 
prior to study vaccine dose 1. 
3. Willing and able to comply with all scheduled visits, vaccination plan, laboratory tests 
and other study procedures.  
4. Determined by medical history, targeted physical examination and clinical judgement of 
the investigator to be in stable state of health.  
Note: Participants with pre-existing stable chronic medical conditions defined as 
condition not requiring significant change in therapy or hospitalization for worsening 
disease within 4 weeks from enrollment, can be included at the discretion of the 
investigator. 
Exclusion Criteria:  
Participants meeting any of the following criteria will be excluded from the study:  
1. Confirmed SARS-CoV-2 infection < 16 weeks prior to any study vaccine dose.  
2. Pregnant and breastfeeding participants. 
3. Prior administration of an investigational coronavirus vaccine at any time or SARS-CoV-
2 immunoglobulin, monoclonal antibody or plasma antibody therapy in the preceding 3 
months. 
Note: subjects that participated in clinical trials of products that are now FDA 
approved/authorized are allowed to participate. 
4. Current/planned simultaneous participation in another interventional study or receipt of 
any investigational study product within 28 days prior to vaccine study dose(s). 


 
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5. A history of anaphylaxis, urticaria, or other significant adverse reaction requiring medical 
intervention after receipt of a vaccine, polyethylene glycol (PEG), polysorbate or nanolipid 
particles. 
6. A history of myocarditis or pericarditis at any time prior to enrollment (for subjects in 
stages 1, 2 and 4).   
7. Received or plans to receive a vaccine within 28 days prior to or after any dose of study 
vaccine. 
Note: Receipt of seasonal influenza vaccine is allowed at any time.   
8. Bleeding disorder diagnosed by a healthcare provider (e.g., factor deficiency, 
coagulopathy, or platelet disorder requiring special precautions) or bleeding difficulties with 
intramuscular injections or blood draws.   
9. Current or previous diagnosis of an immunocompromising condition or other 
immunosuppressive condition. 
10. Advanced liver or kidney diseases. 
11. Advanced (CD4 count < 200) and/or untreated HIV, untreated Hepatitis B or untreated 
Hepatitis C. 
12. Received oral, intramuscular or intravenous systemic immunosuppressants, or immune-
modifying drugs for >14 days in total within 6 months prior to any study vaccine dose (for 
corticosteroids ≥ 20 mg/day of prednisone equivalent).  
Note: Topical medications are allowed.   
13. Received immunoglobulin or blood-derived products, within 3 months prior any study 
vaccine dose.   
14. Received chemotherapy, immunotherapy or radiation therapy within 6 months prior to 
any study vaccine dose. 
15. Study personnel or an immediate family member or household member of study 
personnel.   
16. Is acutely ill or febrile 72 hours prior to or at vaccine dosing (fever defined as ≥ 
38.0°C/100.4°F). Participants meeting this criterion may be rescheduled within the relevant 
window periods.  
Note: Afebrile participants with minor illnesses can be enrolled at the discretion of the 
Investigator, as long as the illness is not suggestive of COVID-19. 
17. Plan to receive a COVID-19 booster vaccine outside of the study within the next 180 
days. (for subjects in Stage 4 only) 
 
Safety 
• 
Solicited Adverse Events will be collected for 7 days following each vaccine dose. 


 
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• 
Unsolicited Adverse Events will be collected from Dose 1 to 28 days following each 
vaccine dose.  
• 
SAEs, MAAEs, AESIs, NOCMCs, and AEs leading to withdrawal from the study will be 
collected from Dose 1 to 12 months after last vaccine dose.  
• 
The study will use halting rules for vaccination. See Section 7.1 for details. 


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1.2 
Schedule of Activities (SOA) 
Table 2: SOA for single dose 
Study Day 
D-28 
to 
D-1 
1 
4 
8
b 
15 
29 
91 
181 
271 
366 
Illness/ 
Unsche
duled 
Visitk,m 
Early 
Terminati
on Visit 
Visit Number 
00
a 
1 
1A 
2 
3 
4 
5 
6 
7 
8 
 
 
Window (+/-) 
 
0 
1 
1 
2 
2 
7m 
14m 
14m 
28m 
 
 
Informed Consent
a 
X 
 
 
 
 
 
 
 
 
 
 
 
Eligibility Criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
Vaccination 
 
X 
 
 
 
 
 
 
 
 
 
 
Concomitant Meds 
X 
X 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Interim History 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical Examc - Targeted 
X 
X 
 
 
 
 
 
 
 
 
(X) 
 
Vital Signs
c 
X 
X 
 
 
 
 
 
 
 
 
(X) 
 
Height/Weight (BMI)
a 
X 
 
 
 
 
 
 
 
 
 
 
 
Urine β-HCG
d 
X 
X 
 
 
 
 
 
 
 
 
 
 
Memory Aide 
 
X 
X 
X 
 
 
 
 
 
 
 
 
Solicited AEs 
 
X 
X 
X 
 
 
 
 
 
 
 
 
Unsolicited AEs 
 
X 
X 
X 
X 
X 
 
 
 
 
 
 
MAAEs, SAEs, NOCMCs, AEs leading 
to withdrawal from the study and AESIs 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Nasal swab for PCR & Sequencingf 
 
 
 
 
 
 
 
 
 
 
(X) 
 
Assays 
Serum for Serological Immunogenicity 
Assaysg and Biomarker Testingl 
 
34l 
 
4l 
 
34 
34 
34 
34 
34 
34 
4l-34m 
34 
PBMC Cellular Assays & Plasmag,h 
 
64-70 
 
 
64-70 
 
64-70 64-70 64-70 
 
64-70m 
64-70 


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(select sites only) 
Daily Volume (mL)g,i 
 
98-
104 
4 
 
98-
104 
34 
98-
104 
98-
104 
98-
104 
34 
4-104 
98-104 
Cumulative Volume (mL) over 56 day-
periodg,i 
 
98-
104 
102-
108 
 
200-
212 
234-
246 
132-
138 
98-
104 
98-
104 
132-
138 
 
 
Total Cumulative Volume (mL)g,i 
 
98-
104 
102-
108 
 
200-
212 
234-
246 
332-
350 
430-
454 
528-
558 
562-
592 
 
 
a Optional screening visit – informed consent and screening activities can be a separate visit or combined with Day 1. 
b Telephone visit 
c Vital signs and targeted physical exam will be performed on screening and before vaccination otherwise, only as clinically indicated or based on interim medical 
history. 
d For subjects of childbearing potential, a urine pregnancy will be performed at screening. If enrollment occurs on a separate day, a repeat urine pregnancy test will 
be done within 24 hours of study vaccine administration and negative results confirmed prior to dosing.  
e  The memory aid will be distributed at the Day 1 visit, queried for completion at the Day 8 telephone call and reviewed during an interview with the subject at the 
D15 visit and confirmed data recorded on the DCF. 
fCollect nasal swab for PCR (1-2). Swabs can be self-collected and visit done by phone. Sequencing will be performed on all Illness visit-confirmed SARS-CoV-
2 specimens. 
g Inability (e.g., failure of venipuncture) to collect all baseline samples on Day 1 will not exclude the subject from further participation in this study as long as a 
minimum of baseline blood volume is collected (refer to the MOP for the protocol defined minimum number of required aliquots). Blood volume for PBMC varies 
depending on the type of tubes used for blood collection (refer to the MOP). 
h Selected sites will perform PBMC separation on selected subjects (refer to MOP for more guidance). 
i Blood volumes for early termination visit are not included in the blood volume totals. 
j After vaccination on Day 1, immunosuppressant drugs, COVID-19 related prophylaxis and therapies as well as vaccines will be recorded. For any SAE occurring 
at any time during the study, all medications will be recorded. 
k If an unscheduled visit is performed to evaluate an adverse event, vital signs and targeted physical exam will be performed, as indicated. If, in the judgement of 
the site investigator, the event, occurring within 4 weeks after vaccination, is a case of suspected myocarditis and/or pericarditis, the site will coordinate an 
appropriate diagnostic workup to make a determination of probable or confirmed myocarditis and/or pericarditis which may include, but is not limited to, an ECG, 
cardiac troponin testing and referral to a cardiologist (directly, or through the emergency department or primary care clinic). The suspected myocarditis and/or 
pericarditis case should be reported to the DMID Medical Monitor within 24 hours of site awareness.  
lSerum for biomarker testing will be collected on Day 4 and stored for potential biomarker testing at a central laboratory and compared to testing of an aliquot from 
serum obtained on Day 1.  If an unscheduled visit is related to a concern for myocarditis and/or pericarditis within 4 weeks after vaccination, a 4 mL SST will be 
collected and stored for potential biomarker testing at a central laboratory.  
mIf a participant is planning to receive a COVID-19 booster outside the study, an unscheduled visit will be performed where safety and immunogenicity (collection 
of sera, plasma and PBMC) assessments will be performed. However, if that planned visit falls within twice the window for an upcoming visit ( e.g +/- 14 days for 


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D 91, +/-28 days for D 181 and D 271, +/- 56 days for D 366) then it will occur  and be documented as out of window for the planned upcoming scheduled visit 
(refer to MOP for more guidance).  
 
Table 3: SOA for 2 doses  
Study Day 
D-28 
to 
D-1 
1 
4 
8b 
15 
29 
57 
60 
64b 
71 
85 
147 
237 
327 
422 
Illness/ 
Unsche
duled 
Visitk,m 
Early 
Termi
nation 
Visit 
Visit Number 
00a 
1 
1A 
2 
3 
4 
5 
5A 
6 
7 
8 
9 
10 
11 
12 
  
  
Window (+/-) 
  
0 
1 
1 
2 
2 
3 
1 
1 
2 
2 
7m 
14m 
14m 
28m 
  
  
Informed Consenta 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility Criteria 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Vaccination 
 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Concomitant Meds 
X 
X 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Interim History 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical Examc – 
Targeted 
X 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
(X) 
 
Vital Signsc 
X 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
(X) 
 
Height/Weight (BMI)a 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine β-HCG
d 
X 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Memory Aide 
 
X 
X 
X 
 
 
X 
X 
X 
 
 
 
 
 
 
 
 
Solicited AEs 
 
X 
X 
X 
 
 
X 
X 
X 
 
 
 
 
 
 
 
 
Unsolicited AEs 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
MAAEs, SAEs, 
NOCMCs, AEs leading 
to withdrawal from the 
study and AESIs 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


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Nasal swab for PCR & 
Sequencingf 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(X) 
 
Assays 
Serum for Serological 
Immunogenicity Assaysg 
and Biomarker Testingl 
 
34l 
 
4l 
 
34 
34 
34l 
 
4l 
 
34 
34 
34 
34 
34 
34 
4l-34m 
34 
PBMC Cellular Assays & 
Plasmag,h 
(select sites only) 
 
64-
70 
 
 
64-
70 
 
64-
70 
 
 
64-
70 
 
64-
70 
64-
70 
64-
70 
 
64-70m 
64-70 
Daily Volume (mL)g,i 
 
98-
104 
4 
 
98-
104 
34 
98-
104 
4 
 
98-
104 
34 
98-
104 
98-
104 
98-
104 
34 
4-104 
98-104 
Cumulative Volume (mL) 
over 56 day-periodg.i 
 
98-
104 
102
-
108 
 
200
-
212 
234
-
246 
332
-
350 
238
-
250 
 
336
-
354 
268
-
280 
132-
138 
98-
104 
98-
104 
132
-
138 
 
 
Total Cumulative Volume 
(mL)g,i 
 
98-
104 
102
-
108 
 
200
-
212 
234
-
246 
332
-
350 
336
-
354 
 
434
-
458 
468
-
492 
566-
596 
664
-
700 
762
-
804 
796
-
838 
 
 
a Optional screening visit – informed consent and screening activities can be a separate visit or combined with Day 1. 
b Telephone visit 
c Vital signs and targeted physical exam will be performed on screening and before vaccination otherwise, only as clinically indicated or based on interim medical 
history.  
d For subjects of childbearing potential, a urine pregnancy test will be performed at screening. If enrollment occurs on a separate day as screening, a repeat urine 
pregnancy test will be done within 24 hours of first study vaccine administration and repeated on day 57 prior to second study vaccine administration. Negative 
results must be confirmed prior to each dosing.    
e The memory aid will be distributed at the Day 1 and Day 57 visits, queried for completion at the Day 8 and Day 64 telephone calls and reviewed during an 
interview with the subject at the D15 and Day 71 visits and confirmed data recorded on the DCF. 
f Collect nasal swab for PCR (1-2). Swabs can be self-collected and visit done by phone. Sequencing will be performed on all Illness visit-confirmed SARS-CoV-
2 specimens. 
g Inability (e.g., failure of venipuncture) to collect all baseline samples on Day 1 will not exclude the subject from further participation in this study as long as a 
minimum of baseline blood volume is collected (refer to the MOP for the protocol defined minimum number of required aliquots). Blood volume for PBMC varies 
depending on the type of tubes used for the blood collection (refer to the MOP). 
h Selected sites will perform PBMC separation on selected subjects (refer to MOP for more guidance). 
i Blood volumes for early termination visit are not included in the blood volume totals. 


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j After vaccination on Day 1, immunosuppressant drugs, COVID-19 related prophylaxis and therapies as well as vaccines will be recorded. For any SAE occurring 
at any time during the study, all medications will be recorded. 
k If an unscheduled visit is performed to evaluate an adverse event, vital signs and targeted physical exam will be performed, as indicated. If, in the judgement of 
the site investigator, the event, occurring within 4 weeks after each vaccination, is a case of suspected myocarditis and/or pericarditis, the site will coordinate an 
appropriate diagnostic workup to make a determination of probable or confirmed myocarditis and/or pericarditis which may include, but is not limited to, an ECG, 
cardiac troponin testing and referral to a cardiologist (directly, or through the emergency department or primary care clinic). The suspected myocarditis and/or 
pericarditis case should be reported to the DMID Medical Monitor within 24 hours of site awareness. 
lSerum for biomarker testing will be collected on Days 4 and 60 and stored for potential biomarker testing at a central laboratory and compared to testing of an 
aliquot of serum obtained on Days 1 and 57, respectively.  If an unscheduled visit is related to a concern for myocarditis and/or pericarditis within 4 weeks after 
vaccination, a 4 mL SST will be collected and stored for potential biomarker testing at a central laboratory. 
mIf a participant is planning to receive a COVID-19 booster outside the study, an unscheduled visit will be performed where safety and immunogenicity (collection 
of sera, plasma and PBMC) assessments will be performed. However, if that planned visit falls within twice the window for an upcoming visit ( e.g +/- 14 days for 
D 147, +/-28 days for D 237 and D 327, +/- 56 days for D 422) then it will occur and be documented as out of window for the planned upcoming scheduled visit 
(refer to MOP for more guidance).  
 
Note Windows for subsequent visits should be based off the preceding vaccination visit. 
If intercurrent SARS- CoV-2 infection occurs between the first and prior to the planned second study dose or if a COVID-19 vaccine is given outside the study 
between the first and prior to the planned second study dose, no second vaccination will be given. Participants who do not receive a second dose will revert to the 
schedule of activities for single dose participants. 


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2. 
INTRODUCTION 
2.1 
Background and Study Rationale  
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was first detected in 
Wuhan, Hubei Province, China in December 2019. The corresponding illness designation, 
coronavirus disease 2019 (COVID-19), was declared as a pandemic respiratory illness in March 
2020.1 As of 18 August 2022, it has infected close to 600 million people worldwide and resulted 
in more than 6  million deaths, including 1 million in the United States.1,2  
Six Phase 3 efficacy trials of SARS-CoV-2 vaccine constructs were conducted and are in long-
term follow-up in the U.S. The ModernaTX, Inc mRNA-1273 and Pfizer/BioNTech BNT162b2 
mRNA platforms encode for the full-length spike (S) protein of SARS-CoV-2, modified to 
introduce 2 proline residues to stabilize the S protein (S-2P) in a prefusion conformation, derived 
from the Wuhan-Hu-1 strain (prototype).3 The Janssen Pharmaceutical/Johnson & Johnson 
COVID-19 Vaccine (Ad26.COV.2) is composed of recombinant, replication-incompetent human 
adenovirus type 26, encoding a prefusion-stabilized SARS-CoV-2 spike antigen.4  Studies of the 
Pfizer and Moderna mRNA vaccines demonstrated high efficacy against all symptomatic and 
severe disease and received Emergency Use Authorization (EUA) on December 12 and 18, 2020, 
respectively and full FDA approval on August 23, 2021 and January 31, 2022. Similarly, Janssen 
Pharmaceuticals reported 66% vaccine efficacy with a single dose and high-level protection 
against severe disease and death. FDA EUA was issued on February 26, 2021. Novavax’s NVX-
CoV2373, a recombinant nanoparticle vaccine containing the full-length spike protein received 
FDA EUA on July 13, 2022.5 AstraZeneca/Oxford’s ChAdOx-2, a recombinant, replication-
incompetent chimpanzee adenovirus vector that expresses the spike protein, , and Sanofi/GSK’s 
adjuvanted recombinant spike protein vaccine are currently not licensed.6,7  
 
Despite widespread vaccine distribution and availability, and high coverage among adults in the 
United States (89.1% of the US population ≥ 18 years of age have received at least one dose)8, 
ongoing waves of the pandemic continue to cause significant disease burden, notable for increasing 
incidence of breakthrough infections in fully vaccinated individuals. Studies have suggested that 
vaccine protection against symptomatic SARS-CoV-2 infection wanes over time though protection 
against severe COVID-19 outcomes remains relatively intact.9-12 However, the evolution of variant 
strains may favor immune escape or reinfection among previously infected or vaccinated 
individuals. A variant first identified in late 2020 (B.1.351), is associated with increased 
transmission, higher viral burden, and possibly increased mortality in infected persons.13  Another 
variant identified in December 2020 (B.1.617.2) is associated with increased transmission, higher 
risk of severe disease and hospitalization than the ancestral strain.14 B.1.617.2 was the dominant 
strain worldwide before being replaced by B.1.1.529 in November 2021 which is characterized by 
a replication advantage, higher re-infection rates and evasion of humoral immunity mediated by 
more than 30 mutations in the spike protein.15  
 
Recent data suggest that a booster dose given as either a third dose for most vaccines (mRNA, 
protein and ChAdOx-2) or a second dose for Janssen improved vaccine effectiveness against new 
variants in the short term.16-18 Data on immunogenicity with booster doses of BNT162b2, mRNA-


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1273, and AD26.COV2.S demonstrated higher antibody titers to D614G after either homologous 
and heterologous prime-boost combinations.19 The result is better neutralizing activity against 
B.1.351,  B.1.617.2 and B.1.1.529.20-22 In an open label phase study of participants who received 
a single 50 mcg booster dose of mRNA-1273 ≥ 6 months after a primary series, a 13 fold rise in 
antibody titers against D614G were noted from pre-boost levels as well as a 17-fold rise in in titers 
against the B.1.617.2 variant.20 In another study, participants boosted with 50 mcg of mRNA-1273 
demonstrated ID50 GMTs against the omicron variant 20 times higher than those described 1 month 
after the second vaccination of the primary series; these titers were 2.9 times lower than titers for 
the D614G variant.21  
 
The Sanofi/GSK adjuvanted recombinant prefusion spike protein vaccine (CoV2 preS dTM-AS03 
[D614]) was developed from an established, platform used for influenza vaccines. A phase 2 study 
showed the safety and immunogenicity of a two-dose primary series of CoV2 preS dTM-AS03 
[D614] in adults who were SARS-CoV-2 naïve and those who were previously infected.23 The 
dose-finding results informed selection of the adjuvanted formulation with 10 mcg antigen as 
primary dose and the adjuvanted formulation with 5 mcg antigen as boost dose for further 
evaluation. Neutralizing antibody titers were higher in non-naïve participants after one dose than 
in naïve participants after two doses. In addition, 5 mcg booster dose increased neutralizing 
antibody titers when used as a heterologous (18-30 times) or homologous (≥ 84 times) boost 
compared to pre boost.24 Interim results from an international phase 3 trial showed 57.9% (95% 
confidence interval 26.5% to 76.7%) efficacy of the two-dose primary series against any 
symptomatic disease and 75% efficacy against moderate or severe COVID-19 with an acceptable 
safety and reactogenicity profile.24   
 
FDA EUA was subsequently issued for a booster 30 ug dose of Pfizer BNT162b2 on September 
24, 2021, 50 ug booster dose of Moderna mRNA-1273 on October 21, 2021, and a 5×1010 viral 
particles booster dose of J&J AD26.COV2 on October 21, 2021. This was recommended for adults 
18 years of age and older who received a FDA authorized and CDC recommended primary booster 
series with an mRNA vaccine at least 5 months prior or a primary series with AD26.COV2 at least 
2 months prior. The Sanofi/GSK vaccine is currently undergoing regulatory review for approval 
of their vaccine candidate for the prevention of COVID-19.   
 
Published reports have also provided some early evidence for the safety and immunogenicity of a 
fourth dose of an mRNA vaccine. An open-label study of healthcare workers in Israel suggests 
that a fourth dose was well-tolerated and restored neutralizing antibody titers for variants to levels 
similar to those after a third dose.25 Notably, this study did not include older adults, and rates of 
infection with B.1.1.529 (omicron) were similar for the control and Pfizer or Moderna 4th dose 
groups. In a retrospective study conducted by the Israeli Ministry of Health, of 1,138,681 adults 
aged 60 to 100 years of age, a fourth dose of mRNA was associated with 2 times lower rate of 
confirmed infection 12 or more days after vaccination compared to those who had only received 3 
doses and the rate of severe illness was lower by a factor of 4.3.26 However, the added protection 
of an additional booster shot is small in absolute terms since less than 0.1% mortality was noted 
after a 3rd dose. Additionally, a separate study of adults age 60 or older suggests that vaccine 
effectiveness of a fourth dose against infection wanes quickly declining from a peak of 64% to 
29% within 2 months though effectiveness of >72% was maintained against severe disease.27  


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On March 29, 2022, the FDA authorized an additional booster dose of an mRNA vaccine for 
adults 50 years of age or older, or for those with immunocompromising conditions (12 years and 
older with immunocompromising conditions could receive a second booster with the Pfizer 
vaccine and 18 years and older could receive a second booster with the Moderna vaccine). 
Subsequent to this authorization, the CDC updated vaccination guidance to permit an additional 
booster dose for these groups in recognition of the increased and ongoing risk for severe disease 
in these populations.   
The emergence of variant strains has raised concerns about the breadth and duration of immunity 
and protection achieved by the current vaccines. Studies of vaccine immunogenicity for early 
variants of concern demonstrated those vaccinated with prototype vaccines may have reduced 
neutralizing activity to the variants.28 For variants like B.1.351, pivotal studies testing both viral 
vector and adjuvanted protein technologies had lower efficacy in regions where B.1.351 was 
known to be circulating.29,30 Moreover, sera from individuals vaccinated with mRNA-based 
vaccines had a 6-to-9-fold lower neutralizing activity against a B.1.351-matched pseudovirion 
relative to a Wuhan-matched pseudovirion.10,11 Similarly, sera from individuals vaccinated with 
mRNA-1273 had an 8-fold lower neutralizing activity against the B.1.617.2 variant compared to 
titers against the D614G variant.21  
Studies have also demonstrated 6.7 fold lower neutralizing activity for Pfizer BNT162b2 against 
B.1.351 with two doses of Pfizer BNT162b2.31 Additionally, in one assessment of sera obtained 
from individuals vaccinated with Pfizer BNT162b2, obtained one month after the second dose, a 
25 fold lower neutralizing antibody geometric mean titers against B.1.1.529 was noted compared 
to the wild-type virus.32 Neutralizing activity has been shown to be partially restored by 
vaccination with a third dose of Pfizer BNT162b2. However, even with three doses, neutralizing 
activity was 4 times lower against B.1.1.529 and 3 times lower against B.1.351 compared to 
B.1.617.2 and 7-8 times lower compared to wild-type virus.33 Thus, additional vaccinations, 
higher doses or variant specific vaccines may improve protection against current and emerging 
variants of concern.  
 
Vaccine manufacturers have performed some trials of candidate variant vaccines. For example, a 
phase 2a open label clinical trial to examine the immunological benefit of boosting subjects 
previously vaccinated 6 months prior with mRNA-1273 with mRNA-1273.351, a B.1.351 strain-
specific mRNA construct (50 mcg), or mRNA-1273.211 (50 mcg) showed 61.6 and 33.7 times 
higher titers against B.1.351 compared to titers from participants one month after the second 
dose of the primary series, with similar titers against B.1.617.2.22 Similar findings were seen 
from a study of a boost with a bivalent mRNA-1273.213 vaccine (a 1:1 mix of beta and delta 
variant mRNA).21  
Similarly, several BNT162b2-based variant vaccines that target these variants are also being 
developed including BNT162b2 (B.1.617.2), BNT162b2 (B.1.351) and BNT162b2 (B.1.1.529).  
In addition, Sanofi has developed a SARS-CoV2 prefusion Spike delta TM with AS03 adjuvant 
(CoV2 preS dTM-AS03 [B.1.351]) monovalent vaccine and a SARS-CoV2 prefusion Spike delta 
TM with AS03 adjuvant bivalent vaccine (D614/B.1.351 (CoV2 preS dTM-AS03 [D614 + 


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B.1.351]). In a nonhuman primate model, these vaccines used as boosters induced cross-
neutralizing antibodies against variants of concern including Delta and Omicron.34 
However, current efforts are directed towards modifying the existing vaccines to include the 
recently  circulating Omicron subvariants (United Kingdom and Canada: Prototype + Omicron 
BA.1 and the US: Prototype + Omicron BA.4/BA.5), though this may not be the circulating variant 
during the next wave of COVID-19. It is therefore important to look beyond Omicron, and 
understand the immunologic landscape and how we can use prototype and variant vaccines alone 
or in combination to address emerging variants.  
For seasonal influenza viruses, the antigenic, viral genetic and epidemiological data guide annual 
updates of the seasonal influenza virus vaccines. Antigenic cartography is a visualization tool 
aimed at understanding the relationship among SARS-CoV-2 variants of concern (VOCs) in terms 
of their ability to induce cross-neutralizing antibodies. A recent study using the antigenic mapping 
approach showed that Omicron represents the first widely circulating new major SARS-CoV-2 
variant.35 Though the dimensions of the cartography, representing new VOCs that could circulate 
in the future, remain largely unknown, a better understanding of diverse immune landscape 
induced by vaccination and natural infection could lead, along with vaccine modification, to more 
durable and broadly protective immunity. The update in vaccine formulations proposed in this 
study will still rely on similar platforms, route of administration and dosing, though will include 
an update of immunogens with VOCs alone or in combination that could result in broadly cross 
reactive serological and cellular immune responses especially in groups with high risk for mortality 
(e.g., older adults).  
This phase 2 clinical trial will evaluate the safety and immunogenicity of additional doses of 
vaccine to expand and optimize immune coverage of the existing and emerging antigenic space. 
Utilizing several prototype and variant specific COVID-19 vaccines based on mRNA and other 
approved platforms, we propose to evaluate innate, cellular, and humoral immune responses 
elicited from different vaccine candidates. As part of an adaptive design, we anticipate adding 
groups with other variant-lineage spike proteins and other vaccine platforms, subject to 
availability. 
2.1.1 
Public Readiness and Emergency Preparedness Act 
The study vaccines and the efforts for this clinical trial are covered under the Public Readiness and 
Emergency Preparedness Act (PREP Act) and the Declaration issued by the Secretary of the U.S. 
Department of Health and Human Services under that Act. Under the PREP Act and the 
Declaration, covered persons (such as manufacturers, distributers, program planners, and other 
qualified persons who prescribe, administer, or dispense study product) are immune from liability 
from the administration, or use of a covered countermeasure. The PREP Act provides immunity 
for covered persons from liability unless the injury was caused by willful misconduct. The 
Declaration invoking the PREP Act for COVID-19 covered countermeasures was made on March 
10, 2020 and is retroactively effective from February 4, 2020.  


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The PREP Act also established the Countermeasures Injury Compensation Program (CICP) to 
provide compensation for serious injuries or death that occur as the direct result of the 
administration or use of certain countermeasures. Any requests for compensation must be filed 
within one year of the administration or use of the covered countermeasure. Requests for Benefits 
must be made to the Health Resources and Services Administration’s (HRSA) Countermeasures 
Injury Compensation Program (http://www.hrsa.gov/cicp/) by filing a Request for Benefits Form 
and all required medical records and supporting documentation. Additional information on filing 
a Request for Benefits is available on the CICP’s website at http://www.hrsa.gov/cicp/. 
Compensation may then be available for reasonable and necessary medical benefits, lost wages 
and/or death benefits to eligible individuals for certain injuries in accordance with regulations 
published by the Secretary of HHS (found at 42 CFR part 110).  
If an individual suffers a serious physical injury or death from the administration or use of a 
covered countermeasure in this study, the individual, the individual’s legal or personal 
representative, the administrator/executor of a deceased individual’s estate, or certain survivors 
may request benefits from the CICP. A serious physical injury means an injury that warranted 
hospitalization (whether or not the person was actually hospitalized) or that led to a significant loss 
of function or disability. The CICP is the payer of last resort. This means that it only covers 
expenses or provides benefits that other third-party payers (such as health insurance, the 
Department of Veterans Affairs, or Workers’ Compensation programs) do not have an obligation 
to pay.  
If the Secretary of DHHS does not make a final determination on the individual’s request within 
240 days, or if the individual decides not to accept the compensation, the injured individual or his 
representative may pursue a tort claim in the US District Court for the District of Columbia, but 
only if the claim involves willful misconduct and meets the other requirements for suit under the 
PREP Act. Any award is reduced by any public or private insurance or worker’s compensation 
available to the injured individual. Awards for non-economic damages, such as pain, suffering, 
physical impairment, mental anguish, and loss of consortium are also limited. If the individual 
accepts compensation, or if there is no willful misconduct, then the individual does not have a tort 
claim that can be filed in a US Federal or a State court. 
2.2 
Risk/Benefit Assessment 
2.2.1 
Known Potential Risks 
The potential risks of participating in this trial are those associated with having blood drawn, IM 
injection, possible reactions to COVID-19 vaccines and breach of confidentiality. 
Risks of blood draw and IM injection 
Drawing blood may cause transient discomfort and fainting. Bruising at the blood draw site may 
occur but can be prevented or lessened by applying pressure to the blood draw site for a few 
minutes after the blood is taken. IM injection may also cause transient discomfort and fainting. 
Vasovagal syncope (fainting) can occur before or after vaccination or blood draw, is usually 
triggered by the pain or anxiety caused by the needlestick and is not related to the substance 


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injected. It is important that standard precautions and procedures be followed to avoid injury from 
fainting. Fainting is usually transient and managed by having the subject lie down and elevate 
his/her legs. 
Drawing blood and IM injection may cause infection. The use of aseptic (sterile) technique will 
make infection at the site where blood will be drawn or where the vaccination will be given 
extremely unlikely. 
Risks of study vaccines  
• mRNA-1273, mRNA-1273.351, mRNA-1273.617.2 and mRNA-1273.529 
mRNA-1273 was granted full FDA approval in 2022 and more than 200 million doses of mRNA-
1273 have been administered in the US alone as of early 2022.36 While the other SARS-CoV-2 
mRNA vaccine candidates manufactured by Moderna have been given to a small number of 
individuals in the setting of clinical trials, the safety profile of these vaccine candidates is believed 
to be largely similar to the approved prototype vaccine. The total amount of immunogens within 
any study vaccine will be 50 mcg, similar to the authorized boost dose of mRNA-1273. 
Immediate systemic allergic reactions (e.g., anaphylaxis) can occur following any vaccines. For 
the mRNA-1273 vaccines, the rate of anaphylaxis is around 2.5 cases per million doses 
administered.37 Most of these reactions have onset within 30 minutes of vaccination and most of 
these events occurred in persons with a prior history of allergy. As a precaution, all subjects will 
remain under observation at the study site for at least 30 minutes after injection. Risk management 
also includes exclusion of participants with history of anaphylaxis, urticaria, or other significant 
adverse reaction requiring medical intervention after receipt of a vaccine or nanolipid particle. 
Infrequently, people who have received dermal fillers might experience swelling at or near the site 
of filler injection (usually face or lips) following administration of a dose of an mRNA-1273 
vaccine. The swelling appears to be temporary and resolves with medical treatment, including 
corticosteroid therapy. COVID-19 vaccines can be administered to people who have received 
injectable dermal fillers who have no contraindications or precautions for vaccination.38 
Reactogenicity has been noted after mRNA-1273 vaccination. Local (pain, redness, swelling and 
pruritus) and systemic adverse effects (headache, myalgia, fatigue, joint pain, chills, and fever) are 
relatively common, most are of mild or moderate severity and are limited to the first few days after 
vaccination.39 A small percentage of participants may experience late local inflammatory 
reactions, with onset seven or more days after, usually the first vaccination, and characterized by 
redness in the deltoid area of the upper arm and/or pain or itching.39 These reactions are self-
limited and are not a contraindication to subsequent vaccinations in the vaccination series. 
Laboratory abnormalities (including increases in liver function tests and serum lipase levels) 
following injection were observed in clinical studies with similar mRNA-based vaccines. These 
abnormalities were without clinical symptoms or signs and returned toward baseline, pre-
vaccination (Day 1) values over time. The clinical significance of these observations is unknown. 
Myocarditis and pericarditis have been reported following mRNA vaccines in a younger 
population (mostly in adolescents and young adults), and are more common in males especially 
after the second dose of mRNA-1273 and within a few days following receipt of the vaccines.40 
The rate per million second doses given in a 7-day risk period in individuals between the ages of 


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18-39 years of age is estimated to be around 33 per million.41 Symptoms can include chest pain, 
shortness of breath, or palpitations. Whilst some severe cases have been reported, most cases have 
been associated with full resolution of symptoms in the short term; however, long-term follow-up 
is limited.42 It is not known whether the risk of myocarditis or pericarditis is increased following 
additional doses of the vaccine, though data after a third dose of mRNA vaccine are reassuring 
especially with the extended interval between primary series and booster doses compared to the 
doses given within the primary series.43-45 
There is limited experience with administration of an additional dose of the mRNA COVID-19 
vaccines, and it is possible that this additional dose may be associated with more frequent or more 
severe adverse events. 
Further details are provided in the FDA-approved fact sheet and current IB.  
• BNT162b2, BNT162b2 (B.1.351) BNT162b2 (B.1.1.529) and bivalent vaccines for 
Stage 4 (with BA.1 + Wildtype or BA.4/BA.5 + Wildtype) 
BNT162b2 was granted full FDA approval in 2021 and more than 300 million doses of 
BNT162b2 have been administered in the US alone as of early 2022. While the other SARS-
CoV-2 mRNA vaccine candidates manufactured by Pfizer have been given to a small number of 
individuals in the setting of clinical trials, the safety profile of these vaccine candidates is 
believed to be largely similar to the approved wildtype (prototype) vaccine. The total amount of 
immunogens within any study vaccine will be 30 mcg, similar to the authorized boost dose of 
BNT162b2. 
Immediate systemic allergic reactions (e.g., anaphylaxis) can occur following any vaccines. For 
the BNT162b2 vaccine, the rate of anaphylaxis is around 11 cases per million doses 
administered.46 Most of these reactions have onset within 15 minutes of vaccination and most of 
these events occurred in persons with a prior history of allergy. As a precaution, all subjects will 
remain under observation at the study site for at least 30 minutes after injection. Risk management 
also includes exclusion of participants with history of anaphylaxis, urticaria, or other significant 
adverse reaction requiring medical intervention after receipt of a vaccine or nanolipid particle. 
Reactogenicity has been noted after BNT162b2 vaccination. Local (pain, redness, swelling and 
pruritus) and systemic adverse effects (headache, myalgia, fatigue, lethargy, decreased appetite, 
night sweats, malaise, joint pain, diarrhea, nausea, vomiting, chills, and fever) are relatively 
common, most are of mild or moderate severity and are limited to the first few days after 
vaccination.47  Lymphadenopathy has been reported in < 1% of study participants. A subset from 
Study C4591001 Phase2/3 participants of 306 adults at least 18 through 55 years of age who 
completed the primary BNT162b2 two-dose course, received a booster dose (third dose) of 
BNT162b2 ~6 months (range of 4.8 to 8.0 months) after receiving Dose 2. The most frequent 
reactogenicity in participants 18 through 55 years of age were injection site pain (>80%), fatigue 
(>60%), headache (>40%), myalgia (>30%), chills and arthralgia (>20%). 
Myocarditis and pericarditis have been reported following BNT162b2 vaccines in a younger 
population (mostly in adolescents and young adults), and are more common in males especially 
after the second dose of BNT162b2 and within a few days following receipt of the vaccines.40 
According to one study, the rate in individuals 18-24 years of age is 5 times lower after BNT162b2 
second dose compared to mRNA-1273 second dose. Symptoms can include chest pain, shortness 


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of breath, or palpitations. Whilst some severe cases have been reported, most cases have been 
associated with full resolution of symptoms in the short term; however, long-term follow-up is 
limited.40 It is not known whether the risk of myocarditis or pericarditis is increased following 
additional doses of the vaccine, though data after a third dose of mRNA vaccine are reassuring 
especially with the extended interval between primary series and booster doses compared to the 
doses given within the primary series.40  
There is limited experience with administration of an additional dose of the mRNA COVID-19 
vaccines, and it is possible that this additional dose may be associated with more frequent or more 
severe adverse events.  
Further details are provided in the FDA-approved fact sheet and current IB.  
• CoV2 preS dTM-AS03 [B.1.351]) and CoV2 preS dTM-AS03 [D614 + B.1.351]. 
CoV2 preS dTM-AS03 has been found to have an acceptable safety profile in phase 2 and phase 
3 trials totaling 25,000 participants including more than 13,000 receiving the vaccine.24 The total 
amount of immunogens within any Sanofi-manufactured study vaccine candidates will be 5 mcg. 
Immediate systemic allergic reactions (e.g., anaphylaxis) can occur following any vaccine. In the 
phase 2 trial involving 721 participants who received at least one injection, no anaphylaxis was 
reported.23 In the phase 2 booster cohorts, one participant reported a possible anaphylactic reaction 
among 1276 participants. As a precaution, all subjects will remain under observation at the study 
site for at least 30 minutes after injection. Risk management also includes exclusion of participants 
with history of anaphylaxis, urticaria, or other significant adverse reaction requiring medical 
intervention after receipt of a vaccine.  
Reactogenicity has been noted after CoV2 preS dTM-AS03 vaccination. Local (pain, redness, 
swelling and pruritus) and systemic adverse effects (headache, myalgia, fatigue, lethargy, 
decreased appetite, night sweats, malaise, joint pain, diarrhea, chills, and fever) are relatively 
common, most are of mild or moderate severity and are limited to the first few days after 
vaccination.23 Per the current IB, a similar reactogenicity profile was observed in participants who 
received a booster dose.  
Based on the theoretical concern that vaccination with an adjuvanted vaccine containing potent 
immunostimulants may interfere with immunological self-tolerance, potential Immune-Mediated 
Diseases (pIMDs) are adverse events of special interest (AESIs) undergoing special safety 
monitoring for vaccines containing Adjuvant Systems. pIMDs are a subset of AEs that include 
autoimmune diseases and other inflammatory and/or neurological disorders of interest which may 
or may not have an autoimmune etiology. One example of pIMD is narcolepsy. An increased risk 
of narcolepsy was noted in some individuals after vaccination with Pandemrix, a different AS03-
adjuvanted vaccine for H1N1 influenza Current data suggest that cases of narcolepsy seen 
immediately following the 2009/2010 pandemic were the result of an immune cascade, triggered 
by CD4 T cell cross-reactivity to HA proteins from the H1N1 virus itself and hypocretin. This 
conclusion is consistent with the position reached by the EMA in 2016 when it concluded that “a 
hypothesis that takes into account the potential role of antigen is more likely to explain the 
increased risk of narcolepsy observed with Pandemrix than hypotheses that are based on a direct 
role for the AS03 adjuvant”.48 Safety concerns regarding narcolepsy have not been identified in 
trials of AS03-adjuvanted SARS-CoV-2 vaccine candidates to date.23,24 


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There is limited experience with administration of an additional dose of COVID-19 vaccines, and 
it is possible that an additional dose may be associated with more frequent or more severe adverse 
events.  
Further details are provided in the current IB. 
Risks to Privacy 
Subjects will be asked to provide personal health information (PHI). All attempts will be made to 
keep this PHI confidential within the limits of the law. However, there is a chance that 
unauthorized persons will see the subject’s PHI. All study records will be kept in a locked file 
cabinet or maintained in a locked room at the participating site. Electronic files will be password 
protected. Only people who are involved in the conduct, oversight, monitoring, or auditing of this 
trial will be allowed access to the PHI that is collected. Any publications from this trial will not 
use information that will identify subjects by name. Organizations that may inspect and/or copy 
research records maintained at the participating site for quality assurance (QA) and data analysis 
include groups such as the IRB, NIAID and the FDA. 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by US Law. This web site will not include information that can identify subjects. 
There may be other risks, discomforts or side effects that are unknown at this time. 
Risks of Genetic Testing 
Any genetic data generated will be kept private. There may be a risk that information resulting 
from research genetic testing could be misused for discriminatory purposes. However, state and 
federal laws provide protections against genetic discrimination. Researchers will need to maintain 
confidentiality in order to be granted access to genetic information. 
2.2.2 
Known Potential Benefits 
On March 29, 2022, the FDA authorized an additional booster dose (fourth dose) of mRNA 
vaccine for adults 50 years of age or older and adults with immunocompromising conditions. 
Subsequent to this authorization, the CDC updated its guidance to permit an additional booster 
dose for these groups, acknowledging the potential benefit of a second booster for those at risk for 
severe COVID-19 illnesses as well as for those who received two doses of the Johnson & Johnson 
vaccine. The exact benefit of this second booster dose is difficult to ascertain given the design of 
the studies supporting these recommendations. Variant specific mRNA vaccine candidates have 
been shown to induce similar D614G antibody responses as the prototype mRNA vaccine (i.e. 
back boost). Therefore, receipt of a variant vaccine in this study is not expected to be inferior to 
any benefits received from a second booster dose of a Pfizer or Moderna mRNA vaccine obtained 
outside this trial (i.e. is not inferior to standard care). The Sanofi/GSK COVID-19 vaccine is not 
yet FDA authorized; the potential benefit of a booster dose is unknown.  
On August 31th, 2022, the  FDA amended the EUAs of the Moderna COVID-19 Vaccine and the 
Pfizer-BioNTech COVID-19 Vaccine to authorize bivalent formulations of the vaccines for use as 
a single booster dose at least two months following primary or booster vaccination. The updated 
bivalent booster vaccines contain two mRNA components  that code for 2 different Spike proteins 
of SARS-CoV-2 virus, one for the original or “prototype” strain Spike protein, and the other for 


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the S protein variant common in o BA.4 and BA.5 lineages of the Omicron variant of SARS-CoV-
2. Roll-out of a different bivalent vaccine, Prototype + Omicron BA.1 for use as a booster dose 
,will occur in other countries including the United Kingdom and Canada.49,50 We do know from 
this study and others conducted by the companies that antibody levels to various variants can be 
significantly increased by a fourth booster dose.  Also based on the current study and studies 
conducted by the companies,  a Prototype + Omicron BA.1 bivalent booster does increase the 
overall levels of antibody to various variants. However, there are no data to determine if one of 
these bivalent variant vaccines will provide better protection against symptomatic disease and a 
more robust immune response. Knowing that the highest risk of severe disease is still seen in the 
older population andto minimize the risk for participants in arms 16 and 17 (stage 4)  we will limit 
enrollment to individuals between the ages of 18 to 49 years.  
There may be benefit to society resulting from insights gained from participation in this study due 
to the emerging threat of the SARS-CoV-2 variants.  
 


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3. 
OBJECTIVES AND ENDPOINTS 
Table 4: Objectives and Endpoints (Outcome Measures) 
OBJECTIVES 
ENDPOINTS  (OUTCOME MEASURES) 
Primary 
 
• 
To evaluate humoral immune responses of 
candidate SARS-CoV-2 variant vaccines.  
 
Response rate, and magnitude of SARS-CoV-2-specific 
antibody binding and neutralization titers in serum 
samples as assessed via a range of assays at all 
timepoints. 
Secondary 
 
• 
To evaluate the safety of candidate SARS-
CoV-2 variant vaccines 
• 
Local and systemic solicited Adverse Events for 7 days 
following each vaccine dose. 
• 
Unsolicited Adverse Events from Dose 1 to 28 days 
following each vaccine dose. 
• 
SAEs, MAAEs, NOCMCs, AESIs, and AEs leading to 
withdrawal from the study from Dose 1 to 12 months 
after last vaccine dose. 
Exploratory 
 
• 
To assess, in at least a subset of samples, the 
B cell immune response of candidate SARS-
CoV-2 variant vaccines. 
• 
Magnitude, phenotype and percentage of SARS-CoV-2 
specific B cells, as measured by flow cytometry and 
targeted B cell subset analysis at selected time points 
post-vaccination. 
• 
To assess, in at least a subset of samples, the 
SARS-CoV-2 spike protein-specific T cell 
responses of candidate SARS-CoV-2 variant 
vaccines. 
• 
Magnitude, phenotype, and percentage of cytokine 
producing S protein T cells as measured by flow 
cytometry at selected time points post-vaccination. 
• 
To assess, in at least a subset of samples, the 
magnitude, phenotype, and percentage of 
innate immune cells with candidate SARS-
CoV-2 variant vaccines. 
• 
Magnitude, phenotype, and percentage of innate 
immune cells as measured by flow cytometry at D1 and 
14 days after each vaccination.  


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OBJECTIVES 
ENDPOINTS  (OUTCOME MEASURES) 
• 
To assess, in at least a subset of samples, the 
functional potential of SARS-CoV-2 specific 
antibodies to mediate Fc-effector functions 
across candidate SARS-CoV-2 variant 
vaccines.  
 
• 
Characterization of antigen-specific antibody by a) 
subclass, b) isotype, c) ability to interact with Fc 
receptors, d) innate immune receptors, e) lectin-like 
molecules and f) lectins at different times post-
vaccination.  
• 
Functional Fc effector assessments which may include 
quantification of antigen specific antibody-mediated 
NK cell activation (ADCC-NK) levels, antibody-
dependent cellular phagocytosis (ADCP) levels, 
antibody-dependent complement deposition (ADCD) 
and/or antibody-dependent neutrophil 
activation/phagocytosis levels at different times post-
vaccination. 
• 
To evaluate breakthrough SARS-CoV-2 
infection by sequencing strains for variant 
spike lineage and assessing anti- nucleocapsid 
serology. 
• 
Sequence analysis on breakthrough NAAT-confirmed 
SARS-CoV-2 strains at any time post-vaccination 
• 
Anti- nucleocapsid immunoassay at different times 
post-vaccination. 
 
 
 


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4. 
STUDY DESIGN 
4.1 
Overall Design 
This is a Phase 2 randomized, adaptive, open label, non-placebo controlled multi-site, multi-stage 
clinical trial in individuals, 18 years of age and older, who are in stable state of health, have 
received a complete authorized/approved vaccine series (primary series + booster either with 
homologous or heterologous vaccine products) and meet all other eligibility criteria. 
Approximately 1500 subjects will be enrolled at up to 30 clinical research sites. At enrollment, 
subjects will be stratified by i) age (18-64 and ≥ 65 years of age) (however arms 16 and 17 or stage 
4 will only enroll participants between the ages of 18-49 years) and ii) confirmed prior SARS-
CoV-2 infection, and randomly assigned to one of several study arms of variant vaccines. The 
study will target the enrollment of approximately 45% of older adults (≥ 65 years of age) for stages 
1, 2 and 3. Additionally, the study will target to enroll approximately 20% enrollment of 
participants with a history of confirmed SARS-CoV-2 infection. It is estimated that another 10-
30% will have undiagnosed prior infection.  Taken together, we anticipate about 40% of the total 
population will have prior infection. The study team will decide, based on latest epidemiology, if 
enrollment of participants in any particular groups are slowed in order to ensure good 
representation of previously infected and not previously infected.   
The adaptive design of this study will include additional arms, an increase in sample size, or 
additional vaccine doses or different dosing and provide rapid information about the 
immunogenicity and the safety of candidate SARS-CoV-2 variant vaccines to inform near term 
public health policy. This trial will provide proof of concept on how variant vaccines could shift 
the immune response to become more specific to the VOCs’ antigens or broaden the antigenic 
landscape for emergent variants.   
Study arms and stages are described in Section 1.1.  
Screening can occur up to 28 days prior to the first dose of study product or on Day 1 prior to 
administration of Dose 1. Safety will be assessed during the study and blood will be drawn for 
immunogenicity assays at enrollment and in-person follow-up visits. Swabs will be self-collected 
or collected by staff at unscheduled illness visits to evaluate breakthrough SARS-CoV-2 infection 
(symptomatic infection or asymptomatic infection with a positive SARS-CoV-2 test outside the 
study).  
Schedules of assessments are found in Section 1.2. 
4.2 
Scientific Rationale for Study Design 
An open-label study will facilitate the need for rapid review and dissemination of study data for 
public health reasons. Safety findings are not expected to be dissimilar from Phase 1/2/3 studies 
conducted for similar vaccine constructs. Randomization will improve comparisons between the 
different arms. Each stage will contain an arm with the prototype vaccine with the exception of 
stage 4.  


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Selected arms will assess 2 study doses of vaccine candidates to assess if 2 doses provide a more 
durable response and more specific to variant viruses.  
We chose the interval of 4 months since a recent study performed by our investigators showed that 
an interval of 3 months between primary series and boost had acceptable safety and 
immunogenicity responses.19  
4.3 
Justification for Doses 
The dosages of mRNA vaccines selected are those authorized for booster doses under EUA, and 
previously shown in prior studies to elicit good immune responses with no major safety concerns. 
In an open label study of participants in the Moderna Phase 3 clinical trial who received a single 
50 mcg booster dose of mRNA-1273 ≥ 6 months after a primary series, a 13 fold rise in antibody 
titers against D614G was noted from pre-boost levels as well as a 17-fold rise in in titers against 
the B.1.617.2 variant.20 This is now the CDC recommended dose for booster vaccinations with the 
Moderna mRNA-1273 product in immunocompetent adults, to be given at least 5 months from the 
last inoculation in the primary series.51 Similarly, in a recent study, boosting with a 50 mcg total 
antigen dose of a bivalent mRNA-1273.213 vaccine (a 1:1 mix of beta and delta variant mRNA) 
produced only modestly lower antibody titers than using a 100 mcg booster dose.21 A separate 
study evaluating safety and immunogenicity of multiple boost strategies suggests that a 
heterologous boost strategy generates antibody and neutralizing responses and that 100 mcg of 
mRNA-1273 (the authorized dose at the time) is likely higher than needed for a booster dose after 
primary mRNA series.52 In addition, surveillance data indicate that following an mRNA boost, 
local and systemic reactions are less common and myocarditis is rarely reported, suggesting that 
the currently authorized doses are safe.45 These findings support the evaluation of mRNA-1273, 
mRNA-1273.351, mRNA-1273.617.2 and mRNA-1273.529 at total dosages of 50 mcg per 
vaccination.  
For BNT162b2, the dose is the same for primary or booster doses in adults. In an open-label 
clinical study, immunogenicity and safety of a fourth dose of either 30 mcg of BNT162b2 (Pfizer–
BioNTech) or 50 mcg of mRNA-1273 (Moderna) administered 4 months after the third dose was 
assessed in 154 and 120 health care workers, respectively.25 After the fourth dose, both messenger 
RNA (mRNA) vaccines increased neutralizing antibody titers to D614G, B.1.617.2 and B.1.1.529 
by a factor of 9 to 10 and were slightly higher than those achieved after the third dose.25 There 
were no significant adverse events with only mild system and local reactogenicity reported which 
was comparable with previous doses of mRNA vaccines. The bivalent booster of BNT162b2  was 
authorized by the FDA based  on pre-clinical data (Omicron BA.4/BA.5 + prototype).53  
For CoV2 preS dTM-AS03 vaccines, none is currently approved. The dose used for booster 
vaccination is as established in the phase 2 trial and is the adjuvanted formulation with 5 mcg for 
any variant vaccine candidate in stage 3.24 That booster dose increased neutralizing antibody titers 
when used as a heterologous (18-30 times) or homologous (≥ 84 times) boost.24 However, no data 
exist on CoV2 preS dTM-AS03 vaccines as a second boost after primary series with mRNA or 
adenoviral vectored vaccines. 


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5. 
STUDY POPULATION 
All participants will have received a complete (primary and booster) US approved/authorized 
vaccine series. The US population has received either homologous primary series and boost (i.e. 
Moderna mRNA-1273 for 1st dose, second dose, and booster), or heterologous boosters, and 
some were infected with SARS-CoV-2 either prior to or after vaccination. This trial will enroll 
this immunologically diverse population, to ensure any findings are applicable to the larger 
population.  
Based on CDC data about use of primary vaccine or boost (https://covid.cdc.gov/covid-data-
tracker/#vaccinations_vacc-total-admin-rate-total), it is estimated that of people in the US that 
have received a primary vaccine series and booster: 
50% will have received Pfizer primary series and Pfizer boost, 
37% will have received Moderna primary series and Moderna boost, 
4% will have received Pfizer primary series and Moderna boost, 
3% will have received Moderna primary series and Pfizer boost, 
1% will have received Janssen primary series and Janssen boost, 
2% will have received Janssen primary series and Moderna boost, 
2% will have received Janssen primary series and Pfizer boost. 
Additionally, approximately 20% of the US population has been infected with SARS-CoV-2, 
likely higher with asymptomatic infections.54 
It is anticipated the enrollment into this trial will be similar to these proportions.  
Subject Inclusion and Exclusion Criteria must be confirmed by a study clinician, licensed to 
make medical diagnoses and listed on the Form FDA 1572. No exemptions are granted on 
Subject Inclusion or Exclusion Criteria in DMID-sponsored studies. 
5.1 
Inclusion Criteria 
See Inclusion Criteria in Section 1.1.  
5.2 
Exclusion Criteria 
See Exclusion Criteria in Section 1.1. 
5.2.1 
Exclusion of specific populations 
The effects of SARS-CoV-2 vaccines on the developing fetus are not known, though there are 
data to suggest that mRNA vaccines are safe. Pregnant subjects will not be eligible for the trial as 
the immune responses to vaccines can be different than non-pregnant subjects. Children will not 
be included in this trial as presently there are limited safety data in adults for the variant strains.  
5.3 
Inclusion of Vulnerable Subjects 
No vulnerable subjects will be enrolled in this trial.  
5.4 
Lifestyle Considerations 
During this study subjects are asked to: 


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• Follow public health guidance on preventing SARS-CoV-2 infection. 
5.5 
Screen Failures 
Screening and enrollment visits may be combined. However, the participating site PI or qualified 
designee is to review the inclusion and exclusion criteria and determine the subject’s eligibility 
for the study. Individuals who do not meet the criteria for participation in the study (screen 
failure) can be rescreened if the exclusionary condition is considered to be temporary in nature 
by the investigator.  
Only the following information will be collected on screen failures: demographics (age, screen 
number, sex, ethnicity, and race) and reason for ineligibility. Subjects who are found to be 
ineligible will be told the reason for ineligibility. 
5.5.1 
Strategies for Recruitment and Retention 
The study will target recruitment of racial and ethnic diversity of the community in which the study 
will be conducted. Potential subjects will learn about the study via IRB-approved recruitment 
strategies, including direct mailing, recruitment from an IRB-approved trial registry, press 
releases, social media and local advertisements/flyers. Screening will begin with a brief approved 
telephone call from study staff. Information about the study will be presented to potential subjects 
and questions about their health and ability to comply with the study visit schedule will be asked 
of potential subjects to presumptively determine eligibility. Appointments will be made at the 
research clinic for potential subjects who are interested in the study for further screening 
procedures and additional protocol-specific information. 
5.5.2 
Retention 
Study retention strategies will include education and explanation of the study schedule and 
procedures during screening and enrollment/baseline visits and restriction of enrollment to 
persons who can attend all study visits. Participating subjects will be reminded of subsequent 
visits during each visit, and study staff will contact subjects prior to appointments. Study staff 
will contact subjects who miss appointments to encourage them to return for completion of 
safety evaluations. 
5.5.3 
Compensation Plan for Subjects 
Subjects may be compensated for their participation in this trial. Compensation will be in 
accordance with local IRB requirements, and subject to local IRB approval. Reimbursements will 
be disbursed at specific timepoints during the study with the amount contingent on completing 
study procedures. 
5.5.4 
Costs 
There is no cost to subjects for the research tests, procedures/evaluations or study product while 
taking part in this trial. Procedures and treatment for clinical care may be billed to the subject, 
subject’s insurance or third party.


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6. 
STUDY PRODUCT 
6.1 
Study Product(s) and Administration 
6.1.1 
Study Product Description 
mRNA-1273 (prototype), mRNA-1273.351 (Beta), mRNA-1273.617.2 (Delta) and mRNA-
1273.529 (Omicron) 
mRNA-1273 (0.2 mg/mL) is an LNP dispersion containing an mRNA that encodes for the pre 
fusion stabilized S protein of the Wuhan-Hu-1 strain of SARS-CoV-2. mRNA-1273 consists of 
an mRNA Drug Substance that is manufactured into LNPs composed of the proprietary ionizable 
lipid, SM-102, and 3 commercially available lipids, cholesterol, 1,2-distearoyl-sn-glycero-3-
phosphocholine (DSPC), and PEG2000 DMG. 
mRNA-1273.351 (0.1 mg/mL) is formulated in the same way but contains mRNA that encodes 
for the prefusion stabilized S protein of the B.1.351 (Beta) variant SARS-CoV-2 strain. 
mRNA-1273.617.2 (0.2 mg/mL) is formulated in the same way but contains mRNA that 
encodes for the prefusion stabilized S protein of the B.1.617.2 (Delta) variant SARS-CoV-2 
strain. 
mRNA-1273.529 (0.2 mg/mL) is formulated in the same way but contains mRNA that encodes 
for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain. 
BNT162b2 (wildtype), BNT162b2 (B.1.351, Beta), BNT162b2 (B1.1.529, Omicron), 
BNT162b2 bivalent  (wildtype and  Omicron BA.1) and BNT162b2 bivalent (wildtype and 
Omicron BA.4/BA.5) 
BNT162b2 (500 mcg/mL for stage 2) is a preservative-free, sterile dispersion of RNA 
formulated in LNP in aqueous cryoprotectant buffer. mRNA encodes for the pre fusion stabilized 
S protein of the ancestral strain of SARS-CoV-2.  
BNT162b2 (B.1.351) (500 mcg/mL for stage 2) is formulated in the same way but contains 
mRNA that encodes for the prefusion stabilized S protein of the B.1.351 (Beta) variant SARS-
CoV-2 strain. 
BNT162b2 (B.1.1.529)(500 mcg/mL for stage 2) is formulated in the same way but contains 
mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant 
SARS-CoV-2 strain. 
BNT162b2 bivalent (wildtype and  Omicron BA.1 100mcg/mL for stage 4) is formulated in 
the same way but contains mRNA that encodes for the prefusion stabilized S protein of the 
Omicron BA.1 variant SARS-CoV-2 strain and the ancestral strain of SARS-CoV-2.. 
BNT162b2 bivalent (wildtype and  Omicron BA.4/BA.5 100mcg/mL for stage 4) is 
formulated in the same way but contains mRNA that encodes for the prefusion stabilized S 
protein of the Omicron BA.4/BA.5 variant SARS-CoV-2 strain and the ancestral strain of SARS-
CoV-2. 
 


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CoV2 preS dTM-AS03 [D614] (prototype), CoV2 preS dTM-AS03 [B.1.351] (Beta), and 
CoV2 preS dTM-AS03 [D614 + B.1.351] (prototype + Beta) 
CoV2 preS dTM-AS03 [D614] (Recombinant COVID-19 Vaccine 20 mcg/mL + AS03) is a 
liquid formulation made of recombinant protein placed in a formulation buffer and to be mixed 
with equal volumes of AS03 adjuvant (supplied separately) at the study site before 
administration. The antigen solution contains the Spike protein sequence of the ancestral strain of 
SARS-CoV-2.  AS03 is an adjuvant system containing α-tocopherol and squalene in an oil/water 
emulsion. For this formulation, the antigen and AS03 vials are not packaged in a carton box 
together but are supplied as individual vials. 
CoV2 preS dTM-AS03 [B.1.351] (Recombinant COVID-19 Vaccine B1.351 20 mcg/mL+ 
AS03) is formulated in the same way but contains the Spike protein sequence of the B.1.351 
(Beta) variant SARS-CoV-2 strain.  Both antigen and AS03 vials are packaged in a carton box. 
CoV2 preS dTM-AS03 [D614 + B.1.351] (Recombinant COVID-19 Bivalent Vaccine 10/10 
mcg/mL + AS03) is formulated in the same way but contains the Spike protein sequences of the 
ancestral and B.1.351 (Beta) variant SARS-CoV-2 strains.  Both antigen and AS03 vials are 
packaged in a carton box.Diluent: 0.9% NaCl for injection, USP 
The USP grade 0.9% NaCl or normal saline for injection is a sterile, nonpyrogenic, isotonic 
solution; each mL contains NaCl 9 mg. It contains no bacteriostatic agent, antimicrobial agent, 
preservatives, or added buffer and is supplied only in single-dose containers. This product should 
be used to dilute the vaccine to the desired concentration. 
6.1.2 
Dosing and Administration 
 mRNA-1273, mRNA-1273.351, mRNA-1273.617.2 and mRNA-1273.529 
mRNA-1273 (0.2 mg/mL), mRNA-1273.351 (0.1 mg/mL), mRNA-1273.529 (0.2 mg/mL), and 
mRNA-1273.617.2 (0.2 mg/mL).   
Products will be used alone or in combination as specified in Table 1, and will be diluted in 0.9% 
NaCl for injection, USP to obtain an antigen content of 50 mcg in a 0.5 mL dose. Each dose will 
be administered via IM injection into the deltoid muscle. 
The expiration time of the dosing syringe containing the prepared study vaccine is 8 hours at room 
temperature after the solution is drawn into the dosing syringe. 
When applicable, the second dose of study vaccine can be administered in either arm regardless of 
the arm that previously administered.  
BNT162b2, BNT162b2 (B.1.351), BNT162b2 (B1.1.529, Omicron), BNT162b2 bivalent 
(wildtype and  Omicron BA.1) and BNT162b2 bivalent (wildtype and Omicron BA.4/BA.5) 
BNT162b2, BNT162b2 (B.1.351) and BNT162b2 (B.1.1.529 Omicron) at 500 mcg/mL 
concentration for stage 2 and  will be used alone or in combination as specified in Table 1 and will 
be diluted in 0.9% NaCl for injection, USP to obtain an antigen content of 30 mcg in a 0.3 mL 
dose. Each dose will be administered via IM injection into the deltoid muscle. 


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For stage 4, BNT162b2 bivalent (wildtype and Omicron BA.1 or wildtype and BA.4/BA.5) are 
provided at 100 mcg/mL concentration and neither dilution nor mixing are needed for these 
formulations. 
CoV2 preS dTM-AS03 [D614], CoV2 preS dTM-AS03 [B.1.351], and CoV2 preS dTM-AS03 
[D614 + B.1.351] 
The multi-dose vial of CoV2 preS dTM antigen, either monovalent or bivalent antigen, will be 
mixed with the multi-dose vial of AS03 adjuvant prior to administration to obtain an antigen 
content of 5 mcg in a 0.5 mL dose. Vaccine formulations will be prepared in the CoV2 preS dTM 
antigen vials by adding an equal volume of adjuvant. A maximum of 10 doses can be used from a 
single prepared investigational vaccine final product. 
After mixing the investigational product, the combined final product can be held for up to 12 hours 
post preparation at 2 to 8 °C or at controlled room temperatures (up to 23 to 27 °C) and must be 
protected from light. Syringes containing the final product should be covered to limit exposure to 
light as well. 
 
For all stages , the pharmacist will prepare a single dose for each subject based on study arm 
assignment.  
See the protocol-specific Manual of Procedures (MOP) for detailed information on the preparation, 
labeling, storage, and administration of vaccine for each cohort. Vaccine preparation will be 
performed by the participating site’s research pharmacist on the same day of vaccine 
administration to the subject. 
Subjects will be observed in the clinic for at least 30 minutes post each vaccination. Any AEs will 
be recorded on the appropriate DCF prior to discharge from the clinic 
6.1.3 
Dose Modifications 
Not applicable. 
6.2 
Accountability/Handling/Storage/Preparation 
6.2.1 
Acquisition and Accountability 
All the vaccines (and diluents as needed) will be provided by the DMID repository: 
DMID Clinical Materials Services Contract 
Fisher BioServices 
20439 Seneca Meadows Parkway 
Germantown, MD 20876 
Phone: 240-477-1350 
Fax: 240-477-1360 
Email: DMID.CMS@thermofisher.com 
All study products will be shipped to the clinical research site upon request and approval from 
DMID. 
Accountability 


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The participating site PI is responsible for study product distribution and disposition and has 
ultimate responsibility for study product accountability. The participating site PI may delegate to 
the participating site’s research pharmacist responsibility for study product accountability. The 
participating site’s research pharmacist will be responsible for maintaining complete records and 
documentation of study product receipt, accountability, dispensation, storage conditions, and final 
disposition of the study product(s).  
Destruction 
After the study treatment period has ended or as appropriate over the course of the study after 
study product accountability has been performed, disposition of unused and used study product 
vials should occur as noted: 
Unused and used study product vials: 
Should be destroyed on-site following applicable site procedures or by the site’s selected 
destruction vendor. Following the site’s procedure for the destruction of hazardous 
material or study product destruction policy/SOP when destroying used and unused items 
with a second staff member’s observation and signed verification (two signatures) that 
the vials were discarded. 
A certificate of destruction or documentation of destruction should be provided to the 
sponsor and retained in the Pharmacy Binder once completed. 
Used syringes may be destroyed in accordance with site-specific SOPs. 
6.2.2 
Formulation and Appearance 
mRNA-1273, mRNA-1273.351, mRNA-1273.617.2 and mRNA-1273.529 are provided as a 
sterile liquid for injection, white to off-white suspension in appearance. 
BNT162b2, BNT162b2 (B.1.351) and BNT162b2 (B.1.1.529 Omicron) and BNT162b2 bivalent 
(wildtype and Omicron BA.1 or wildtype and  Omicron BA.4/BA.5) are provided as a sterile, 
clear colorless liquid for injection. 
CoV2 preS dTM-AS03 [D614], CoV2 preS dTM-AS03 [B.1.351], and CoV2 preS dTM-AS03 
[D614 + B.1.351] antigen formulations are provided as a sterile, clear, colorless solution of 
SARS-CoV-2 prefusion S proteins. The antigen solutions can contain endogenous particles. If 
present, these light-colored particles are slow sinking and suspended in solution. AS03 adjuvant 
is a whitish to yellowish homogenous milky liquid emulsion. After mixing, the vaccine is a 
whitish to yellowish homogeneous milky liquid emulsion. 
Diluent: 0.9% NaCl for injection, USP 
The USP grade 0.9% NaCl or normal saline for injection is a sterile, nonpyrogenic, isotonic 
solution; each mL contains NaCl 9 mg. It contains no bacteriostatic agent, antimicrobial agent, 
preservatives, or added buffer and is supplied only in single-dose containers.  
Each of the study products will be labeled according to manufacturer specifications and include 
the statement “Caution: New Drug Limited by Federal Law to Investigational Use.” 
6.2.3 
Product Storage and Stability 


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The storage of mRNA-1273,BNT162b2, and CoV2 preS dTM-AS03 vials depend on the 
presentation (i.e. commercial lots have different storage conditions from investigational lots).  For 
these reasons, refer to the MOP for storage conditions for vaccine candidates as well as storage of 
diluent.  
Prepared doses are stable for clinical in-use for:  
• mRNA-1273, mRNA-1273.351, mRNA-1273.617.2 and mRNA-1273.529: up to 8 hours 
at room temperature  
•  BNT162b2 bivalent (wildtype and Omicron BA.1 or wildtype and Omicron BA.4/BA.5): 
up to 12 hours between 2 and 30C (35 to 86F)  after vial is first punctured. 
• BNT162b2, BNT162b2 (B.1.351) and BNT162b2 (B.1.1.529 Omicron BA.1 and 
BA.4/BA.5): up to 6 hours at room temperature after 1st vial is punctured. 
• CoV2 preS dTM-AS03 [D614], CoV2 preS dTM-AS03 [B.1.351], and CoV2 preS dTM-
AS03 [D614 + B.1.351]: up to 12 hours post preparation at 2 to 8 °C or at controlled room 
temperatures (up to 23 to 27 °C) and must be protected from light 
 
Study Product Temperature Accountability 
The temperature of the storage unit must be manually recorded daily (excluding non-business days 
and holidays, as applicable) and continuously monitored and recorded during the course of this 
trial per site-specific SOPs, and documentation will be maintained. If the temperature fluctuates 
outside of the required range, the affected study product(s) must be quarantined at the correct 
storage temperature and labeled as ‘Do Not Use’ (until further notice).  
Study product must be stored in a secure area with limited access (pharmacy staff only) and must 
be stored as above.  
6.2.4 
Preparation 
Refer to the protocol-specific MOP for details about preparation. 
6.3 
Measures to Minimize Bias: Randomization and Blinding 
6.3.1 
Treatment Assignment Procedures 
Per International Council for Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use (ICH) guideline E6: GCP, screening records will be kept at the participating site to 
document the reason why an individual was screened, but failed trial entry criteria. The reasons 
why individuals failed screening will be recorded in Advantage eClinical, the electronic data 
capture (EDC) system that the Statistical and Data Coordinating Center (SDCC) develops and 
manages.  
Once consented and upon entry of demographic data and confirmation of eligibility for this trial, 
the subjects will be enrolled. 
6.3.2 
Randomization and Blinding 
Subjects will be randomized to study intervention in an equal allocation ratio for each stage.  The 
study will be open label and study sites will administer product to a subject according to which 
study arm the subject has been assigned. Sites will be asked to recruit for all arms within a stage. 


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6.3.3 
Blinding and Masking Procedures 
This study is unblinded. 
6.4 
Study Intervention Compliance 
Each dose of study product will be administered by a member of the clinical research team that is 
qualified and licensed to administer the study product. Administration and date, time, and 
location of injection will be recorded on the appropriate DCF. 
6.5 
Concomitant Therapy 
Concomitant medications include prescription medications and vaccinations taken within 28 
days of screening or Day 1. Topical, ophthalmic and otic medications, herbal supplements and 
vitamins will not be collected. This information is asked to assess eligibility. Only COVID-19 
vaccination received at any time in the past will be captured in the trial database.  After 
enrollment, immunosuppressant drugs, COVID-19 vaccines received outside of the study as well 
as COVID-19 related treatment and prophylaxis should be reported at any time during study 
participation and captured in the trial database. At each study visit, if there are new SAEs, 
concomitant medications should be recorded on the appropriate DCF and not included in the 
database unless these are immunosuppressant drugs, COVID-19 vaccines received outside of the 
study or COVID-19 related treatment and prophylaxis. 
6.5.1 
Rescue Medicine 
Not Applicable. 
6.5.2 
Non-Research Standard of Care 
Not Applicable. 


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7. 
STUDY INTERVENTION DISCONTINUATION AND 
SUBJECT DISCONTINUATION/WITHDRAWAL 
7.1 
Halting Criteria and Discontinuation of Study Intervention 
7.1.1 
Halting Criteria 
The study will be halted in a given arm if any of the following events occur following any dose: 
1- Any subject experiences an SAE after administration of the vaccine that is considered 
related to vaccine. 
2- Any subject experiences laryngospasm, bronchospasm or anaphylaxis within 24 hours 
after administration of vaccine that is considered related to vaccine. 
3- Any subject experiences ulceration, abscess or necrosis at the injection site that is 
considered related to vaccine administration. 
4- Two (2) or more subjects experience an immediate IgE-mediated allergic reaction such as 
generalized urticaria (defined as occurring at three or more body parts) that is considered 
related to vaccine. 
5- Three (3) or more subjects experience a Grade 3 AE (unsolicited) related to vaccine 
administration, in the same Preferred Terms based on the Medical Dictionary for 
Regulatory Activities (MedDRA) coding. 
6- One (1) or more participant with myocarditis and/or pericarditis meeting the CDC case 
definition that is considered related to study vaccine. 
7.1.2 
Criteria for Continuation of Dosing and Redosing 
In the event a halting rule is met: 
An unscheduled safety analysis by the DSMB will be required for approval of further enrollment 
Further administration of any study vaccine boost arms will be suspended until an assessment by 
the DSMB takes place. 
7.1.3 
Discontinuation of Study Intervention 
For any arm of the study where participants will receive more than a single dose, subjects will 
need to be reassessed prior to the second dose. The following events constitute contraindications 
to any further administration of study vaccines. If any of these events occur during the study 
prior to the next vaccination, the subject will not receive the next vaccination but will be 
encouraged to continue study participation for safety and immunogenicity evaluations as per the 
Schedule of Activities for subjects receiving a single dose of vaccine.  
• Any clinically significant medical condition that, in the opinion of the participating site 
PI or appropriate sub-investigator, poses an additional risk to the subject if he/she 
continues to participate in the study. 
• Receipt of SARS-CoV-2 vaccine outside of the study or SARS-CoV-2 immunoglobulin, 
monoclonal antibody or plasma antibody. 


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• Confirmed symptomatic or asymptomatic SARS-CoV-2 infection after entry. 
• Anaphylaxis or unexpected systemic hypersensitivity reaction following the 
administration of a prior study vaccination. 
• Any SAE judged to be related to vaccine. 
• Pregnancy. 
• New information becomes available that makes further participation unsafe or interferes 
with the evaluation of responses. 
• 
Termination of this trial. 
7.1.3.1 
Delay of Study Vaccination 
If any of these events occur at the time scheduled for vaccination, the subject may be vaccinated 
at a later date. 
• 
Acute moderate or severe infection with or without fever at the time of vaccination. 
• 
Fever, defined as oral temperature ≥38.0°C (100.4°F) at the time of vaccination. 
Subjects with a minor illness without fever, as assessed by the participating site PI or appropriate 
sub-investigator, can be administered vaccines. Subjects with an oral temperature of 38.0°C 
(100.4°F) or higher will be re-contacted within the window specified in the SOA and re-
evaluated. 
For subjects for whom a second dose is planned, it is preferred that the vaccination still occur 
within the window specified in the SOA if possible but delays outside the windows are permitted 
(would still be a protocol deviation).  If intercurrent SARS- CoV-2 infection occurs between the 
first and prior to the planned second study dose, no second vaccination will be given. 
7.1.4 
Follow-up for Subjects that Discontinued Study Intervention 
Discontinuation of study intervention does not require discontinuation from the study, and the 
remaining study procedures should be completed. Participants who do not receive a second dose 
will revert to the schedule of activities (SOA) for single dose participants.   
If a clinically significant finding is identified, including, but not limited to, changes from 
baseline, after enrollment, the participating site PI or qualified designee will determine if any 
change in subject management is needed (Table 3).  
7.1.5 
Follow up for Subjects with a Suspicion for Myocarditis and/or Pericarditis 
In the event that a subject develops symptoms which in the judgement of the investigator, is 
consistent with a case of suspected myocarditis and/or pericarditis within 4 weeks from 
vaccination, the site will conduct an unscheduled illness visit. Additionally, a serum sample will 
be obtained and stored for potential biomarker testing at a central laboratory. The site will 
coordinate an appropriate diagnostic workup to make a determination of probable or confirmed 
myocarditis and/or pericarditis which may include, but is not limited to, an ECG, cardiac 
troponin testing (T or I) and referral to a cardiologist (directly, or through the emergency 
department or primary care clinic). The suspected myocarditis and/or pericarditis case should be 
reported to the DMID Medical Monitor within 24 hours of site awareness. 


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The definitions below are intended to serve as a guide to help in the reporting of suspected cases 
of myocarditis and/or pericarditis; however, the diagnosis of suspected cases is left to the 
investigator’s clinical judgement.  
7.1.5.1 
Probable Case of Acute Myocarditis 
Presence of ≥ 1 new or worsening of the following clinical symptoms:  
• Chest pain/pressure/discomfort  
• Dyspnea/shortness of breath/pain with breathing  
• Palpitations  
• Syncope  
AND  
Presence of ≥ 1 new finding of the following:  
• Troponin level above upper limit of normal (any type of troponin)  
• Abnormal electrocardiogram (ECG or EKG) or rhythm monitoring findings consistent with 
myocarditis which includes at least one of the following:  
▪ ST segment or T-wave abnormalities  
▪ Paroxysmal or sustained atrial, supraventricular, or ventricular arrhythmias  
▪ AV nodal conduction delays or intraventricular conduction defects  
• Abnormal cardiac function or wall motion abnormalities on echocardiogram  
• Cardiac magnetic resonance imaging (cMRI) finding consistent with myocarditis55  
AND  
• No other identifiable cause of the symptoms and findings 
 
7.1.5.2 
Confirmed Case of Acute Myocarditis  
Meets the case definition for a probable case  
AND 
• Histopathologic confirmation of myocarditis (using Dallas criteria)56 OR 
• cMRI findings consistent with myocarditis in the presence of troponin level above upper limit 
of normal (any type of troponin)  
AND 
• No other identifiable cause of the symptoms and findings  
7.1.5.3 
Acute Pericarditis Case Definition  
Presence of ≥ 2 new or worsening of the following clinical features57:  


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• Acute chest pain (Typically described as pain made worse by lying down, deep inspiration, or 
cough; and relieved by sitting up or leaning forward, although other types of chest pain may 
occur)  
• Pericardial rub on examination  
• New ST-elevation or PR-depression on EKG  
• New or worsening pericardial effusion on echocardiogram or magnetic resonance imaging  
 
7.1.5.4 
Myopericarditis Case Definition  
Participants who meet criteria for both myocarditis and pericarditis may be described under 
myopericarditis. 
 
7.2 
Subject Withdrawal from the Study and Replacement 
Subjects are free to withdraw from participation in the study at any time upon request, without 
any consequence. 
A study subject will be discontinued from participation in the study if any of the following 
reasons occur prior to initial dosing: 
• Request by the subject to terminate participation. 
• Initial vaccine is not administered. 
A subject may be removed from the study for the following reasons post initial dosing; however, 
whenever possible the subject should be followed for safety and immunogenicity evaluations per 
protocol: 
• Subject becomes pregnant before receiving the additional dose of vaccine. 
• Study non-compliance to protocol requirements that in the opinion of the participating 
site PI or appropriate sub-investigator poses an increased risk or compromises the validity 
of the data. 
• Lost to follow-up. 
• If the subject met an exclusion criterion for participation in the study (either newly 
developed or not previously recognized) that precludes further study participation. 
• Request of primary care provider, the IRB, FDA, or NIAID. 
• Medical disease or condition, or new clinical finding(s) for which continued 
participation, in the opinion of the participating site PI or appropriate sub-investigator 
might compromise the safety of the subject, interferes with the subject’s successful 
completion of this study, or interferes with the evaluation of responses. 
• If any AE or situation occurs such that continued participation in the study would not be 
in the best interest of the subject. 


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• Any SAE judged to be related to vaccine. 
If the subject agrees, every attempt will be made to follow all AEs through resolution or 
stabilization. 
Subjects who withdraw, or are withdrawn from this study, or are lost to follow-up after signing 
the informed consent form (ICF) and administration of the study product will not be replaced. 
Subjects who withdraw, or are withdrawn from this study, or are lost to follow-up after signing 
the ICF but before administration of the first study product may be replaced. 
The reason for subject discontinuation or withdrawal from the study will be recorded on the 
appropriate DCF. 
7.3 
Lost to Follow-Up 
A subject will be considered lost to follow-up if he or she fails to appear for a follow-up 
assessment. Extensive effort (i.e., generally three documented contact attempts via telephone 
calls, e-mail, etc., made on separate occasions) will be made to locate or recall the subject, or at 
least to determine the subject’s health status. These efforts will be documented in the subject’s 
study file. 


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8. 
STUDY ASSESSMENTS AND PROCEDURES 
8.1 
Screening and Immunogenicity Assessments 
8.1.1 
Screening or Enrollment/Baseline Procedures 
There is a small amount of risk to subjects who report that they are in stable state of health but 
have an unknown health problem at the time of the enrollment/baseline visit. Screening 
assessments can occur up to 28 days before or at the subject’s first vaccination visit (Day 1). At 
the screening (optional) or enrollment visit, and prior to any other study-related activities, the 
participating site PI or appropriate designee will provide the subject with detailed study 
information and will obtain written informed consent. 
Some or all of the following assessments are performed during the screening (optional) or 
enrollment visit to determine eligibility requirements as specified in the inclusion and exclusion 
criteria: 
• 
Obtain a complete medical history. 
• 
Demographic information. 
• 
Review pre-study medications at screening and record on the appropriate DCF (refer to 
Section 6.5). Review all licensed/approved and any experimental vaccines (the review of 
licensed/approved vaccines other than COVID-19 vaccines is limited to 28 days prior to 
screening/enrollment). 
• 
Review any participation in investigational trials in the last 28 days. 
• 
Measure vital signs (HR, BP, and oral temperature), and height and weight for 
determination of BMI. 
• 
Targeted physical examination.  A targeted exam is one that is targeted to assess any 
symptoms or medical conditions.  The site PI (or designee) determines what exam is 
needed. An individual with no symptoms and no relevant medical history (or a medical 
history that is unlikely to reveal anything on medical exam) may not need any physical 
exam. 
• Urine pregnancy test (in subjects of childbearing potential). If urine pregnancy is done at 
separate screening visit, repeat urine pregnancy test will be done within 24 hours of study 
vaccine administration. 
• 
Review inclusion and exclusion criteria. 
The screening process can be suspended prior to complete assessment at any time if exclusions are 
identified by the study team. 
Study subjects who qualify for inclusion will be contacted and scheduled for enrollment and first 
vaccination within the window for enrollment unless the screening and vaccination are scheduled 
on the same day. 
If a physiologic parameter, e.g., vital signs, is abnormal and potentially clinically significant, then 
the measurement may be repeated if, in the judgment of the participating site PI or appropriate 
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stress, anxiety or “white coat syndrome”) or other source of error. A physiologic parameter may 
also be repeated if there is a technical problem with the measurement caused by malfunctioning, 
or an inappropriate measuring device (i.e., inappropriate-sized BP cuff). 
A subject may be re-screened if there is a transient disease status (e.g., subject complained of a 
“cold or fever” and met a temporary delaying enrollment criterion of acute illness or fever), or if 
a protocol eligibility criterion that is not met at the initial time of screening, will be met by 
rescreening at a later date (e.g., a medication taken within exclusionary window at the time of first 
screening that would not be within exclusionary window at a later rescreen). 
Subjects will be provided the results of abnormal clinical findings necessitating follow-up at the 
discretion of the participating site PI or appropriate designee. Research laboratory results will not 
be provided to the subject with the exception of urine pregnancy test and SARS-CoV-2 local 
testing results.  
The screening and first vaccination procedures both can be conducted at the enrollment visit. 
8.1.2 
Immunogenicity Evaluations 
Humoral Immunogenicity Assays: 
The following humoral immunogenicity assays may be performed: 
• IgG ELISA or Multiplex MSD antibody binding assays to SARS-CoV-2 proteins (may 
include nucleocapsid protein, and multiple variant Receptor binding domains and variant 
spike proteins). 
• Neutralization assays using SARS-CoV-2 variant specific S-pseudotyped viruses. 
• Neutralization assay using different strains of live SARS-CoV-2. 
• Characterization of antigen-specific antibody by a) subclass, b) isotype, c) ability to 
interact with Fc receptors, d) innate immune receptors, e) lectin-like molecules and f) 
lectins at different times post-vaccination.   
• Functional Fc effector assays which may include quantification of antigen specific 
antibody-mediated NK cell activation (ADCC-NK) levels, antibody-dependent cellular 
phagocytosis (ADCP) activity, Antibody-dependent complement deposition (ADCD) 
and/or Antibody-dependent neutrophil activation/phagocytosis activity.  
Preparation of blood samples and shipping instructions for serological immunogenicity assays are 
outlined in the protocol-specific MOP. Inability (e.g., failure of venipuncture) to collect all 
baseline samples on Day 1 will not exclude the subject from further participation in this study as 
long as a minimum of baseline serum for serological immunogenicity assays is collected (refer to 
protocol-specific MOP). 
Cellular Immunology Assays: 
This trial may also investigate innate, B and T cell immune responses using multiparametric flow 
cytometry. Refer to the protocol-specific immune monitoring plan for details. 
Preparation of blood samples and shipping instructions for cellular immunology assays are 
outlined in the protocol-specific MOP. 


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The volume of venous blood to be collected for immunogenicity evaluations is presented in Table 
2 and Table 3. 
8.1.3 
Samples for Suspected SARS-CoV-2 infection 
In the event that a subject develops symptoms compatible with COVID-19, the site will follow 
with an unscheduled Illness Visit in person or by phone (with the participant self-collecting the 
swab). If a participant is asymptomatic but tests positive for COVID-19 outside the study, the 
site will follow the same procedure. Wide discretion is given to sites for the assessment of 
COVID-19 illness. Guidance can be found at the CDC website (2021 Case Definition):  
Coronavirus Disease 2019 (COVID-19) 2021 Case Definition | CDC 
The following intervention will be performed in the event of an illness visit: 
• Nasal swabs for PCR and sequencing 
One to two nasal swabs will be obtained for the purposes of 1) conducting qualitative analysis to 
assess for the presence of SARS-CoV-2 virus, and 2) conducting PCR quantitation/sequencing in 
the event that nasal swab #1 is positive for SARS-CoV-2. If a test outside the study was found to 
be positive only one swab is needed for sequencing. 
The first nasal swab, as applicable, will be processed at the local level with results informing the 
disposition of the second nasal swab. The sites will freeze and store the second swab (refer to 
MOP for labeling, storage, and shipping instructions) for potential shipment to the central 
repository for testing. 
8.1.4 
Samples for Genetic/Genomic Analysis 
8.1.4.1 
Genetic/Genomic Analysis 
DNA obtained from B-cells may be sequenced to identify B cell receptors and monoclonal 
antibodies. The DNA data may be used to synthesize antigen-specific antibodies to characterize 
antibody binding. Secondary research samples may also be used for other genomic analysis, 
including, but not limited to, single nucleotide polymorphisms (SNP) arrays, human leukocyte 
antigen (HLA) typing, transcriptomic analysis, evaluation of the immune response to the 
vaccine, and/or evaluation of any AE from the vaccine. 
8.1.4.2 
Genetic Privacy and Confidentiality 
Any genetic data generated will be kept private. Informed consent permitting data sharing will be 
part of the consent process. Subjects will be informed that the evolution of genomic technology 
and analytical methods raises the risk of re-identification, even when specimens are de-
identified. No data that may identify specific subjects will be kept with the genetic data. 
8.1.4.3 
Management of Results 
All genetic testing in this protocol will be performed for research purposes only and is not 
performed in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. 
Therefore, results will not be shared with the subjects. 
8.1.5 
SARS-CoV-2 infection  


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Confirmed SARS-CoV-2 infection at any time during the study, defined as a positive RT-PCR 
test performed by the site or using a non-site testing method (RT-PCR or antigen test), will be 
documented. While this event would occur on study, it is not a typical AE and therefore captured 
as an exploratory efficacy assessment.   
8.1.6. 
Retained Samples for Biomarker Testing  
For all subjects, sera will be collected at  Day 4 and Day 60 (as applicable) and stored for 
potential biomarker assessment at a central laboratory and comparison to testing of an aliquot of 
sera obtained at Day 1 and Day 57, respectively 
Additionally, in the event that a subject develops symptoms compatible with myocarditis and/or 
pericarditis or the site is notified of a diagnosis of myocarditis and/or pericarditis, occurring 
within 4 weeks from vaccination, the site will follow with an in-person unscheduled illness and 
collect serum for potential biomarker testing at a central laboratory.    
The following sample will be collected: 
• 4 mL SST collection for potential biomarker testing at a central laboratory 
 
8.2 
Safety and Other Assessments 
All safety endpoints for this trial are obtained by reporting of adverse events. 
• New symptoms will be queried with both broad open-ended questions at the Day 8 
telephone call and by specifically asking about symptoms of chest pain, shortness of 
breath or palpitations that may represent myocarditis and/or pericarditis. 
• Data on new medical conditions, doctors' office visits (outside of routine care), 
emergency room visits, and hospitalizations will be collected. 
• Memory Aid: All subjects will complete a Memory Aid from the time of each 
vaccination through 7 days after each vaccination. Subjects will be asked to confirm 
completion of the Memory Aid and will be queried on the presence of any grade 3 
symptoms. Based on the information provided, subjects may be asked to return to the 
clinic for evaluation. Fourteen days after each vaccination, Memory Aids are reviewed 
thoroughly with the subject and confirmed data recorded in the CRF.   
 
As these are similar to licensed vaccines, there are no laboratory assessments for safety that will 
be done for this trial. 
8.3 
Adverse Events and Serious Adverse Events 
8.3.1 
Definition of Adverse Event (AE) 
AE means any untoward medical occurrence associated with the use of an intervention in humans, 
whether or not considered intervention-related [21 CFR 312.32 (a)]. An AE can therefore be any 
unfavorable and unintended sign, symptom or disease temporally associated with the use of 
medicinal (investigational) product. 


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Any medical condition that is present at the time that the subject is screened will be considered as 
baseline and not reported as an AE. However, if the severity of any pre-existing medical condition 
increases, it should be recorded as an AE. 
AEs can be further divided into solicited AEs and unsolicited AEs. Solicited AEs are those that 
are described in the package insert as local or systemic reactogenicity occurring in the first 7 days 
after vaccination. Unsolicited AEs are those events that the subject reports occurring without being 
queried about the specific event.  
AEs will be assessed for severity and relationship to study intervention (Section 8.3.4). Reporting 
of all AEs, solicited and unsolicited, will occur during the period from study product 
administration on Day 1 through 28 days after each vaccination. After 28 days post last vaccination 
through the end of study, only SAEs, Protocol Specified AESIs, MAAEs, NOCMCs, and AEs 
leading to withdrawal from the study will be reported. 
All AEs, solicited and unsolicited, will be captured on the appropriate DCF. Solicited AEs will be 
regarded as related to the study product and will not require separate entry into the AE log. 
Information to be collected for unsolicited AEs includes event description, date of onset, 
assessment of severity, relationship to study product and alternate etiology (assessed only by those 
with the training and authority to make a diagnosis and listed on the Form FDA 1572 as the 
participating site PI or appropriate sub-investigator), date of resolution, seriousness, and outcome. 
AEs occurring during the study-collection and reporting period will be documented appropriately 
regardless of relationship. 
AEs will be followed to resolution or stabilization. 
8.3.1.1 
Solicited Adverse Events 
Solicited AEs are anticipated local and systemic AEs for which consistent collection of 
information is desired. Study clinicians will follow and collect resolution information for any 
reactogenicity symptoms that are not resolved within 7 days. 
Solicited AEs (i.e., reactogenicity) will be collected using a memory aid and confirmed data 
recorded on the appropriate DCF from the time of each vaccination through 7 days post each 
vaccination. 
For this study, solicited AEs will be: 
• Injection site Pain 
• Injection site Erythema 
• Injection site Edema/Induration 
• Headache 
• Fatigue 
• Myalgia 
• Arthralgia 
• Nausea 
• Fever 
• Chills 


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8.3.1.2 
Unsolicited Adverse Events 
All AEs spontaneously reported by the subject and/or in response to an open question from study 
staff or revealed by observation, physical examination or other diagnostic procedures must be 
recorded on the appropriate DCF. 
Unsolicited AEs of all severities will be reported from the time of study product administration 
through 28 days post each vaccination. 
After 28 days post last vaccination through the end of study, only SAEs, AESIs, NOCMCs,  
MAAEs, and AEs leading to withdrawal from the study (as detailed in Section 8.3.7 and 8.3.9) 
will be reported. 
8.3.2 
Definition of Serious Adverse Event (SAE) 
An SAE is defined in 21 CFR 312.32 as follows: “An AE or suspected adverse reaction is 
considered serious if, in the view of either the participating site PI or appropriate sub-investigator 
or the sponsor, it results in any of the following outcomes: 
• Death, 
• a life-threatening AE, 
• inpatient hospitalization or prolongation of existing hospitalization, 
• a persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions, 
• or a congenital anomaly/birth defect. 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical judgment, they 
may jeopardize the patient or subject and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias 
or convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse.” 
“Life-threatening” refers to an AE that at occurrence represents an immediate risk of death to a 
subject. An event that may cause death if it occurs in a more severe form is not considered life-
threatening. Similarly, a hospital admission for an elective procedure is not considered an SAE. 
All SAEs, as with any AE, will be assessed for severity and relationship to study intervention. 
All SAEs will be recorded on the appropriate SAE DCF. 
All SAEs will be followed through resolution or stabilization by a study clinician, licensed to 
make medical diagnoses and listed on the Form FDA 1572 as the participating site PI or 
appropriate sub-investigator. 
All SAEs will be reviewed and evaluated by DMID and will be sent to the DSMB (for periodic 
review unless related) and IRB/IEC as needed. 
8.3.3 
Suspected Unexpected Serious Adverse Reactions (SUSAR) 


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A SUSAR is any SAE where a causal relationship with the study product is at least reasonably 
possible but is not listed in the Investigator’s Brochure (IB), Package Insert, and/or Summary of 
Product Characteristics. 
8.3.4 
Classification of an Adverse Event 
The determination of seriousness, severity and causality will be made by an on-site investigator 
who is qualified (licensed) to diagnose AE information, provide a medical evaluation of AEs and 
classify AEs based upon medical judgment. This includes, but is not limited to, physicians, 
physician assistants and nurse practitioners. 
8.3.4.1 
Severity of Adverse Events 
All AEs, AESIs, NOCMCs, MAAEs, SAEs, and AEs leading to withdrawal from the study will 
be assessed for severity, according to the toxicity grading scales in the FDA “Toxicity Grading 
Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical 
Trials”. 
For AEs not included in the FDA-defined grading system, the following guidelines will be used 
to describe severity. 
Mild (Grade 1): Events that are usually transient and may require only minimal or no 
treatment or therapeutic intervention and generally do not interfere with the subject’s 
usual activities of daily living. 
Moderate (Grade 2): Events that are usually alleviated with additional specific 
therapeutic intervention. The event interferes with usual activities of daily living, causing 
discomfort but poses no significant or permanent risk of harm to the research subject. 
Severe (Grade 3): Events interrupt usual activities of daily living, or significantly affect 
clinical status, or may require intensive therapeutic intervention. Severe events are 
usually incapacitating. 
AEs characterized as intermittent require documentation of onset and duration of each episode. 
The start and stop date of each reported AE will be recorded on the appropriate DCF. Changes in 
the severity of an AE will be documented to allow an assessment of the duration of the event at 
each level of intensity. 
8.3.4.2 
Relationship to Study Intervention 
For each reported adverse reaction, the participating site PI or qualified designee must assess the 
relationship of the event to the study product using the following guidelines: 
• Related – The AE is known to occur with the study intervention, there is a reasonable 
possibility that the study intervention caused the AE, or there is a temporal relationship 
between the study intervention and event. Reasonable possibility means that there is 
evidence to suggest a causal relationship between the study intervention and the AE. 
• Not Related – There is not a reasonable possibility that the administration of the study 
intervention caused the event, there is no temporal relationship between the study 
intervention and event onset, or an alternate etiology has been established. 


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Solicited adverse events reported in the 7 days after each vaccination are considered related to 
study product unless they are also recorded as an unsolicited event, in which case the relationship 
to study product will be determined by the PI or qualified designee. 
8.3.5 
Time Period and Frequency for Event Assessment and Follow-Up 
For this study: 
• Solicited Adverse Events will be collected for 7 days following each vaccine dose. 
• Unsolicited AEs will be collected until 28 days after each vaccination. 
• AESIs, NOCMCs, MAAEs, SAEs, and AEs leading to withdrawal from the study  will be 
collected from Day 1 through the end of the study. 
8.3.6 
Adverse Event Reporting 
8.3.6.1 
Investigators Reporting of AEs 
Information on reportable AEs should be recorded on the appropriate DCF. All clearly related 
signs, symptoms and results of diagnostic procedures performed because of an AE should be 
grouped together and recorded as a single diagnosis. If the AE is a clinical laboratory abnormality 
that is part of a clinical condition or syndrome, it should be recorded as the syndrome or diagnosis 
rather than the individual clinical laboratory abnormality. Each AE will also be described in terms 
of duration (start and stop date), severity, association with the study product, action(s) taken, and 
outcome. 
8.3.7 
Serious Adverse Event Reporting 
8.3.7.1 
Investigators Reporting of SAEs 
Any AE that meets a protocol-defined criterion as an SAE must be submitted immediately (within 
24 hours of site awareness) on an SAE form to the DMID Pharmacovigilance Group, at the 
following address: 
DMID Pharmacovigilance Group 
Clinical Research Operations and Management Support (CROMS) 
6500 Rock Spring Dr. Suite 650 
Bethesda, MD 20817, USA 
SAE Hot Line: 1-800-537-9979 (US) or 1-301-897-1709 (outside US) 
SAE FAX Number: 1-800-275-7619 (US) or 1-301-897-1710 (outside US) 
SAE Email Address: PVG@dmidcroms.com 
In addition to the SAE form, select SAE data fields must also be entered into Advantage eClinical. 
Refer to the protocol-specific MOP for details regarding this procedure. 
Other supporting documentation of the event may be requested by the DMID Pharmacovigilance 
Group and should be provided as soon as possible. The DMID Medical Monitor will review and 
assess the SAE for regulatory reporting and potential impact on study subject safety and protocol 
conduct. 


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At any time after completion of the study, if the participating site PI or appropriate sub-investigator 
becomes aware of an SAE that is suspected to be related to study product, the participating site PI 
or appropriate sub-investigator will report the event to the DMID Pharmacovigilance Group. 
8.3.7.2 
Regulatory Reporting of SAEs 
Following notification from the participating site PI or appropriate sub-investigator, DMID, as the 
IND sponsor, will report any SUSAR in an IND safety report to the FDA and will notify all 
participating site PIs (i.e., all PIs to whom the sponsor is providing drug under its IND(s) or under 
any PI’s IND(s)) of potential serious risks from clinical studies or any other source, as soon as 
possible. DMID will report to the FDA any unexpected fatal or life-threatening suspected adverse 
reaction as soon as possible, but in no case later than 7 calendar days after the sponsor’s initial 
receipt of the information. If the event is not fatal or life-threatening, the IND safety report will be 
submitted within 15 calendar days after the sponsor determines that the information qualifies for 
reporting as specified in 21 CFR Part 312.32. Relevant follow-up information to an IND safety 
report will be submitted as soon as the information is available. Upon request from FDA, DMID 
will submit to the FDA any additional data or information that the agency deems necessary, as 
soon as possible, but in no case later than 15 calendar days after receiving the request. 
SAEs that are not SUSARs will be reported to the FDA at least annually in a summary format 
which includes all SAEs. 
8.3.8 
Reporting Events to Subjects 
Subjects will be informed of any major safety event that occurs as part of their participation in 
this trial. 
8.3.9 
Adverse Events of Special Interest (AESIs), New Onset of Chronic Medical 
Conditions (NOCMCs) and Medically Attended Adverse Events (MAAEs)  
Adverse Events of Special Interest (AESIs) represent any events for which additional data 
(besides the standard AE data) are desired. An adverse event of special interest (serious or 
nonserious) is one of scientific and medical concern specific to the sponsor’s product or program, 
for which ongoing monitoring and rapid communication by the investigator to the sponsor is 
required. Such an event may require further investigation in order to characterize and understand 
it. Depending on the nature of the event, rapid communication by the trial sponsor to other parties 
(e.g., regulators) may also be required. These may be at the request of the regulatory agency, 
industry partner or DMID, and driven by a regulatory requirement, or known or potential risk from 
the product or class.  
 
Protocol Specified AESIs are listed in Section 12. In addition, for stage 3, AESIs will also include 
a list of pIMD. 
 
Potential Immune-mediated Diseases (pIMDs)  
Potential immune-mediated diseases (pIMDs). pIMDs are a subset of AESIs that include 
autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may 
or may not have an autoimmune etiology. AESIs that need to be recorded and reported as pIMDs 
for Stage 3 participants are listed in Section 12. 


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However, the investigator will exercise their medical and scientific judgement in deciding whether 
other diseases have an autoimmune origin (that is pathophysiology involving systemic or organ-
specific pathogenic autoantibodies) and should also be recorded as a pIMD. 
 
When there is enough evidence to make any of the diagnoses mentioned in Section 12, the AESI 
must be reported as a pIMD. Symptoms, signs or conditions which might (or might not) 
represent the above diagnoses, should be recorded and reported as AEs but not as pIMDs until 
the final or definitive diagnosis has been determined, and alternative diagnoses have been 
eliminated or shown to be less likely. 
New Onset of Chronic Medical Conditions (NOCMCs) are defined as any new ICD diagnosis 
(per current International Statistical Classification of Diseases and Related Health Problems) that 
is applied to the subject during the course of the study, after receipt of the study agent, that is 
expected to continue for at least 3 months and requires continued health care intervention. 
Medically Attended Adverse Events (MAAEs) are defined as a hospitalization < 24 hours, 
emergency room visit or an otherwise unscheduled visit to or from medical personnel for any 
reason; and considered related or possibly related to study product. 
 
All AESIs, MAAEs, NOCMCs, are assessed, recorded, and followed as described above under 
AEs. The following need to be reported to DMID pharmacovigilance: 
All AESIs, MAAEs or NOCMCs that meet SAE criteria (reported within 24 hours); 
Any AESIs even if not SAE (reported within 24 hours); 
MAAEs only when requested by the sponsor; 
NOCMCs only when requested by the sponsor. 
As indicated, these should be reported to DMID Pharmacovigilance Group at the following 
address: 
DMID Pharmacovigilance Group 
Clinical Research Operations and Management Support (CROMS) 
6500 Rock Spring Dr. Suite 650 
Bethesda, MD 20817, USA 
SAE Hot Line: 1-800-537-9979 (US) or 1-301-897-1709 (outside US) 
SAE FAX Number: 1-800-275-7619 (US) or 1-301-897-1710 (outside US) 
 SAE Email Address: PVG@dmidcroms.com 
8.3.10 
Reporting of Pregnancy 
Pregnancy is not an AE. Pregnancy outcomes will be reported on the appropriate DCF if a new 
pregnancy occurs within 3 months from last study vaccine dose.   If pregnancy is associated with 
an SAE to the mother or fetus (e.g., miscarriage or preeclampsia), the SAE should be reported to 
PVG.   
8.4 
Unanticipated Problems 
8.4.1 
Definition of Unanticipated Problems (UPs) 


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The Department of Health and Human Services (DHHS) OHRP considers unanticipated 
problems involving risks to subjects or others to include, in general, any incident, experience, or 
outcome that meets all of the following criteria: 
 Unexpected in terms of nature, severity, or frequency given (a) the research procedures 
that are described in the protocol-related documents, such as the IRB-approved research 
protocol and informed consent document; and (b) the characteristics of the subject 
population being studied; 
 Related or possibly related to participation in the research (“possibly related” means there 
is a reasonable possibility that the incident, experience, or outcome may have been 
caused by the procedures involved in the research); and 
 Suggests that the research places subjects or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized. 
8.4.2 
Unanticipated Problem Reporting 
To satisfy the requirement for prompt reporting, UPs will be reported using the following 
timeline: 
 UPs that are SAEs will be reported to the IRB, to the DMID Pharmacovigilance Group, 
and in the clinical database within 24 hours of the participating site PI or appropriate sub-
investigator becoming aware of the event per the above-described SAE reporting process. 
 UPs that are SAEs will be collected from Day 1 through the end of the study. 
 Any other UP will be reported to the IRB and in the clinical database within 3 days of the 
participating site PI or appropriate sub-investigator becoming aware of the problem. 
8.4.3 
Reporting Unanticipated Problems to Subjects 
Subjects will be informed of any UPs that occur as part of their participation in this trial. 
 


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9. 
STATISTICAL CONSIDERATIONS 
9.1 
Statistical Hypotheses 
This is a phase 2, open-label, multi-site clinical trial that is not designed to test a specific 
hypothesis. Rather, it is intended to obtain preliminary estimates in adults of the safety and 
immunogenicity of additional booster doses of SARS-CoV-2 variant vaccines.  
9.2 
Sample Size Determination  
9.2.1 
Sample Size Calculation for the Safety Endpoint 
Rare AEs are not demonstrable in a clinical study of this size; however, the probabilities of 
observing one or more AEs given various true event rates are presented in Table 5. With the 
assumption that all enrolled subjects will likely complete immunizations and safety visits in this 
relatively short duration study, the following statistical considerations apply. With approximately 
100 subjects in each arm there is a greater than 99.9% chance of observing at least one AE of 
probability 10%. With approximately 50 subjects in each of the strata subgroups (or arms), there 
is a 99.5% chance of observing at least one AE of probability 10%. With approximately 25 subjects 
in each of the strata subgroup combinations (assuming equal numbers and 100 per arm), there is a 
92.8% chance of observing at least one AE of probability 10%. Finally, with approximately 15 
subjects in the smallest of the strata subgroup combinations (assuming unequal numbers and 100 
per arm or 50 per arm), there is a 79.4% chance of observing at least one AE of probability 10%. 
Therefore, if no AEs of a given type occur in a group (or strata), we can be relatively confident 
that they will occur in fewer than 10% of people if the vaccine is implemented.  
 Table 5: Probability of Observing one or more Adverse Event for Various Event Rates in 
one vaccine group (or strata).  
N 
“True” Event 
Rate 
Probability of Observing ≥ 
1 events (%) 
N 
“True” Event 
Rate 
Probability of Observing ≥ 
1 events (%) 
100 
0.1% 
9.5 
50 
0.1% 
4.9 
0.5% 
39.4 
0.5% 
22.2 
1.0% 
63.4 
1.0% 
39.5 
2.0% 
86.7 
2.0% 
63.6 
3.0% 
95.2 
3.0% 
78.2 
4.0% 
98.3 
4.0% 
87 
5.0% 
99.4 
5.0% 
92.3 
10.0% 
>99.9 
10.0% 
99.5 
15.0% 
>99.9 
15.0% 
>99.9 
20.0% 
>99.9 
20.0% 
>99.9 
30.0% 
>99.9 
30.0% 
>99.9 


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N 
“True” Event 
Rate 
Probability of Observing ≥ 
1 events (%) 
N 
“True” Event 
Rate 
Probability of Observing ≥ 
1 events (%) 
25 
0.1% 
2.5 
15 
0.1% 
1.5 
0.5% 
11.8 
0.5% 
7.2 
1.0% 
22.2 
1.0% 
14 
2.0% 
39.7 
2.0% 
26.1 
3.0% 
53.3 
3.0% 
36.7 
4.0% 
64.0 
4.0% 
45.8 
5.0% 
72.3 
5.0% 
53.7 
10.0% 
92.8 
10.0% 
79.4 
15.0% 
98.3 
15.0% 
91.3 
20.0% 
99.6 
20.0% 
96.5 
30.0% 
>99.9 
30.0% 
99.5 
9.2.2 
Sample Size Calculation for the Immunogenicity Endpoints 
The primary objective of this study is to evaluate the magnitude and durability of SARS-CoV-2 
specific antibody titers in serum samples. This objective is descriptive in nature and will be 
accomplished by estimating 95% confidence intervals (CI) for the geometric mean titer (GMT) 
at each timepoint when samples are collected. 
The precision with which the GMT can be estimated from observed data depends on the standard 
deviation (SD) of the measurements, on the logarithmic scale, and the sample size. Table 6 
displays two-sided 95% confidence intervals for the GMT for several values of the observed 
antibody titer. Table 6 also shows results assuming up to 10% attrition. 
Table 6: Two-sided 95% confidence intervals based on observing a particular average loge-
antibody titer in subjects’ vaccine groups and potential strata sizes  
Observed 
average loge 
antibody titer 
SD of loge 
antibody 
titer 
95% confidence interval of  
GMT in vaccine groups and strata 
N = 100 
N = 50 
N = 25 
N = 15 
loge (5) 
0.5 
(4.5, 5.5) 
(4.3, 5.8) 
(4.1, 6.1) 
(3.8, 6.6) 
loge (20) 
(18.1, 22.1) 
(17.4, 23.1) 
(16.3, 24.6) 
(15.2, 26.4) 
loge (50) 
(45.3, 55.2) 
(43.4, 57.6) 
(40.7, 61.5) 
(37.9, 66) 
loge (100) 
(90.6, 110.4) 
(86.8, 115.3) 
(81.4, 122.9) 
(75.8, 131.9) 
loge (250) 
(226.4, 276.1) 
(216.9, 288.2) 
(203.4, 307.3) 
(189.5, 329.8) 
loge (500) 
(452.8, 552.1) 
(433.8, 576.3) 
(406.8, 614.6) 
(379.1, 659.5) 
loge (1000) 
(905.6, 1104.3) 
(867.5, 1152.7) 
(813.5, 1229.2) 
(758.1, 1319) 
loge (5) 
1.0 
(4.1, 6.1) 
(3.8, 6.6) 
(3.3, 7.6) 
(2.9, 8.7) 


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Observed 
average loge 
antibody titer 
SD of loge 
antibody 
titer 
95% confidence interval of  
GMT in vaccine groups and strata 
N = 100 
N = 50 
N = 25 
N = 15 
loge (20) 
(16.4, 24.4) 
(15.1, 26.6) 
(13.2, 30.2) 
(11.5, 34.8) 
loge (50) 
(41, 61) 
(37.6, 66.4) 
(33.1, 75.6) 
(28.7, 87) 
loge (100) 
(82, 121.9) 
(75.3, 132.9) 
(66.2, 151.1) 
(57.5, 174) 
loge (250) 
(205, 304.9) 
(188.2, 332.2) 
(165.5, 377.8) 
(143.7, 435) 
loge (500) 
(410, 609.7) 
(376.3, 664.3) 
(330.9, 755.5) 
(287.4, 869.9) 
loge (1000) 
(820, 1219.5) 
(752.6, 1328.7) 
(661.8, 1511) 
(574.8, 1739.8) 
*  Assumes approximately 10% attrition. 
9.3 
Populations for Analyses 
The safety analysis population includes all enrolled subjects who received at least one dose of 
study vaccine. Analyses for the safety population will include safety reported through the end of 
the study. The modified intent-to-treat (mITT) population includes all subjects who received at 
least one dose of vaccine and contributed both pre- and at least one post-vaccination venous 
blood sample for immunogenicity testing for which valid results were reported. 
In the final analysis, protocol deviations will be reviewed to determine which protocol deviations 
may affect the analysis. The per protocol (PP) population will then be defined – and this includes 
all subjects in the mITT subset with the following exclusions: 
• 
Data from all available visits for subjects found to be ineligible at baseline. 
• 
Data from all visits subsequent to the protocol deviations that are considered to affect the 
science. 
• 
Data from any visit that occurs substantially out of window. 
9.4 
Statistical Analyses 
Interim analyses of safety and immunologic response data will be done, as needed. 
The final analysis will be performed after the final data lock and clinical study report (CSR) 
completed when all primary safety endpoint data and all secondary immunogenicity endpoint data 
are available and received by the SDCC. Any available data from the exploratory immunogenicity 
endpoints may also be included in the CSR. Remaining exploratory immunogenicity endpoint data 
may be included in an addendum to the CSR, publication of manuscript(s), or other report(s). 
Abbreviated analysis plans that describe planned analyses to facilitate dissemination of study data 
for public health reasons, including manuscript publication(s), will be developed by the SDCC as 
needed. A full statistical analysis plan (SAP) will be developed by the SDCC and finalized prior 
to the primary data lock.  
9.4.1 
General Approach 


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Unless otherwise noted in the SAP, continuous variables will be summarized using the following 
descriptive statistics: n (non-missing sample size), mean, standard deviation, median, maximum 
and minimum. The frequency and percentages (based on the non-missing sample size) of 
observed levels will be reported for all categorical measures. 
9.4.2 
Analysis of the Primary Endpoint(s) 
Descriptive summaries of immunogenicity data will be presented for the mITT population. If 
there are protocol deviations which may affect the analysis, a per-protocol (PP) analysis may 
also be performed. 
Geometric Mean Titers (GMT) and Geometric Mean Fold Rise (GMFR) from baseline of SARS-
CoV-2 specific antibody binding and neutralization titers will be calculated, along with 95% CIs, 
for all groups, at each timepoint. Summaries will also be displayed graphically. Geometric Mean 
Ratio (GMRD614G) is defined as the ratio of a variant of concern to D614G ( i.e Beta to D614G) 
will also be reported for all groups, at each timepoint, along with 95% CIs.  
9.4.3 
Analysis of the Secondary Endpoints 
Section 9.4.4 describes the analyses of Safety Endpoints, which is the secondary endpoint of this 
protocol.  
9.4.4 
Safety Analyses 
Summaries and analysis of safety data will be presented for the Safety Analysis Population. 
Solicited non serious AEs will be collected from the time of each vaccination until 7 days after. 
Solicited AEs will be summarized by severity for each day post vaccination (Days 1-8) and as the 
maximum severity over all 8 days. Additionally, solicited AEs will be analyzed using standard 
techniques, such as exact confidence intervals (CI), to summarize the proportion of subjects 
reporting each symptom, any application site symptom, and any systemic symptom.  
Unsolicited non-serious AEs will be collected from the time of first vaccination through 28 days 
after each vaccination. Unsolicited AEs will be coded by MedDRA for preferred term and system 
organ class (SOC). SAEs, MAAEs, NOCMCs, AESIs, and AEs leading to withdrawal from the 
study will be collected from the time of first vaccination through 12 months after the last vaccine 
dose. The numbers of SAEs, MAAEs, NOCMCS, AESIs, and AEs leading to withdrawal from the 
study will be reported by detailed listings showing the event description, MedDRA preferred term 
and SOC, relevant dates (vaccinations and AEs), severity, relatedness, and outcome for each event. 
Non-serious unsolicited AEs will be summarized as number and percentage of subjects reporting 
at least one event in each MedDRA preferred term and SOC, cross tabulated by severity and 
relationship to study product. Additionally, the proportion of subjects and exact 95% CIs of AEs 
in aggregate and by MedDRA categories will be computed.  
9.4.5 
Baseline Descriptive Statistics 
Summaries of demographic variables such as age, sex, ethnicity, race, and prior infection status 
will be presented by vaccination arm and overall.  
9.4.6 
Planned Interim and Early Analyses 


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Data may be disseminated to public health officials and partners as needed and included in 
publications and presentations to inform the global scientific community. Early analyses will 
include safety and immunogenicity as described in Sections 9.4.6.1, 9.4.6.2, and 9.4.6.3. Further, 
the protocol team will review data periodically to confirm no halting criteria have been met as 
described in Section 7.1.1. 
Cumulative safety information, study status, and primary endpoint results may be published, 
presented at a public forum, or presented as summaries aggregated by study arm at the discretion 
of the sponsor while the study is ongoing. None of the interim analyses will include any formal 
statistical hypothesis testing; therefore, p value adjustment will not be made to any analyses.  
9.4.6.1 
Interim Safety Analyses 
Given the need for rapid review and dissemination of study data for public health reasons, AEs 
and SAEs may be reviewed as necessary outside of DSMB reviews. The DSMB may not need to 
meet (unless halting rules are met), and materials will be provided electronically. Documentation 
of review and any concerns noted will be solicited electronically. 
The DSMB will review separate cumulative AE data reports for all subjects within each arm.  
Given the safety database known for authorized/approved vaccines, there is no routine mandatory 
review by the DSMB unless halting rules are triggered.  
9.4.6.2 
Interim Immunogenicity Review 
Interim data review of immunogenicity will be performed as often as needed to inform public 
health decisions. 
Statistical analyses of immunogenicity endpoints, by vaccine arm, may be performed when 
subjects have completed key immunogenicity visits. Immunogenicity reviews may be shared with 
the DSMB, as determined by DMID. 
Data may be disseminated to public health officials and partners as needed and included in 
publications and presentations to inform the global scientific community. 
9.4.6.3 
Interim Immunogenicity and Safety Review 
Interim analyses of safety, reactogenicity, and immunologic response data may be done, as 
needed. 
9.4.7 
Sub-Group Analyses 
Subgroup analyses, by age group and infection status, may be performed. Detailed information 
will be provided in the Statistical Analysis Plan.  
9.4.8 
Tabulation of Individual Subject Data 
In general, all data will be listed, sorted by vaccine arm and subject, and when appropriate by 
visit number within subject. 
9.4.9 
Exploratory Analyses 
Summaries and analysis of immunologic assay data will be presented for the mITT population. If 
there are protocol deviations which may affect the analysis, a PP analysis may also be performed. 


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10. 
SUPPORTING DOCUMENTATION AND 
OPERATIONAL CONSIDERATIONS 
10.1 
Regulatory, Ethical, and Study Oversight Considerations 
This study will be conducted in conformity with the principles set forth in The Belmont Report: 
Ethical Principles and Guidelines for the Protection of Human Subjects of Research (US 
National Commission for the Protection of Human Subjects of Biomedical and Behavioral 
Research; April 18, 1979), and the federal policy for the Protection of Human Subjects codified 
in 45 CFR Part 46, 21 CFR Part 50 (Protection of Human Subjects), and the ICH E6(R2). 
An OHRP-registered IRB will review and approve this protocol, associated informed consent 
documents, recruitment materials, and handouts or surveys intended for the subjects, prior to the 
recruitment, screening and enrollment of subjects. The IRB review shall be in accordance with 
45 CFR 46 and 21 CFR 50, 21 CFR 56 (IRBs), and other federal, state, and local regulations and 
policies, as applicable. 
Each institution engaged in this research will hold an OHRP-approved FWA. 
Any amendments to the protocol or informed consent documents will be approved by the IRB 
before they are implemented. IRB review and approval will occur at least annually throughout 
the duration of the study. The participating site PI will notify the IRB of deviations from the 
protocol and reportable SAEs, as applicable to the IRB policy. 
DMID must receive the documentation that verifies IRB approval for this protocol, informed 
consent documents and associated documents, prior to the recruitment, screening and enrollment 
of subjects, and any IRB approvals for continuing review or amendments as required by the 
DMID. 
10.1.1 
Informed Consent Process 
Informed consent is a process that is initiated prior to an individual agreeing to participate in a 
trial and continuing throughout the individual’s trial participation. Investigators or designated 
research staff will obtain a subject’s informed consent in accordance with the requirements of 45 
CFR 46, 21 CFR 50 and 21 CFR 56 for FDA-regulated studies, state and local regulations and 
policy, and ICH E6 GCP before any study procedures or data collection are performed. The 
participating site PI or other study staff may obtain oral or written information for the purpose of 
screening, recruiting, or determining the eligibility of prospective subjects without the informed 
consent of the prospective subject if the process is approved by the IRB. 
At the first study visit, informed consent will be obtained and documented before any study 
procedures are performed. Subjects will receive a concise and focused presentation of key 
information about the clinical trial, verbally and with a written consent form. The key 
information about the purpose of the study, the procedures and experimental aspects of the study, 
study interventions/products, risks and discomforts, the expected duration of the subject’s 
participation in the trial, any expected benefits to the subject, and alternative treatments and 
procedures that may be available to the subject. The explanation will be organized and presented 
in lay terminology and language that facilitates understanding why one might or might not want 
to participate. 


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Subjects will receive an explanation as to whether any compensation and any medical treatments 
are available if injury occurs, and, if so, what they consist of, or where further information may 
be obtained. Subjects will be informed of the anticipated financial expenses, if any, to the subject 
for participating in the trial, as well as any anticipated prorated payments, if any, to the subject 
for participating in the trial. They will be informed of whom to contact (e.g., the participating site 
PI) for answers to any questions relating to the research project. Information will also include the 
foreseeable circumstances and/or reasons under which the subject’s participation in the trial may 
be terminated. The subjects will be informed that participation is voluntary and that they are free 
to withdraw from the study for any reason at any time without penalty or loss of benefits to 
which the subject is otherwise entitled. Subjects will be allowed sufficient time to consider 
participation in this research trial and have the opportunity to discuss this trial with their family, 
friends or legally authorized representative, or think about it prior to agreeing to participate. 
Subjects will be informed that records identifying the subject will be kept confidential, and, to 
the extent permitted by the applicable laws and/or regulations, will not be made publicly 
available. If the results of the trial are published, the subject’s identity will remain confidential. 
Subjects will be informed, even if identifiers are removed, that information collected from this 
research and/or specimens may be used for secondary research, including the sharing of 
deidentified data. 
Subjects will be informed that the monitor(s), auditors(s), IRB, NIAID, and regulatory 
authority(ies) will be granted direct access to the subject’s original medical records for 
verification of clinical trial procedures and/or data without violating the confidentiality of the 
subject, to the extent permitted by the applicable laws and regulations, and that, by signing a 
written ICF, the subject is authorizing such access. 
ICFs will be IRB-approved, and subjects will be asked to read and review the consent form. 
Subjects must sign the ICF prior to starting any study procedures being done specifically for this 
trial. Once signed, a copy of the ICF will be given to the subject for their records. 
New information will be communicated by the participating site PI or designee to subjects who 
consent to participate in this trial in accordance with IRB requirements. The informed consent 
document will be updated, and subjects will be re-consented per IRB requirements, if necessary. 
10.1.1.1 
Requirements for Permission by Parents/Guardians and Assent by Children (in 
case of a minor) 
Not Applicable 
10.1.1.2 
Other Informed Consent Procedures 
The rights and privacy of human subjects who participate in genomic or phenotypic research 
studies will be protected at all times. The consent process, including relevant language in the ICF, 
will provide an explanation of the potential risks to the individual study subjects and their families. 
Clinical metadata, genomic, or other datasets or a subset of the clinical and other metadata that 
may potentially identify human subjects will not be released in unrestricted databases. Subjects 
will be informed that the evolution of genomic technology and analytical methods raises the risk 
of re-identification, even when specimens are de-identified. 


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Subjects will be asked for consent to collect additional blood, nasal swabs, the use of residual 
specimens, and the sharing of genetic information and samples for secondary research. This 
extra/residual blood and corresponding serum, plasma and PBMCs will be used as back-up 
specimens for PP defined assays or designated for secondary research use and stored indefinitely 
at a designated storage facility. 
Subjects will be asked to consent specifically to genetic testing on primary and secondary research 
samples, including but not limited to transcriptomics and DNA sequencing. DNA sequencing data 
will be kept private. DNA data may be used to produce commercial antibody-based therapeutics. 
Subjects will not share in profits or commercial rights to those products. 
If subjects choose not to provide permission for extra blood and secondary research use, they will 
not be eligible for enrollment into the study. 
Collection of extra/residual samples during the course of the study will help facilitate rapid follow-
on analyses, if warranted, to provide more comprehensive scientific insights into the impact (safety 
and immunological) of the vaccine on the host response to vaccination. To maintain statistical 
power in follow-on analyses it is important that extra blood collection and secondary research use 
be included in as many subjects as possible, due to the limited sample size per treatment arm. 
The stored samples will be labeled with barcodes to maintain confidentiality. Research with 
identifiable samples and data may occur as needed, however, subject confidentiality will be 
maintained as described for this protocol and with IRB approval. 
Samples designated for secondary research use may be used for additional immunological 
assessments that may include but are not limited to antibody epitope mapping, B and T cell 
repertoire determination, non-traditional immune assay development, determination of innate 
immune factors and the ability of vaccine-induced antibodies to cross-react to different proteins 
and virus strains. These blood samples might be used in new or different immunological laboratory 
tests, to provide information for the development of new vaccines or therapeutics, or for the studies 
of SARS-CoV-2 or other infections. Secondary research using DNA may also be warranted to 
understand genetic factors involved in vaccination failures. 
Samples will not be sold for commercial profit. Although the results of any future research may 
be patentable or have commercial profit, subjects will have no legal or financial interest in any 
commercial development resulting from any future research. 
There are no direct benefits to the subject for extra specimens collected or from the secondary 
research. No results from secondary research will be entered into the subject’s medical record. 
Incidental findings will not be shared with the subject, including medically actionable incidental 
findings, unless required by law. 
Risks are associated with the additional volume of blood collected, such as anemia. Risks for loss 
of privacy and confidentiality are described below. 
Subjects may withdraw permission to use samples for secondary use at any time. They will need 
to contact the participating site and the samples will be removed from the study repository after 
this study is completed and documentation will be completed that outlines the reason for 
withdrawal of permission for secondary use of samples. Subjects who withdraw consent before 
the last visit will not have the extra blood drawn for secondary use. 


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Human Genetic Testing 
The research staff will seek the subjects’ consent for extra and residual specimens to be stored and 
used for secondary research, including genetic research, evaluating human genomic and 
phenotypic markers. The rights and privacy of human subjects who participate in genomic or 
phenotypic research studies will be protected at all times. 
The consent process will include an explanation of the potential risks to the individual subjects 
and their families associated with data submitted to an NIH data repository and subsequent sharing. 
Data that may potentially identify human subjects will not be released in unrestricted databases. 
Subjects will be informed that the evolution of genomic technology and analytical methods raises 
the risk of re-identification, even when specimens are de-identified. The consent will include 
whether individual subject data will be shared through a NIH controlled access data repository. 
Data for genomic or phenotypic research will be submitted to a controlled access data repository, 
therefore, informed consent permitting the data sharing must be documented, even if the specimens 
are de-identified. 
10.1.2 
Study Termination and Closure 
In Section 7, Study Intervention Discontinuation and Subject Discontinuation/Withdrawal, 
describes the temporary halting of the study. 
This study may be prematurely terminated if there is sufficient reasonable cause, including, but 
not limited to: 
• Determination of unexpected, significant, or unacceptable risk to subjects 
• Results of interim analysis 
• Insufficient compliance to protocol requirements 
• Data that are not sufficiently complete and/or not evaluable 
• Regulatory authorities 
If the study is prematurely terminated, the PI or designee will promptly inform study subjects 
and the IRB will be notified. The PI will assure appropriate follow-up for the subjects, as 
necessary. 
The sponsor will notify regulatory authorities as applicable. 
10.1.3 
Confidentiality and Privacy 
Subject confidentiality is strictly held in trust by the participating investigators, their staff, and the 
sponsor(s) and their agents. This confidentiality is extended to cover clinical information relating 
to subjects, test results of biological samples and genetic tests, and all other information generated 
during participation in the study. No identifiable information concerning subjects in the study will 
be released to any unauthorized third party. Subject confidentiality will be maintained when study 
results are published or discussed in conferences. 
The study monitor, other authorized representatives of the sponsor, representatives of the IRB, 
and/or regulatory agencies may inspect all documents and records required to be maintained by 
the participating site PI, including, but not limited to, medical records (office, clinic, or hospital) 


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and pharmacy records for the subjects in this study. The participating site will permit access to 
such records. 
All source records, including electronic data, will be stored in secured systems in accordance with 
institutional policies and federal regulations. 
All study data and research specimens that leave the participating site (including any electronic 
transmission of data) will be identified only by a coded number that is linked to a subject through 
a code key maintained at the participating site. Names or readily identifying information will not 
be released unless DMID approves and it aligns with the consent form, or according to laws for 
required reporting. 
Because it may be possible to re-identify de-identified genomic data, even if access to data is 
controlled and data security standards are met, confidentiality cannot be guaranteed, and re-
identified data could potentially be used to discriminate against or stigmatize subjects, their 
families, or groups. In addition, there may be unknown risks. 
As this research is funded by the NIH, it is covered by NIH policy which effectively issues the 
research a Certificate of Confidentiality (COC). By this policy, researchers cannot be forced to 
disclose or provide, in any Federal, State, or local civil, criminal, administrative, legislative, or 
other proceeding, the name of such individual or any such information, document, or biospecimen 
that contains identifiable, sensitive information about the individual and that was created or 
compiled for purposes of the research, unless such disclosure or use is made with the consent of 
the individual to whom the information, document, or biospecimen pertains. 
The Certificate cannot be used to resist a demand for information from personnel of the United 
States Government that is used for auditing or evaluation of federally funded projects, like this 
study, or for information that must be released in order to meet the requirements of the FDA. 
A COC does not prevent subjects from voluntarily releasing information about themselves or their 
involvement in this research. If any person or agency obtains a written consent to receive research 
information, then the researchers may not use the Certificate to withhold that information. 
The COC does not prevent the researchers from reporting, without the subject’s consent, 
information that would identify the subject as a subject in the research project in the case of matters 
that must be legally reported, including child and elder abuse, sexual abuse, or wanting to harm 
themselves or others. 
The release of individual private information or specimens for other research will only occur if 
consent was obtained from the individual to whom the information, document, or biospecimen 
pertains, or that the release is in compliance with applicable Federal regulations governing the 
protection of human subjects in research. 
10.1.4 
Secondary Use of Stored Specimens and Data 
Secondary Human Subject Research is the re-use of identifiable data or identifiable biospecimens 
that were collected from some other ‘‘primary’’ or ‘‘initial’’ activity, such as the data and samples 
collected in this protocol. This section will detail the samples and data available for secondary 
research. Any use of the secondary sample or data, however, will be presented in a separate 
protocol and require separate IRB approval. 


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10.1.4.1 
Samples for Secondary Research 
The following types of samples will be stored and used for secondary research: 
Residual Research Sample: Any leftover Primary Research Sample after the laboratory testing 
specified in this protocol is completed will be stored for future studies with the subject’s consent. 
Repository Research Sample: Samples will be collected with the subject’s consent in this 
protocol with the intent to store for additional research (i.e., samples collected beyond those 
needed for primary research) and will be used in future studies. Amendments to this protocol 
with additional assays may use repository research samples. 
Samples will be stored indefinitely at a DMID-designated storage facility. Each sample will be 
encoded (labeled) only with a barcode and a unique tracking number to protect subject 
confidentiality. Secondary research with coded samples and data may occur, however, subject 
confidentiality will be maintained as described for this protocol. An IRB review of the secondary 
research using coded specimens is required. 
Residual/Repository Research Samples, upon written request and approval from DMID and any 
approvals required by the site or network, may be shared for secondary research with investigators 
at the participating site, with researchers at other sites or other institutions, or company-designated 
research laboratories. The samples will not be sold or used directly for production of any 
commercial product. DMID will authorize shipment from the DMID CMS. 
The subject’s decision can be changed at any time by notifying the study doctors or nurses in 
writing. To participate in this study, subjects must consent for storage of samples for secondary 
use. If the subject subsequently changes his/her decision, the samples will be destroyed if the 
samples have not been used for research or released for a specific research project. 
10.1.4.2 
Data Sharing for Secondary Research 
Data from this study may be used for secondary research. All of the individual subject data 
collected during this study will be made available after de-identification. The SAP and Analytic 
Code will also be made available. Data will be available immediately following publication, with 
no end date. Upon written request, with provision of a methodologically sound proposal, and 
approval from DMID and any approvals required by the site or network, data may be shared for 
secondary research with investigators/researchers. The data will be available for only the purpose 
outlined in the approved proposal. 
For access to genomic data in the NIH designated controlled access database, an investigator (or 
data requestor) must submit a Data Access Request which certifies adherence to the NIH Security 
Best Practices for Controlled-Access data subject to the NIH Genomic Data Sharing (GDS) Policy. 
The participating site PI may request removal of data on individual study subjects from NIH data 
repositories in the event that a research subject withdraws or changes his or her consent. 
However, some data that have been distributed for approved research use cannot be retrieved. 
10.1.5 
Key Roles and Study Governance 
This study is sponsored by DMID. Key Roles are noted in the protocol-specific MOP. 
10.1.6 
Safety Oversight 


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10.1.6.1 
Data Safety Monitoring Board (DSMB) 
The DSMB is an independent group of at least three experts that monitors subject safety and 
advises DMID. DSMB members will be separate and independent of study staff participating in 
this trial and should not have scientific, financial, or other conflicts of interest related to this trial. 
The DSMB will consist of members with appropriate expertise to contribute to the interpretation 
of data from this trial. A quorum will consist of a simple majority. 
The DSMB will hold an organizational meeting or electronic review prior to enrollment. At this 
meeting, the DSMB will review the charter, protocol, ICF, IBs, and safety report templates. 
The DSMB will not need to meet unless halting rules are met.  The DSMB will be provided 
periodic updates on enrollment, safety, and immunogenicity. Documentation of review and any 
concerns noted will be solicited electronically. 
Ad hoc reviews will occur when trial halting criteria are met, or as requested by the sponsor or 
PI. 
Procedures for DSMB reviews/meetings will be defined in the DSMB charter. The DSMB will 
review applicable data, including, but not limited to, enrollment, demographics, dosing data, 
clinical laboratory data, and safety data, at scheduled timepoints during this trial as defined in the 
DSMB charter. 
Additional data may be requested by the DSMB, and interim statistical reports may be generated 
as deemed necessary and appropriate by DMID. As an outcome of each review/meeting, the 
DSMB will make a recommendation as to the advisability of proceeding with study product 
administration, and to continue, modify, or terminate this trial. 
10.1.7 
Clinical Monitoring 
Clinical site monitoring is conducted to ensure that the rights and well-being of trial subjects are 
protected, that the reported trial data are accurate, complete, and verifiable. Clinical Monitoring 
also ensures conduct of the trial is in compliance with the currently approved protocol/ 
amendment(s), ICH, GCP, and with applicable regulatory requirement(s) and sponsor 
requirements. Clinical monitoring will also verify that any critical study procedures are completed 
following specific instructions in the protocol-specific MOP. 
Monitoring for this study will be performed by DMID. Details of clinical site monitoring are 
documented in a CMP. The CMP describes in detail who will conduct the monitoring, at what 
frequency monitoring will be done, at what level of detail monitoring will be performed, and the 
distribution of monitoring reports. Monitoring visits will include, but are not limited to, review of 
regulatory files, accountability records, electronic case report forms (eCRFs), ICFs, medical and 
laboratory reports, site study intervention storage records, training records, and protocol and GCP 
compliance. Site monitors will have access to each participating site, study staff and all study 
documentation according to the DMID-approved CMP. Study monitors will meet with all 
participating site PIs to discuss any problems and outstanding issues and will document site visit 
findings and discussions. 
10.1.8 
Quality Control (QC) and Quality Assurance (QA) 


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To ensure the reliability of study data, each participating site will develop a Clinical Quality 
Management Plan (CQMP). The CQMP will describe: 
• routine internal QC and QA activities for the purposes of measuring, documenting and 
reporting study conduct, protocol adherence, human subjects’ protections, and reliability 
of the protocol-driven data collected and independent of sponsor site monitoring. 
• a process for addressing data quality issues (i.e., collecting, recording) or systemic issues 
(i.e., protocol conduct, non-compliance, human subject protections), and implementation 
and evaluation of Corrective and Preventative Action Plan (CAPA) procedures as needed. 
10.1.9 
Data Handling and Record Keeping 
10.1.9.1 
Data Collection and Management Responsibilities 
Data collection is the responsibility of the study staff at the participating site under the 
supervision of the participating site PI. The participating site PI must maintain complete and 
accurate source documentation. 
Clinical research data from source documentation, including, but not limited to, AEs/SAEs, 
concomitant medications, medical history, physical assessments, and clinical laboratory data, 
will be entered by the participating site into eCRFs via a 21 CFR Part 11-compliant internet data 
entry system provided by Emmes. The data system includes password protection and internal 
quality checks, such as automatic range checks, to identify data that appear inconsistent, 
incomplete, or inaccurate. AEs and concomitant medications will be coded according to the most 
current versions of MedDRA and WhoDrug, respectively. 
The SDCC will be responsible for data management, quality review, analysis, and reporting of 
the study data. 
The IND sponsor is responsible for review of data collection tools and processes, and review of 
data and reports. 
AEs will be coded according to the MedDRA dictionary version 23.0 or higher. 
A separate study specific Study Data Standardization Plan (SDSP) appendix will be developed 
which describes the technical recommendations for the submission of human study data and 
related information in a standardized electronic format throughout product development. 
At the end of the study, a copy of all datasets, including annotated CRFs and data dictionary, will 
be provided to DMID. 
10.1.9.2 
Study Record Retention 
Study-related records, including the regulatory file, study product accountability records, consent 
forms, subject source documents and electronic records, should be maintained for a period of 2 
years following the date a marketing application is approved for the investigational product for the 
indication for which it is being investigated; or, if no application is to be filed or if the application 
is not approved for such indication, until 2 years after the investigation is discontinued and FDA 
is notified. These documents should be retained for a longer period, however, if required by local 
policies or regulations. No records will be destroyed without the written consent of DMID. 
Consent forms with specimen retention linked to identifiable specimens will be maintained for as 


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long as the specimens remain in identifiable format, and a minimum of three years after use of the 
identifiable specimens in nonexempt human subject research. 
10.1.9.3 
Source Records 
Source data are all information in original records (and certified copies of original records) of 
clinical findings, observations, or other activities in a clinical trial necessary for the 
reconstruction and evaluation of the trial. Source data should be attributable, legible, 
contemporaneous, original, accurate, and complete. Each participating site will maintain 
appropriate medical and research records for this trial, in compliance with ICH GCP, regulatory, 
and institutional requirements. Study data will be collected on paper CRFs and entered the eCRF 
or data will be entered directly into the eCRF. Data recorded in the eCRF derived from source 
documents should be consistent with the data recorded on the source documents. Data entered 
directly into the eCRFs will be considered the source document. 
Interview of subjects is sufficient for obtaining medical history. Solicitation of medical records 
from the subject’s primary care provider is not required. 
10.1.9.4 
Protocol Deviations 
A protocol deviation is any non-compliance with the clinical trial protocol, any process that is 
noted in the protocol and refers to details in the protocol-specific MOP or GCP requirements, or 
any critical study procedures with specific instructions in ancillary documents referenced in the 
protocol such as a protocol-specific MOP. 
The non-compliance may be either on the part of the subject, the participating site PI or the study 
staff. Following a deviation(s), corrective actions should be developed by the participating site and 
implemented promptly. All individual protocol deviations will be addressed in subject study 
records. 
It is the responsibility of the participating site PI and study staff to use continuous vigilance to 
identify and report deviations within five working days of identification of the protocol deviation, 
or within five working days of the scheduled protocol-required activity. All deviations must be 
promptly reported to DMID per the protocol deviation reporting procedures. Protocol deviations 
must be sent to the local IRB/IEC per their guidelines. The participating site PI and study staff are 
responsible for knowing and adhering to their IRB requirements. A completed copy of the DMID 
Protocol Deviation Form must be maintained in the Regulatory File, as well as in the subject’s 
chart if the deviation is subject specific. 
10.1.9.5 
Data Sharing Plan 
Data will be available immediately following publication, with no end date, with data sharing at 
the discretion of the PI.  
10.1.9.6 
Genomic Data Sharing (GDS) Plan 
This study will comply with the NIH GDS Policy, which applies to all NIH-funded research that 
generates large-scale human or non-human genomic data, as well as the use of these data for 
subsequent research. Large-scale data include genome-wide association studies (GWAS), SNP 
arrays, and genome sequence, transcriptomic, epigenomic, and gene expression data. 


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10.1.9.7 
Publication 
At intervals throughout the study at the discretion of the sponsor and following completion of the 
study, the results of this research will be published in a scientific journal. This study will adhere 
to the NIH Public Access Policy, which ensures that the public has access to the published results 
of NIH funded research. As such, the final peer-reviewed journal manuscripts will be accessible 
to the public on PubMed Central no later than 12 months after publication. 
10.1.9.8 
Conflict of Interest Policy 
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical. Therefore, any actual conflict of interest of persons who have 
a role in the design, conduct, analysis, publication, or any aspect of this trial will be disclosed 
and managed. Furthermore, persons who have a perceived conflict of interest will be required to 
have such conflicts managed in a way that is appropriate to their participation in the design and 
conduct of this trial. DMID has established policies and procedures for all study team members 
to disclose all conflicts of interest and will establish a mechanism for the management of all 
reported dualities of interest. 
10.2 
Additional Considerations 
10.2.1 
Research Related Injuries 
For any potential research related injury, the participating site PI or designee will assess the 
subject. Study staff will try to reduce, control and treat any complications from this trial. 
Immediate medical treatment may be provided by the participating site, such as giving 
emergency medications to stop immediate allergic reactions to the vaccine. As needed, referrals 
to appropriate health care facilities will be provided to the subject. The participating site PI 
should then determine if an injury occurred as a direct result of the tests or treatments that are 
done for this trial. 
If it is determined by the participating site PI that an injury occurred to a subject as a direct result 
of the tests or treatments that are done for this trial, then referrals to appropriate health care 
facilities will be provided to the subject. Study staff will try to reduce, control and treat any 
complications from this trial. Immediate medical treatment may be provided by the participating 
site, such as giving emergency medications to stop immediate allergic reactions to the vaccine. No 
financial compensation will be provided to the subject by NIAID, NIH, the vaccine manufacturer, 
or the participating site for any injury suffered due to participation in this trial. 
For this protocol, the study vaccines are covered under the PREP Act, as described in Section 
2.1.1. 
10.3 
Abbreviations 
Table 7: Abbreviations 
ACIP 
Advisory Committee on Immunization Practices 
Ad 
Adenovirus 


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ADCC-NK 
Antibody-Mediated Natural Killer 
ADCD 
Antibody-Dependent Complement Deposition 
ADCP 
Antibody-Dependent Cellular Phagocytosis 
AE 
Adverse Event 
AESI 
Adverse Event of Special Interest 
PBMC 
Peripheral Blood Mononuclear Cell  
BMI 
Body Mass Index 
BP 
Blood Pressure 
°C 
Degrees Celsius 
CAPA 
Corrective and Preventative Action Plan 
CD4 
Cluster of Differentiation 4 
CDC 
Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
CI 
Confidence Interval 
CICP 
Countermeasures Injury Compensation Program 
CLIA 
Clinical Laboratory Improvement Amendments 
CMP 
Clinical Monitoring Plan 
CMS 
Clinical Material Services 
COC 
Certificate of Confidentiality 
CoV 
Coronavirus 
COVID-19 
Coronavirus Disease 2019 
CRF 
Case Report Form 
CROMS 
Clinical Research Operations and Management Support 


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CSR 
Clinical Study Report 
CQMP 
Clinical Quality Management Plan 
DCF 
Data Collection Form 
DHHS 
Department of Health and Human Services 
DMID 
Division of Microbiology and Infectious Diseases 
DNA 
Deoxyribonucleic Acid 
DSMB 
Data and Safety Monitoring Board 
DSPC 
1,2-distearoyl-sn-glycero-3-phosphocholine 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
EKG 
Electrocardiogram 
ELISA 
Enzyme-Linked Immunosorbent Assay 
EUA 
Emergency Use Authorization 
°F 
Degrees Fahrenheit 
FDA 
Food and Drug Administration 
FWA 
Federal Wide Assurance 
GCP 
Good Clinical Practice 
GDS 
Genomic Data Sharing 
GMFR 
Geometric Mean Fold Rise 
GMT 
Geometric Mean Titer 
GWAS 
Genome-Wide Association Studies 
β-HCG 
β Human Chorionic Gonadotropin 


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HHS 
Health and Human Services 
HIV 
Human Immunodeficiency Virus 
HLA 
Human Leukocyte Antigen 
HR 
Heart Rate 
HRSA 
Health Resources and Services Administration 
IB 
Investigator’s Brochure 
ICD 
International Classification of Diseases 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
IDCRC 
Infectious Disease Clinical Research Consortium 
IDE 
Investigational Device Exemption 
IEC 
Independent or Institutional Ethics Committee 
IM 
Intramuscular 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
IV 
Intravenous 
kg 
Kilogram 
LNP 
Lipid Nanoparticle 
MAAE 
Medically Attended Adverse Event 
mcg 
Microgram 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligrams 
min 
Minute 


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mITT 
Modified Intent-To-Treat 
mL 
Milliliter 
MOP 
Manual of Procedures 
mRNA 
Messenger Ribonucleic Acid 
MSD 
Meso Scale Discovery 
N 
Number (typically refers to subjects) 
NAAT 
Nucleic Acid Amplification Test 
NaCl 
Sodium Chloride 
NDA 
New Drug Application 
NEUT 
Neutralizing 
NIAID 
National Institute of Allergy and Infectious Diseases 
NIH 
National Institutes of Health 
NOCMC 
New Onset Chronic Medical Condition 
OHRP 
Office for Human Research Protections 
pIMD 
Potential Immune Mediated Diseases 
PBMC 
Peripheral Blood Mononuclear Cell 
PCR 
Polymerase Chain Reaction  
PEG 
Polyethylene Glycol 
PHI 
Protected Health Information 
PI 
Principal Investigator 
PP 
Per Protocol 
PREP Act 
Public Readiness and Emergency Preparedness Act 
QA 
Quality Assurance 


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QC 
Quality Control 
RNA 
Ribonucleic Acid 
RT-PCR 
Reverse Transcription Polymerase Chain Reaction 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SARS 
Severe Acute Respiratory Syndrome 
SARS-CoV 
SARS Coronavirus 
SARS-CoV-2 
SARS Coronavirus 2 
SD 
Standard Deviation 
SDCC 
Statistical and Data Coordinating Center 
SDSP 
Study Data Standardization Plan 
SNP 
Single Nucleotide Polymorphisms 
SOA 
Schedule of Activities 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SST 
Serum Separator Tube 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
Th 
T helper 
TTS 
Thrombosis with Thrombocytopenia Syndrome 
UP 
Unanticipated Problem 
US 
United States 
USP 
United States Pharmacopeia 
VOC 
Variants Of Concern 


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VRC 
Vaccine Research Center 
WHO 
World Health Organization 
WIV1 
Chinese Horseshoe Bat Coronavirus WIV1 
 
10.4 
Protocol Amendment History 
Protocol Amendment History 
Version, Date 
Section 
Description of Change 
Brief Rationale 
Version 2.0, 15, April 
2022 
Throughout 
Administrative. 
Advanced version 
and date. 
 
1.2, 7.1.5, 8.1.6 
4 cc will be stored and 
sent to central lab for 
potential biomarker 
testing at Day 4 and 
Day 60 (new visits 
added), and at 
unscheduled visit for 
suspected case 
myocarditis or 
pericarditis 
To address FDA 
comment. 
 
1.1 
Exploratory Objective 
5 addition of assessing 
anti-nucleocapsid 
serology 
To assess for 
asymptomic SARS-
CoV2 infections. 
 
1.1, 4.1 and 5 
Changed “35%” of 
confirmed infection to 
“20%” confirmed 
infection. 
To reflect a realistic 
percentage of 
participants with 
confirmed infection 
enrolling in the study 
based on US 
serologic data54  
 
1.1 
“A history of 
myocarditis or 
pericarditis at any time 
prior to enrollment” 
added as an exclusion 
criteria. 
To address FDA 
comment. 


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1.2 
Blood volume updated 
for 2 extra cc of sera 
collected at any in-
person scheduled visit 
or early termination 
visit. 
As the volume of 
blood per SST is 8.5 
cc rather than 8 cc. 
 
1.2, 7.1.5, 8.1.6 
Added information on 
management of 
suspected cases of 
myocarditis and/or 
pericarditis. 
To address FDA 
comment. 
 
1.2 
Added clarification 
that pregnancy testing 
is conducted at 
screening as well as 
prior to each 
vaccination.  
Clarification. 
 
1.2, 8.2, 8.3.1.1 
Added clarifications 
regarding confirmation 
of information 
collected in the 
Memory Aid. 
Clarification.  
 
2.1 and 2.2.2 
Added additional 
information relevant to 
the second booster 
currently part of 
standard of care. 
Provided justification 
on how the receipt of 
a variant vaccine in 
the study is not 
expected to be 
inferior to any 
benefits received 
from a second 
booster dose of a 
Pfizer or Moderna 
mRNA vaccine 
obtained outside this 
trial. 
 
Throughout 
“Women” was 
changed to “subjects”. 
To maintain gender 
neutrality.  


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6.5 and 8.1.1 
Non COVID-19 
approved/authorized 
vaccinations are only 
recorded if received 28 
days prior to first dose. 
Clarification.  
 
7.1.1 
Added “immediate IgE 
mediated” to halting 
criteria relevant to 
allergic reactions 
related to study 
vaccine. 
Clarification. 
 
7.1.1. 
Added halting criteria 
relevant to myocarditis 
and /or pericarditis. 
To address FDA 
comment. 
 
8.1.1 
Description provided 
for targeted physical 
exam. 
Clarification.  
 
8.1.5 and 8.3.9 
SARS-CoV2 is not an 
AE but an exploratory 
efficacy assessment.  
To address 
manufacturer 
comment. 
 
8.3.9 and 12 
Listing of types of 
AEs requiring 
reporting to DMID 
pharmacovigilance. 
To address 
manufacturer 
comment. 
 
11 
Changes in references. 
Updates. 
Version 3.0, 29, April 
2022 
Throughout 
Administrative. 
Advanced version 
and date. 
 
1.1, 2.1 
Changes to number of 
cases and deaths from 
COVID-19. 
Updates. 
 
1.1 
Addition of study 
arms. 
Update to include 
Pfizer/ BioNTech 
BNT162b2 vaccine 
platform. 


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2.1  
Data on 
immunogenicity for 
Pfizer/BioNTech 
BNT162b2 vaccine 
against variants of 
concern and type of  
variant vaccines 
available from 
Pfizer/BioNTech  
Addition of 
information relevant 
to new arms of 
Pfizer/BioNTech 
variant vaccines. 
 
2.2.1 
Information on risks 
associated with 
Pfizer/BioNTech 
BNT162b2 variant 
vaccine candidates. 
Addition of 
information relevant 
to new arms of 
Pfizer/BioNTech 
variant vaccines. 
 
2.2.1 
Additional systemic 
adverse effects listed. 
Addition of 
lethargy, decreased 
appetite, night 
sweats, diarrhea and 
malaise. 
 
4.1 
Addition of stage 2. 
Update. 
 
4.3 
Addition of language 
relevant to dosing 
justification for 
Pfizer/BioNTech 
BNT162b2 variant 
vaccine candidates. 
Addition of 
information relevant 
to new arms of 
Pfizer/BioNTech 
variant vaccines. 
 
6.1.1, 6.1.2,  6.2.2, 
6.2.3 
Addition of language 
relevant to study 
product description, 
dosing, 
administration, 
appearance, 
formulation, stability, 
storage for 
Pfizer/BioNTech 
BNT162b2 variant 
vaccine candidates. 
Addition of 
information relevant 
to new arms of 
Pfizer/BioNTech 
variant vaccines. 
Version 4.0, 19, May 
2022 
Throughout 
Administrative. 
Advanced version 
and date. 
 
Throughout  
Clarifications and 
updates 
Clarifications and 
updates 


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1.1 
Addition of study 
arms. 
Update to include 
Sanofi GSK CoV2 
preS dTM-AS03 
vaccine platform. 
 
1.1 
Update to eligibility 
criteria 
 
Addition of history 
of anaphylaxis, 
urticaria, or other 
significant adverse 
reaction requiring 
medical intervention 
after receipt of 
“polysorbate” has 
been added as an 
exclusion criteria. 
 
1.1 
Update to eligibility 
criteria 
Exclusion criterion 
#6 does not apply to 
stage 3. 
 
2.1 
Data on 
immunogenicity  and 
efficacy for Sanofi 
GSK CoV2 preS 
dTM-AS03 vaccine 
against variants of 
concern and type of  
variant vaccines 
available  
Addition of 
information relevant 
to new arms of 
Sanofi GSK variant 
vaccines. 
 
2.2.1 
Information on risks 
associated with 
Sanofi GSK variant 
vaccine candidates. 
Addition of 
information relevant 
to new arms of 
Sanofi GSK variant 
vaccines. 
 
4.3 
Addition of language 
relevant to dosing 
justification for 
Sanofi GSK variant 
vaccine candidates. 
Addition of 
information relevant 
to new arms of 
Sanofi GSK variant 
vaccines 


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6.1.1, 6.1.2,  6.2.2, 
6.2.3 
Addition of language 
relevant to study 
product description, 
dosing, 
administration, 
appearance, 
formulation, stability, 
storage for Sanofi 
GSK variant vaccine 
candidates. 
Addition of 
information relevant 
to new arms of 
Sanofi GSK variant 
vaccines. 
 
8.3.9 
For stage 2, AESIs 
also include a list of 
pIMD. Description of 
pIMD provided.  
Updated safety 
reporting language  
 
12 
List of pIMD 
Updated list of 
AESIs for stage 3 
Version 5.0, 21 
September 2022 
Throughout 
Administrative. 
Advanced version 
and date. 
 
Throughout 
Clarifications and 
updates. 
Clarifications and 
updates. 
 
Throughout 
Replaced “Sanofi 
Pasteur” with 
“Sanofi”, as 
applicable. 
Company name 
updated to reflect 
change made within 
the organization. 
 
1.1 
Addition of study 
arms and stage 4. 
Update to include 
Pfizer BioNTech 
bivalent Prototype + 
Omicron BA.1 and 
Prototype + 
Omicron BA.4/BA.5 
as stage 4. 


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1.1 
Update to eligibility 
criteria. 
Age 18-49 years 
only for arms 16 and 
17 (stage 4). 
Exclusion criteria of 
history of 
pericarditis and 
myocarditis still 
applies to stage 4.   
Only participants 
not willing to 
receive vaccine 
outside the study for 
180 days will be 
enrolled. 
 
 
1.2 
Update for how to 
proceed if participant 
is about to receive a 
COVID-19 vaccine 
outside the study. 
Either plan for an 
unscheduled visit or 
allowing double the 
window for an 
upcoming scheduled 
visit.  
 
1.1 and 2.1 
Update that Novavax 
vaccine received 
FDA EUA. 
Updates to include 
that Novavax 
vaccine received 
FDA EUA on July 
13, 2022. 
 
2.1 and 2.2  
Updates on new 
bivalent boosters that 
will be used in the 
US and the UK and 
Canada in the fall of 
2022. 
Bivalent Prototype+ 
Omicron BA.1 will 
be used as a booster 
vaccine in the UK 
and Canada and 
bivalent Prototype+ 
Omicron BA.4/BA.5 
will be used as a 
booster vaccine in 
the US. 


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2.2.1 
Added nausea, 
vomiting and 
lymphadenopathy as 
side effects of 
Pfizer/BioNTech 
vaccines per IB 
Updates on safety 
 
4.1 and 4.2 
Update to include 
arms 16 and 17. 
Updates to include 
stage 4. 
 
6 
Update to include 
arms 16 and 17. 
Addition of 
information relevant 
to new arms of 
Pfizer/BioNTech 
bivalent variant 
vaccines in stage 4. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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11. 
REFERENCES 
 
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16. Barda N, Dagan N, Cohen C, et al. Effectiveness of a third dose of the BNT162b2 mRNA 
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18. Patalon T GS, Pitzer VE et al. Odds of Testing Positive for SARS-CoV-2 Following Receipt 
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19. Atmar RL, Lyke KE, Deming ME, et al. Homologous and Heterologous Covid-19 Booster 
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20. Miller J. Safety and Immunogenicity of a 50 μg Booster Dose of Moderna COVID-19 
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21. Pajon R, Doria-Rose NA, Shen X, et al. SARS-CoV-2 Omicron Variant Neutralization after 
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22. Choi A, Koch M, Wu K, et al. Safety and immunogenicity of SARS-CoV-2 variant mRNA 
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23. Sridhar S, Joaquin A, Bonaparte MI, et al. Safety and immunogenicity of an AS03-
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24. Sanofi/GSK. Sanofi and GSK to seek regulatory authorization for COVID-19 vaccine. 2022. 
25. Regev-Yochay G, Gonen T, Gilboa M, et al. Efficacy of a Fourth Dose of Covid-19 mRNA 
Vaccine against Omicron. N Engl J Med 2022. DOI: 10.1056/NEJMc2202542. 
26. Arbel R, Sergienko R, Friger M, Peretz A. Second Booster Vaccine and Covid-19 Mortality 
in Adults 60 to 100 Years Old. Research Square2022. 
27. Gazit S, Saciuk Y, Perez G, Peretz A, Pitzer VE, Patalon T. Short term, relative effectiveness 
of four doses versus three doses of BNT162b2 vaccine in people aged 60 years and older in 
Israel: retrospective, test negative, case-control study. BMJ 2022;377:e071113. DOI: 
10.1136/bmj-2022-071113. 
28. Shen X, Tang H, McDanal C, et al. SARS-CoV-2 variant B.1.1.7 is susceptible to 
neutralizing antibodies elicited by ancestral Spike vaccines. bioRxiv 2021. DOI: 
10.1101/2021.01.27.428516. 
29. Callaway E, Mallapaty S. Novavax offers first evidence that COVID vaccines protect people 
against variants. Nature 2021;590(7844):17. DOI: 10.1038/d41586-021-00268-9. 
30. Wang P, Nair MS, Liu L, et al. Antibody resistance of SARS-CoV-2 variants B.1.351 and 
B.1.1.7. Nature 2021;593(7857):130-135. DOI: 10.1038/s41586-021-03398-2. 
31. Muik A, Lui BG, Wallisch AK, et al. Neutralization of SARS-CoV-2 Omicron by 
BNT162b2 mRNA vaccine-elicited human sera. Science 2022;375(6581):678-680. DOI: 
10.1126/science.abn7591. 
32. Cele S, Jackson L, Khoury DS, et al. Omicron extensively but incompletely escapes Pfizer 
BNT162b2 neutralization. Nature 2022;602(7898):654-656. DOI: 10.1038/s41586-021-
04387-1. 
33. Nemet I, Kliker L, Lustig Y, et al. Third BNT162b2 Vaccination Neutralization of SARS-
CoV-2 Omicron Infection. N Engl J Med 2022;386(5):492-494. DOI: 
10.1056/NEJMc2119358. 
34. Pavot V, Berry C, Kishko M, et al. Protein-based SARS-CoV-2 spike vaccine booster 
increases cross-neutralization against SARS-CoV-2 variants of concern in non-human 
primates. Nat Commun 2022;13(1):1699. DOI: 10.1038/s41467-022-29219-2. 
35. van der Straten K, Guerra D, van Gils MJ, et al. Mapping the antigenic diversification of 
SARS-CoV-2. medRxiv 2022:2022.01.03.21268582. DOI: 10.1101/2022.01.03.21268582. 
36. CDC. COVID-19 Vaccinations in the United States. Centers for Disease Control and 
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37. Team CC-R, Food, Drug A. Allergic Reactions Including Anaphylaxis After Receipt of the 
First Dose of Moderna COVID-19 Vaccine - United States, December 21, 2020-January 10, 


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2021. MMWR Morb Mortal Wkly Rep 2021;70(4):125-129. DOI: 
10.15585/mmwr.mm7004e1. 
38. McMahon DE, Amerson E, Rosenbach M, et al. Cutaneous reactions reported after Moderna 
and Pfizer COVID-19 vaccination: A registry-based study of 414 cases. J Am Acad Dermatol 
2021;85(1):46-55. DOI: 10.1016/j.jaad.2021.03.092. 
39. Baden LR, El Sahly HM, Essink B, et al. Efficacy and Safety of the mRNA-1273 SARS-
CoV-2 Vaccine. N Engl J Med 2021;384(5):403-416. DOI: 10.1056/NEJMoa2035389. 
40. Oster ME, Shay DK, Su JR, et al. Myocarditis Cases Reported After mRNA-Based COVID-
19 Vaccination in the US From December 2020 to August 2021. JAMA 2022;327(4):331-
340. DOI: 10.1001/jama.2021.24110. 
41. Oliver S. ACIP Meeting: Evidence to Recommendation Framework. 4 Feb 2022 
(https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-02-04/07-COVID-
Oliver-508.pdf). 
42. Kracalik I. ACIP Meeting: Update on myocarditis outcomes. 4 Feb 2022 
(https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-02-04/04-COVID-
Kracalic-508.pdf). 
43. Gilboa M, Mandelboim M, Indenbaum V, et al. Early Immunogenicity and safety of the third 
dose of BNT162b2 mRNA Covid-19 vaccine among adults older than 60 years; real world 
experience. J Infect Dis 2021. DOI: 10.1093/infdis/jiab584. 
44. Buchan SA, Seo CY, Johnson C, et al. Epidemiology of myocarditis and pericarditis 
following mRNA vaccines in Ontario, Canada: by vaccine product, schedule and interval. 
medRxiv 2021:2021.12.02.21267156. DOI: 10.1101/2021.12.02.21267156. 
45. Hause AM, Baggs J, Marquez P, Myers TR. Safety Monitoring of COVID-19 Vaccine 
Booster Doses Among Adults — United States, September 22, 2021–February 6, 2022. 
MMWR Morb Mortal Wkly Rep 2022. DOI: http://dx.doi.org/10.15585/mmwr.mm7107e1. 
46. Team CC-R, Food, Drug A. Allergic Reactions Including Anaphylaxis After Receipt of the 
First Dose of Pfizer-BioNTech COVID-19 Vaccine - United States, December 14-23, 2020. 
MMWR Morb Mortal Wkly Rep 2021;70(2):46-51. DOI: 10.15585/mmwr.mm7002e1. 
47. Polack FP, Thomas SJ, Kitchin N, et al. Safety and Efficacy of the BNT162b2 mRNA 
Covid-19 Vaccine. N Engl J Med 2020;383(27):2603-2615. DOI: 10.1056/NEJMoa2034577. 
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49. Mahase E. Covid-19: UK will roll out Moderna's omicron BA.1 vaccine as part of autumn 
booster programme. BMJ 2022;378:o2038. DOI: 10.1136/bmj.o2038. 
50. (FDA) UFaDA. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-
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51. Guidelines CCVB. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/booster-
shot.html?s_cid=11737:cdc covid booster shot 
guidelines:sem.ga:p:RG:GM:gen:PTN:FY22.Accessed February 13, 2022. 
52. Munro APS, Janani L, Cornelius V, et al. Safety and immunogenicity of seven COVID-19 
vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 
in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial. 
Lancet 2021;398(10318):2258-2276. DOI: 10.1016/S0140-6736(21)02717-3. 
53. Pfizer asks FDA to greenlight new omicron booster shots, which could arrive this fall. NPR. 
(https://www.npr.org/sections/health-shots/2022/08/22/1118788439/vaccine-maker-asks-fda-
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54. Jones JM, Stone M, Sulaeman H, et al. Estimated US Infection- and Vaccine-Induced SARS-
CoV-2 Seroprevalence Based on Blood Donations, July 2020-May 2021. JAMA 
2021;326(14):1400-1409. DOI: 10.1001/jama.2021.15161. 
55. Ferreira VM, Schulz-Menger J, Holmvang G, et al. Cardiovascular Magnetic Resonance in 
Nonischemic Myocardial Inflammation: Expert Recommendations. J Am Coll Cardiol 
2018;72(24):3158-3176. DOI: 10.1016/j.jacc.2018.09.072. 
56. Aretz HT. Myocarditis: the Dallas criteria. Hum Pathol 1987;18(6):619-24. DOI: 
10.1016/s0046-8177(87)80363-5. 
57. Adler Y, Charron P, Imazio M, et al. 2015 ESC Guidelines for the diagnosis and 
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2964. DOI: 10.1093/eurheartj/ehv318. 
 
 


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12. 
APPENDIX A: Adverse Events of Special Interest (AESIs) 
Terms 
Investigators should report all events which fall into the following categories as an AESI per the 
reporting processes specified in the protocol. The following AESIs are medical concepts that 
may be related to COVID-19 or are of interest in COVID-19 vaccine safety surveillance. Even if 
the events below occur in the setting of a SARS-CoV-2 infection, the event should still be 
reported as an AESI if it is one of the medical concepts below. SARS-CoV-2 infection will  not 
be reported using the AESI reporting system.  For documentation and medical assessment 
purposes all AESIs will also be reported on an SAE form and must be submitted immediately 
(within 24 hours of site awareness) to the DMID Pharmacovigilance Group; however, when 
applicable, the narrative will indicate that the AESI did not meet SAE criteria. 
 
 
Medical Concept 
Additional Notes 
Anosmia, Ageusia 
• New onset COVID associated or idiopathic events without other 
etiology excluding congenital etiologies or trauma 
Subacute thyroiditis 
• Including but not limited to events of: atrophic thyroiditis, 
autoimmune thyroiditis, immune-mediated thyroiditis, silent 
thyroiditis, thyrotoxicosis and thyroiditis 
Acute pancreatitis 
• Including but not limited to events of: autoimmune pancreatitis, 
immune-mediated pancreatitis, ischemic pancreatitis, edematous 
pancreatitis, pancreatitis, acute pancreatitis, hemorrhagic 
pancreatitis, necrotizing pancreatitis, viral pancreatitis, and 
subacute pancreatitis 
• Excluding known etiologic causes of pancreatitis (alcohol, 
gallstones, trauma, recent invasive procedures) 
Appendicitis 
• Include any event of appendicitis  
Rhabdomyolysis 
• New onset rhabdomyolysis without known etiology such as 
excessive exercise or trauma 
Acute respiratory distress 
syndrome (ARDS) 
• Including but not limited to new events of ARDS and respiratory 
failure 
Coagulation disorders 
• Including but not limited to thromboembolic and bleeding 
disorders, disseminated intravascular coagulation, pulmonary 
embolism, deep vein thrombosis 


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Acute cardiovascular injury 
• Including but not limited to myocarditis, pericarditis, 
microangiopathy, coronary artery disease, arrhythmia, stress 
cardiomyopathy, heart failure, or acute myocardial infarction 
Acute kidney injury 
• Include events with idiopathic or autoimmune etiologies 
• Exclude events with clear alternate etiology (trauma, infection, 
tumor, or iatrogenic causes such as medications or radiocontrast 
etc.) 
• Include all cases that meet the following criteria:  
o Increase in serum creatinine by ≥ 0.3 mg/dl (≥26.5 umol/l) 
within 48 hours; 
o OR Increase in serum creatinine to ≥ 1.5 times baseline, 
known or presumed to have occurred within prior 7 days 
o OR Urine volume ≤0.5 ml/ kg/ hour for 6 hours 
Acute liver injury 
Include events with idiopathic or autoimmune etiologies 
Exclude events with clear alternate etiology (trauma, infection, 
tumor, etc.) 
Include all cases that meet the following criteria 
> 3-fold elevation above the upper normal limit for ALT or 
AST 
OR • > 2-fold elevation above the upper normal limit for total 
serum bilirubin or GGT or ALP 
Dermatologic findings 
• Chilblain-like lesions 
• Single organ cutaneous vasculitis 
• Erythema multiforme 
• Bullous rashes 
• Severe cutaneous adverse reactions including but not limited to: 
Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis 
(TEN), Drug Reaction with Eosinophilia and Systemic Symptoms 
(DRESS) and fixed drug eruptions 
Multisystem inflammatory 
disorders 
Multisystem inflammatory syndrome in adults (MIS-A) 
Multisystem inflammatory syndrome in children (MIS-C) 
Kawasaki’s disease 
Thrombocytopenia and/or 
Thrombosis with 
Thrombocytopenia 
Syndrome (TTS) 
• Platelet counts < 150 x10^9 
• Thrombotic events:  Suspected deep vessel venous or arterial 
thrombotic events 
• Including but not limited to TTS (default operative diagnosis if 
boosted with Ad26.COV2.S), immune thrombocytopenia, platelet 
production decreased, thrombocytopenia, thrombocytopenic 


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purpura, thrombotic thrombocytopenic purpura, or HELLP 
syndrome 
Acute aseptic arthritis 
• New onset aseptic arthritis without clear alternate etiology (e.g., 
gout, osteoarthritis, and trauma) 
New onset of or worsening of 
neurologic disease 
Including but not limited to: 
Guillain-Barre Syndrome 
Acute disseminated encephalomyelitis (ADEM) 
Peripheral facial nerve palsy (Bell’s palsy)  
Transverse myelitis 
Encephalitis/Encephalomyelitis 
Aseptic meningitis 
Febrile seizures 
Generalized seizures/convulsions 
Stroke (Hemorrhagic and non-hemorrhagic) 
Narcolepsy 
Anaphylaxis 
Anaphylaxis is an acute hypersensitivity reaction with multi-
organ-system involvement that can present as, or rapidly 
progress to, a severe life-threatening reaction. It may occur 
following exposure to allergens from a variety of sources. 
Anaphylaxis is a clinical syndrome characterized by: 
o sudden onset AND 
o rapid progression of signs and symptoms AND 
o involving two or more organ systems, as follows: 
o Skin/ mucosal: urticaria (hives), generalized erythema, 
angioedema, generalized pruritus with skin rash, 
generalized prickle sensation, red and itchy eyes 
o Cardiovascular: measured hypotension, clinical diagnosis of 
uncompensated shock, loss of consciousness or decreased 
level of consciousness, evidence of reduced peripheral 
circulation 
o Respiratory: bilateral wheeze (bronchospasm), difficulty 
breathing, stridor, upper airway swelling (lip, tongue, 
throat, uvula, or larynx), respiratory distress, persistent dry 
cough, hoarse voice, sensation of throat closure, sneezing, 
rhinorrhea 
o Gastrointestinal: diarrhea, abdominal pain, nausea, vomiting 
Follow reporting procedures in protocol. 
Myocarditis and/or pericarditis 
Symptoms and diagnostic findings include but are not limited to: 
Chest pain 
Dyspnea 
ST or T wave changes on ECG 
Elevated cardiac enzymes 


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Abnormal echocardiography or other cardiac imaging.  
Other syndromes 
• Fibromyalgia 
• Postural Orthostatic Tachycardia Syndrome 
• Chronic Fatigue Syndrome (Includes Myalgic encephalomyelitis 
and Post viral fatigue syndrome) 
• 
Myasthenia gravis 
 
List of potential Immune-mediated Diseases (pIMDs) for Stage 3  
Medical Concept 
Additional Notes 
Blood disorders and coagulopathies 
Antiphospholipid 
syndrome 
 
Autoimmune aplastic 
anemia 
 
Autoimmune hemolytic 
anemia 
• Includes warm antibody hemolytic anemia and cold 
antibody hemolytic anemia 
Autoimmune 
lymphoproliferative 
syndrome (ALPS) 
 
Autoimmune neutropenia  
 
Autoimmune 
pancytopenia 
 
Autoimmune 
thrombocytopenia 
• Frequently used related terms include: “autoimmune 
thrombocytopenic purpura”, “idiopathic thrombocytopenic 
purpura (ITP)”,  “idiopathic immune thrombocytopenia”, 
“primary immune thrombocytopenia”. 
Evans syndrome 
 
Pernicious anemia 
 
Thrombosis with 
thrombocytopenia 
syndrome (TTS) 
 
Thrombotic 
thrombocytopenic 
purpura 
• Also known as “Moschcowitz-syndrome” or 
“microangiopathic hemolytic anemia” 
Cardio-pulmonary inflammatory disorders 


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Medical Concept 
Additional Notes 
Idiopathic 
Myocarditis/Pericarditis 
Including but not limited to: 
• Autoimmune / Immune-mediated myocarditis 
• Autoimmune / Immune-mediated pericarditis 
• Giant cell myocarditis 
Idiopathic pulmonary 
fibrosis 
Including but not limited to: 
• Idiopathic interstitial pneumonia (frequently used related 
terms include “Interstitial lung disease”, “Pulmonary 
fibrosis”, “Immune-mediated pneumonitis”) 
• Pleuroparenchymal fibroelastosis (PPFE) 
Pulmonary alveolar 
proteinosis (PAP) 
• Frequently used related terms include: “pulmonary alveolar 
lipoproteinosis”, “phospholipidosis” 
Endocrine disorders 
Addison’s disease 
 
Autoimmune / Immune-
mediated thyroiditis  
Including but not limited to: 
• Hashimoto thyroiditis (autoimmune hypothyroidism, 
lymphocytic thyroiditis) 
• Atrophic thyroiditis  
• Silent thyroiditis  
• Thyrotoxicosis 
Autoimmune diseases of 
the testis and ovary 
• Includes autoimmune oophoritis,  autoimmune ovarian 
failure and autoimmune orchitis 
Autoimmune 
hyperlipidemia 
 
Autoimmune hypophysitis 
 
Diabetes mellitus type I 
 
Grave's or Basedow’s 
disease 
• Includes Marine Lenhart syndrome and Graves' 
ophthalmopathy, also known as thyroid eye disease (TED) 
or endocrine ophthalmopathy 
Insulin autoimmune 
syndrome 
 
Polyglandular 
autoimmune syndrome 
• Includes Polyglandular autoimmune syndrome type I, II and 
III 
Eye disorders 


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Medical Concept 
Additional Notes 
Ocular Autoimmune / 
Immune-mediated 
disorders 
Including but not limited to: 
• Acute macular neuroretinopathy (also known as acute 
macular outer retinopathy) 
• Autoimmune / Immune-mediated retinopathy  
• Autoimmune / Immune-mediated uveitis, including 
idiopathic uveitis and sympathetic ophthalmia  
• Cogan's syndrome: an oculo-audiovestibular disease 
• Ocular pemphigoid 
• Ulcerative keratitis 
• Vogt-Koyanagi-Harada disease 
Gastrointestinal disorders 
Autoimmune / Immune-
mediated pancreatitis 
 
Celiac disease 
 
Inflammatory Bowel 
disease  
Including but not limited to:  
• Crohn’s disease  
• Microscopic colitis  
• Terminal ileitis 
• Ulcerative colitis  
• Ulcerative proctitis 
Hepatobiliary disorders 
Autoimmune cholangitis 
 
Autoimmune hepatitis 
 
Primary biliary cirrhosis 
 
Primary sclerosing 
cholangitis 
 
Musculoskeletal and connective tissue disorders  
Gout 
• 
Includes gouty arthritis 
Idiopathic inflammatory 
myopathies 
Including but not limited to: 
• Dermatomyositis 
• Inclusion body myositis 
• Immune-mediated necrotizing myopathy 


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Medical Concept 
Additional Notes 
• Polymyositis 
Mixed connective tissue 
disorder 
 
Polymyalgia rheumatica 
(PMR) 
 
Psoriatic arthritis (PsA) 
 
Relapsing polychondritis 
 
Rheumatoid arthritis  
Including but not limited to: 
• Rheumatoid arthritis associated conditions 
• Juvenile idiopathic arthritis 
• Palindromic rheumatism 
• Still's disease 
• Felty’s syndrome 
Sjögren’s syndrome 
 
Spondyloarthritis 
Including but not limited to:  
• Ankylosing spondylitis 
• Juvenile spondyloarthritis 
• Keratoderma blenorrhagica 
• Psoriatic spondylitis  
• Reactive Arthritis (Reiter's Syndrome) 
• Undifferentiated spondyloarthritis 
Systemic Lupus 
Erythematosus  
• Includes Lupus associated conditions (e.g. Cutaneous lupus 
erythematosus, Lupus nephritis, etc.) or complications such 
as shrinking lung syndrome (SLS) 
Systemic Scleroderma 
(Systemic Sclerosis) 
• Includes Reynolds syndrome (RS), systemic sclerosis with 
diffuse scleroderma and systemic sclerosis with limited 
scleroderma (also known as CREST syndrome) 
Neuroinflammatory/neuromuscular disorders 
Acute disseminated 
encephalomyelitis 
(ADEM) and other 
inflammatory-
demyelinating variants  
Includes the following: 
• Acute necrotising myelitis 
• Bickerstaff's brainstem encephalitis  
• Disseminated necrotizing leukoencephalopathy (also known 
as Weston-Hurst syndrome, acute hemorrhagic leuko-


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Medical Concept 
Additional Notes 
encephalitis,  or acute necrotizing hemorrhagic 
encephalomyelitis)  
• Myelin oligodendrocyte glycoprotein antibody-associated 
disease 
• Neuromyelitis optica (also known as Devic’s disease) 
• Noninfective encephalitis / encephalomyelitis / myelitis 
• Postimmunization encephalomyelitis  
Guillain-Barré syndrome 
(GBS) 
• Includes variants such as Miller Fisher syndrome and the 
acute motor and sensory axonal neuropathy (AMSAN) 
Idiopathic cranial nerve 
palsies/paresis and 
inflammations (neuritis) 
Including but not limited to: 
• Cranial nerve neuritis (e.g. Optic neuritis) 
• Idiopathic nerve palsies/paresis (e.g. Bell’s palsy) 
• Melkersson-Rosenthal syndrome 
• Multiple cranial nerve palsies/paresis  
Multiple Sclerosis (MS) 
Includes the following: 
• Clinically isolated syndrome (CIS)  
• Malignant MS (the Marburg type of MS)  
• Primary-progressive MS (PPMS) 
• Radiologically isolated syndrome (RIS) 
• Relapsing-remitting MS (RRMS) 
• Secondary-progressive MS (SPMS) 
• Uhthoff's phenomenon  
Myasthenia gravis 
• Includes ocular myasthenia and Lambert-Eaton myasthenic 
syndrome 
Narcolepsy 
• Includes narcolepsy with or without presence of 
unambiguous cataplexy 
Peripheral inflammatory 
demyelinating 
neuropathies and 
plexopathies 
Including but not limited to: 
• Acute Brachial Radiculitis (also known as Parsonage-
Turner Syndrome or neuralgic amyotrophy) 
• Antibody-mediated demyelinating neuropathy 
• Chronic idiopathic axonal polyneuropathy (CIAP) 
• Chronic Inflammatory Demyelinating 
Polyradiculoneuropathy (CIDP), including atypical CIDP 


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Medical Concept 
Additional Notes 
variants (e.g. multifocal acquired demyelinating sensory 
and motor neuropathy also known as Lewis-Sumner 
syndrome) 
• Multifocal motor neuropathy (MMN)  
Transverse myelitis (TM) 
• Includes acute partial transverse myelitis (APTM) and acute 
complete transverse myelitis (ACTM) 
Renal disorders 
Autoimmune / Immune-
mediated 
glomerulonephritis  
Including but not limited to: 
• IgA nephropathy 
• IgM nephropathy 
• C1q nephropathy 
• Fibrillary glomerulonephritis 
• Glomerulonephritis rapidly progressive 
• Membranoproliferative glomerulonephritis 
• Membranous glomerulonephritis 
• Mesangioproliferative glomerulonephritis 
• Tubulointerstitial nephritis and uveitis syndrome 
Skin and subcutaneous tissue disorders 
Alopecia areata 
 
Autoimmune / Immune-
mediated blistering 
dermatoses  
Including but not limited to:  
• Bullous Dermatitis 
• Bullous Pemphigoid  
• Dermatitis herpetiformis  
• Epidermolysis bullosa acquisita (EBA)  
• Linear IgA-mediated bullous dermatosis (LABD), also 
known as Linear IgA disease 
• Pemphigus  
Erythema multiforme 
 
Erythema nodosum 
 
Reactive granulomatous 
dermatitis  
Including but not limited to 
• Interstitial granulomatous dermatitis 
• Palisaded neutrophilic granulomatous dermatitis 


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Medical Concept 
Additional Notes 
Lichen planus 
• Includes liquen planopilaris 
Localised Scleroderma 
(Morphoea) 
• Includes Eosinophilic fasciitis (also called Shulman 
syndrome) 
Psoriasis 
 
Pyoderma gangrenosum 
 
Stevens-Johnson 
Syndrome (SJS) 
 
Including but not limited to:  
• Toxic Epidermal Necrolysis (TEN)  
• SJS-TEN overlap 
Sweet’s syndrome 
• Includes Acute febrile neutrophilic dermatosis 
Vitiligo 
 
Vasculitis 
Large vessels vasculitis  
Including but not limited to: 
• Arteritic anterior ischemic optic neuropathy (AAION or 
arteritic AION) 
• Giant cell arteritis (also called temporal arteritis)  
• Takayasu's arteritis  
Medium sized and/or 
small vessels vasculitis  
Including but not limited to: 
• Anti-neutrophil cytoplasmic antibody (ANCA) positive 
vasculitis (type unspecified)  
• Behcet's syndrome  
• Buerger’s disease (thromboangiitis obliterans) 
• Churg–Strauss syndrome (allergic granulomatous angiitis)  
• Erythema induratum (also known as nodular vasculitis) 
• Henoch-Schonlein purpura (also known as IgA vasculitis) 
• Microscopic polyangiitis 
• Necrotizing vasculitis 
• Polyarteritis nodosa 
• Single organ cutaneous vasculitis, including 
leukocytoclastic vasculitis, hypersensitivity vasculitis and 
acute hemorrhagic edema of infancy (AHEI) 
• Wegener's granulomatosis  
Other (including multisystemic) 


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Medical Concept 
Additional Notes 
Anti-synthetase syndrome 
 
Capillary leak syndrome 
• Frequently used related terms include : “systemic capillary 
leak syndrome (SCLS)” or “Clarkson's Syndrome” 
Goodpasture syndrome 
• Frequently used related terms include : “pulmonary renal 
syndrome” and “anti-Glomerular Basement Membrane 
disease (anti-GBM disease)” 
Immune-mediated 
enhancement of disease 
• Includes vaccine associated enhanced disease (VAED and 
VAERD). Frequently used related terms include “vaccine-
mediated enhanced disease (VMED)”, “enhanced 
respiratory disease (ERD)”, “vaccine-induced enhancement 
of infection”, “disease enhancement”, “immune 
enhancement”, and “antibody-dependent enhancement 
(ADE) 
Immunoglobulin G4 
related disease 
 
Langerhans' cell 
histiocytosis 
 
Multisystem inflammatory 
syndromes 
Including but not limited to: 
• Kawasaki’s disease 
• Multisystem inflammatory syndrome in adults (MIS-A) 
• Multisystem inflammatory syndrome in children (MIS-C)  
Overlap syndrome 
 
Raynaud’s phenomenon 
 
Sarcoidosis 
• Includes Loefgren syndrome 
Susac's syndrome