Multi-Center, Randomized, Efficacy Study of COVID-19 mRNA Vaccine in Regions With SARS-CoV-2 Variants of Concern
Phase: PHASE2
Conditions: SARS-CoV-2 Infection, HIV Infections, COVID-19
Sponsor: COVID-19 Prevention Network

PROTOCOL 
CoVPN 3008 (Ubuntu) 
Multi-Center, Randomized, Efficacy Study of COVID-19 
mRNA Vaccine in Regions with SARS-CoV-2 Variants of 
Concern  
DAIDS DOCUMENT ID 38838 
CLINICAL TRIAL SPONSORED BY 
South African Medical Research Council (SAMRC) 
Cape Town, South Africa 
June 28, 2023 
Final 
CoVPN 3008 (Ubuntu) 
Version 8.0 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 2 of 169 
Contents 
1 Overview ........................................................................................................................ 5 
1.1 
Protocol Team ................................................................................................ 9 
2 Background .................................................................................................................. 12 
2.1 
Rationale for trial concept ............................................................................ 12 
2.2 
Moderna mRNA-1273 and mRNA-1273.222 vaccines ............................... 24 
2.3 
Population to be studied ............................................................................... 33 
3 Objectives and endpoints ............................................................................................. 36 
4 Ethical considerations .................................................................................................. 41 
5 IRB/EC review considerations ..................................................................................... 43 
5.1 
Minimized risks to participants .................................................................... 43 
5.2 
Reasonable risk/benefit balance ................................................................... 43 
5.3 
Equitable participant selection ..................................................................... 44 
5.4 
Appropriate informed consent ...................................................................... 44 
5.5 
Adequate safety monitoring ......................................................................... 44 
5.6 
Protect privacy/confidentiality ..................................................................... 45 
5.7 
Pregnant participants .................................................................................... 45 
6 Statistical considerations .............................................................................................. 46 
6.1 
Summary of statistical design ...................................................................... 46 
6.2 
Definitions of study cohorts for analysis ...................................................... 46 
6.3 
Accrual and sample size ............................................................................... 49 
6.4 
Statistical analyses ........................................................................................ 52 
6.5 
Operational monitoring for quality of trial conduct ..................................... 57 
6.6 
Final analyses timing .................................................................................... 57 
6.7 
Roles of the DSMB, OG, and EAC .............................................................. 57 
6.8 
Randomization implementation ................................................................... 57 
7 Selection and withdrawal of participants ..................................................................... 59 
7.1 
Inclusion criteria ........................................................................................... 59 
7.2 
Exclusion criteria .......................................................................................... 60 
8 Study products ............................................................................................................. 62 
8.1 
Vaccine regimen ........................................................................................... 62 
8.2 
Storage, handling, preparation and dispensing of the study products .......... 62 
8.3 
Acquisition of the study products ................................................................. 62 
8.4 
Administration of study products ................................................................. 63 
8.5 
Pharmacy records and accountability ........................................................... 63 
8.6 
Final disposal of the study products ............................................................. 63 
9 Clinical procedures ...................................................................................................... 64 
9.1 
Informed consent .......................................................................................... 64 
9.2 
Pre-enrollment procedures ........................................................................... 65 
9.3 
Enrollment and vaccination visits ................................................................ 66 
9.4 
Follow-up procedures ................................................................................... 68 
9.5 
Active COVID-19 symptomatic surveillance .............................................. 69 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 3 of 169 
9.6 
COVID-19 Symptom Visits and COVID-19 Post-diagnosis Schedule ....... 70 
9.7 
Visit windows and missed visits .................................................................. 73 
9.8 
Assessments of reactogenicity for a subset of participants (Safety Subset) 73 
9.9 
Delaying vaccinations for a participant ........................................................ 74 
9.10 Discontinuing vaccination for a participant who receives a COVID-19 
vaccine outside the study .............................................................................. 75 
9.11 Early termination visit .................................................................................. 75 
9.12 Pregnancy ..................................................................................................... 75 
10 Laboratory .................................................................................................................... 77 
10.1 CRS laboratory procedures .......................................................................... 77 
10.2 Total blood volume ...................................................................................... 77 
10.3 Endpoint assays ............................................................................................ 77 
10.4 Lab assay portfolio ....................................................................................... 79 
10.5 Exploratory studies ....................................................................................... 79 
10.6 Specimen storage and other use of specimens ............................................. 79 
10.7 Biohazard containment ................................................................................. 80 
11 Safety monitoring and safety review ........................................................................... 81 
11.1 Safety monitoring and oversight .................................................................. 81 
11.2 Safety reporting ............................................................................................ 82 
11.3 Safety reviews .............................................................................................. 85 
12 Protocol conduct .......................................................................................................... 87 
12.1 Study termination ......................................................................................... 87 
12.2 Emergency communication with study participants .................................... 88 
12.3 Site monitoring ............................................................................................. 89 
13 Version history ............................................................................................................. 90 
14 Document references (other than literature citations) ................................................ 100 
15 Acronyms and abbreviations...................................................................................... 102 
16 Literature cited ........................................................................................................... 104 
Appendix A Sample informed consent form .................................................................. 117 
Appendix B Laboratory procedures table for Groups 1 and 3 (SARS-CoV-2 seronegative 
participants, main study) ............................................................................ 135 
Appendix C Laboratory procedures table for Groups 2 and 4 (SARS-CoV-2 seropositive 
participants, main study) ............................................................................ 136 
Appendix D Laboratory Procedures for PBMC Immunogenicity subset, Groups 1 and 3
 137 
Appendix E Laboratory Procedures for PBMC Immunogenicity subset, Groups 2 and 4
 138 
Appendix F Laboratory Procedures for the PBMC Immune Correlates subset (Group 1, 
HIV positive, SARS-CoV-2 seronegative participants) ............................. 139 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 4 of 169 
Appendix G Laboratory Procedures for the PBMC Immune Correlates subset (Group 2, 
HIV positive, SARS-CoV-2 seropositive participants) .............................. 141 
Appendix H Schedule of clinic procedures for Groups 1 and 3 (SARS-CoV-2 
seronegative participants) ........................................................................... 142 
Appendix I Schedule of clinic procedures for Groups 2 and 4 (SARS-CoV-2 seropositive 
participants) ................................................................................................ 144 
Appendix J COVID-19 symptom visits ......................................................................... 146 
Appendix K Visit windows ............................................................................................. 149 
Appendix L Addendum to the sample informed consent form ...................................... 151 
Appendix M Addendum 2 to the sample informed consent form for additional procedures
 157 
Appendix N Addendum 3 to the sample informed consent form for additional procedures
 163 
Appendix O Adverse Events of Special Interest AESIs ................................................. 168 
Appendix P Protocol signature page .............................................................................. 169 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 5 of 169 
1 
Overview 
Title 
Multi-Center, Randomized, Efficacy Study of COVID-19 mRNA Vaccine in 
Regions with SARS-CoV-2 Variants of Concern 
Primary objectives 
Primary objective 1: 
PRE–MONTH 6 STAGE: to assess the relative risk of virologically confirmed 
symptomatic COVID-19 between a 2-dose mRNA-1273 vaccine regimen in adult 
people living with HIV (PLWH) who are SARS-CoV-2 negative at baseline 
(Group 1, vaccine-only immunity) vs. a 1-dose mRNA-1273 regimen in adult 
PLWH who are SARS-CoV-2 positive at baseline (Group 2, hybrid immunity), 
counting endpoints starting 1 day after Month 0 dose until Month 6 dose. 
Primary objective 2: 
PRE–MONTH 6 STAGE: to assess the relative risk of severe COVID-19 between 
a 2-dose mRNA-1273 vaccine regimen in adult PLWH who are SARS-CoV-2 
negative at baseline (Group 1, vaccine-only immunity) vs. a 1-dose mRNA-1273 
regimen in adult PLWH who are SARS-CoV-2 positive at baseline (Group 2, 
hybrid immunity), counting endpoints starting 1 day after Month 0 dose until 
Month 6 dose. 
Primary objective 3: 
POST–MONTH 6 STAGE: to assess the relative risk of symptomatic COVID-19 
after the Month 6 dose among those who received mRNA-1273 at Month 6 vs. 
those who received mRNA-1273.222 at Month 6, counting endpoints at least 14 
days after the Month 6 dose until end of follow up. 
Primary objective 4: 
POST–MONTH 6 STAGE: to assess the relative risk of severe COVID-19 after 
the Month 6 dose among those who received mRNA-1273 at Month 6 vs. those 
who received mRNA-1273.222 at Month 6, counting endpoints at least 14 days 
after the Month 6 dose until end of follow up. 
Primary objective 5: 
To assess the safety and tolerability of the mRNA-1273 and mRNA-1273.222  
vaccines in adults who are at risk of severe COVID-19 in both pre-Month 6 and 
post-Month 6 stages. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 6 of 169 
Study product, route of administration and regimen 
Vaccines: The COVID-19 vaccine mRNA-1273, developed by Moderna, Inc. and 
commercially sold as Spikevax®, is a lipid nanoparticle (LNP) dispersion of a 
messenger ribonucleic acid (mRNA) encoding the prefusion stabilized spike (S) 
protein of the ancestral strain of SARS-CoV-2 (Wuhan-Hu-1) formulated in LNPs 
composed of 4 lipids (1 proprietary and 3 commercially available). The vaccine is 
full approved in the United States and has been widely used worldwide.  
The COVID-19 vaccine mRNA-1273.222 is an updated bivalent version of 
Moderna’s mRNA-1273 vaccine, composed of equal parts of mRNA-1273 and 
mRNA that encodes the S protein of the Omicron subvariants BA.4/.5 (which have 
the same S protein). On August 31, 2022, Moderna received Emergency Use 
Authorization (EUA) from the US Food and Drug Administration (FDA) and 
endorsement from the US Centers for Disease Control and Prevention (CDC) and 
the CDC Advisory Committee on Immunization Practices (ACIP) to permit use of 
mRNA-1273.222 as a COVID-19 booster vaccine in adults. Over 19 million 
previously vaccinated Americans have already received doses of this new bivalent 
Moderna vaccine (1-3). 
In this study, at Month 0 (enrollment) all participants will receive a 100 mcg dose 
of mRNA-1273. At Month 1, all participants without evidence of prior SARS-
CoV-2 infection at baseline (based on serology) will receive a second dose of 
mRNA-1273. At Month 6, all participants (regardless of baseline SARS-CoV-2 
status) will receive a 100 mcg dose of either mRNA-1273 or mRNA-1273.222, 
depending on their randomization at enrollment. As a safety precaution, after the 
first approximately 120 participants have been vaccinated at Month 6 (the “Month 
6 sentinel cohort”), Month 6 vaccinations will be paused. Reactogenicity data from 
this Month 6 sentinel cohort will be reviewed to decide whether it is safe to 
continue with Month 6 vaccinations.  All vaccines in the study will be delivered as 
intramuscular (IM) injections into the deltoid muscle.  
The final phase of the study, which will last until 18 months from the last 
enrolment, will focus on follow up for participants vaccinated with mRNA-1273 
versus mRNA-1273.222, per randomization, and those with certain conditions 
considered at risk of prolonged SARS-CoV-2 infection (active TB, HIV with low 
CD4 count, and/or HIV with unsuppressed viral load). Most participants 
vaccinated at Month 6 prior to implementation of the bivalent vaccine (ie, all 
received mRNA-1273) will be exited from the trial prior to completing 12 months 
of follow up. The remaining participants will be administered monthly nasal swabs 
for nucleic acid amplification tests [NAATs] in addition to swabs initiated in 
response to symptoms or otherwise scheduled.  

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 7 of 169 
Table 1-1 Schema 
Group 
Max 
sample  
size* 
HIV-1  
sero-status** 
SARS-CoV-2 
sero-status** 
M0 
M1 
M6 
1A 
2100 
Positive 
Negative 
mRNA-1273 
mRNA-1273 
mRNA-1273 
1B 
2100 
mRNA-1273 
mRNA-1273 
mRNA-1273.222 
2A 
4200 
Positive 
Positive 
mRNA-1273 
- 
mRNA-1273 
2B 
4200 
mRNA-1273 
- 
mRNA-1273.222 
3A 
500 
Negative 
Negative 
mRNA-1273 
mRNA-1273 
mRNA-1273 
3B 
500 
mRNA-1273 
mRNA-1273 
mRNA-1273.222 
4A 
1000 
Negative 
Positive 
mRNA-1273 
- 
mRNA-1273 
4B 
1000 
mRNA-1273 
- 
mRNA-1273.222 
Total 
15,600 
 
* These sample sizes are approximate and ceiling numbers.  
**HIV infection and SARS-CoV-2 serostatus are evaluated at screening. 
Participants 
Up to 15,600 SDUWLFLSDQWVDJHZKRDUHOLYLQJZLWK+,9RUanother 
comorbidity known to be associated with severe COVID-19. 
Design 
Multicenter trial comparing different regimens of the Moderna mRNA-1273 and 
mRNA-1273.222 vaccines (see Table 1-1 Schema). 
Duration per participant 
Up to 18 months per participant. 
Estimated total study duration 
27 months (includes enrollment and follow-up). 
Core operations 
CoVPN Vaccine Leadership Group/Core Operations Center, Fred Hutchinson 
Cancer Center (Fred Hutch) (Seattle, Washington, USA) 
Statistical and Data Management Center (SDMC) 
Biostatistics, Bioinformatics and Epidemiology Program, Fred Hutch (Seattle, 
Washington, USA) 
The Emmes Company, LLC (Rockville, Maryland, USA) 
Bioinformatico (Johannesburg, South Africa) 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 8 of 169 
Laboratory Center (LC) 
Endpoint assay laboratories 
x Bio Analytical Research Corporation South Africa (Pty) Ltd (Johannesburg, 
South Africa) 
x HIV Sero-Molecular Laboratory–National Institute for Communicable 
Diseases (Johannesburg, South Africa) 
x Fred Hutchinson Cancer Center (Seattle, Washington, USA) 
x Cape Town Immunology Laboratory (CHIL, Cape Town, South Africa) 
x KwaZulu-Natal Research and Innovation Sequencing Platform (KRISP, 
Durban, South Africa) 
x South African Immunology Laboratory-National Institute for Communicable 
Diseases (SAIL-NICD, Johannesburg, South Africa)  
x Duke University Medical Center (Durham, North Carolina, USA) 
x Center for Epidemic Response and Innovation (CERI, Durban, South Africa) 
x Yerkes National Primate Research Center (Atlanta, Georgia, USA) 
Study sites 
x Clinical research sites (CRSs) to be specified in the Site Announcement Memo 
Study monitoring 
CoVPN 3008 (Ubuntu) Protocol Safety Review Team (PSRT); NIAID HIV Data 
and Safety Monitoring Board (DSMB). The conduct of the study will be monitored 
by the NIAID Oversight Group (OG). All the aforementioned groups will conduct 
their reviews based on their respective operation Charters. 
 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 9 of 169 
1.1 
Protocol Team 
Protocol leadership 
Cochairs 
Nigel Garrett 
eThekwini CRS / Centre for the AIDS 
Programme of Research in South Africa 
(CAPRISA) 
+27 76 330 8300 
Nigel.Garrett@caprisa.org 
 
Philip Kotze  
Ladysmith CRS / Qhakaza Mbokodo 
Research Clinic 
+27 82 458 8969 
plkotze@gmail.com 
 
Sufia Dadabhai 
Blantyre CRS / Johns Hopkins Research 
Project 
+265 8 8213 0694 
Sufia@jhu.edu 
 
Nyaradzo Mgodi 
University of Zimbabwe Clinical Trials 
Research Centre 
+263 24 270 4920; +263 772 264 616 
nmgodi@uz-ctrc.org 
 
Protocol 
Lead 
Advisors 
Larry Corey 
CoVPN LOC, Fred Hutch 
+1-206-667-6770 
lcorey@fredhutch.org 
 
Glenda Gray 
Perinatal HIV Research Unit (PHRU), Chris 
Hani Baragwanath Hospital, Soweto; President, 
South African Medical Research Council 
+27-11-989 9702 
glenda.gray@mrc.ac.za 
 
Linda-Gail Bekker 
The Desmond Tutu HIV Centre, Cape Town, 
South Africa 
+27-21-650-6959 
linda-gail.bekker@hiv-research.org.za 
 
Julie McElrath 
CoVPN LOC, Fred Hutch 
+1-206-667-6704 
jmcelrath@fhcrc.org 
 
Myron Cohen  
University of North Carolina 
 +1-919-966-2537 
myron_cohen@med.unc.edu 
 
James Kublin 
CoVPN LOC, Fred Hutch 
+1-206-667-1970 
jkublin@fredhutch.org 
Lead 
Statisticians 
Yunda Huang 
CoVPN SDMC, Fred Hutch 
+1-206-667-5780 
yunda@fredhutch.org 
 
Peter Gilbert 
CoVPN SDMC, Fred Hutch 
+1-206-667-7299 
pgilbert@scharp.org 
 
Laboratory 
Leads 
John Hural 
CoVPN Laboratory Program 
+1-206-667-1683 
jhural@fredhutch.org 
 
Erica Andersen-Nissen 
CoVPN Laboratory Program  
 +27 82 385 0625 
eanderse@hcrisa.org.za 
 
Guido Ferrari 
CoVPN Laboratory Program 
+1-919-684-2862 
guido.ferrari@duke.edu 
Protocol Team 
Leaders 
Manuel Villaran 
CoVPN LOC, Fred Hutch 
+1-206-349-4938 
mvillar2@fredhutch.org 
 
Asa Tapley 
CoVPN LOC, Fred Hutch 
+1-260-667-1204 
atapley@fredhutch.org 
DAIDS 
Medical 
Officers 
Margaret Yacovone 
DAIDS, NIAID 
+1-240 292 0826 
margaret.yacovone@nih.gov 
 
Laura Polakowski 
DAIDS, NIAID 
+1-240-627-3040 
laura.polakowski@nih.gov 
 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 10 of 169 
In Country Lead Investigators 
Botswana 
Joe Makhema 
Botswana Harvard AIDS Institute 
+267 390 2671 
jmakhema@bhp.org.bw 
 
 
Uganda 
Peter James Elyanu 
Baylor – Uganda CRS / Baylor College of Medicine 
Children’s Foundation 
+256 417-119200 
Pelyanu@baylor-uganda.org 
 
eSwatini 
Harriet Nuwagaba-Biribonwoha 
Eswatini Prevent Center CRS 
+268 7602 4678 
hn2158@cumc.columbia.edu 
Zambia 
Ethel Kamuti 
Matero CRS / Centre for Infectious Disease Research in 
Zambia 
+260 972-877-556 
Ethel.Kamuti@cidrz.org 
 
 
Kenya 
 
Taraz Samandari 
Kisumu CRS / KEMRI-CDC 
+254-703-485-481 
tts0@cdc.gov 
 
Malawi 
Sufia Dadabhai 
Blantyre CRS / Johns Hopkins 
Research Project 
+26 5882130694 
Sufia@jhu.edu 
Zimbabwe 
Zvavahera Chirenje 
University of Zimbabwe Clinical Trials Research Centre 
+263 24 2704920;  
+263 772272813 
zvavahera.chirenje@ucsf.edu 
 
Nyaradzo Mgodi 
University of Zimbabwe Clinical Trials Research Centre 
+263 24 2704920 
+263 772264616 
nmgodi@uz-ctrc.org 
 
South Africa 
Nigel Garrett 
eThekwini CRS / Centre for the 
AIDS Programme of Research in 
South Africa (CAPRISA) 
+27 76 330 8300 
Nigel.Garrett@caprisa.org 
 
Philip Kotze  
Ladysmith CRS / Qhakaza 
MbokodoResearch Clinic 
+27 824588969 
plkotze@gmail.com 
 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 11 of 169 
Other contributors to the original protocol 
Core medical 
monitors 
Nzeera Ketter 
CoVPN LOC, Fred Hutch 
Asa Tapley 
CoVPN LOC, Fred Hutch 
Manuel Villaran 
CoVPN LOC, Fred Hutch 
Regional medical 
liaison 
Azwidhwi Takalani 
CoVPN LOC, Fred Hutch 
Clinical Research 
Physician 
Aida Asmelash 
CoVPN, FHI360 
Clinical safety 
specialists 
Maija Anderson 
Megan Jones 
CoVPN LOC, Fred Hutch 
Clinical Research 
Project Manager 
Marianne Gildea 
CoVPN, FHI360 
Clinical trials 
managers 
Michelle Nebergall 
Carrie Sopher 
Lori Proulx-Burns 
Dhevium Govender 
CoVPN LOC, Fred Hutch 
Laboratory center 
representatives 
Nicole Espy 
Lisa Sanders  
Jen Hanke 
CoVPN Laboratory Center, 
Fred Hutch 
Clinical data 
managers 
Melissa Peda 
CoVPN SDMC, Fred Hutch 
Regulatory affairs 
associate 
Laurie Rinn 
CoVPN LOC, Fred Hutch 
SDMC Associate 
Director of Operations 
Jessica Andriesen 
CoVPN SDMC, Fred Hutch 
Community 
educator/recruiter 
Sam Sandile Mthiya 
Durban – eThekwini CRS 
SDMC Associate 
director of lab science 
April Randhawa 
CoVPN SDMC, Fred Hutch 
Community 
Advisory Board 
(CAB) member 
Nosipho Cynthia Zungu 
Durban – eThekwini CRS 
Protocol Pharmacist 
Jackline Odhiambo 
CoVPN LOC, Fred Hutch 
Statistical 
research 
associate 
Jin Jia Kee 
CoVPN SDMC, Fred Hutch 
Lead Site Liaison 
manager 
Bert Le Roux 
CoVPN LOC, Fred Hutch 
Community 
engagement unit 
representative 
Kagisho Baepanye 
CoVPN LOC, Fred Hutch 
Protocol development 
manager 
Smitha Sripathy 
CoVPN LOC, Fred Hutch  
Project 
coordinator 
Haven Wilvich 
CoVPN LOC, Fred Hutch 
 
 
 
 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 12 of 169 
2 
Background  
2.1 
Rationale for trial concept  
As the global COVID-19 pandemic has persisted, it has become clear not only that 
there are great risks faced by people who are immunocompromised, but also that 
there is an urgent need to better understand infection and disease in these 
populations so we can prevent severe COVID-19 as well as chronic SARS-CoV-2 
infections that could promote transmission and the emergence of new, dangerous 
variants. This is particularly true for the over 37 million people living with HIV 
(PLWH) who are concentrated in sub-Saharan Africa and have been significantly 
underrepresented in COVID-19 vaccine trials. This novel study aims to address 
critical knowledge gaps by evaluating COVID-19 mRNA vaccine efficacy among 
PLWH, including the influence of prior infection and degree of 
immunocompromise. The study will be the largest to date to assess one of the 
original, monovalent mRNA vaccines versus a new bivalent version that better 
targets new variants. The study will also seek to characterize viral shedding and 
the evolution of viral mutations among participants who become SARS-CoV-2 
infected. By collecting efficacy and safety data in over half-a-dozen countries 
across sub-Saharan Africa, the study authors hope to inform regulators in the 
region and help facilitate access to mRNA vaccine technology across Africa (4) . 
Evaluating the effectiveness of mRNA vaccines, including bivalent vaccines, against 
COVID-19 from VOCs among PLWH 
Since the emergence of the COVID-19 global pandemic, two highly efficacious 
mRNA vaccines targeting the S protein of the ancestral strain of SARS-CoV-2 
(Wuhan-Hu-1) have been approved and used widely, Pfizer-BioNTech’s 
BNT162b2 vaccine and Moderna’s mRNA-1273 vaccine (5, 6). For 
immunocompetent individuals the recommended primary series consists of two 
vaccinations followed months later by at least one booster vaccination, depending 
on age and comorbidities (7). Evidence from clinical trials and the real world have 
consistently demonstrated the efficacy of mRNA vaccines in preventing at least 
severe disease in this population (8-13). In addition, after hundreds of millions of 
doses administered, these COVID-19 vaccines have proven to be remarkably safe 
and well tolerated in the general population (14). 
Although immunocompromised individuals including PLWH are at elevated risk 
of severe COVID-19 (15, 16), the optimal approach for vaccinating this population 
with mRNA vaccines is unclear. Current guidelines from the US Centers for 
Disease Control and Prevention (CDC) for “moderately and severely 
immunocompromised” individuals recommend three vaccinations as part of the 
primary series and at least one booster vaccination (17). But these guidelines are 
largely based on studies involving people with malignancies or people on 
immunosuppressive medications (eg, solid organ transplant recipients, people with 
rheumatic disease) (18-21). While observational studies of PLWH suggest good 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 13 of 169 
immunogenicity and safety from mRNA vaccines (22-24), to date, COVID-19 
vaccine efficacy trials have generally only included a small number of PLWH, 
most of whom were required to have well-controlled disease, and very few studies 
have reported the number of endpoints in this population (8, 13, 25, 26). Neither 
the Pfizer-BioNTech nor the Moderna phase 3 efficacy trials enrolled adequate 
numbers of PLWH to define vaccine efficacy in this population (8, 13). This will 
be the first large scale study evaluating the effectiveness of mRNA vaccines 
against symptomatic and severe COVID-19 among PLWH. 
Table 2-1 Vaccine efficacy and effectiveness for the ancestral strain of SARS-CoV-2 and 
Variants of Concern  
Manufacturer Vaccine 
Vaccine efficacy 
against ancestral 
strain for 
symptomatic 
infection (severe 
COVID-19) 
Vaccine Effectiveness for VOC against Symptomatic 
Infection (Severe COVID-19) (27) 
Alpha 
(B.1.1.7) 
Beta / Gamma 
(B.1.351 / P.1) 
Delta 
(B.1.617.2) 
Omicron  
(B.1.1.529)1 
Moderna 
mRNA-
1273 
94 (100)% 
(8) 
91 (94)% 
78 (94)% 
70 (96)% 
75.1 (75-85 
against 
hospitalization)% 
Pfizer 
BNT162b2 
95(100)% 
(13) 
90 (95)% 
85 (98)% 
85 (95)% 
65.5 (80 against 
hospitalization)% 
Johnson and 
Johnson (JNJ) 
Ad26.COV
2.S 
66 (85.4)% 
(28, 29) 
N/A (N/A) 
52 (65-66 against 
hospitalization; 
91-95 against 
mortality)% 
N/A (71)% 
N/A (N/A) 
Novavax 
NVX-
CoV2373 
89.7 (100)% 
(26) 
86% 
60% 
60% 
N/A (N/A) 
AstraZeneca 
AZD1222 
(ChAdOx1) 
67 (100)% 
(30) 
80 (95)% 
Under 70% (N/A) 
70 (95)% 
48.9 (70 against 
hospitalization)% 
Note: refer to Tregoning et al., 2021 (31) and Cevik et al, 2021 (27) for a review of the COVID-19 vaccine 
effort, SARS-CoV-2 variants versus efficacy, effectiveness, and escape. 
1 Effectiveness at week 4 post 2nd dose; effectiveness dropped in the following weeks (32, 33). 
While the currently approved mRNA vaccines have demonstrated durable efficacy 
against severe COVID-19 disease (34, 35), high rates of breakthrough and repeat 
infections have highlighted their reduced efficacy against infections from new 
variants of concern (VOCs) (see Table 2-1), particularly Omicron (B.1.1.529 
[BA.1]) and its lineages (eg, BA.2, BA.2.12.1, BA.3, BA.4, BA.5). There is 
therefore a strong interest in developing updated vaccines to provide broader 
protection against current and future VOCs. To that end, Moderna, along with 
Pfizer-BioNTech, has developed new bivalent versions of its mRNA vaccine that 
include equal parts of mRNA encoding the S protein of the ancestral SARS-CoV-2 
(eg, mRNA-1273) as well as mRNA encoding for that of a VOC. Preliminary 
studies of such bivalent vaccines have been highly encouraging. The vaccine 
candidate mRNA-1273.211 (mRNA-1273 plus mRNA encoding the S protein of 
Beta) elicited significantly higher neutralizing antibody responses to the ancestral 
strain as well as variants (eg, Beta, Delta, and Omicron) compared to mRNA-1273 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 14 of 169 
alone or other monovalent formulations evaluated (36). The bivalent vaccine 
mRNA-1273.214 (mRNA-1273 plus mRNA encoding the S protein of Omicron 
[BA.1]) similarly demonstrated superior neutralizing antibody responses to prior 
variants as well as the Omicron subvariants BA.4/.5 (37). This bivalent vaccine has 
already been approved for use in the United Kingdom (37). And as of August 31, 
2022, the bivalent vaccine mRNA-1273.222 (mRNA-1273 plus mRNA encoding 
the S protein of BA.4/.5) has received authorization in the United States for use as 
a booster vaccine in adults. By randomizing participants at Month 6 to either 
mRNA-1273 or mRNA-1273.222, this trial will provide valuable efficacy and 
safety/tolerability data for both monovalent and newer bivalent mRNA vaccines in 
this high-risk population. 
Characterizing SARS-CoV-2 viral persistence and evolution among PLWH on ART and 
starting ART. 
Protecting PLWH and other immunocompromised individuals from SARS-CoV-2 
is important for their safety as well as the safety of the global community. Many of 
the VOCs, from Alpha and Beta to Omicron, have been found to carry mutations 
that can increase transmissibility, viral binding affinity, and/or immunologic 
escape (38-40). Multiple studies involving people with immunocompromising 
conditions have demonstrated long-term viral shedding, which may be infectious 
(41-43). In addition, an increasing number of studies suggest that prolonged 
infections in immunocompromised individuals, such as PLWH, may be a major 
source of the multistep mutational changes associated with VOCs (44-46). In one 
study, researchers in South Africa examined a SARS-CoV-2 infection persisting 
over 6 months in a person with advanced HIV that started as the ancestral strain 
but progressively evolved various mutations found in Omicron and other VOCs 
and developed substantial immunologic escape from vaccine-associated immunity 
(45). Given the large number of PLWH globally who have uncontrolled disease 
(47), there is an urgent need for a better understanding of viral shedding and 
mutational evolution within PLWH of different degrees of immunosuppression. 
Therefore, this study will monitor participants who acquire SARS-CoV-2 with 
sequential nasal swabs to track positivity through PCR testing and potential 
mutational changes via whole genome sequencing. To our knowledge, this will be 
the first systematic study to do so among a large cohort of persons closely 
monitored for such events. Given the size of the trial, we anticipate that this 
monitoring could provide novel insights into the dynamics of viral shedding and 
accumulation of viral mutations in SARS-CoV-2-infected PLWH of varying stages 
of HIV disease.   
Comparing the effectiveness of a hybrid immunity regimen with vaccine-induced 
immunity 
In addition to immunocompromise, prior SARS-CoV-2 infection has been 
underexamined in vaccine trials in terms of its impact on vaccine-associated 
immunity. It is unclear if people who have a history of past SARS-CoV-2 infection 
require the same vaccination regimen to achieve robust immunity as people who 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 15 of 169 
are infection naïve. This is especially relevant in sub-Saharan Africa where many 
areas likely have SARS-CoV-2 antibody seroprevalence in excess of 85% (48, 49). 
There is now significant evidence suggesting that natural infection may prime the 
immune system, like a vaccination, and synergistically enhance immunity when a 
vaccine is later administered (50). This has been termed “hybrid immunity” 
because it is a combination of natural immunity (derived from infection) and 
vaccine-induced immunity. Numerous observational studies have shown that 
previously infected individuals who are subsequently vaccinated demonstrate a 
particularly vigorous immune response, even after just one dose of mRNA vaccine 
(51-56). In one study, a single dose of mRNA vaccine given to previously infected 
individuals boosted neutralizing titers against multiple strains of SARS-CoV-2 
(and even SARS-CoV-1) by up to 1,000 times above those measured prior to the 
vaccination (52). Large prospective studies like this trial are needed to assess 
hybrid immunity compared to vaccine-only immunity to inform our vaccination 
strategies in a world now where most people have been previously infected. In 
addition, the post-Month 6 dose follow up in this trial will also provide 
information on whether individuals with hybrid versus vaccine-only immunity 
have different responses to the bivalent vaccine, which is of significant importance 
in the context of the ongoing epidemic of Omicron variants now globally 
prevalent. 
Modifying the final phase of the study based on findings from interim analyses 
Interim analyses of the pre-Month 6 study data have provided new information 
related to some of the study’s main research questions and have informed 
modifications to the final phase of the study. Consistent with observations in HIV-
negative populations, mRNA-1273 appears safe and well tolerated in PLWH. 
Reactions after vaccinations were largely mild, with few severe reactions (3%) and 
no life-threatening or fatal reactions. To date, adverse events in general have been 
overwhelmingly mild and only one serious adverse event (a case of angioedema) 
has been considered potentially related to the vaccine. The pre-Month 6 data also 
suggest that in our study population, participants with hybrid immunity (ie, 
immunity from both prior infection and vaccination) experienced a reduced 
incidence of symptomatic SARS-CoV-2 infections compared to participants with 
only vaccine-induced immunity. Specifically, PLWH and HIV-negative 
participants who had evidence of prior SARS-CoV-2 infection at baseline and 
received one dose of mRNA-1273 had an annual COVID-19 incidence rate of 
2.2% and 1.5% respectively, compared to 7.1% and 5.8% among such groups 
without evidence of prior infection at baseline and received two doses of mRNA-
1273. This reduction in SARS-CoV-2 incidence could be due to the combination 
of natural immunity and mRNA-1273 vaccination or due to natural immunity 
alone. In addition, serious COVID-19 has been very rare in our study population 
during the pre-Month 6 period, with only 9 cases identified to date, including 7 in 
PLWH and 2 in people who were HIV-negative. However, asymptomatic SARS-
CoV-2 infections were more common than previously appreciated, representing 
86% of pre-Month 6 cases. In addition, the data suggest that there are a significant 
number of likely persistent infections. Of the 1298 (9.3%) participants with at least 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 16 of 169 
one SARS-CoV-2 positive NAAT, 5.6%, 1.8%, and 1.5% were persistently NAAT 
SRVLWLYHDWGD\VUHVSHFWLYHO\'HHSJHQRPHVHTXHQFLQJRIWKH
sequential samples will help determine if these are persistent infections or 
reinfections (likely both) and what proportion of infections have acquired 
mutations. The persistent/recurrent infections appear to be more common among 
the participants without prior SARS-CoV-2 infection, those with active 
tuberculosis, and PLWH who have low CD4 T-cell counts and/or HIV viremia.  
The interim analyses suggest that PLWH with prior SARS-CoV-2 infection who 
receive one dose of mRNA vaccine, are at significantly lower risk of symptomatic 
COVID-19 compared with those without prior infection who received a two-dose 
regimen. Moreover, the mRNA-1273 vaccine has been demonstrated to be safe and 
well tolerated by PLWH. Given this, and the fact that monovalent mRNA vaccines 
like mRNA-1273 will likely not be commercially available much longer (to be 
replaced by bivalent and other next-generation vaccines), the study authors and the 
Sponsor decided to end routine research follow up for most participants vaccinated 
with only mRNA-1273. This change in the follow-up schedule was communicated 
to clinical research sites in January 2023.  
For the final phase of the Ubuntu study, the study will focus on participants 
vaccinated under protocol version 6.0 (ie, mRNA-1273 versus mRNA-1273.222, 
per randomization), and those with certain conditions that may increase the risk of 
prolonged SARS-CoV-2 infections (ie, active TB, HIV with low CD4 count, 
and/or HIV with unsuppressed viral load). To improve surveillance of 
asymptomatic infections, participants be administered nasal swab NAATs 
monthly, in addition to those initiated in response to symptoms or otherwise 
scheduled. And given the potential association between HIV disease and persistent 
SARS-CoV-2 infections, additional blood samples will be collected periodically 
among participants who are nasal swab NAAT positive for prolonged periods. 
Twelve months of follow up after enrolment will be adequate to accomplish the 
study objectives.  
In addition, a second approach for determining symptomatic COVID-19 cases, 
based on CDC criteria, will be used. To date the Ubuntu study has used the same 
approach for determining symptomatic COVID-19 cases as used in the COVE 
study (8, 12), which was developed early in the pandemic when herd immunity to 
SARS-CoV-2 was low; symptomatic disease was common; and presymptomatic, 
paucisymptomatic, and asymptomatic infections were under appreciated. Since 
then, it has become clear that subclinical infections with few symptoms are 
common with SARS-CoV-2, particularly with the newer variants. Symptom-driven 
testing, as required by COVE, may be insensitive to detecting mildly symptomatic 
infections. The CDC criteria are meant to adjust for the changing pandemic and 
our greater understanding of the disease in order to better capture mild COVID-19 
cases, requiring only 1 symptom be present and not requiring the onset of the 
symptom(s) to follow the NAAT positive result. The CDC criteria also do not 
require an Endpoint Adjudication Committee (EAC), although an EAC would 
continue to be used for determination of the COVE criteria-based endpoints. Two 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 17 of 169 
sets of endpoints will be calculated in parallel using both the CDC criteria and the 
more restrictive COVE criteria. 
2.1.1 
Overall study design 
This study will, to our knowledge, involve the largest cohort of PLWH enrolled 
into a COVID-19 vaccine clinical trial, and the study is constructed to help inform 
which vaccine regimen, likely in combination with enhanced HIV care, could 
serve as a public health model for an effective and cost-efficient approach to 
preventing SARS-CoV-2 disease, prolonged viral shedding, and the emergence of 
VOCs within this population. Moreover, we will evaluate whether immune 
responses post-vaccination can be correlated to these clinically important 
outcomes. 
This multicentered trial aims to enroll up to 15,600 participants, with 
approximately 80 percent of participants being PLWH. Among these, the majority 
will be confirmed SARS-CoV-2 seropositive at baseline. All participants will 
receive at least two vaccines during this trial. Participants will be grouped based on 
their HIV and SARS-CoV-2 serostatus. Regularly planned safety assessments and 
interim analyses of vaccine safety will be performed. Trial participants are 
followed for up to 18 months post-enrollment to evaluate the durability of vaccine 
efficacy, as well as safety.  
Because this study is evaluating a potential primary regimen, 100 mcg doses are 
used for both vaccines being used, mRNA-1273 and mRNA-1273.222. All 
vaccines will be delivered as an intramuscular (IM) injection into the deltoid 
muscle and, as with prior versions of the protocol, modest variations in the 
injection volume are acceptable assuming no change in dose. The mRNA-
1273.222 is currently authorized to be administered as a 50 mcg booster dose, 
whereas mRNA-1273 is approved for both 50- and 100 mcg doses. All available 
data on the bivalent vaccine formulations suggest that they have a similar rate of 
reactogenicity as an equivalent dose of the monovalent mRNA-1273 vaccine. 
Nevertheless, the study will take an extra safety precaution at the beginning of 
Month 6 vaccinations, when mRNA-1273.222 is introduced, as described below. 
The study is designed essentially with two phases. At Month 0 (enrollment) all 
participants will receive a dose of mRNA-1273. At Month 1, all participants 
without evidence of prior SARS-CoV-2 infection at baseline (based on serology) 
will receive a second dose of mRNA-1273. At Month 6 all participants (regardless 
of baseline SARS-CoV-2 status) will receive a vaccination, either mRNA-1273 or 
mRNA-1273.222 depending on their randomization at enrollment. As a safety 
precaution, after the first approximately 120 participants have been vaccinated at 
Month 6 (the “Month 6 sentinel cohort”), Month 6 vaccinations will be paused. 
Reactogenicity data from this Month 6 sentinel cohort will be reviewed to decide 
whether it is safe to continue with Month 6 vaccinations. After all Month 6 doses 
are administered, most participants who received their final vaccination prior to 
implementation of the bivalent mRNA-1273.222 vaccine (i.e., all received mRNA-

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 18 of 169 
1273) will be exited and the trial will focus on follow up for participants 
vaccinated with mRNA-1273 versus mRNA-1273.222, per randomization, and 
those with certain conditions (active TB, HIV with low CD4 count, and/or HIV 
with unsuppressed viral load) considered at risk of prolonged SARS-CoV-2 
infection.  
The relative risk of symptomatic and severe COVID-19 will be assessed between 
the 2-dose vaccine regimen in adult PLWH who were SARS-CoV-2 negative at 
baseline vs. a 1-dose regimen in adult PLWH who were SARS-CoV-2 positive at 
baseline, counting new cases of COVID-19 after the Month 0 vaccination and 
before the Month 6 vaccination. Next, the study will assess the relative risk of 
symptomatic and severe COVID-19 between the two different Month 6 vaccines 
(mRNA-1273 versus mRNA-1273.222) until end of follow-up at Month 18. The 
study will also assess the safety and tolerability of the two vaccines from the time 
of administration until the end of follow up. 
Approximately 1,500 participants who are baseline SARS-CoV-2 negative PLWH 
(Group 1) and 1,500 who are baseline SARS-CoV-2 positive PLWH (Group 2) 
will be included in the PBMC Immune Correlates subset with PBMC collected at 
Months 0, 1 or 2, and 7. In addition, about 300 participants with representation 
from all study groups will be included in the PBMC Immunogenicity subset with 
PBMC collected at more frequent timepoints to match the schedule for serum 
samples collected for humoral immune markers (Figure 2-1, Appendix D and 
Appendix E). The extra blood samples collected from these subsets of participants 
will allow the characterization of cellular immune responses through the end of 
study follow-up (Month 18) in all groups. This trial will be, to our knowledge, the 
first efficacy trial to evaluate correlates of protection associated with T-cell 
immune responses. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 19 of 169 
 
Figure 2-1 Representation of participant inclusion in the PBMC Immune Correlates and PBMC 
Immunogenicity subsets. (Note: the indicated sample sizes are approximate and ceiling numbers) 
With over 10,000 PLWH, the study will have sufficient sample size to provide 
important outcome information in order to assess the impact of an mRNA vaccine 
on the incidence of symptomatic and severe COVID-19. Baseline CD4 T-cell 
counts and viral loads will be measured to assess the impact of viral control and 
stage of disease on the immune response where possible. Those with newly 
diagnosed HIV will be offered counseling and referral for evaluation and care 
according to local guidelines. Study immunizations will be deferred for 2-4 weeks 
after the initiation of ART to reduce the difficulty in the interpretation of adverse 
events. The study team will support sites in monitoring for PLWH participating in 
the study with unsuppressed viral loads so that they can be referred to local 
resources in case they need adjustment of their ART regiment or interventions to 
support adherence. 
All participants who acquire new SARS-CoV-2 infection will be monitored with 
nasal swabs sent for NAAT at 14-day intervals until negative, to characterize the 
duration of viral shedding. In addition, viral load changes over time will be 
estimated through cycle threshold values for each NAAT-positive swab. All 
NAAT-positive swabs will be submitted for gene sequencing to evaluate for the 
development of new mutations. Participants will also be monitored closely for 
symptoms. These data will be used to assess potential correlations between these 
outcomes and degree of immunocompromise, post-vaccination immune response, 
and other factors. To improve surveillance of asymptomatic infections, participants 
will be administered nasal swab NAATs monthly after Month 6 in addition to 
those performed in response to symptoms or otherwise scheduled. Additional 
blood samples will be collected periodically among participants who are nasal 
swab NAAT positive for prolonged periods to better assess the potential 
association between HIV disease and persistent SARS-CoV-2 infections. 
Clinical trial sites will be enabled to optimize the detection, management, and 
follow-up of symptomatic COVID-19 acquired by participants during the course of 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 20 of 169 
the trial, including providing access to temperature monitoring, personal pulse 
oximetry monitoring, oxygen, medications such as steroids, and hospitalization at 
facilities that are both prepared and experienced with the management of severe 
cases to minimize potential complications of COVID-19 disease. Study data 
collected on the duration of viral shedding, PCR cycle thresholds, and viral 
sequencing may also contribute to optimizing management of SARS-CoV-2 
infected participants. The incidence of breakthrough infections will be carefully 
monitored throughout the study and if there are concerning relative rates of 
infections among study groups (eg, high incidence of infections in the hybrid 
immunity group), the DSMB or OG will make recommendations to adjust the 
course of the study to protect the safety and wellbeing of participants (eg, it could 
recommend that the study be modified to include an additional vaccine dose, if 
appropriate). In addition, as previously mentioned, at the start of Month 6 
vaccinations (involving mRNA-1273 versus mRNA-1273.222), there will be a 
vaccination pause after the approximately first 120 participants are vaccinated (the 
“Month 6 sentinel cohort”) so that reactogenicity data may be reviewed before a 
decision is made on whether to continue with these vaccinations.  
Specific features not present in most study designs of US Government’s 
Department of Health and Human Services [HHS] Coordination Operations and 
Response Element (HCORE) (previously known as Federal COVID-19 Response, 
Operation Warp Speed [OWS], and Countermeasures Accelerations Group [CAG]) 
are included in this study to assess vaccine efficacy against severe COVID-19 as a 
coprimary efficacy objective in addition to assessing vaccine efficacy against 
symptomatic infection. Severe COVID-19 is included as a coprimary endpoint 
because: (1) this endpoint is highly clinically significant, (2) it is feasible to power 
the study for this endpoint given data showing that a sizable percentage of 
symptomatic infections are severe in trial countries, and (3) the use of coprimary 
endpoints can improve statistical power (57). 
As noted, the pre-Month 6 vaccine regimens are assigned based on serological 
evidence of previous SARS-CoV-2 infection. Given demonstrated protection 
against severe disease and anamnestic immune responses upon re-exposure, we 
believe that the risk-benefit profile is acceptable for this trial and that the 
conditions outlined by expert panels are met, namely: 1) the social value of the 
data is high, 2) the risks to participants are low and justified by the social value of 
the trial, and 3) the research is responsive to local health needs (58, 59). 
2.1.2 
Background on the evolution of SARS-CoV-2 variants 
Since it was first recognized as a global threat in late 2019, the SARS-CoV-2 virus 
has adapted to immunologic selection pressures mediated by antibodies that limit, 
but do not necessarily eliminate, viral replication. Even before the availability of 
vaccines against SARS-CoV-2, new virus variants had begun to emerge worldwide 
and are thought to have significantly contributed to new waves of infections and 
deaths (60, 61). Mutations that lead to increased transmissibility and immunologic 
escape seem to most determine the success of new variants (38-40) (62-65). 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 21 of 169 
Vaccine efficacy against VOCs can be compromised by alterations in the shape of 
the S protein, which can impair or inactivate binding sites for neutralizing 
antibodies (66-70). 
The first major evidence of SARS-CoV-2 evolutionary change in response to 
selective pressure was the D614G mutation in the spike protein that emerged in 
early 2020 and has since become ubiquitous, likely because of its association with 
increased infectivity (71, 72). By the second half of 2020 the world entered a new 
stage of the pandemic characterized by the emergence of new SARS-CoV-2 
variants with accumulations of mutations facilitating transmission despite 
population immunity while maintaining or even increasing viral replication (73). In 
September 2020 the United Kingdom first reported a new variant, B.1.1.7 (Alpha), 
which had D614G as well as several other important mutations that lent to 
increased transmission (74-76). By early 2021 Alpha had become the dominant 
variant in most of Europe, North America, and many parts of Asia and Africa (77). 
Soon after Alpha was identified, additional highly transmissible variants emerged 
in populations with significant immunity from prior infection, B.1.351 (Beta) in 
South Africa and P.1 (Gramma) in Brazil (78, 79). In addition to both strains being 
more transmissible, convalescent plasma or vaccine sera showed substantial 
reductions in neutralizing antibody titers compared to Alpha (80, 81). Both 
variants became dominant within their immediate region and some other countries, 
but both were displaced virtually entirely – along with most other variants 
worldwide – by the emergence of B.1.617.2 (Delta). First detected in India in 
December 2020, Delta had a number of previously detected and novel mutations 
which increased transmissibility, immune escape, and severity of disease (67, 82, 
83) and led to an increase in cases and deaths in much world (84-86). 
The emergence of B.1.1.529 (Omicron), first identified in Botswana and South 
Africa in November 2021, led to an massive global wave of infections and 
COVID-19 disease that dwarfed all previous surges (87). Genetically, Omicron 
had significantly more mutations than had been previously seen in variants, 
including over 30 in the S gene alone (88). Some of the mutations were ones seen 
in prior variants that were known to be associated with increased transmissibility, 
higher viral binding affinity, and immunologic escape (89, 90). But many of the 
mutations were novel. Phenotypically, the Omicron variant distinguished itself by 
its remarkable transmissibility, over three-fold greater than Delta, and by its ability 
to quickly spread in populations with prior immunity. Indeed, studies of the plasma 
neutralization of the Omicron variant demonstrated an unprecedented degree of 
neutralizing antibody escape (91, 92). 
A leading hypothesis for the origin of Omicron is that it evolved during a chronic 
infection in someone immunocompromised (93). Indeed, an increasing number of 
studies suggest that prolonged infections in immunocompromised individuals, 
including PLWH, may be a major source of the multistep mutational changes 
associated with VOCs (44-46). In one study, researchers in South Africa examined 
a SARS-CoV-2 infection persisting over 6 months in a person with advanced HIV 
that started as ancestral virus but evolved various mutations found in Omicron and 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 22 of 169 
other variants and developed substantial immune escape from mRNA-1273 
vaccine-associated immunity (45). These findings highlight the urgent need for a 
better understanding mutational evolution within PLWH of different degrees of 
immunosuppression to help inform strategies to prevent emergence of further 
VOCs. 
2.1.3 
Burden of infections from SARS-CoV-2 variants of concern in Eastern 
and Southern Africa 
SARS-CoV-2 was first identified on the Africa continent in mid-February 2020, 
and within three months it had been confirmed in every country in Africa (94, 95). 
From early on, VOCs have been detected in Africa; the Beta variant was first 
discovered in South Africa in March 2021, and to date, virtually every VOC has 
been reported on the continent (96, 97).  
For the first year of the pandemic, it appeared that Africa had generally avoided 
the direst predicted consequences of SARS-CoV-2 (although widespread low 
testing capacity and underreporting obscured assessments). That all changed with 
the arrival of the Delta variant in early 2021. By July, the variant was the dominant 
strain across the continent, and by August death rates had surged by nearly 90% 
(98, 99). The rising toll was particularly severe in Eastern and Southern Africa. 
Between June 1 and September 1, 2021, total confirmed deaths from COVID-19 in 
South Africa rose by 46% to 82,496, and in Kenya, Zambia, and Uganda, deaths 
rose by 49%, 181%, and 735%, respectively, over the same period (100). 
Southern Africa was the first region in the world impacted by Omicron, and it and 
its subvariants rapidly spread despite significant population immunity from prior 
infection. Figure 2-2 illustrates the rapid rise of the Omicron variant in 2021 across 
Africa, and Figure 2-3 demonstrates the associated rise in confirmed SARS-CoV-2 
cases. Table 2-2 provides tallies of SARS-CoV-2 cases and associated deaths for a 
selection of countries across Eastern and Southern Africa. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 23 of 169 
 
Figure 2-2 Share of SARS-CoV-2 sequences that are the Omicron variant. Shown is the 
Omicron variant's share of total analyzed sequences in the last two weeks for selection of countries 
in Sub-Saharan Africa with available data. This share may not reflect the complete breakdown of 
cases, since only a fraction of all cases are sequenced (Source: Our World in Data (101). Original 
data from: COVID-19 Data Repository by the Center for Systems Science and Engineering [CSSE] 
at Johns Hopkins University.) 
 
Figure 2-3 Cumulative confirmed COVID-19 cases. The number of confirmed cases is lower than 
the number of actual cases, mainly due to limited testing. (Source: Our World in Data (101). Original 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 24 of 169 
data from: COVID-19 Data Repository by the Center for Systems Science and Engineering [CSSE] 
at Johns Hopkins University.) 
Table 2-2 Cumulative morbidity and mortality due to SARS-CoV-2 in Eastern and Southern 
Africa. The number of confirmed cases and deaths is lower than the actual numbers, mainly due to 
limited testing. Data current as of 22 Sep 2022. (Sources: COVID-19 Data Repository by the Center 
for Systems Science and Engineering [CSSE] at Johns Hopkins University (102) and Worldometer, 
Countries in the world by population (103).) 
Country / Region 
Confirmed Cases 
Deaths 
Population 
Worldwide 
614.00 M 
6.53 M 
7.929 M 
South Africa 
4.02 M 
102,169 
59.31 M 
Botswana 
326,127 
2,787 
2.35 M 
Zimbabwe 
257,259 
5,598 
14.86 M 
Zambia 
333,439 
4,017 
18.38 M 
Malawi 
87,997 
2,680 
19.13 M 
Eswatini 
73,379 
1,422 
1.16 M 
Uganda 
169,396 
3,630 
45.74 M 
Kenya 
338,379 
5,675 
53.77 M 
Since the initiation of this study in December of 2021, the Omicron variant 
epidemic has persisted worldwide including in sub-Saharan Africa. BA.1/BA.2 
and then extension of the epidemic by the BA.4/.5 variants has persisted in all 
regions of the world, with GSAID viral genomic surveillance indicating that, over 
98 percent of circulating strains of SARS-CoV-2 are of BA.4/BA.5 subvariants as 
of September 2022. Many unique subvariants have also been identified, almost all 
of which appear to fit phylogenetically within the Omicron subgroup. Thus, the 
consensus now is that vaccines that target these variants may provide additional 
protection against Omicron-related disease, and perhaps infections as well. This 
study will shed light on this issue.   
2.2 
Moderna mRNA-1273 and mRNA-1273.222 vaccines 
This trial will utilize two Moderna vaccines, the monovalent mRNA-1273, which 
encodes the S protein of the ancestral (Wuhan-Hu-1) SARS-CoV-2 strain, and a 
bivalent mRNA-1273.222, containing equal parts mRNA-1273 and mRNA 
encoding the S protein of the Omicron subvariants BA.4/.5. The mRNA-1273 
vaccine has been fully approved for adults in the United States and has been 
widely used in North America and Europe for both the primary vaccine series as 
well as boosters. The bivalent mRNA-1273.222 is currently authorized in the 
United States to be used as a booster vaccine, and it is very similar to another 
bivalent vaccine, mRNA-1273.214, that has been approved by the United 
Kingdom (37). To date, COVID-19 vaccine access – particularly access to mRNA 
vaccines – has been limited in Africa. As of September 22, 2022, only 23 percent 
of Africans had completed a primary vaccination regimen (104). Botswana, 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 25 of 169 
Eswatini, Kenya, Malawi, South Africa, Uganda, Zambia, and Zimbabwe have 
agreed to participate in the COVID-19 Vaccines Global Access (COVAX) 
initiative, and Moderna has previously committed to provide over 500 million 
doses to be made available to COVAX (105). 
2.2.1 
Clinical studies of Moderna mRNA-1273 and bivalent vaccines  
The full approval of mRNA-1273 for use in adults in early 2022 was based on a 
number of large clinical studies in the general population establishing the vaccine’s 
safety, immunogenicity, and efficacy against COVID-19 (Table 2-3). Hundreds of 
millions of doses of the vaccine have been administered and real-world data have 
further supported the vaccine’s safety and efficacy. 
Table 2-3 Summary of clinical studies in adults establishing safety, immunogenicity, and 
vaccine efficacy of mRNA-1273 in the general population 
ClinicalTrials.gov 
Identifier 
Study 
number 
Phase 
N 
Dose groups 
Route 
Schedule 
Reference 
NCT04283461 
P101 
1 
120 
25, 50, 100, 
or 250 mcg 
IM 
M0, M1 
(106, 107) 
NCT04405076 
P201 
2 
600 
50 or 100 
mcg 
IM 
M0, M1 
(108-110) 
NCT04470427 
P301 
3 
30,351 
100 mcg 
IM 
M0, M1 
(108-110) 
While current monovalent mRNA vaccines such as mRNA-1273 do increase 
antibody responses to VOCs including Omicron when given to previously 
vaccinated individuals, and real-world data suggests these boosters continue to be 
effective against severe COVID-19, neutralizing antibody titers are lower against 
the new VOCs and efficacy against infection appears decreased (111, 112). For 
this reason, there have been significant efforts to develop bivalent mRNA vaccines 
that better target VOCs, particularly Omicron. 
An ongoing multi-part, open-label, phase 2/3 study (NCT04927065) has been 
assessing the safety, reactogenicity, and immunogenicity of single doses of 
Moderna bivalent mRNA candidate vaccines in adults who already received two 
100 mcg doses of mRNA-1273 in the phase 3 COVE trial at least 6 months earlier 
(8, 12, 36, 113). The bivalent vaccines contain equal parts mRNA-1273 and 
mRNA encoding for the S protein of a VOC. Initial data on these bivalent vaccines 
have shown significant promise in retaining neutralizing activity against the 
ancestral SARS-CoV-2 while also providing stronger and more durable immune 
responses to current VOCs, while being safe and well tolerated.  

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 26 of 169 
Table 2-4 Clinical studies with Moderna COVID-19 bivalent vaccines ( 18 years of age). All 
participants previous received a primary series of mRNA-1273 (100 mcg); participants in Parts G & 
H also previously received a 3rd dose (50 mcg) of mRNA-1273. Part G enrolled Mar 8-23, 2022; 
Part H enrolled Aug 10-23, 2022. Table adapted from Miller J. Booster Doses of Moderna COVID-19 
Vaccines in Adults, Adolescents & Children (114). 
Bivalent vaccine 
Study (Part) 
Dose 
N 
Median follow-up 
Beta  
(mRNA-1273.211) 
205 (A) 
3rd 
300 
245 days 
BA.1 Omicron  
(mRNA-1273.214) 
205 (G) 
4th 
437 
43 days 
BA.4/.5 Omicron  
(mRNA-1273.222) 
205 (H) 
4th 
512 
Ongoing 
 
 
Total 
1249 
 
In study 205 (A) (Table 2-4), 50- and 100 mcg doses of the bivalent vaccine 
mRNA-1273.211 (containing mRNA-1273 and mRNA encoding for the S protein 
of the Beta strain) were evaluated. Both doses of the bivalent vaccine elicited 
significantly higher neutralizing antibody responses against the ancestral, Beta, 
Delta, and Omicron strains at 1 and 6 months than an extra mRNA-1273 
vaccination (36). In addition, both doses were very well tolerated. While the 100 
mcg dose of mRNA-1273.211 was associated with slightly more reactogenicity 
than the 50 mcg dose, it was comparable to what is seen with the FDA-approved 
100 mcg dose of mRNA-1273 that is part of the current Moderna primary 
vaccination regimen and has been given safely to hundreds of millions of people. 
And in study 205 (G), the bivalent vaccine mRNA-1273.214 (containing mRNA-
1273 and mRNA encoding for the S protein of the Omicron BA.1 strain), 
demonstrated non-inferior neutralizing antibody titers in response to the ancestral 
SARS-CoV-2 strain and clearly superior titers to VOCs including Omicron and its 
subvariants BA.4/.5 compared to the mRNA-1273 booster (113) (Table 2-4 and 
Figure 2-4). Safety and tolerability were similar to second and third doses of 
mRNA-1273. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 27 of 169 
 
Figure 2-4 Omicron BA.1 neutralizing titers were significantly higher following 4th dose (2nd booster) using 
Omicron BA.1 bivalent (mRNA-1273.214) than with mRNA-1273. Study 205, Per-Protocol Immunogenicity 
Set with No Prior Infection. 1. ĂƐĞĚŽŶEKsŵŽĚĞůĂĚũƵƐƚŝŶŐĨŽƌĂŐĞŐƌŽƵƉ;фϲϱ͕шϲϱǇĞĂƌƐͿĂŶĚpre-
booster titer. 2. Common risk difference and 97.5% CI were calculated by Miettinen-Nurminen method 
ĂĚũƵƐƚĞĚĨŽƌĂŐĞŐƌŽƵƉ;фϲϱ͕шϲϱǇĞĂƌƐͿ. Table adapted from Miller J. Booster Doses of Moderna COVID-19 
Vaccines in Adults, Adolescents & Children ;ϭϭϯ͕ϭϭϱͿ. 
Although study 205 (H), which involves mRNA-1273.222, is ongoing, there is 
already preclinical (non-human) study data strongly suggesting the efficacy of this 
bivalent vaccine. In studies with transgenic mice that express human ACE2 on 
their airway epithelia (to mimic human susceptibility to SARS-CoV-2) and that 
have previously been given a two-dose primary series of mRNA-1273, an 
additional dose of mRNA-1273.222 significantly increased the titers of 
neutralizing antibodies against BA.1 and BA.5 compared to an extra dose of 
mRNA-1273 (Figure 2-5) (115) . In addition, mice who received the additional 
dose of mRNA-1273.222 were better protected from infection when challenged 
with high-dose exposure to BA.5. Similar findings were found with mRNA-
1273.214 (Figure 2-6). 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 28 of 169 
 
Figure 2-5 Increased immunogenicity after booster dose of the BA.1 & BA.4/.5 Omicron 
bivalent vaccines (mRNA-1273.214 & mRNA-1273.222) in mice. Figure adapted from Miller J. 
Booster Doses of Moderna COVID-19 Vaccines in Adults, Adolescents & Children (115). 
 
 
Figure 2-6 Increased protection from BA.5 challenge after booster dose of BA.4/.5 & BA.1 
Omicron vaccines (mRNA-1273.214 & mRNA-1273.222) in mice. Figure adapted from Miller J. 
Booster Doses of Moderna COVID-19 Vaccines in Adults, Adolescents & Children (115). 
2.2.2 
Rationale for the safety approach in this study 
The study takes participant safety very seriously. The COVID-19 mRNA vaccines 
have excellent safety profiles in clinical trials and based on real-world data. No 
safety concerns were identified in the initial safety and efficacy trials for the 
COVID-19 mRNA vaccines other than transient local and systemic reactions (8, 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 29 of 169 
13). On January 31, 2022, after thorough review of the available safety and 
efficacy data, the FDA approved use of mRNA-1273 for the prevention of 
COVID-19 in individuals 18 years of age and older. As of August 2022, over 228 
million doses of the mRNA-1273 vaccine and 358 million doses of Pfizer-
BioNTech’s BNT162b2 mRNA vaccine have been administered in the US alone 
(116). In addition, over 221 million doses of the Moderna vaccine and 797 million 
doses of the Pfizer-BioNTech vaccine have been administered under the CMA in 
European countries (103). To date, numerous observational studies have suggested 
that significant adverse events associated with mRNA vaccines are rare in both the 
general population as well as specifically immunocompromised populations, 
including PLWH (7, 14, 22, 117-119).  
The safety of mRNA-1273.222 is based on safety data on the nearly identical 
mRNA-1273.214 from the previously mentioned open-label phase 2/3 study 205 
(NCT04927065) (113), safety data from clinical trials involving mRNA-1273 (8, 
12), and huge amounts of postmarking safety data with mRNA-1273 (120-122). 
All of Moderna’s bivalent vaccines to date are exceedingly similar to mRNA-
1273. In fact, these vaccines include one half portion of mRNA-1273. Study 205 
(G) found that the safety and tolerability of mRNA-1273.214 (targeting Omicron 
as well, albeit BA.1 instead of BA.4/.5) to be comparable to second or third doses 
of mRNA-1273 (36, 113). After extensive reviews of available safety data, on 
August 15, 2022, the United Kingdom’s Medicines and Healthcare Products 
Regulatory Agency (MAHPRA) authorized the use of mRNA-1273.214 (37), and 
on August 31, 2022, the United States FDA authorized the use of mRNA-1273.222 
– the bivalent vaccine to be used in this clinical trial (123).  To date, over 19 
million Americans have received as a booster the same bivalent vaccine being used 
in the Ubuntu study (3). Recent research examining real-world safety monitoring 
data for tens of millions of bivalent vaccinations, including millions involving 
mRNA-1273.222, suggests no difference in safety or tolerability compared to the 
monovalent mRNA vaccines (124). As of early November 2022, five reports of 
myocarditis and four reports of pericarditis after bivalent booster vaccination have 
been received by the US CDC’s Vaccine Adverse Event Reporting System 
9$(56IROORZLQJDGPLQLVWUDWLRQRIPLOOLRQGRVHVDPRQJSHUVRQVDJHG
years in the United States (124). In January 2023, an advisory committee to the US 
FDA endorsed an agency proposal to allow vaccine-naïve Americans  to receive 
the newer bivalent formulations, including the mRNA-1273.222, for their primary 
regimen (125). 
This study will evaluate regimens involving one or two doses of mRNA-1273 in 
the first month of the trial, and then a final Month 6 dose of either mRNA-1273 or 
mRNA-1273.222. Because this study is assessing a potential primary regimen, all 
doses will be 100 mcg to reflect the dosing used in Moderna’s standard primary 
regimen involving mRNA-1273. The administration of three initial 100 mcg doses 
of mRNA-1273 is already standard for people who are immunocompromised, 
studies of safety and immunogenicity of a third 100 mcg dose of mRNA-1273 are 
very reassuring (126, 127), and such dosing of the Moderna vaccine is already part 
of multiple approved/ongoing clinical trials (128-130). Although mRNA-1273.222 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 30 of 169 
is currently authorized in the United States only as a 50 mcg booster vaccine dose, 
all available data to date suggests that at the equivalent dose, the bivalent vaccines 
have similar reactogenicity and safety profiles as mRNA-1273. For example, as 
previously noted, study 205 (A) evaluated 100 mcg doses of the bivalent vaccine 
mRNA-1273.211 (containing mRNA-1273 and mRNA encoding for the S protein 
of the Beta strain), which is highly biosimilar to mRNA-1273.222, and found it 
was very well tolerated, with reactogenicity and safety event patterns comparable 
to what is seen with the 100 mcg dose of mRNA-1273. 
One of the primary objectives of this study is to collect additional data on the 
safety and tolerability of the mRNA-1273 and mRNA-1273.222 vaccines in adults 
who are at risk for severe COVID-19 disease, particularly PLWH. In order to 
achieve this goal, the study will collect all reports of SAEs and AESIs for all 
participants throughout the study period, as well as collect solicited local and 
systemic AEs and unsolicited AEs in a subset of study participants after each 
vaccination. In addition, after the first approximately 120 participants have 
received their Month 6 vaccination (a 100 mcg dose of either mRNA-1273 or 
mRNA-1273.222, depending on their randomization at enrollment), there will be a 
vaccination pause. Reactogenicity data on all members of this Month 6 sentinel 
cohort will be collected and reviewed before a decision is made on whether it is 
safe to continue Month 6 vaccinations.  
As previously noted, the vaccine regimens before Month 6 of one versus two doses 
of mRNA-1273 are assigned based on serological evidence of prior SARS-CoV-2 
infection. This is based on significant evidence that prior infection provides 
protection potentially comparable to a vaccination, and we believe that the risk-
benefit profile is acceptable for this trial in terms of the high social value of the 
data, the low risks to participants that are justified by the social value of the trial, 
and the responsiveness of the research to local health needs (58, 59). 
Clinical trial sites will be enabled to optimize the detection, management, and 
follow-up of symptomatic COVID-19 acquired by participants during the course of 
the trial. For example, this includes access to temperature monitoring, personal 
pulse oximetry monitoring, oxygen, medications such as steroids, and 
hospitalization at facilities that are both prepared and experienced with the 
management of severe COVID-19. Study data such as the duration of viral 
shedding, PCR cycle thresholds, and viral sequencing may contribute to 
optimizing management of COVID-19 among participants. The study has robust 
safety and reactogenicity monitoring, with a PSRT and DSMB providing ongoing 
assessment of this data at the individual and aggregate level, respectively. The 
rates of breakthrough infections and safety and reactogenicity events will be 
carefully monitored and if there are concerning relative rates among study groups, 
the DSMB will be able to make recommendations to adjust the course of the study 
to protect the safety and wellbeing of participants. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 31 of 169 
2.2.3 
Potential risks of mRNA-1273 and mRNA-1273.222 vaccines 
Known risks associated with receipt of the Moderna mRNA-1273 vaccine in the 
general population are described in the “Fact Sheet For Healthcare Providers 
Administering Vaccine (Vaccination Providers) Emergency Use Authorization 
(EUA) of the Moderna COVID-19 Vaccine To Prevent Coronavirus Disease 2019 
(COVID-19),” available at https://www.modernatx.com/covid19vaccine-eua/ 
(revised August 31, 2022). Similarly, known risks associated with receipt of the 
Moderna mRNA-1273.222 vaccine are described in “ Fact sheet for Healthcare 
Providers Administering Vaccine (Vaccination Providers) Emergency Use 
Authorization of the Moderna COVID-19 Vaccine, Bivalent (Original and 
Omicron BA.4/.5),” available at https://www.fda.gov/media/161318/download  
(revised August 31, 2022). Some of the risks are also described below. Regarding 
participants who are PLWH, please refer to Section 2.3. Documented adverse 
reactions include pain, swelling, and erythema at the injection site; axillary 
swelling/tenderness; fatigue; headache; myalgia; arthralgia; chills; 
nausea/vomiting; and fever. Figure 2-7 below renders published reactogenicity 
data for the mRNA-1273 SARS-CoV-2 vaccine in the P301 (COVE) phase 3 
efficacy trial NCT04470427, in which over 30,000 participants were enrolled and, 
aside from transient local and systemic reactions, no safety concerns were 
identified (8). Solicited local and systemic reactions to mRNA-based COVID-19 
vaccines (Moderna and Pfizer-BioNTech) collected by CDC via the v-safe active 
surveillance system from more than 3 million people (from December 14, 2020 to 
March 14, 2021) have been published and continue to support an excellent safety 
profile of this vaccine platform (131). CDC’s reports of myocarditis and 
pericarditis following the two-dose mRNA primary vaccination series among 
individuals 18-39 years of age show that young men are the group at highest risk 
(40 cases per million doses administered in the group between 18-24 years of age) 
and most events occur after the second dose; overall reporting rates exceed the 
background rates for males and females (132). Nevertheless, the CDC has 
analyzed the risk-benefit of mRNA vaccination for both Moderna and Pfizer-
BioNTech and recommended vaccination in all population groups being enrolled 
in this trial. SARS-CoV-2 infection has a 5- to 20-fold higher rate of myocardial 
disease than vaccination with mRNA vaccines (133). The addition of a third dose 
of the Moderna vaccine, according to an interim analysis of an ongoing clinical 
trial (NCT04405076) (134), does not introduce further risk of AEs, since the safety 
profile of a single booster dose was similar to the one observed following the 
primary vaccination series. In addition, clinical trial and real-world data on the 
safety of a third dose of the Pfizer-BioNTech vaccine have been very reassuring, 
indicating reactions comparable to those seen after a second dose (135, 136). 
 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 32 of 169 
Figure 2-7 Solicited local and systemic adverse events. Shown is the percentage of participants 
who had a solicited local or systemic adverse event within 7 days after injection 1 or injection 2 of 
either the placebo or the mRNA-1273 vaccine (from Baden et al, Efficacy and Safety of the mRNA-
1273 SARS-CoV-2 Vaccine. N Engl J Med. 2021 (8)). 
In terms of potential risks from mRNA-1273.222, as summarized in sections 2.2.1 
and 2.2.2, ongoing phase 2/3 studies of bivalent vaccine candidates have found that 
its safety and tolerability is consistently comparable to second or third doses of 
mRNA-1273 (36, 113).  

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 33 of 169 
Figure 2-8 shows reactogenicity data for mRNA-1273.214, which is highly similar 
to the mRNA-1273.222, with both targeting a strain of Omicron. 
 
Figure 2-8 Local reactogenicity of BA.1 Omicron bivalent (mRNA-1273.214) as 4th dose similar to 2nd dose 
of primary series and 3rd dose of original (mRNA-1273) in adults. Study 205 ;'Ϳ, safety subset. Solicited 
local adverse reactions within 7 days after injection. No Grade 4 events reported. Figure adapted from 
Miller J. Booster Doses of Moderna COVID-19 Vaccines in Adults, Adolescents & Children (8, 113, 115, 
ϭϯϰͿ. 
2.3 
Population to be studied 
This study will enroll up to 15,600 adults at risk of severe COVID-19 based on 
individual risk factors in order to enrich the study population for SARS-CoV-2 
infection and severe COVID-19 disease. The study will enroll participants 18 years 
and older, approximately 80 percent PLWH and 20 percent HIV-negative people 
with one or more comorbidities associated with increased risk of severe COVID-
19. The proportions of these various risk groups will be operationally managed to 
ensure that there is adequate representation within this study to draw conclusions 
about clinical outcomes. 
The underlying medical conditions that have compelling evidence for an increased 
risk of severe illness from COVID-19 have been summarized and regularly 
updated by the CDC. The conditions for which the strongest and most consistent 
evidence is available include hypertension, cancer, chronic kidney disease, chronic 
lung diseases (chronic obstructive pulmonary disease [COPD], interstitial lung 
disease, pulmonary embolism, bronchiectasis, pulmonary hypertension), heart 
conditions (eg, heart failure, coronary artery disease, cardiomyopathy,), disabilities 
(including attention-deficit/hyperactivity disorder [ADHD], cerebral palsy, 
limitations with self-care or activities of daily living, intellectual and 
developmental disabilities, learning disabilities, spinal cord injuries), 
cerebrovascular disease, chronic liver diseases (cirrhosis, non-alcoholic fatty liver 
disease, alcoholic liver disease, autoimmune hepatitis), cystic fibrosis, dementia, 
HIV, mental health disorders (mood disorders including depression, schizophrenia 
spectrum disorder), alpha-1 antitrypsin deficiency, asthma, bronchopulmonary 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 34 of 169 
dysplasia, hepatitis B, hepatitis C, obesity (body mass index [BMI]  30 kg/m2), 
severe obesity (BMI  40 kg/m2), sickle cell disease, tuberculosis, smoking, type 1 
and type 2 diabetes mellitus, pregnancy, immunocompromised states (eg, 
medication-induced immunosuppression after solid organ transplant, use of 
corticosteroids), and physical inactivity. Additional risk factors may be identified 
in the future. The reason for this weighting is to provide early and strong evidence 
that the data from the trial can be utilized for population-based efficacy globally. 
This study may enroll pregnant persons as part of the study, and study participants 
who become pregnant during the study may remain enrolled, but the number of 
pregnant persons enrolled is unlikely to be adequate to provide specific relative 
vaccine efficacy data for this population. Safety of mRNA vaccines in pregnant 
women has been adequately demonstrated and the CDC and WHO recommend 
vaccination against COVID-19 during pregnancy (102, 137-139). A recent study 
has also shown that COVID-19 vaccination is not associated with a reduction in 
chances for conception (140). Study sites that enroll pregnant persons will be 
selected based on well-established and proven experience for the optimal care and 
management of pregnant persons, including prenatal ultrasound evaluation to 
assess gestational age and potential fetal abnormalities. Participants who are 
pregnant at the time of enrollment or become pregnant during the study and are not 
known to be living with HIV will receive or be referred for HIV testing and 
counseling, as well as syphilis testing and potential treatment if indicated. 
People living with HIV 
PLWH are a major focus of this study, given the current significant evidence gap 
regarding what COVID-19 vaccine regimens would best benefit this group. PLWH 
will constitute the largest proportion of the study population, and study sites will 
be selected based on the presence of well-established systems for the diagnosis and 
care of PLWH. 
Studies have consistently suggested that PLWH are at elevated risk of poor 
outcomes from COVID-19 compared to HIV-uninfected individuals. In a 
multicenter registry of 286 PLWH who got COVID-19, 94 percent were on HIV 
antiretroviral therapy and 57 percent were hospitalized, of which 16 percent were 
in the ICU with a 9 percent mortality rate. This study found that severe COVID-19 
outcomes were associated with older age, lung disease, hypertension, and overall 
comorbidity burden (141). In the UK, a study of 123 PLWH out of 47,000 
individuals hospitalized with COVID-19 found that the overall mortality was 
similar (27 percent for PLWH and 32 percent for people without HIV) but the 
adjusted hazard ratio was slightly higher for PLWH (1.52 vs 1.92) (142). A study 
of 50,167 people with COVID-19, of which 404 were PLWH, showed that the 
latter were more likely to have comorbidities that have risk factors for severe 
COVID-19, such as hypertension, diabetes, chronic kidney disease, and nicotine 
dependence (143). The degree of immunosuppression may play an important role 
in poor outcomes. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 35 of 169 
In addition to the elevated risk of morbidity and mortality from COVID-19, PLWH 
also face a risk of prolonged infections and the potential for a longer period of 
infectiousness and the development of new mutations. A growing number of 
studies involving people with immunocompromising conditions have demonstrated 
many instances of long-term viral shedding, sometimes infectious (41-43). In 
addition, an increasing number of studies suggest that prolonged infections in 
immunocompromised individuals, including PLWH, may be a major source of the 
multistep mutational changes associated with the emergence of VOCs (44-46). The 
evolution of new mutations enabling increased immunologic escape during chronic 
SARS-CoV-2 infection has been well-documented in PLWH (45). 
To date, COVID-19 vaccine efficacy trials have generally only included a small 
number of PLWH, most of whom were required to have well-controlled disease, 
and very few studies have reported the number of endpoints in this population (12, 
13). None of the primary vaccine efficacy trials enrolled adequate numbers of 
PLWH to determine vaccine efficacy in this population. Although there continues 
to be a lack of efficacy and safety data from controlled clinical trials on mRNA 
vaccines in PLWH, an increasing number of observational studies of PLWH 
suggest acceptable immunogenicity and safety (22, 24, 118, 119) . 
In the case of a new HIV diagnosis, participants will be referred for HIV standard 
of care according to local guidelines. Participants with newly diagnosed HIV 
infection will have a CD4 and viral load assessment. If a participant is diagnosed 
with HIV infection at screening and antiretroviral treatment is initiated, the study 
vaccines may be administered approximately 2-4 weeks later to avoid overlapping 
AEs. In addition, the study team will support sites in monitoring for PLWH 
participating in the study with unsuppressed viral loads so that they can be referred 
to local resources in case they need adjustment of their ART regiment or 
interventions to support adherence. 
Monitoring of the trial will include safety and efficacy monitoring of symptomatic 
cases of COVID-19. All confirmed cases of COVID-19 that develop during the 
study will receive special attention and close follow-up to permit early intervention 
to prevent complications, morbidity, and mortality. These include temperature 
monitoring, routine pulse oximetry, provision of oxygen, steroids and other 
medications, and hospitalization. 
 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 36 of 169 
3 
Objectives and endpoints 
All symptomatic COVID-19 endpoints will be evaluated using two case 
definitions, one used in the COVE study (8, 12) and the other using a case 
definition based on criteria from the CDC (144, 145). The first two primary 
objectives count COVID-19 and severe COVID-19 endpoints starting 14 days after 
the last pre-Month 6 dose until the Month 6 dose in the pre-Month 6 stage, and 
compare the rate of these endpoints between adult PLWH with vaccine-only 
immunity vs. adult PLWH with hybrid immunity. The third and fourth primary 
objectives count COVID-19 and severe COVID-19 endpoints starting 14 days after 
dose 3 until the end of follow-up in the post-Month 6 stage, and compare the rate 
of these endpoints in adult PLWH who were randomized and received mRNA-
1273 vs. mRNA-1273.222 vaccine. Secondary objective 1 compares rates of 
COVID-19 and severe COVID-19 in the pre-Month 6 stage during a different 
period of follow-up: starting 14 days after dose 2 for participants who are SARS-
CoV-2 negative at baseline and starting 14 days after dose 1 for participants who 
are SARS-CoV-2 positive at baseline. Answers to primary objectives 1 and 2 will 
be available earlier than answers to primary objectives 3 and 4, such that 
essentially, the trial has two stages answering study questions comparing hybrid 
vs. vaccine-only immunity, and comparing two different month 6 vaccinations.  
Primary Objectives  
Primary Endpoints 
1. PRE-MONTH 6 STAGE: to assess the relative risk of 
symptomatic COVID-19 in Group 1 (PLWH who are 
SARS-CoV-2 negative at baseline) who receive a 2-dose 
mRNA-1273 vaccine regimen vs. in Group 2 (PLWH who 
are SARS-CoV-2 positive at baseline) who receive a 1-
dose mRNA-1273 regimen, counting endpoints starting 1 
day after Month 0 dose until Month 6 dose. 
1. COVID-19: Positive result of acute 
SARS-CoV-2 infection as assessed by 
nucleic acid amplification testing 
(NAAT) of a nasal swab and the 
presence of a prespecified symptom 
or symptoms (see footnotes 2 and 3) 
2. PRE-MONTH 6 STAGE: to assess the relative risk of 
severe COVID-19 in Group 1 (PLWH who are SARS-
CoV-2 negative at baseline) who receive a 2-dose mRNA-
1273 vaccine regimen vs. in Group 2 (PLWH who are 
SARS-CoV-2 positive at baseline) who receive a 1-dose 
mRNA-1273 regimen, counting endpoints starting 1 day 
after Month 0 dose until Month 6 dose. 
2. Severe COVID-19: COVID-19 that 
meets the criteria listed in footnote 4 
3. POST-MONTH 6 STAGE: to assess the relative risk of 
symptomatic COVID-19 after the Month 6 dose among 
those who received mRNA-1273 at Month 6 vs. those who 
received mRNA-1273.222 at Month 6, counting endpoints 
at least 14 days after the Month 6 dose until end of follow 
up. 
3. COVID-19: same as above 
4. POST-MONTH 6 STAGE: to assess the relative risk of 
severe COVID-19 after the Month 6 dose among those 
who received mRNA-1273 at Month 6 vs. those who 
received mRNA-1273.222 at Month 6, counting endpoints 
at least 14 days after the Month 6 dose until end of follow 
up. 
4. Severe COVID-19: same as above 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 37 of 169 
Primary Objectives 
Primary Endpoints 
5. To assess the safety and tolerability of mRNA-1273 and 
mRNA-1273.222 in adults who are at risk of severe 
COVID-19 in both the pre-Month 6 and post-Month 6 
stages. 
5. Adverse events: Solicited and 
unsolicited AEs collected for a subset 
of study participants. Serious adverse 
events (SAEs), adverse events of 
special interest (AESIs), collected for 
all participants throughout the study 
1 HIV-infection status and SARS-CoV-2 status are confirmed for each participant based on testing of samples 
collected during screening (serology) and at enrollment (NAAT). SARS-CoV-2 negative indicates both NAAT 
negative and serology negative. 
2 To be considered as a case of COVID-19 using the COVE case definition for the evaluation of the Primary 
Efficacy Endpoint, the following criteria must be met: 
1. 7KHSDUWLFLSDQWPXVWKDYHH[SHULHQFHGDWOHDVW7:2RIWKHIROORZLQJV\VWHPLFV\PSWRPV)HYHU&
chills, myalgia, headache, sore throat, new loss of taste or smell, OR 
2. The participant must have experienced at least ONE of the following respiratory signs/symptoms: cough, 
shortness of breath or difficulty breathing, OR clinical or radiographical evidence of pneumonia; AND 
3. The participant must have at least 1 nasal swab (or respiratory sample, if hospitalized) positive for SARS-
CoV-2 by NAAT within 14 days following the above systemic or respiratory symptoms. 
3 To be considered as a case of COVID-19 using the CDC-derived case definition for the evaluation of the Primary 
Efficacy Endpoint, the following criteria must be met: 
1. 7KHSDUWLFLSDQWPXVWKDYHH[SHULHQFHGDWOHDVW21(RIWKHIROORZLQJV\VWHPLFV\PSWRPV)HYHU&
chills, myalgia, headache, sore throat, new loss of taste or smell, OR 
2. The participant must have experienced at least ONE of the following respiratory signs/symptoms: cough, 
shortness of breath or difficulty breathing, OR clinical or radiographical evidence of pneumonia; AND 
3. The participant must have at least 1 nasal swab (or respiratory sample, if hospitalized) positive for SARS-
CoV-2 by NAAT within 14 days of any of the above systemic or respiratory symptoms. 
 
4 To be considered as a case of severe COVID-19 for the evaluation of the Secondary Efficacy Endpoint, the 
following criteria must be met:  
x 
A confirmed case of COVID-19, per a Primary Efficacy Endpoint case definition, plus any of the 
following: 
 
&OLQLFDOVLJQVLQGLFDWLYHRIVHYHUHV\VWHPLFLOOQHVV5HVSLUDWRU\5DWHSHUPLQXWH+HDUW
5DWHEHDWVSHUPLQXWH6S2RQURRPDLUDWVHDlevel or PaO2/FIO2 < 300 mm 
Hg, OR 
 
Respiratory failure or Acute Respiratory Distress Syndrome (ARDS), (defined as needing high-
flow oxygen, noninvasive or mechanical ventilation, or ECMO), evidence of shock (systolic 
blood pressure < 90 mmHg, diastolic BP < 60 mmHg or requiring vasopressors), OR 
 
Significant acute renal, hepatic, or neurologic dysfunction, OR 
 
Admission to an intensive care unit or death. 
 
Secondary Objectives 
Secondary Endpoints 
1. PRE-MONTH 6 STAGE: to assess the relative risk of 
symptomatic COVID-19 and of severe COVID-19 in 
Group 1 (PLWH who are SARS-CoV-2 negative at 
baseline) vs. in Group 2 (PLWH who are SARS-CoV-2 
positive at baseline), counting endpoints at least 14 days 
after the last pre-Month 6 dose (i.e., dose 2 for Group 1 and 
dose 1 for Group 2) until the Month 6 dose. 
COVID-19 and severe COVID-19 as 
defined for the primary endpoints 
2. PRE-MONTH 6 STAGE: to assess the relative risk of 
symptomatic COVID-19 and of severe COVID-19 in 
Groups 1 and 3 together (participants who are SARS-CoV-
2 negative at baseline regardless of HIV status) vs. in 
Groups 2 and 4 together (participants who are SARS-CoV-
COVID-19 and severe COVID-19 as 
defined for the primary endpoints 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 38 of 169 
Secondary Objectives 
Secondary Endpoints 
2 positive at baseline regardless of HIV status), counting 
endpoints starting 1 day after dose 1, and counting 
endpoints at least 14 days after the last pre-Month 6 dose  
(ie,, dose 2 for Group 1 and dose 1 for Group 2) until the 
Month 6 dose. 
3. POST-MONTH 6 STAGE: to assess the relative risk of 
symptomatic COVID-19 and of severe COVID-19 after the 
Month 6 dose in Group 1 (PLWH who are SARS-CoV-2 
negative at baseline) and Group 2 (PLWH who are SARS-
CoV-2 positive at baseline), separately and combined, 
among those who received mRNA-1273 at Month 6 vs. 
those who received mRNA-1273.222 at Month 6, counting 
endpoints at least 14 days after the Month 6 dose until end 
of follow up. 
COVID-19 and severe COVID-19 as 
defined for the primary endpoints 
4. POST-MONTH 6 STAGE: to assess the relative risk of 
virologically confirmed symptomatic COVID-19 and of 
severe COVID-19 after the Month 6 dose in Groups 1 and 
3 together (participants who are SARS-CoV-2 negative at 
baseline regardless of HIV status) and in Groups 2 and 4 
together (participants who are SARS-CoV-2 positive at 
baseline regardless of HIV status), respectively, among 
those who received mRNA-1273 at Month 6 vs. those who 
received mRNA-1273.222 at Month 6, counting endpoints 
at least 14 days after Month 6 dose until the end of follow 
up. 
COVID-19 and severe COVID-19 as 
defined for the primary endpoints 
5. PRE-MONTH 6 & POST-MONTH 6 STAGES: to assess 
the relative risk of symptomatic COVID-19 and of severe 
COVID-19 after the Month 6 dose by neutralization 
phenotype and Spike sequence features of acquired SARS-
CoV-2 viruses (sieve analysis) in Groups 1 and 3 together 
(participants who are SARS-CoV-2 negative at baseline 
regardless of HIV status) and in Groups 2 and 4 together 
(participants who are SARS-CoV-2 positive at baseline 
regardless of HIV status), respectively, among those who 
received mRNA-1273 at Month 6 vs. those who received 
mRNA-1273.222 at Month 6, counting endpoints starting 1 
day after dose 1, 14 days after the last pre-Month6 dose , or 
14 days after Month 6 dose until the end of follow up. 
COVID-19 and severe COVID-19 as 
defined for the primary endpoints; 
neutralization phenotypes and viral 
genotypic characteristics of SARS-
CoV-2 at diagnosis.  
6. PRE-MONTH 6 & POST-MONTH 6 STAGES: to assess 
the relative risk of SARS-CoV-2 infection defined by 
nucleocapsid protein seroconversion regardless of 
symptomology after the Month 6 dose in Group 1 (PLWH 
who are SARS-CoV-2 negative at baseline) and in Group 3 
(people HIV-negative who are SARS-CoV-2 negative at 
baseline) combined, among those who received mRNA-
1273 at Month 6 vs. those who received mRNA-1273.222 
at Month 6, counting endpoints starting 1 day after dose 1, 
14 days after the last pre-Month 6 dose , or 14 days after 
Month 6 dose until the end of follow up. 
SARS-CoV-2 infection diagnosed by 
seroconversion throughout the study.  

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 39 of 169 
Secondary Objectives 
Secondary Endpoints 
7. PRE-MONTH 6 & POST-MONTH 6 STAGES: to assess 
the relative risk of asymptomatic SARS-CoV-2 infection 
defined by nucleocapsid protein seroconversion after the 
Month 6 dose in Group 1 (PLWH who are SARS-CoV-2 
negative at baseline) and in Group 3 (people HIV-negative 
who are SARS-CoV-2 negative at baseline) combined, 
among those who received mRNA-1273 at Month 6 vs. 
those who received mRNA-1273.222 at Month 6, counting 
endpoints starting 1 day after dose 1, 14 days after the last 
dose before Month 6 dose, or 14 days after Month 6 dose 
until the end of follow up. 
SARS-CoV-2 infection diagnosed by 
seroconversion in the absence of 
symptoms.  
8. PRE-MONTH 6 & POST-MONTH 6 STAGES: to assess 
the relative risk of symptomatic COVID-19, and severe 
COVID-19 after the Month 6 dose in Groups 1 and 3 
together (participants who are SARS-CoV-2 negative at 
baseline regardless of HIV status) and in Groups 2 and 4 
together (participants who are SARS-CoV-2 positive at 
baseline regardless of HIV status), respectively, among 
those who received mRNA-1273 at Month 6 vs. those who 
received mRNA-1273.222 at Month 6, counting endpoints 
starting 1 day after dose 1 or 14 days after the last dose 
before Month 6 dose until the end of follow up. 
COVID-19 and severe COVID-19 as 
defined above 
9. To assess post-vaccination immune response markers and 
immune markers as correlates of risk of COVID-19 and as 
correlates of protection against COVID-19 in all study 
groups together. 
SARS-CoV-2-specific neutralization 
antibody, binding antibody and 
cellular immune responses 
10. To assess SARS-CoV-2 viral persistence and evolution 
among participants virologically diagnosed of SARS-CoV-
2 infection in all study groups together. 
SARS-CoV-2 viral load (as inferred 
from RT-PCR cycle threshold values) 
and viral whole genome sequences 
 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 40 of 169 
Exploratory Objectives 
Exploratory Endpoints 
1. 
To assess the relative risk of COVID-19 
and severe COVID-19 by baseline HIV 
infection status in participants. 
COVID-19 and severe COVID-19 as defined for 
the primary endpoints  
2. 
To estimate VE of COVID-19 and 
severe COVID-19 using counterfactual 
placebo  
COVID-19 and severe COVID-19 as defined for 
the primary endpoints  
3. 
Assess post-infection T-cell responses in 
participants who develop COVID-19  
SARS-CoV-2-specific T-cell immune responses; 
COVID-19 as defined above 
Additional Exploratory Objectives 
4. 
To further evaluate immunogenicity of the vaccine, additional assays may be performed  
5. 
To conduct analyses related to furthering the understanding of SARS-CoV-2, coronavirus, 
immunology, vaccines, and clinical trial conduct 
 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 41 of 169 
4 
Ethical considerations 
It is critical that universally accepted ethical guidelines are followed at all sites 
involved in the conduct of clinical trials. The COVID-19 Prevention Network 
(CoVPN) have addressed ethical concerns in the following ways:  
x CoVPN trials are designed and conducted to enhance the scientific knowledge 
base necessary to find a preventive vaccine, using methods that are 
scientifically rigorous and valid, and are in accordance with International 
Council for Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use (ICH) and/or other Good Clinical Practice (GCP) guidelines. 
x CoVPN scientists and operational staff incorporate the philosophies underlying 
major codes (146-148), declarations, and other guidance documents relevant to 
human subjects research into the design and conduct of SARS-CoV-2 vaccine 
clinical trials. 
x CoVPN scientists and operational staff are committed to substantive 
community input—into the planning, conduct, and follow-up of its research—
to help ensure that locally appropriate cultural and linguistic needs of study 
populations are met. 
x The CoVPN provides training so that all participating sites similarly ensure fair 
participant selection, protect the privacy of research participants, and obtain 
meaningful informed consent. During the study, participants will have their 
well-being monitored, and to the fullest extent possible, their privacy protected. 
Participants may withdraw from the study at any time. 
x Prior to implementation, CoVPN trials are rigorously reviewed by scientists 
who are not involved in the conduct of the trials under consideration. 
x CoVPN trials are reviewed by local and national regulatory bodies and are 
conducted in compliance with all applicable national and local regulations. 
x The CoVPN designs its research to minimize risk and maximize benefit to both 
study participants and their local communities. For example, CoVPN protocols 
provide enhancement of participants’ knowledge of SARS-CoV-2 and SARS-
CoV-2 prevention, as well as counseling, guidance, and assistance with any 
social impacts that may result from research participation. CoVPN protocols 
also include careful medical review of each research participant’s health 
conditions and reactions to study products while in the study. 
x CoVPN research aims to benefit local communities by directly addressing the 
health and SARS-CoV-2 prevention needs of those communities and by 
strengthening the capacity of the communities through training, support, shared 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 42 of 169 
knowledge, and equipment. Researchers involved in CoVPN trials are able to 
conduct other critical research in their local research settings. 
x The CoVPN values the role of in-country Institutional Review Boards (IRBs), 
Ethics Committees (ECs), and other Regulatory Entities (REs) as custodians 
responsible for ensuring the ethical conduct of research in each setting. 
x All participants will receive vaccine during this trial. 
x If a participant is diagnosed with COVID-19 during the course of the study, 
country-specific guidelines on administration of vaccination if available will be 
followed. 
x All participants with COVID-19 will receive the optimal local standard of care 
for prevention and treatment of COVID-19, including access to temperature 
monitoring, pulse oximetry, oxygen, medications such as steroids, and 
hospitalization at facilities that are both prepared and experienced at the 
management of severe cases to minimize mortality. 
x All participants who are pregnant at any time during the study will be offered 
HIV counseling and testing if they are not known to be PLWH, and referral for 
prenatal and obstetrical care. All PLWH will be referred for HIV care if not 
already in a program. 
 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 43 of 169 
5 
IRB/EC review considerations 
US FDA and other US federal regulations require IRBs/ECs/REs to ensure that 
certain requirements are satisfied on initial and continuing review of research 
(Title 45, Code of Federal Regulations (CFR), Part 46.111(a) 1-7; 21 CFR 
56.111(a) 1-7). The following section highlights how this protocol addresses each 
of these research requirements. Each CoVPN Investigator welcomes IRB/EC/RE 
questions or concerns regarding these research requirements. 
HCORE is paying for this study through funding to NIAID and the trial is being 
conducted in countries outside of the United States. Due to this, the trial is subject 
to both US and local regulations and guidelines on the protection of human 
research subjects and ethical research conduct. Where there is a conflict in 
regulations or guidelines, the CoVPN strives toward maximum protection of 
human research participants. 
In compliance with international and local (as appropriate) ICH and/or other GCP 
guidelines, each research location has a locally based Principal Investigator (PI) 
who is qualified to conduct (and supervise the conduct of) the research. The 
investigators take responsibility for the conduct of the study, including obtaining 
all appropriate regulatory and ethical reviews of the research. 
5.1 
Minimized risks to participants 
45 CFR 46.111 (a) 1 and 21 CFR 56.111 (a) 1: Risks to subjects are 
minimized. 
This protocol minimizes risks to participants by (a) correctly and promptly 
informing participants about risks so that they can join in partnership with the 
researcher in recognizing and reporting harms; (b) respecting local/national blood 
draw limits; (c) performing direct observation of participants postvaccination; (d) 
having staff properly trained in administering study procedures that may cause 
physical harm or psychological distress, such as blood draws, vaccinations, 
COVID-19 testing and counseling; (e) providing safety monitoring; (f) ensuring 
any participant with COVID-19–like symptoms have access to optimal local 
standard of care for prevention of acquisition and treatment of COVID-19; and (g) 
participants are permitted to get vaccinated outside the study if they have access. 
5.2 
Reasonable risk/benefit balance 
45 CFR 46.111(a) 2 and 21 CFR 56.111(a) 2: Risks to subjects are 
reasonable in relation to anticipated benefits, if any, to subjects, and 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 44 of 169 
the importance of the knowledge that may reasonably be expected to 
result. 
In all public health research, the risk-benefit ratio may be difficult to assess 
because the benefits to participants in prevention protocols are not as apparent as 
they would be in treatment protocols, where a study participant may be ill and may 
have exhausted all conventional treatment options. However, this protocol is 
designed to minimize the risks to participants while maximizing the potential value 
of the knowledge it is designed to generate. 
5.3 
Equitable participant selection  
45 CFR 46.111 (a) 3 and 21 CFR 56.111 (a) 3: Subject selection is 
equitable 
This protocol has specific inclusion and exclusion criteria for investigators to 
follow in admitting participants into the protocol. Participants are selected because 
of these criteria and not because of positions of vulnerability or privilege. 
Investigators are required to maintain screening and enrollment logs to document 
participants who screened into and out of the protocol and for what reasons. 
5.4 
Appropriate informed consent 
45 CFR 46.111 (a) 4 and 5 and 21 CFR 56.111 (a) 4 and 5: Informed 
consent is sought from each prospective subject or the subject’s 
legally authorized representative as required by 45 CFR 46.116 and 21 
CFR Part 50; informed consent is appropriately documented as 
required by 45 CFR 46.117 and 21 CFR 50.27 
The protocol specifies that informed consent must be obtained before any study 
procedures are initiated and assessed throughout the trial (see Section 9.1). Each 
site is provided training in informed consent by the CoVPN and is required to have 
a Standard Operating Procedure (SOP) on the informed consent process. The 
CoVPN requires a signed consent document for documentation, in addition to 
chart notes or a consent checklist. 
5.5 
Adequate safety monitoring 
45 CFR 46.111 (a) 6 and 21 CFR 56.111 (a) 6: There is adequate 
provision for monitoring the data collected to ensure the safety of 
subjects. 
This protocol has extensive safety monitoring in place (see Section 11). Safety is 
monitored daily by CoVPN clinical staff and routinely by the CoVPN 3008 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 45 of 169 
(Ubuntu) PSRT. In addition, an independent DSMB periodically reviews study 
data, including unblinded study data if/when needed. 
5.6 
Protect privacy/confidentiality 
45 CFR 46.111 (a) 7 and 21 CFR 56.111 (a) 7: There are adequate 
provisions to protect the privacy of subjects and maintain the 
confidentiality of data. 
Privacy refers to an individual’s right to be free from unauthorized or unreasonable 
intrusion into his/her private life and the right to control access to individually 
identifiable information about him/her. The term “privacy” concerns research 
participants or potential research participants as individuals whereas the term 
“confidentiality” is used to refer to the treatment of information about those 
individuals. This protocol respects the privacy of participants by informing them 
about who will have access to their personal information and study data (see 
Appendix A). The privacy of participants is protected by assigning unique 
identifiers in place of the participant’s name on study data and specimens. In 
addition, each staff member at each study site in this protocol signs an Agreement 
on Confidentiality and Use of Data and Specimens with the CoVPN. In some 
cases, a comparable confidentiality agreement process may be acceptable. Each 
study site participating in the protocol is required to have a standard operating 
procedure on how the staff members will protect the confidentiality of study 
participants. 
5.7 
Pregnant participants 
45 CFR 46.203 and 45 CFR 46.204: There are adequate protections for pregnant 
women, human fetuses, and neonates involved in research. 
The NIH is mandated by law to ensure that pregnant women and children be 
included in clinical research when appropriate. This study responds to that 
mandate and will provide valuable research data on the clinical and immunologic 
outcomes in pregnant women. Per the US Code of Federal Regulations (CFR), site 
IRBs/ECs must consider the potential risks and benefits to maternal and fetal 
participants as described in 45 CFR 46 Subpart B (for pregnant women, fetuses, 
and neonates). In addition to the US regulations cited above, sites not in the US 
must also comply with all applicable local and national guidelines and regulations. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 46 of 169 
6 
Statistical considerations 
6.1 
Summary of statistical design 
The statistical design primarily aims to evaluate 1) in the pre-Month 6 stage, the 
relative risk of COVID-19 and severe COVID-19 between the PLWH vaccine-
only immunity group  who are SARS-CoV-2 negative at enrollment, and assigned 
to receive 2 doses of pre-Month 6 vaccinations, and the PLWH hybrid immunity 
group who are SARS-CoV-2 positive at enrollment and assigned to receive 1 dose 
of pre-Month 6 vaccination (i.e., co-primary objectives 1 and 2) and; 2) in the post-
Month 6 stage the relative risk of COVID-19 and severe COVID-19 between the 
mRNA-1273 and mRNA-1273.222 randomized arms (i.e., co-primary objectives 3 
and 4). In the pre-Month 6 stage, the evaluation considers follow-up after 
enrollment until the Month 6 dose; in the post-Month 6 stage, the evaluation 
considers follow-up after the Month 6 dose until the end of study. 
Severe COVID-19 is included as a coprimary endpoint, which recognizes the 
importance of evaluating severe COVID-19 in PLWH. Given uncertainty in the 
rate of severe COVID-19 at the time of the primary analysis, an adaptive decision 
based on the treatment-blinded number of severe COVID-19 endpoints is made of 
whether to retain severe COVID-19 as a primary endpoint or to change it to a 
secondary endpoint. In addition, as secondary objectives of this trial, the relative 
risk of COVID-19 and severe COVID-19 will be evaluated in Groups 1 and 3 
combined vs. Groups 2 and 4 combined, accounting for baseline HIV-1 serostatus. 
For the pre-Month 6 stage, given that the analysis groups defined by HIV and 
SARS-CoV-2 statuses, and the number of vaccinations received are not 
randomized, and the assignment of individuals to study groups is known to 
participants and study staff, the study objectives are assessed using methods that 
adjust for measured potential confounder variables (see Section 6.4.3). For the 
post-Month 6 stage, because participants were randomized at baseline to the 
assignment of the two different Month 6 vaccinations within each of Groups 1-4, 
adjustment for potential confounder variables is only considered for the assessment 
of secondary objectives, not the primary objectives. 
6.2 
Definitions of study cohorts for analysis 
Throughout the protocol, unless otherwise noted, baseline SARS-CoV-2 negative 
indicates both (anti-Spike and anti-Nucleocapsid) seronegative and virus detection 
negative, and SARS-CoV-2 positive indicates either (anti-Spike or anti-
Nucleocapsid) seropositive or virus detection positive of participants’ samples 
collected prior to the first vaccination. Of note, baseline SARS-CoV-2 anti-Spike 
(anti-S) sero-status (which does not account for virus or anti-Nucleocapsid (anti-N) 
detection) is used to determine treatment group assignment, not analyses cohorts. 
The definitions of study cohorts that will be analyzed for addressing various study 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 47 of 169 
objectives are provided in Table 6-1 below. The Full Analysis Set (FAS) and the 
Safety Subset (SS) will be the cohorts for the primary safety analyses according to 
the treatment that participants actually received. The subgroups of FAS 
participants will be the cohort for the pre-Month 6 stage primary efficacy analyses. 
The subgroups of Per-Protocol (PP) participants will be the cohort for the post-
Month 6 stage primary efficacy analyses. The subgroups of PP participants that are 
sampled for cellular and humoral immunogenicity and immune correlates analyses 
comprise the Immunogenicity Subset (IS). In addition to those measured at Month 
7 (one month after the Month 6 dose) across all groups in the IS, immune 
responses at Month 1 (one month after dose 1) among baseline SARS-CoV-2 
seropositive participants in Groups 2 and 4 and immune responses at Month 2 (one 
month after the second dose) among baseline SARS-CoV-2 seronegative 
participants in Groups 1 and 3 will be used to characterize vaccine-induced 
immunogenicity proximal to vaccination. Immunogenicity at baseline (Month 0) 
and at the Month 6 visit immediately prior to the Month 6 dose, and durability of 
immunogenicity at Months 12 and 18 will also be assessed across all groups in the 
IS. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 48 of 169 
Table 6-1 Analysis Cohorts and Corresponding Primary, Secondary or Exploratory Objectives 
Cohort 
Definition 
Objectives 
Full Analysis Set (FAS) 
$OOUDQGRPL]HGSDUWLFLSDQWVZLWKDGPLQLVWUDWLRQRI
study product 
Primary objective 5 
x Subgroup FAS.Grp1 
x PLWH who are SARS-CoV-2 negative1 at baseline 
(Group 1) in the FAS  
Primary objectives 1 & 2 
Secondary objectives 1-2, 10 
Exploratory objectives 1-5 
x Subgroup FAS.Grp2 
x PLWH who are SARS-CoV-2 positive2 at baseline 
(Group 2) in the FAS, who received either 1 or 2 pre-
Month 6 vaccination doses  
Primary objectives 1 & 2 
Secondary objectives 1-2, 10 
Exploratory objectives 1-5 
x Subgroup FAS.Grp3 
x People who are HIV-1 seronegative and SARS-CoV-2 
negative1 at baseline (Group 3) in the FAS 
Secondary objectives 2, 10 
Exploratory objectives 1-5  
x Subgroup FAS.Grp4 
x People who are HIV-1 seronegative and SARS-CoV-2 
positive2 at baseline (Group 4) in the FAS, who 
received either 1 or 2 pre-Month 6 vaccination doses  
Secondary objectives 2, 10 
Exploratory objectives 1-5 
Safety Subset (SS) 
Participants in the FAS who are sampled for solicited and 
unsolicited AE assessment  
Primary objective 5 
x Subgroups SS.Grp1–4 
x Groups 1-4 participants in the SS 
Primary objective 5 
Per-Protocol (PP) 
Participants in the FAS who received all planned 
immunizations according to the current study schema and 
have no major protocol violations3 
Primary objectives 3 & 4  
x Subgroup PP.Grp1 
x Group 1 PP participants who are SARS-CoV-2 
negative1 at baseline 
Secondary objectives 3-8 
Exploratory objectives 1-5 
x Subgroup PP.Grp2 
x Group 2 PP participants who are SARS-CoV-2 
positive2 at baseline, receiving 1 or 2 pre-Month 6 
vaccination doses 
Secondary objectives 3-5, 8 
Exploratory objectives 1-5 
x Subgroup PP.Grp3 
x Group 3 PP participants who are SARS-CoV-2 
negative1 at baseline 
Secondary objectives 4-8   
Exploratory objectives 1-5 
x Subgroup PP.Grp4 
x Group 4 PP participants who are SARS-CoV-2 
positive2 at baseline, receiving 1 or 2 pre-Month 6 
vaccination doses 
Secondary objectives 4-5, 8 
Exploratory objectives 1-5 
Immunogenicity Subset (IS) 
Participants who are sampled into the subset for 
measuring humoral immunologic markers4 at Months 0, 1 
(Groups 2 and 4 only), 2 (Groups 1 and 3 only), 6, 7 and 
12. 
Secondary objective 9 
Exploratory objectives 4-5 
x Subgroups IS.Grp1–4 
x Groups 1-4 participants in the IS 
x Subgroup 
IS.PBMC.Imm.Grp1–4 
x Groups 1-4 participants in the IS who are also sampled 
into the PBMC Immunogenicity subset for measuring 
cellular immunologic markers at Months 0, 1 (Groups 2 
and 4 only), 2 (Groups 1 and 3 only), 6, 7 and 12. 
x Subgroup 
IS.PBMC.Cor.Grp1-2 
x Groups 1 and 2 participants in the IS who are also 
sampled into the PBMC Immune Correlates subset for 
measuring cellular immunogenicity markers at Months 
0, 1 (Group 2 only), 2 (Group 1 only), and 7.  
1 SARS-CoV-2 negative is defined by both seronegative and virus detection negative or by seronegative alone if 
missing virus detection test results. 
2 SARS-CoV-2 positive is defined by seropositive and/or virus detection positive. 
3 Major protocol violations are protocol deviations that compromise study integrity; for example, protocol 
deviations related to collection or reporting of data necessary to interpret the primary efficacy endpoint. 
4 Immunologic markers measured will include binding antibody and neutralizing antibody markers. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 49 of 169 
6.3 
Accrual and sample size 
This study will enroll up to 15,600 participants into four groups defined by 
baseline HIV-1 and SARS-CoV-2 sero-statuses and randomized to receive the 
same vaccination series of mRNA-1273 at month 0 and month 1 (if applicable), 
but two different vaccines (mRNA-1273 or mRNA-1273.222) at month 6 at a 1:1 
randomization ratio within each group as shown in the study schema. The sample 
sizes of Groups 1 and 2 are driven by the total number of COVID-19 cases that are 
needed to achieve sufficient statistical power to evaluate the relative risk of 
COVID-19 between Groups 1 and 2 in the pre-Month 6 stage, as well as between 
randomized interventions at Month 6 within each group in the post-Month 6 stage. 
The sample sizes of Groups 3 and 4 are primarily driven by the precision to 
characterize safety and immunogenicity of the regimens in each group of 
participants while keeping the same 1:2 ratio between the SARS-CoV-2 negative 
and positive groups as for Groups 1 and 2.  
6.3.1 
Power calculations for coprimary objectives 1-4 (Efficacy)  
Let VE(COVID) and VE(Severe COVID) denote vaccine efficacy of the vaccine 
regimen vs. counterfactual placebo among baseline SARS-CoV-2 negative 
participants against COVID-19 and severe COVID-19, respectively. The relative 
risk objectives are assessed in terms of cumulative incidence ratios between the 
active vaccine regimens without analysis of counterfactual placebo arms; the 
notations VE(COVID) and VE(Severe COVID) are mainly used for purposes of 
communicating effect sizes. 
The following calculations focus on the COVID-19 endpoint because the severe 
COVID-19 endpoint could potentially be changed to be a secondary endpoint if 
there are insufficient severe COVID endpoints (Section 6.4.3). For the assessment 
of pre-Month 6 stage objectives, sample sizes of Groups 1 and 2 in the FAS are 
considered. For the assessment of post-Month 6 stage objectives, the following 
calculations consider approximately 4000 participants in Groups 1-4 received their 
Month 6 vaccination (mRNA-1273 vs. mRNA-1273.222) per randomization under 
protocol version 6. This sample size is consistent with study data as of June 2023. 
As shown in the upper portion (pre-Month 6 stage) of Table 6-2, there is ample 
power (> 90%) to detect a relative risk of 2.0 between Groups 1 and 2 against the 
null hypothesis H0: RR = 1.0 during Month 0 and 6 in the pre-Month 6 stage. In 
reality, the sample sizes of the PLWH hybrid immunity group who receive 1 pre-
Month 6 dose and the PLWH pure vaccine group who receive 2 pre-Month 6 doses 
are likely smaller than the sample sizes of Groups 1 and 2, respectively. As shown 
in the lower portion (post-Month 6 stage) of Table 6-2, when the annual incidence 
of the primary endpoint is in the range of 2.5%- 3.5% in the mRNA-1273 arm, 
there is approximately 80-90% power to detect a relative risk of 2.0 – 2.5 between 
mRNA-1273 vs. mRNA-1273.222 vaccination during Month 6.5 and 18 in the 
post-Month 6 stage.  

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 50 of 169 
These calculations are carried out assuming 5% annual dropout, 5% probability of 
missing any of the 3 doses, VE(COVID) of 63% between Month 0 and Month 6 in 
Group 1 (SARs-CoV-2 negative) and in Group 2, and 5% six-month COVID-19 
incidence rate among unvaccinated PLWH SARs-CoV-2 negative individuals in 
the community. The assumption on VE(COVID) of 63% between Month 0 and 
Month 6 accounts for a possible reduced protection of the vaccine regimen in 
PLWH against the SARS-CoV-2 variant at the time of the trial conduct. The 5% 
six-month background incidence rate assumption was based on the observed 4.7%, 
5.25%, and 10.38% placebo arm six-month incidence rates among baseline SARS-
CoV-2 negative participants in, respectively, the AstraZeneca phase 3 (149), 
Novavax phase 2 (107), and Janssen ENSEMBLE phase 3 (28) trials restricted to 
South African study sites, and building in conservative margin given the 
availability of vaccines to potentially reduce transmission and infection in the 
region. The background SARS-CoV-2 (re-infection) incidence rate among 
unvaccinated PLWH SARS-CoV-2 positive individuals in the community is 
assumed to be half of that of unvaccinated PLWH SARS-CoV-2 negative 
individuals based on the reported protection of approximately 55% against the 
Omicron variant from previous SARS-CoV-2 infection in South Africa (150-152) 
and in other countries (153). The statistical power is calculated using an exact 
binomial test with a (two-sided) false positive error rate of 0.05. 
Table 6-2 Pre-Month 6 stage: power to detect relative risk (Months 0-6) being different from 1.0 
between Group 1 (n=4200) and Group 2 (n=8400). 
True VE (0-6) of 
Group 1 (n=4200) 
Relative Risk 
(Groups 1 vs. 2) 
Total expected number of 
events M0-6 
Power 
60% 
1.3 
189 
45% 
1.6 
176 
85% 
2.0 
167 
99% 
70% 
1.2 
149 
17% 
1.5 
135 
59% 
2.0 
125 
96% 
70% 
1/1.3 
207 
45% 
75% 
1/1.6 
203 
85% 
80% 
1/2.0 
200 
99% 
75% 
1/1.2 
159 
17% 
80% 
1/1.5 
153 
59% 
85% 
1/2.0 
150 
96% 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 51 of 169 
Post-Month 6 stage: power to detect relative risk (Months 6.5-18) being different from 1.0 between 
mRNA-1273 vs. mRNA-1273.222 Month 6 vaccination (n=4000, 2000 vs. 2000),. 
Annual incidence for 
mRNA-1273 Month 6 
vaccination arm  
Relative Risk (mRNA-1273 
vs. mRNA-1273.222) 
Total expected number 
of events M6.5-18 
Power 
3.5% 
1.5 
110 
54% 
2.0 
106 
93% 
3.0% 
2.0 
91 
87% 
2.5 
90 
99% 
2.5% 
2.0 
76 
78% 
2.5 
75 
96% 
In addition, Table 6-3 provides the precision of the relative risk estimates with 
different numbers of endpoints accrued in the post-Month 6 stage. 
Table 6-3 Post-Month 6 Stage: precision in relative risk (RR) estimates with 50, 100 or 150 total 
endpoints accrued between Month 6.5 and Month 18. 
Estimate RR of COVID-19 
(mRNA-1273 vs. mRNA-1273.222) 
95% CI of RR 
50 endpoints 
100 endpoints  
150 endpoints  
1.0 
(0.57, 1.74) 
(0.68, 1.48) 
(0.73, 1.38) 
1.25 
(0.72, 2.18) 
(0.84, 1.85) 
(0.91, 1.72) 
1.5 
(0.85, 2.64) 
(1.00, 2.24) 
(1.08, 2.08) 
2.0 
(1.11, 3.60) 
(1.32, 3.03) 
(1.42, 2.81) 
2.5 
(1.36, 4.62) 
(1.62, 3.86) 
(1.75, 3.56) 
3.0 
(1.58, 5.69) 
(1.91, 4.72) 
(2.07, 4.34) 
6.3.2 
Power calculations for coprimary objective 5 (Safety) 
For pre-Month 6 stage, we consider power for evaluating the safety objective using 
a total of N = 15,600 participants in the Full Analysis Set (FAS) and N = 1,500 in 
the Safety Subset (SS). If no SAE or AESI that is considered related to the study 
vaccine is observed in the FAS, or no AE in the SS, the upper limit of the 95% 
confidence interval (CI) for the true event rate will be 0.02% or 0.2%, respectively. 
Hence, observing no SAE/AESI in the FAS or no AE in the SS would provide us 
with 95% confidence that the true event rate is no more than 0.02% or 0.2%, 
respectively. For post-Month 6 stage, we consider power for evaluating the safety 
objective of the mRNA-1273 or mRNA-1273.222 vaccination at Month 6 using 
half of the cohorts assessed for pre-Month 6 stage and additionally assuming 80% 
of these cohorts receiving the Month 6 vaccination under the current protocol 
version. Table 6-4 shows the 95% CIs for event rates ranging from 0% to 5% in 
the full or half of the FAS, FAS.Grp1-4 and SS, demonstrating the degree of 
precision conferred by the trial size for evaluating safety events in these cohorts. 
CIs were calculated using the Clopper-Pearson method (154). 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 52 of 169 
Table 6-4 Pre-Month 6 stage: Confidence intervals (CIs) for observed safety event rates in the FAS 
(N = 15,600), FAS.Grp1-4 (N = 4,200, 8,400, 1,000, 2,000) and the SS (N = 1500) cohorts 
concerning the mRNA-1273 regimen. Confidence intervals were calculated using the Clopper-
Pearson method (154). 
Safety 
Event 
Rate 
(%) 
FAS  
(N = 15,600) 
FAS.Grp1 
(N = 4,200) 
FAS.Grp2 
(N = 8,400) 
FAS.Grp3 
(N = 1,000) 
FAS.Grp4 
(N = 2,000) 
SS  
(N = 1,500) 
CI (%) 
CI (%) 
CI (%) 
CI (%) 
CI (%) 
CI (%) 
0.0 
(0.0, 0.0) 
(0.0, 0.1) 
(0.0, 0.0) 
(0.0, 0.4) 
(0.0, 0.2) 
(0.0, 0.2) 
0.5 
(0.4, 0.6) 
(0.3, 0.8) 
(0.4, 0.7) 
(0.2, 1.2) 
(0.2, 0.9) 
(0.2, 1.0) 
1.0 
(0.8, 1.2) 
(0.7, 1.3) 
(0.8, 1.2)  
(0.5, 1.8) 
(0.6, 1.5) 
(0.6, 1.6) 
2.0 
(1.8, 2.2) 
(1.6, 2.5) 
(1.7, 2.3) 
(1.2, 3.1) 
(1.4, 2.7) 
(1.4, 2.8) 
3.0 
(2.7, 3.3) 
(2.5, 3.6) 
(2.6, 3.4) 
(2.0, 4.3) 
(2.2, 3.8) 
(2.2, 4.0) 
4.0 
(3.7, 4.3) 
(3.4, 4.6) 
(3.6, 4.4) 
(2.9, 5.4) 
(3.2, 5.0) 
(3.1, 5.1) 
5.0 
(4.7, 5.4) 
(4.4, 5.7) 
(4.5, 5.5) 
(3.7, 6.5) 
(4.1, 6.0) 
(4.0, 6.2) 
Post-Month 6 stage: Confidence intervals (CIs) for observed safety event rates in half of the FAS 
(N = 0.8*15,600/2), FAS.Grp1-4 (N = 0.8*4,200/2, 0.8*8,400/2, 0.8*1,000/2, 0.8*2,000/2) and the SS 
(N = 0.8*1500/2) cohorts concerning each type of Month 6 vaccination (mRNA-1273 or mRNA-
1273.222), assuming 80% of these cohorts receiving the Month 6 vaccination under the current 
protocol version. Confidence intervals were calculated using the Clopper-Pearson method (154). 
Safety 
Event 
Rate 
(%) 
N = 6,240 
 
N = 1,680 
 
N = 3, 360 
 
N = 400 
 
N = 800 
 
N = 600 
 
0.0 
(0.0, 0.1) 
(0.0, 0.2) 
(0.0, 0.1) 
(0.0, 0.9) 
(0.0, 0.4) 
(0.0, 0.6) 
0.5 
(0.3, 0.7) 
(0.2, 1.0) 
(0.3, 0.8) 
(0.1, 1.8) 
(0.1, 1.3) 
(0.1, 1.5) 
1.0 
(0.8, 1.3) 
(0.6, 1.6) 
(0.7, 1.4) 
(0.3, 2.5)  
(0.4, 2.0) 
(0.4, 2.2) 
2.0 
(1.7, 2.4) 
(1.4, 2.8) 
(1.6, 2.5) 
(0.9, 3.9) 
(1.1, 3.2) 
(1.0, 3.5) 
3.0 
(2.6, 3.5) 
(2.2, 3.9) 
(2.5, 3.6) 
(1.6, 5.2) 
(1.9, 4.4) 
(1.8, 4.7) 
4.0 
(3.5, 4.5) 
(.1, 5.1) 
(3.4, 4.7) 
(2.3, 6.4) 
(2.8, 5.6) 
(2.6, 5.9) 
5.0 
(4.5, 5.6) 
(4.0, 6.2) 
(4.4, 5.8) 
(3.1, 7.6) 
(3.6, 6.7) 
(3.4, 7.1) 
6.4 
Statistical analyses  
This section describes the primary study analysis. Unless otherwise noted, data 
from enrolled participants will be analyzed according to the initial randomization 
assignment regardless of how many vaccinations they received. 
Analyses for primary endpoints will be performed using SAS and R. All other 
descriptive and inferential statistical analyses will be performed using SAS, 
StatXact, or R statistical software. 
No formal multiple-comparison adjustments will be employed for multiple safety 
endpoints or multiple efficacy endpoints. Multiple comparisons adjustment may be 
performed for secondary endpoints and objectives, which will be specified in the 
Statistical Analysis Plan (SAP). 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 53 of 169 
6.4.1 
Analysis variables 
The analysis variables consist of baseline participant characteristics, safety, 
efficacy, immunogenicity, and COVID-19 disease, severe COVID-19 and SARS-
CoV-2 infection diagnosis variables for the primary and secondary objective 
analyses. 
6.4.2 
Baseline comparability 
Treatment arms will be compared for baseline participant characteristics using 
descriptive statistics. 
6.4.3 
Analysis of relative risk between treatment arms 
For the assessment of the coprimary efficacy objectives, this study uses two 
approaches for determining symptomatic COVID-19 cases, as previously defined 
in Section 3. For survival data analyses, the time of all participant-level failure and 
censoring events are reported relative to the time of enrollment (ie, first 
vaccination) for the pre-Month 6 stage objectives, and relative to the time of 
Month 6 dose for post-Month 6 stage. For the COVE-based endpoint definition, 
the time of diagnosis of COVID-19 and severe COVID-19 will be determined by 
the EAC adjudicators. For the CDC criteria-based definition, the time of diagnosis 
of lab-confirmed clinical COVID-19 is defined as the minimum date of reported 
qualifying COVID-19 symptoms and collection date of SARS-CoV-2 positive 
result (both must occur), and the time of diagnosis of severe COVID-19 to be the 
minimum date of reported qualifying severe COVID-19 symptoms and collection 
date of SARS-CoV-2 positive result (both must occur).  
The time of diagnosis of the SARS-CoV-2 infection endpoint is the draw time of 
the first sample with a positive test result by either antibody seroconversion assays 
or by virus-detection via NAAT. The serology assays are used to ascertain 
infections occurred anytime during the study among baseline SARS-CoV-2 
negative (NAAT and serology negative) participants to address Secondary 
objectives 1-8. The NAAT are used to ascertain recent or ongoing infections 
among both baseline SARS-CoV-2 negative and positive participants to address 
exploratory objectives. The time of diagnosis of the asymptomatic endpoint is the 
draw time of the first sample with a positive test result by virus detection assays or 
seroconversion with no reported COVID-19–like illness episodes between 
enrollment and 14 days after the timepoint at which SARS-CoV-2 infection is 
ascertained. In case of reinfection of SARS-CoV-2, the first occurrence of a given 
endpoint is considered. 
In the primary and most secondary efficacy analyses, the failure times of 
participants never observed to be diagnosed with a given clinical endpoint will be 
right censored at the date of last contact at which endpoint status was assessed or 
study termination. Participants who report outside COVID-19 vaccines will be 
censored at the time of receiving such vaccination. Except where otherwise 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 54 of 169 
specified, efficacy analyses of a given endpoint that is counted starting at some 
specified number of days postvaccination will exclude all participants from the 
analysis who experienced the particular endpoint diagnosed before the counting 
period. 
The statistical analyses described below use the COVID-19 and severe COVID-19 
case definition. Exploratory efficacy analyses may also be considered for a new 
definition of the endpoints that include suspected but unconfirmed COVID-19 
cases. 
The primary efficacy analyses focusing on the pre-Month 6 stage will be carried 
out between the FAS.Grp1 who are SARS-CoV-2 negative at baseline and receive 
2 doses of pre-Month 6 vaccination, and FAS.Grp 2 who are SARS-CoV-2 
positive at baseline and receive 1 dose of pre-Month 6 vaccination, counting 
endpoints >= 1 day post–dose 1. The primary efficacy analyses focusing on the 
post-Month 6 stage will be carried out between the two different Month 6 arms 
across all groups, counting endpoints  14 days post the month 6 vaccination. 
Secondary efficacy analyses will also entail counting endpoints  14 days post the 
primary vaccination series and endpoints  1 day post the first dose at month 0 in 
the pre-Month 6 stage, as well as  14 days post the month 6 dose in Groups 1 and 
3 combined vs. Groups 2 and 4 combined.  
The relative risk (of COVID-19, severe COVID-19, SARS-CoV-2 infection, or 
SARS-CoV-2 asymptomatic infection) is defined as the incidence rate ratio 
between the 2 treatment groups in the pre-Month 6 stage or between the 2 
treatment arms within a group in the post-Month 6 stage. When there are at least 7 
severe COVID-19 endpoints at the primary analysis for a given relative risk 
assessment, both COVID-19 and severe COVID-19 are used as coprimary 
endpoints. Otherwise, severe COVID-19 is considered as a secondary endpoint. 
For the final analyses of the pre-Month 6 objectives, the incidence will be 
compared across groups by estimating the marginalized cumulative incidence of 
the endpoint overtime for each group, using a causal inference method that adjusts 
for potential confounders and accounts for right-censoring of failure times. Under 
causal assumptions, the marginalized cumulative incidence equals the causal 
cumulative incidence, interpreted as cumulative incidence if, hypothetically, the 
entire study population were assigned to the given group under consideration. 
Sensitivity analyses may also be conducted to account for unobserved confounding 
factors. For the final analyses of the post-Month 6 objectives, the RR between 
treatment arms within each group will also be estimated. The causal inference 
approach used for the pre-Month 6 stage analysis may also be applied for 
estimating the relative risk of each endpoint for the post-Month 6 dose objectives. 
More details will be described in the SAP. For analyses before the final analyses, 
the RR may be estimated from a Poisson regression analysis for both pre- and 
post-Month 6 stages. To assess potential time effects of vaccine efficacy, the 
Nelson-Aalen method will be used to plot the estimated cumulative incidence rates 
over time for the comparison groups. Additional analysis of RR by specified viral 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 55 of 169 
strain categories may also be performed using competing risks failure time 
methods, as detailed in the SAP. 
6.4.4 
Safety/Tolerability analysis 
Safety endpoints will be assessed in the FAS cohort. Since enrollment is 
concurrent with receiving the first injection, all participants will have received at 
least 1 vaccination and therefore will provide some safety data. 
During the course of the trial, analyses of safety data will be prepared for review 
by the DSMB at a frequency determined by the DSMB for as long as it is involved 
in the trial. Ad hoc safety reports may also be prepared for DSMB review at the 
request of the PSRT. The OG must approve any other requests for safety data prior 
to the end of the scheduled follow-up visits. 
6.4.4.1 
AEs and SAEs 
 AEs will be summarized using MedDRA System Organ Class and preferred 
terms. Tables will show by treatment group the number and percentage of 
participants experiencing an AE within a System Organ Class or within preferred-
term category by severity and by relationship to study product. For the calculations 
in these tables, a participant with multiple AEs within a category will be counted 
once under the maximum severity and by causal relationship to study product. 
Formal statistical testing comparing arms is not planned for all AEs since 
interpretation of differences must rely heavily upon clinical judgment. Barnard’s 
tests will be used to compare rates of SAEs deemed related to study products 
between vaccine arms. The false discovery rate procedure of Mehrotra and Heyse 
(155) may be applied to compare grouped systemic SAEs divided by body systems 
between treatment arms. 
A listing of SAEs will provide details of the events including severity, relationship 
to study product, time between onset and last vaccination, and number of 
vaccinations received. A separate listing will do the same for AESIs. AESIs for 
this protocol include but are not limited to potential immune-mediated disorders. 
6.4.4.2 
Reasons for Vaccination Discontinuation and Early Study Termination 
The number and percentage of participants who discontinue vaccination and who 
terminate the study early will be tabulated by reason and treatment arm. 
6.4.5 
Immunogenicity and immune correlates analyses 
Data from quantitative immunogenicity assays will be summarized for each 
treatment group using positive response rates and geometric means with 95% CIs, 
for each timepoint for which an assessment is performed. Data from qualitative 
(ie., yielding a positive or negative result) assays will be summarized by tabulating 
the frequency of positive responses for each assay by group at each timepoint that 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 56 of 169 
an assessment is performed. Analyses focus on the key immunogenicity timepoints 
postvaccination (M1, M2, or M7), the M0 prevaccination timepoint, and the 
change in marker value between the 2 timepoints. The analyses will be conducted 
in the Immunogenicity Subset, evaluating subgroups of participants defined by 
baseline HIV-1 and SARS-CoV-2 statuses. A separate Marker SAP will describe 
the complete set of immunogenicity analyses. 
The separate Marker SAP will describe the statistical methods and data analysis 
implementations for assessing immune response markers as correlates of the 
COVID-19, severe COVID-19, and infection study endpoints, as well as various 
types of correlates/surrogates of protection. Objectives include characterizing the 
distribution of immunologic markers at the approximate peak immunogenicity 
timepoint and over time (at Months 0, 1 or 2, 6, 7 and 12); assessing these markers 
at the peak immunogenicity timepoint and over time as correlates of risk of 
COVID-19, severe COVID-19, and of infection using data from all vaccine 
recipients; and assessing these markers at the peak immunogenicity timepoint and 
over time as various types of correlates of protection, using data from both vaccine 
arms. The biomarkers are measured in the Immunogenicity Subset (IS) and in 
infection cases outside the IS. These cases include all primary endpoint cases and 
asymptomatic infection endpoint cases. Sampling of participants into the IS is 
stratified by treatment arm and the randomization strata (except study site, 
although geographic region is accounted for by including South Africa and non-
South Africa as sampling strata factors). In addition, PBMC may be stored at 
Months 0, 1 or 2, 6 and 7 from a subset of participants at selected sites to enable 
study of B- and T-cell markers as correlates of risk and protection (see Laboratory 
Procedures for PBMC Immunogenicity subset (Appendix D and Appendix E) and 
PBMC Immune Correlates subset (Appendix F and Appendix G). 
6.4.6 
Sieve analysis 
SARS-CoV-2 Spike sequences will be determined for all COVID-19 primary 
endpoints, based on the first available NAAT positive sample starting at COVID-
19 diagnosis. SARS-CoV-2 Spike sequences will also be determined for NAAT 
positive samples for asymptomatic infection cases. Statistical analyses will assess 
whether and how vaccine efficacy depends on Spike amino acid sequence features, 
with features of interest including recognized genotypes/variants of 
interest/concern/high consequence, Hamming distances from RBD, NTD, all of S1 
subunit, S2 subunit, and all of Spike to the vaccine insert sequence, whether 
residues at amino acid positions are mismatched to the corresponding positions in 
the vaccine insert sequence, and whether haplotypes, such as 9-mers or antibody-
relevant constellations of AA positions, are mismatched to the vaccine insert 
sequence. In addition, based on the Spike sequence from each COVID-19 primary 
endpoint, a pseudovirus may be made and tested in 1 or more selected 
neutralization assays to characterize the neutralization sensitivity of the infecting 
virus to vaccinee sera. The neutralization sensitivity phenotype will be defined 
using a set of immunogenicity timepoint (eg, Months 2 and 7) serum samples from 
a sample of vaccine recipients in the Immunogenicity Subset. Neutralization sieve 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 57 of 169 
analysis will assess whether and how vaccine efficacy depends on virus 
neutralization sensitivity measures, such as geometric mean serum ID50. Sieve 
analysis will be done for each of the coprimary endpoints, with the severe COVID-
19 endpoint only analyzed if there are sufficient numbers of cases. Sieve analysis 
may be done for the infection endpoint and the asymptomatic infection endpoint. 
Details of the sieve analysis are described in the Marker SAP. 
6.5 
Operational monitoring for quality of trial conduct  
The study OG, protocol team and study investigators will monitor the quality of 
trial conduct related to achievement of targeted levels of various operational 
metrics, such as retention, and adherence to study interventions. Detailed 
operational metrics will be specified in the OG charter. 
6.6 
Final analyses timing 
The final analyses of the study objectives in the pre-Month 6 will be performed 
when all participants who remain in the study have had the Month 6 dose in the 
pre-Month 6 stage. The final analyses of the study objectives in the post-Month 6 
stages and in the entire study period will be performed when all participants who 
remain in the study reach their end of follow-up in the post-Month 6 stage. 
6.7 
Roles of the DSMB, OG, and EAC 
OG oversight of the trial will continue, and adaptations in study design and 
modifications will be made under its recommendations. As the main objectives of 
the study have been achieved, the frequency of DSMB meetings is under 
discussion.  
An Endpoint Adjudication Committee (EAC) will be assembled for the purpose of 
reviewing potential cases per COVE criteria to determine if these criteria for the 
primary and secondary endpoints have been met. More details on the composition, 
role of and the data provided to the EAC will be described in the EAC charter. 
6.8 
Randomization implementation   
The randomization sequence will be computer generated and provided by the data 
monitoring center (DMC) to each CRS, ideally through a Web-based 
randomization system. For statistical efficiency and to avoid chance imbalance in 
exposure or prognostic factors between treatment groups, the randomization will 
be stratified by study site, HIV-1 infection status, and SARS-CoV-2 serostatus at 
enrollment. The randomization will be done in blocks to ensure balance between 
the vaccine arms within levels jointly determined by these factors. The block size 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 58 of 169 
ensures balance among treatment arms over different epidemiological stages of the 
pandemic. At each institution, the pharmacist with primary responsibility for 
dispensing study products is charged with maintaining security of the treatment 
assignments.  
  

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 59 of 169 
7 
Selection and withdrawal of participants 
Participants will be adults who comprehend the purpose of the study and have 
provided written informed consent in their language of choice. Participants will be 
recruited and screened; those determined to be eligible, based on the inclusion and 
exclusion criteria, will be enrolled in the study. Final eligibility determination will 
depend on information available at the time of enrollment, medical history 
questionnaire, physical examinations, and answers to self-administered and/or 
interview questions. 
Investigators should always use good clinical judgment in considering a 
participant’s overall fitness for trial participation. Some participants may not be 
appropriate for enrollment even if they meet all inclusion/exclusion criteria. 
Medical, psychiatric, occupational, or other conditions may make evaluation of 
safety and/or immunogenicity difficult, and some participants may be poor 
candidates for retention. 
Determination of eligibility, taking into account all inclusion and exclusion 
criteria, must be made within 56 days prior to enrollment unless otherwise noted 
below. 
7.1 
Inclusion criteria 
General and Demographic Criteria 
1. $JH\HDUVLIparticipant self-reports living with HIV or another 
comorbidity known to be associated with severe COVID-19, for example 
(CDC.gov for exhaustive list):  
x Hypertension 
x Type 2 diabetes mellitus 
x Overweight, obese, or severely obese (ie, ERG\PDVVLQGH[>%0,@25 
kg/m2) 
x Heart conditions, such as heart failure, coronary artery disease, or 
cardiomyopathies 
x Chronic kidney disease 
x COPD (chronic obstructive pulmonary disease) 
x Cancer 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 60 of 169 
x Non-HIV immunocompromised state (weakened immune system) or solid 
organ transplant 
x Pregnancy 
x Sickle cell disease 
x Smoking 
2. Willingness to be followed and remain in the catchment area for the planned 
duration of the study. 
3. Ability and willingness to provide informed consent. 
4. Willingness to discuss HIV infection status, undergo related testing/monitoring 
labs, and receive counseling and referrals to minimize HIV 
acquisition/improve HIV care as appropriate based on their infection status. 
5. Assessment of Understanding (AoU): Participant demonstrates understanding 
of this study; completes a questionnaire prior to first vaccination with 
demonstration of understanding of all questionnaire items answered 
incorrectly. 
6. Agrees not to enroll in another interventional study of an investigational 
research agent until after the study is completed and all the data has been 
obtained. Enrollment in studies of investigational research agents for the 
treatment of COVID-19 is allowed for participants who develop COVID-19 
disease. 
7.2 
Exclusion criteria  
General 
1. Acutely ill 72 hours prior to or at screening. Participants meeting this 
criterion may be rescheduled within the relevant window periods. Participants 
with minor illnesses can be enrolled at the discretion of the investigator. 
2. History of angioedema or anaphylaxis. 
Vaccines and other injections 
1. Prior receipt of a SARS-CoV-2 vaccine. 
2. History of severe allergic reaction to any ingredient of this vaccine (lipids 
(SM-102, polyethylene glycol [PEG] 2000 dimyristoyl glycerol [DMG], 
cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC]), 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 61 of 169 
tromethamine, tromethamine hydrochloride, acetic acid, sodium acetate 
trihydrate, and sucrose). 
3. Live attenuated vaccines received within 30 days before first vaccination (eg, 
measles, mumps, and rubella [MMR]; oral polio vaccine [OPV]; varicella; 
yellow fever; live attenuated influenza vaccine, live attenuated zoster vaccine). 
4. Any vaccines that are not live attenuated vaccines and were received within 
14 days prior to first vaccination (eg, tetanus, human papilloma virus (HPV), 
pneumococcal, Hepatitis A or B). 
5. Blood products, systemic immunoglobulins, or monoclonal antibodies 
(including against SARS-CoV-2) received within 90 days before first 
vaccination. 
 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 62 of 169 
8 
Study products  
The protocol schema is shown in Table 1-1. 
8.1 
Vaccine regimen 
Groups 1 and 3 (SARS-CoV-2 negative at baseline) 
Treatment 1 (for Groups 1A and 3A): mRNA-1273 vaccine in 100 mcg dose to 
be administered as an IM injection into the deltoid muscle on Day 1, Day 29 and 
Day 169 (Months 0, 1, and 6) 
Treatment 2 (for Groups 1B and 3B): mRNA-1273 vaccine in 100 mcg dose to 
be administered as an IM injection into the deltoid muscle on Day 1 and Day 29 
(Months 0 and 1) 
AND 
mRNA-1273.222 vaccine in 100 mcg dose to be administered as an IM injection 
into the deltoid muscle  on Day 169 (Month 6) 
Groups 2 and 4 (SARS-CoV-2 positive at baseline) 
Treatment 3 (for Groups 2A and 4A): mRNA-1273 vaccine to be administered 
as an IM injection into the deltoid muscle on Day 1 and Day 169 (Months 0 and 6) 
Treatment 4 (for Groups 2B and 4B): mRNA-1273 vaccine to be administered 
as an IM injection into the deltoid muscle on Day 1 (Month 0) 
AND 
mRNA-1273.222 vaccine in 100 mcg dose to be administered as an IM injection 
into the deltoid muscle on Day 169 (Month 6) 
8.2 
Storage, handling, preparation and dispensing of the study products 
Site Pharmacists should consult the CoVPN 3008 (Ubuntu) Pharmacy Manual for 
instructions on handling, storing, preparing, and dispensing the study products. 
8.3 
Acquisition of the study products 
COVID-19 vaccine (mRNA-1273) and bivalent vaccine (mRNA-1273.222) will be 
provided by Moderna, Inc. through the US Government HCORE and allocated to 
the Sponsor for this trial.  

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 63 of 169 
Once a study CRS has completed all procedures for study start, study products can 
be obtained as outlined in the CoVPN 3008 (Ubuntu) Pharmacy Manual. 
8.4 
Administration of study products  
All injections are to be administered intramuscularly into the deltoid muscle by 
study staff assigned for this procedure. 
If an injection cannot be administered in either deltoid muscle due to a medical 
contraindication, the injection should be administered in an alternate body site (eg, 
lateral thigh). The appropriate study staff should document this clearly. Under this 
circumstance, this is NOT a protocol violation. 
Vaccination providers will refer to the CoVPN 3008 (Ubuntu) Study-specific 
Procedures (SSP) for further guidance. 
8.5 
Pharmacy records and accountability 
The CoVPN CRS pharmacist is required to maintain complete records of all study 
products. The site pharmacist is responsible for maintaining randomization codes 
and randomization confirmation notices for each participant in a secure manner. 
8.6 
Final disposal of the study products 
All unused study products must be returned to the Sponsor or destroyed per the 
CoVPN 3008 (Ubuntu) Pharmacy Manual after the study is completed or 
terminated unless otherwise instructed by the Sponsor. 
 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 64 of 169 
9 
Clinical procedures 
Procedures are in place so that study visits may be conducted remotely, such as via 
phone, text message, email, or other electronic means in lieu of, or in combination 
with, in-person visits at the CRS. Furthermore, some visit procedures may be 
conducted outside the CRS. 
Direct data entry or direct data capture of study data into the study database is 
allowed when capturing information from the participant. Study data may also be 
sourced from electronic or paper source documents prior to being entered into the 
study database (see the CoVPN 3008 (Ubuntu) SSP). 
The schedules of clinical and laboratory procedures are shown in Appendix B, 
Appendix D and Appendix H for participants in Groups 1 and 3; Appendix F for 
participants in Group 1 only; Appendix G for participants in Group 2 only and 
Appendix C, Appendix E, and Appendix I for participants in Groups 2 and 4. 
9.1 
Informed consent 
Informed consent is the process of working with participants so that they fully 
understand what will and may happen to them while participating in a research 
study. The CoVPN informed consent form documents that a participant (1) has 
been informed about the potential risks, benefits, and alternatives to participation, 
and (2) is willing to participate in a CoVPN study. Informed consent encompasses 
all written, verbal, and electronic study information CRS staff provide to the 
participant before and during the trial. CRS staff will obtain informed consent of 
participants according to the CRS’s SOP on the informed consent process. 
If any new information is learned that might affect the participants’ decisions to 
stay in the trial, that information will be shared with trial participants. If necessary, 
participants will be asked to provide revised informed consent forms. 
9.1.1 
Protocol-specific consent forms 
The protocol-specific consent forms describe the study products to be used and all 
aspects of protocol participation, including screening and enrollment procedures. A 
sample protocol-specific consent form is located in Appendix Aand an addendum 
to the informed consent form is located in Appendix N 
Each CRS is responsible for developing a protocol-specific consent form(s) for 
local use based on the sample protocol-specific consent forms. The consent 
form(s) must be developed in accordance with requirements of the following: 
x CRS’s IRB/EC and any applicable REs 
x CRS’s institution 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 65 of 169 
x Elements of informed consent as described in Title 45, CFR Part 46 and Title 
21 CFR, Part 50 and in ICH E6(R2), Good Clinical Practice: Consolidated 
Guidance 4.8 
The sample informed consent form includes instructions for developing specific 
content. 
9.1.2 
Assessment of Understanding 
Study staff are responsible for ensuring that participants fully understand the study 
before enrolling them. This process involves reviewing the informed consent form 
with the participant, allowing time for the participant to reflect on the procedures 
and issues presented, and answering all questions completely. 
An Assessment of Understanding (AoU) is used to document the participant’s 
understanding of key concepts in this study. Participants must demonstrate 
understanding of all questions answered incorrectly. This process and the 
participant’s understanding of the key concepts is to be recorded in source 
documentation at the site. 
9.2 
Pre-enrollment procedures 
Screening may occur at the same time as enrollment visit. All inclusion and 
exclusion criteria must be assessed before enrollment. 
After the appropriate informed consent has been obtained and before enrollment, 
the following procedures are performed: 
x Targeted medical history documented in the case history record 
x Abbreviated physical examination 
x Targeted concomitant medications will be assessed for high-risk conditions 
x Obtaining of participant demographics in compliance with the NIH Policy on 
Reporting Race and Ethnicity Data: Subjects in Clinical Research, Aug. 8, 
2001 (available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-01-
053.html) 
x Urine pregnancy test for all participants who were assigned female sex at birth 
and are of reproductive potential 
x For participants who are confirmed to be pregnant and plan to continue the 
pregnancy, the following will be performed: (1) Fetal ultrasound to confirm 
gestational age and developmental status of the pregnancy; (2) Syphilis test 
result and history of treatment will be collected from medical records if 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 66 of 169 
previously done and documented; otherwise, the participant will be referred for 
testing and potential treatment per local standard of care and the results will be 
collected from the subsequent medical records. 
x HIV diagnostic test for all participants will be conducted regardless of self-
reported status, HIV counseling will be offered, and participants with a 
diagnosis of HIV will be referred for treatment per local guidelines if not 
already engaged in care. 
x For participants with a new HIV diagnosis, blood will be collected for HIV 
viral load and CD4 count. If antiretroviral treatment needs to be initiated, 
enrollment into the study may be deferred until approximately 2 to 4 weeks 
after treatment is started. 
x SARS-CoV-2 antibody point of care serological test will be used to manage the 
proportions of participants with prior exposure in the study (see Section 6.3). 
9.3 
Enrollment and vaccination visits 
Once a participant has consented to trial participation and is found to meet all 
eligibility criteria (see Sections 7.1 and 7.2), the CRS requests the randomization 
assignment via a Web-based randomization system. Enrollment is simultaneous 
with first vaccination. 
Enrollment visit only: 
x Participants will be administered the baseline risk assessment questionnaire. 
x Before leaving the clinic, the participant is given the Memory Aid 1 for 
surveillance of any symptoms of COVID-19 and is instructed on how to use it. 
See Section 9.5 and CoVPN 3008 (Ubuntu) SSP for details. 
x Participants will be provided with a thermometer and will be instructed to take 
their temperature if they have symptoms. 
x Sites will instruct the participant to contact study staff if they develop 
symptoms of COVID-19 or are hospitalized. The site will make arrangements 
to be in contact with the participant should they have any AEs or develop 
symptoms of COVID-19 (as described in Sections 9.4 and 9.5). 
x For participants who self-report living with HIV and/or are confirmed to have 
HIV infection: blood will be collected for HIV viral load and CD4 count. 
x Participants who are confirmed to be pregnant at screening will not be included 
in the PBMC Immunogenicity and PBMC Immune correlates subsets. If a 
participant becomes pregnant during the study and is already included in these 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 67 of 169 
subsets, blood for cellular assays will not be drawn while the participant is 
pregnant. 
At vaccination visits, the following procedures are performed before vaccination: 
x Symptom-directed physical examination if needed; if the participant is 
clinically ill or has COVID-19 symptoms, vaccination will be delayed until 
clinically recovered (see Sections 9.5, 9.6, and 9.9 and CoVPN 3008 (Ubuntu) 
SSP for more information). 
x Assessment of targeted concomitant medications (as described in Section 9.2). 
x Nasal swabs collection (as described in Appendix B, Appendix C, Appendix D, 
Appendix E, Appendix F, Appendix G, Appendix H, Appendix I, and 
Appendix J). 
x Blood collection (as described in Appendix B, Appendix C, Appendix D, 
Appendix E, Appendix F, Appendix G, Appendix H, Appendix I, and 
Appendix J). 
x Participants will be instructed to contact the clinic if they have any AEs to 
report. 
x Urine pregnancy test for a participant who reports a new pregnancy and/or as 
clinically indicated. 
x If a participant is confirmed to be pregnant and plans to continue the 
pregnancy, the following will be performed: (1) Fetal ultrasound to confirm 
gestational age and developmental status of the pregnancy; (2) Syphilis test 
result and history of treatment will be collected from medical records if 
previously done and documented; otherwise, the participant will be referred for 
testing and potential treatment per local standard of care and the results will be 
collected from the subsequent medical records. Participants will also receive 
HIV testing and counseling as clinically indicated. 
x Any participant with a new HIV diagnosis will be offered counseling, as 
clinically indicated. They will also be referred for care and treatment according 
to local guidelines. Viral load and CD4+ T cell count must be obtained on 
study. 
x In case of a change in antiretroviral (ARV) medication (for PLWH 
participants), blood will be collected for viral load and CD4+ T cell count 
approximately 4 to 6 weeks since the change in medication. 
Following completion of all procedures in the preceding list, and if results indicate that 
vaccination may proceed, vaccination dose is prepared and administered (see Section 
8.4, Appendix H and Appendix I). 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 68 of 169 
Immediately following vaccination, the participant remains in the clinic for 
observation for 15 minutes or more in accordance with current applicable guidance 
(eg, local guidance). After the observation period, participants will have a 
postvaccination assessment prior to clinic discharge, including assessment of: 
x The injection site, (see Section 9.8.2 and 
x Systemic symptoms (see Section 9.8.1). 
See CoVPN 3008 (Ubuntu) SSP for details. 
9.4 
Follow-up procedures 
The following procedures are performed during follow-up per the schedules in 
Appendix H and Appendix I: 
x At all follow-up visits: symptom-directed physical examination if needed 
x At the last clinic visit: abbreviated physical examination 
x Assessment of targeted concomitant medications 
x Blood collection and nasal swabs (as described in Appendix B, Appendix C, 
Appendix D, Appendix E, Appendix F, Appendix G, Appendix H, Appendix I, 
and Appendix J). 
x Participants will be instructed to contact the clinic if they have any AEs to 
report. The clinic will contact the participant every 2 weeks, as described in 
Section 9.5. 
x Urine pregnancy test for a participant who reports a new pregnancy and/or as 
clinically indicated 
x If a participant is confirmed to be pregnant and plans to continue the 
pregnancy, the following will be performed: (1) Fetal ultrasound to confirm 
gestational age and developmental status of the pregnancy; (2) Syphilis test 
result and history of treatment will be collected from medical records if 
previously done and documented; otherwise, the participant will be referred for 
testing and potential treatment per local standard of care and the results will be 
collected from the subsequent medical records. Participants will also receive 
HIV testing and counseling as clinically indicated. 
x Any participant with a new HIV diagnosis will be offered counseling, as 
clinically indicated. They will also be referred for care and treatment according 
to local guidelines. Viral load and CD4+ T-cell count must be obtained on 
study. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 69 of 169 
x In case of a change in ARV medication (for PLWH participants), blood will be 
collected for viral load and CD4+ T-cell count approximately 4 to 6 weeks 
after the change in medication. For participants being exited less than 4 weeks 
after a change in ART, the site may choose to follow up these individuals after 
exit.  
x All pregnancies should be monitored to record the outcome of the pregnancy 
(eg viability, congenital malformations at birth) (see Section 9.12 and CoVPN 
3008 (Ubuntu) SSP for details). 
9.5 
Active COVID-19 symptomatic surveillance  
Participants will use Memory Aid 1 for surveillance of symptoms and be instructed 
to contact the clinic if they have COVID-19 like symptoms. Additionally, the site 
will make arrangements to contact the participant to elicit symptoms of COVID-19 
as described below. These symptoms will be used to establish whether a 
participant meets criteria for COVID-19 disease as defined by Primary Endpoint 1. 
If a participant has symptoms consistent with COVID-19, they will be instructed to 
contact the clinic to review their symptoms and if needed to schedule a COVID-19 
Symptom visit. Results of testing will be reported through the CRF and 
participants who have a positive SARS-CoV-2 NAAT test result will follow 
procedures described in Section 9.6 and Appendix J. 
The below prespecified symptoms that meet the criteria for suspicion of COVID-
19 will be elicited approximately every 2 weeks from the participant and the 
presence of any one of these symptoms lasting at least 48 hours (except for fever 
and/or respiratory symptoms) will result in the site arranging a Symptom Visit to 
collect a nasal swab within 72 hours. (If the site becomes aware of the symptoms 
>72 hours after they have resolved, nasal swab/symptom visit is not required.) 
x )HYHUWHPSHUDWXUH&RUFKLOOVRIDQ\GXUDWLRQLQFOXGLQJKRXUV 
x 6KRUWQHVVRIEUHDWKRUGLIILFXOW\EUHDWKLQJRIDQ\GXUDWLRQLQFOXGLQJ8 
hours) 
x &RXJKRIDQ\GXUDWLRQLQFOXGLQJKRXUV 
x Fatigue 
x Muscle or body aches 
x Headache 
x 1HZORVVRIWDVWHRUVPHOORIDQ\GXUDWLRQLQFOXGLQJKRXUV 
x Sore throat 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 70 of 169 
x Congestion or runny nose 
x Nausea or vomiting 
x Diarrhea 
It is important to note that some of the symptoms of COVID-19 overlap with 
systemic adverse reactions that are expected after vaccination with mRNA-1273 
and mRNA-1273.222 vaccines (eg, myalgia, headache, fever, chills). During the 
first 7 days after vaccination, when these adverse reactions are common, 
investigators should use their clinical judgement to decide if a COVID-19 symptom 
visit should be scheduled. Any study participant reporting respiratory symptoms 
during the 7-day period after vaccination should be evaluated for COVID-19. 
9.6 
COVID-19 Symptom Visits and COVID-19 Post-diagnosis Schedule 
The following procedures will be performed at the COVID-19 Symptom Visits for 
participants meeting the criteria for COVID-19 Symptom Visits outlined in 
Section 9.5. Participants with COVID-19 confirmed by SARS-CoV-2 NAAT test, 
regardless of symptoms, enter a postdiagnosis schedule (see Appendix J) to assess 
the presence, types, severity, and duration of potential COVID-related symptoms 
as well as duration of viral shedding. Participants found to have a positive SARS-
CoV-2 NAAT test as part of a regularly scheduled visit outlined in Section 9.3 will 
also enter the postdiagnosis schedule (see Appendix J). 
 
 
Figure 9-1 Overview of clinical procedures post–SARS-CoV-2 infection diagnosis. 
Day 1 (see Appendix J): 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 71 of 169 
x Participant history (participants will be queried regarding COVID-19–like 
symptoms and any concomitant medications taken for these symptoms) 
x Symptom-directed physical examination (to include temperature and O2 
saturation) 
x Nasal swabs collection per schedule of procedures (see Laboratory Procedures 
Table for COVID-19 Symptom Visits in Appendix J) 
x Blood collection per schedule of procedures (see Laboratory Procedures Table 
for COVID-19 Symptom Visits in Appendix J) 
x Participant will be provided with Memory Aid 2 – for collection of daily 
symptoms of COVID-19 and recollection of whether clinical care was sought 
or hospitalization occurred (via self-report and/or request for medical records)  
x Participant will be instructed to complete the Memory Aid 2 for a period of 14 
days or until a negative SARS-CoV-2 NAAT test is obtained., whichever is 
longer 
x The study sites will provide a portable pulse oximeter for recording O2 
saturation (at rest and following mild exercise) daily in the Memory Aid 2 and 
train the participant on the use of the pulse oximeter under both conditions (rest 
and mild exercise). The device will be accompanied by careful instructions for 
use and recording of O2 saturation in the Memory Aid 2 and who to contact for 
assistance if the device malfunctions.  
x The purpose of the monitoring of O2 saturation is to enhance the assessment of 
severity and progression of COVID-19, as well as to ensure that participants 
are adequately informed with respect to their medical condition and seek 
medical care per instructions. 
x If results of SARS-CoV-2 NAAT testing indicate infection, the participant is 
considered to have COVID-19 and will follow the postdiagnosis schedule (see 
Appendix J) and procedures below. Retesting is permitted if the participant 
continues to have symptoms and no other diagnosis is apparent. 
x If results of SARS-CoV-2 NAAT testing do not indicate infection, the 
participant will stop recording symptoms on Memory Aid 2 and will return to 
the regular study schedule. 
Hold vaccination until results of SARS-CoV-2 NAAT testing have been received.  
Postdiagnosis Schedule for participants with COVID-19 
All participants with COVID-19 will receive the optimal local standard of care for 
prevention and treatment of COVID-19, including, for example, access to 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 72 of 169 
temperature monitoring, pulse oximetry, oxygen, medications such as steroids, and 
hospitalization at facilities that are both prepared and experienced in the 
management of severe cases to minimize mortality. 
If a participant is diagnosed with COVID-19 between Study Day 1 and Day 28 (ie, 
first and second study vaccinations), country-specific guidelines on administration 
of vaccination if available will be followed. If no country-specific guidelines exist, 
vaccination will be held until participant has recovered adequately to proceed with 
vaccination in the judgement of the clinician (see Section 9.9). 
Postdiagnosis Day 2 – 14:  
x Participants will continue to use Memory Aid 2 to record daily symptoms of 
COVID-19 (if any), and whether clinical care was sought or hospitalization 
occurred, through Day 14 or until a negative SARS-CoV-2 NAAT test, 
whichever is longer. 
x Participant will measure and record in the Memory Aid 2 their O2 saturation 
(at rest and following mild exercise, defined as walking around the room for 1 
minute) using a pulse oximeter through Day 14 or until a negative SARS-CoV-
2 NAAT test, whichever is longer.  
x Participant will be contacted by phone (or alternative contact method) by CRS 
staff every other day, at a minimum, through Day 14 or until symptoms 
improve (if symptomatic), whichever is longer, and will be instructed to 
contact the clinic if their symptoms are getting worse.  
x Acute illness blood collection (Day 3) per schedule of procedures (see 
Laboratory Procedures Table for COVID-19 Symptom Visits in Appendix J). 
x Participants will be instructed to self-isolate per local guidelines. 
x Nasal swabs collection per schedule of procedures (see Laboratory Procedures 
Table for COVID-19 Symptom Visits in Appendix J). 
x Symptoms recorded in the Memory Aid 2 will be entered into the study record 
if not previously entered. 
Postdiagnosis Day 28:  
x Nasal swabs collection, if indicated, per schedule of procedures (see 
Laboratory Procedures Table for COVID-19 Symptom Visits in Appendix J). 
x The participant’s clinical course is reviewed in detail.  
x Convalescent illness blood collection per schedule of procedures (see 
Laboratory Procedures Table for COVID-19 Symptom Visits in Appendix J). 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 73 of 169 
x Following resolution of the self-isolation period, participants return to the main 
study schedule to complete remaining procedures. Follow-up duration for 
participants diagnosed with severe COVID-19 disease may be adjusted in 
consultation with the CRS (eg, to avoid interference with participant initiation 
of SARS-CoV-2 treatment).  
Postdiagnosis Day 42:  
x If participant had positive SARS-CoV-2 NAAT test on Day 14, nasal swab 
collection approximately every 2 weeks will continue until a negative test 
result is obtained. See schedule of procedures for COVID-19 Symptom Visits 
in Appendix J. 
Postdiagnosis Day 56+:  
x If participant had positive SARS-CoV-2 NAAT test on Day 42, blood will be 
collected on Day 56 and approximately every 8 weeks thereafter, along with 
nasal swab collection approximately every 2 weeks, until a negative SARS-
CoV-2 NAAT test result is obtained. See schedule of procedures for COVID-
19 Symptom Visits in Appendix J. 
9.7 
Visit windows and missed visits 
Visit windows are included in Appendix K. Guidance for out of window visits is 
provided in the CoVPN 3008 (Ubuntu)) SSP. 
9.8 
Assessments of reactogenicity for a subset of participants (Safety 
Subset) 
To confirm safety in the local population, reactogenicity events (solicited adverse 
events) may be collected for a subset of participants at selected sites in each 
country participating in this trial. (See CoVPN 3008 (Ubuntu) SSP for details). 
Reactogenicity assessments are performed after each vaccination. All 
reactogenicity symptoms are followed until resolution and graded according to the 
Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse 
Events, Corrected Version 2.1, dated July 2017 (see Section 11.2.2). 
The reactogenicity assessment period is up to 7 days following vaccination. The 
maximum severity reached for each symptom during the assessment period is 
reported on CRFs. Participants will be given a postvaccination memory tool to 
assist with recall of symptoms. The site staff and the participant will make multiple 
efforts in good faith to be in contact after the 7-day reactogenicity period, or 
sooner if indicated. At that time, site staff will discuss reactogenicity events with 
the participant and will record the relevant information on either the appropriate 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 74 of 169 
CRF(s) or participant chart note. Clinic staff will follow new or unresolved 
reactogenicity symptoms present at day 7 to resolution. Participants are instructed 
to contact the clinic for events that arise during the period between vaccination and 
the next scheduled visit. In general, a participant who self-reports any 
postvaccination reaction greater than moderate will be advised to contact the 
clinician within 48 hours after onset, unless the reaction is improving and/or has 
resolved completely. 
Reactogenicity assessments include assessments of systemic and local symptoms 
and vaccine-related lesions. Events meeting SAE/AEs requiring expedited 
reporting criteria, are recorded on an AE log form. 
9.8.1 
Assessment of systemic and local symptoms 
Systemic symptoms include increased body temperature, malaise and/or fatigue, 
generalized myalgia, headache, chills, arthralgia (in several joints), and nausea. 
Local symptoms include pain and/or tenderness, lymphadenopathy at and/or near 
the injection site.  
Body temperature is measured by oral or infrared thermometry and reported in 
degrees Celsius. A measurement may be taken if participant is feeling feverish. 
Body temperature measurement is not required during the in-clinic reactogenicity 
assessment immediately following vaccination. 
9.8.2 
Assessment of injection site(s) 
Typical injection site reactions are erythema/redness and induration/swelling. The 
maximum diameter for all injection site reactions is recorded. 
All injection site reactions are monitored until resolution. Areas with any diameter 
greater than 5 cm are followed daily; otherwise, the frequency of follow-up is 
based on clinician judgment. 
9.9 
Delaying vaccinations for a participant 
Vaccinations will be delayed if the participant is clinically ill, until participant has 
recovered adequately to proceed with vaccination, in the judgement of the 
clinician. 
A participant’s scheduled vaccination will also be delayed if participant is: 
Within 90 days prior to any study injection  
x Receipt of blood products or immunoglobulin 
Within 30 days prior to any study injection 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 75 of 169 
x Receipt of live attenuated vaccines  
x Receipt of allergy treatment with antigen injections 
x Within 14 days prior to any study injection 
x Receipt of any vaccines that are not live attenuated vaccines (eg, 
pneumococcal) 
Within 2 to 4 weeks  
x Initiating/changing antiretroviral therapy. A delay in the vaccination schedule 
is not required if a participant only has changes in dosage as opposed to 
changes in the type of antiretroviral medications. 
Participants who plan to receive licensed vaccines or allergy treatments should be 
counseled to schedule receipt of these substances, when possible, outside the 
intervals indicated above. Therefore, if circumstances allow, these substances 
should also be avoided in the interval between a study vaccination and completion 
of the 2 or 3-week postvaccination follow-up visit. 
9.10 
Discontinuing vaccination for a participant who receives a COVID-19 
vaccine outside the study 
In the event a participant receives another available COVID-19 vaccine outside the 
study, an individual participant’s study vaccinations will be permanently 
discontinued. Participants should be counseled on the importance of continuing 
with the study and strongly encouraged to participate in follow-up visits and 
protocol-related procedures per the protocol for the remainder of the trial, unless 
medically contraindicated. 
9.11 
Early termination visit 
In the event of early participant termination, site staff should consider if final 
specimen collection is appropriate and follow operational guidance from the 
CoVPN protocol team. 
9.12 
Pregnancy 
Pregnancy will be assessed by self-report or confirmed by pregnancy test at 
screening or enrollment visit. Self-reported pregnancy will be evaluated by urine 
pregnancy test. If a participant is confirmed to be pregnant and plans to continue 
the pregnancy, the following will be performed: (1) Fetal ultrasound to confirm 
gestational age and developmental status of the pregnancy; (2) Syphilis test result 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 76 of 169 
and history of treatment will be collected from medical records if previously done 
and documented; otherwise, the participant will be referred for testing and 
potential treatment per local standard of care and the results will be collected from 
the subsequent medical records. In addition, HIV testing and counseling will be 
performed if not already indicated for that visit. 
If the participant terminates from the study prior to the pregnancy outcome, the site 
should make efforts to remain in contact with pregnant participants to ascertain 
and document the pregnancy outcome (maternal and fetal/neonatal) with 
completion of the relevant CRFs even after exiting the study, per protocol. All 
pregnancies and pregnancy outcomes should be recorded and reported (see the 
CoVPN 3008 (Ubuntu) SSP). 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 77 of 169 
10 
Laboratory 
10.1 
CRS laboratory procedures 
The CoVPN 3008 (Ubuntu) SSP and other study materials provide further 
guidelines for operational issues concerning the clinics and laboratories. These 
documents include special considerations for phlebotomy and guidelines for 
general specimen collection, specimen labeling and specimen processing. 
With the exception of SARS-CoV-2 PCR, all assays described below are 
performed as research assays to evaluate the ability of the SARS-CoV-2 virus to 
induce immune responses in the context of the participants’ genetic background 
and are not approved for use in medical care. Results from these research assays 
are not made available to participants or medical professionals to guide treatment 
decisions. 
10.2 
Total blood volume 
Required blood collections per visit are shown in Appendix B, Appendix C, 
Appendix D, Appendix E, Appendix F, Appendix G, Appendix H, Appendix I, and 
Appendix J. The total blood volume drawn for each participant will not exceed 500 
mL in any 56-day (8-week) period. Blood collection for PBMCs for pregnant 
women will be limited to those who are documented to have COVID-19 unless 
they are severely anemic. (See CoVPN 3008 (Ubuntu) SSP for details.) 
10.3 
Endpoint assays  
10.3.1 
SARS-CoV-2 PCR 
Qualitative and/or quantitative, real-time reverse transcription polymerase chain 
reaction (RT-PCR) assays to detect SARS-CoV-2 will be run on nasal samples 
collected from study participants. 
10.3.2 
Anti-SARS-CoV-2 antibodies  
Chemiluminescent microparticle immunoassays (CMIA) to detect SARS-CoV-2 
antibodies will be run on serum samples collected from study participants. 
10.3.3 
SARS-CoV-2 viral sequencing 
Genome sequencing of SARS-CoV-2 virus may be performed on nasal samples 
from study participants using a metagenomic approach. RNA from positive 
specimens is converted to a cDNA library by reverse transcription and the library 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 78 of 169 
is sequenced. Resulting consensus sequences are assembled against a SARS-CoV-
2 reference genome. 
10.3.4 
Neutralizing antibody assay (nAb) 
SARS-CoV-2–specific nAb assays may be performed on serum samples from 
study participants. The assay will test neutralization of S-pseudotyped and/or full-
genome recombinant viruses as measured by a reduction in luciferase (Luc) 
reported gene expression after infection in ACE-2 positive cells. 
10.3.5 
Binding antibody multiplex assay (BAMA) 
SARS-CoV-2 specific total IgG and IgM binding antibodies may be assessed in 
serum samples. In addition, SARS-CoV-2–specific serum IgA and IgG subclass 
(IgG1, IgG2, IgG3, and IgG4) antibodies may also be assessed. 
10.3.6 
T-cell assays 
Flow cytometry may be used to examine SARS-CoV-2-specific CD4+ and CD8+ 
T-cell responses following stimulation of PBMCs with synthetic peptides that span 
the proteins encoded by the SARS-CoV-2 virus. Data will be reported as 
percentages of CD4+ or CD8+ T cells responding to a specific peptide pool. 
Additional cell surface markers, cytokines, or functional markers may also be 
analyzed. Additional T-cell assays may include evaluation of additional cytokines 
using a multiplexed secreted cytokine assay, mapping of individual peptide-level 
T-cell responses, and characterization of viral inhibition. 
10.3.7 
SARS-CoV-2 -specific B cell phenotyping and monoclonal antibody 
isolation 
SARS-CoV-2 -specific memory B cells and plasmablasts induced by infection may 
be identified and characterized using fluorescently labeled recombinant proteins in 
combination with a flow cytometry phenotyping panel. In particular, SARS-CoV-2 
spike and receptor binding domain-specific B cells and plasmablasts will be 
enumerated and may be further characterized for expression of memory, activation, 
inhibitory or other markers of interest. From a subset of individuals, SARS-CoV-2-
specific memory B cells or plasmablasts will be isolated for B-cell receptor 
sequencing and generation of recombinant monoclonal antibodies for in-depth 
characterization (eg, function, binding-specificity). 
10.3.8 
Gene expression 
RNA may be isolated from PBMC or whole blood and used for gene expression 
analysis by RNA sequencing, real-time PCR, single-cell proteogenomic profiling 
or other methods. Gene expression profiles will be correlated with other immune 
responses and clinical outcomes. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 79 of 169 
10.4 
Lab assay portfolio 
Additional assays may be performed per the Laboratory Center assay portfolio, 
which includes immune assessments such as those for cellular, humoral, and innate 
immune responses, and host genetics. The assay portfolio will be updated 
periodically to include new assays and adjust qualification levels of existing 
assays. 
10.5 
Exploratory studies 
Samples may be used for other testing and research related to furthering the 
understanding of SARS-CoV-2 immunology, virology, or vaccines. In addition, 
cryopreserved samples may be used to perform additional assays to support 
standardization and validation of existing or newly developed methods. 
10.6 
Specimen storage and other use of specimens 
The CoVPN stores specimens from all study participants indefinitely, unless a 
participant requests that specimens be destroyed or if required by IRB/EC or RE. 
Other use of specimens is defined as studies not covered by the protocol or the 
informed consent form for the study (see Section 10.5 and Appendix A). 
This research may relate to SARS-CoV-2, vaccines, coronaviruses, the immune 
system, and other diseases. This could include genetic testing and, potentially, 
genome-wide studies. This research is done only to the extent authorized in each 
study site’s informed consent form, or as otherwise authorized under applicable 
law. Other research on specimens (“other use”) will occur only after review and 
approval by the CoVPN, the IRB/EC of the researcher requesting the specimens, 
and the IRBs/ECs/REs of the CRSs if required. 
As part of on-going consenting for the study, participants document their initial 
decision to allow or not allow their specimens to be used in other research, and 
they may change their decision at any time. The participant’s initial decision about 
other use of their specimens, and any later change to that decision, is recorded by 
their CRS in a Web-based tool that documents their current decisions for other use 
of their specimens. The CoVPN will only allow other research to be done on 
specimens from participants who allow such use.  
CRSs must notify CoVPN Regulatory Affairs if institutional or local governmental 
requirements pose a conflict with or impose restrictions on specimen storage or 
other use of specimens. 
 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 80 of 169 
10.7 
Biohazard containment 
The transmission of blood-borne pathogens can occur through contact with 
contaminated needles, blood, and blood products, and the transmission of SARS-
CoV-2 and other respiratory pathogens may occur through contact with 
contaminated respiratory droplets, aerosols, and other biological materials. 
Appropriate precautions will be employed by all personnel in the collection, 
shipping, and handling of all specimens for this study, as currently recommended 
by local health authorities, the CDC, the NIH, or other applicable agencies. 
All dangerous goods materials, including Biological Substances, Category A or 
Category B, must be transported according to instructions detailed in the 
International Air Transport Association Dangerous Goods Regulations. 
 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 81 of 169 
11 
Safety monitoring and safety review 
11.1 
Safety monitoring and oversight 
11.1.1 
CoVPN 3008 (Ubuntu) PSRT 
The CoVPN 3008 (Ubuntu) PSRT is composed of the following members: 
x DAIDS Medical Officer  
x Protocol co-chairs 
x In Country Lead Investigators 
x Protocol Team leaders 
x Clinical Research Physician 
x Core Medical Monitors 
x Regional Medical Liaisons 
x Clinical Safety Specialists 
The clinician members of CoVPN 3008 (Ubuntu) PSRT are responsible for 
decisions related to participant safety.  A quorum and further details for the PSRT 
will be defined in the PSRT Charter. 
The Protocol Team clinical data manager, clinical trial manager, and others may 
also be included in CoVPN 3008 (Ubuntu) PSRT meetings. 
11.1.2 
NIAID Data Safety Monitoring Board (DSMB) 
The NIAID HIV DSMB, for as long as it is involved in the trial, and the OG are 
responsible for safeguarding the interests of clinical trial participants and for 
enhancing the integrity of the trial. The NIAID HIV DSMB assesses the effects of 
the study vaccines during the trial and may give advice to the CoVPN 3008 
(Ubuntu) OG. 
More details on the role of and the data provided to the DSMB will be described in 
a DSMB charter and SAP. 
11.1.3 
SDMC or designee roles and responsibilities in safety monitoring  
The roles and responsibilities of the SDMC in relation to safety monitoring 
include: 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 82 of 169 
x Maintaining a central database management system for CoVPN 3008 clinical 
data;  
x Providing reports of clinical data to appropriate groups such as the CoVPN 
3008 (Ubuntu) PSRT, DSMB, and to support safety reports for submission to 
national regulatory authorities as needed (see Section 11.1.1, 11.1.2 and 
11.2.5). 
11.1.4 
CoVPN LOC or designee roles and responsibilities in safety 
monitoring 
x Daily monitoring of clinical data for events that meet the CoVPN 3008 
(Ubuntu) PSRT AE review criteria (see Section 11.3.1); 
x Notifying CoVPN CRSs and other groups when safety pauses are instituted 
and lifted (see Section 11.3.1); 
x Querying CoVPN CRSs for additional information regarding reported clinical 
data; and 
x Providing support to the CoVPN 3008 (Ubuntu) PSRT. 
11.2 
Safety reporting 
11.2.1 
Submission of safety forms to SDMC 
Site staff must submit all safety forms (eg, reactogenicity, adverse event) within 3 
business days of the site being notified, or sooner per Section 11.3.1 below. The 
forms should not be held in anticipation of additional information at a later date. If 
additional information is received at a later date, the forms should be updated and 
resubmitted before the end of the next business day after receiving the new 
information. For the case of a longer site holiday closure, site staff must submit the 
data by the end of the 5th day (local time) after receiving the information even if 
this day is a holiday. 
For example: If the site becomes aware of an AE on Thursday (Day 1), the site 
must submit the data by the end of the next business day, on Friday. If there is a 
longer site holiday closure, then this AE must be reported no later than the end of 
the fifth day, Monday (Day 5). If Monday is a holiday as well, all safety forms still 
need to be submitted by the end of Monday (Day 5). 
11.2.2 
AE reporting 
Sites are expected to notify CoVPN clinical safety staff or designee of any serious 
safety concern requiring their attention (see Section 11.3.1). Telephone numbers 
and email addresses are found on the CoVPN 3008 (Ubuntu) protocol home page 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 83 of 169 
on the CoVPN Members’ site 
(https://fredhutch.sharepoint.com/sites/CoVPN/covpn3008/SitePages/Home.aspx). 
In the case of email notification, clinical safety staff or designee will reply within 1 
business day. If email service is not available, the CRS should notify clinical safety 
staff of the event by telephone, and then submit CRFs. 
In addition, site investigators are required to submit AE information in accordance 
with IRB/EC and any applicable RE requirements. 
An AE is any untoward medical occurrence in a clinical investigation participant 
administered a study product/procedure(s) and which does not necessarily have a 
causal relationship with this treatment. An AE can therefore be any unfavorable 
and unintended sign (including an abnormal laboratory finding), symptom, or 
disease temporally associated with the use of an investigational study 
product/procedure(s), whether or not related to the investigational study 
product/procedure(s). All AEs are graded according to the Division of AIDS 
(DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, 
Corrected Version 2.1, July 2017, available on the RSC website at 
https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-tables, 
except: 
Injection Site Erythema or Redness and Injection Site Induration or Swelling 
activities such that: 
x Grade 1 is: 2.5 to < 5 cm in diameter; 
x *UDGHLVWRFPLQGLDPHWHU 
x *UDGHLVFPLQGLDPHWHU258OFHUDWLRQ256HFRQGDU\LQIHFWLRQ25
Phlebitis OR Sterile abscess OR Drainage; 
x Grade 4 is: Potentially life-threatening consequences (eg, abscess, exfoliative 
dermatitis, necrosis involving dermis or deeper tissue); 
Clinic staff should evaluate every AE to determine if (1) if the AE meets the 
criteria for prompt PSRT AE review (see Section 11.3.1), (2) the AE meets the 
requirements for expedited reporting (see Section 11.2.4), and (3) if the AE is a 
potential immune-mediated disease that may be listed as an AE of special interest 
(AESI) (see Appendix L). 
For a subset of participants, the following data will be collected and reported: 
x Unsolicited AEs for 28 days following each vaccination 
x Solicited AEs following each vaccination (see Section 9.8) 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 84 of 169 
For all participants, the following AEs will be collected and reported throughout 
the entire study: 
x SAEs/EAEs, 
x AESIs (a list is provided in Appendix L). 
The AEs collected in this study are reported to the SDMC on the appropriate CRF. 
See CoVPN 3008 (Ubuntu) Study-specific Procedures for detail on AE reporting. 
11.2.3 
Serious adverse event 
The term “Serious Adverse Event” (SAE) is defined as follows: An adverse event 
or suspected adverse reaction is considered serious if, in the view of either the 
investigator or the Sponsor, it results in any of the following outcomes: 
x death, 
x a life-threatening adverse event, 
x inpatient hospitalization or prolongation of existing hospitalization, 
x a persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions, 
x congenital anomaly/birth defect. 
x Is Medically Important* 
* 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. 
“Life-threatening” refers to an adverse event that, at occurrence, represents an 
immediate risk of death to the subject. Similarly, a hospital admission for an 
elective procedure is not considered an SAE. 
11.2.4 
Expedited reporting of adverse events 
CRS staff must report all related SAEs within 3 business days of their knowledge 
of the event to the clinical database, so that applicable safety data can be reviewed, 
see CoVPN 3008 (Ubuntu) SSP for details. 
The study products for which expedited reporting are required are: 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 85 of 169 
x mRNA-1273 vaccine 
x mRNA-1273.222 vaccine 
11.2.5 
Reporting of AEs to pertinent national regulatory authorities  
Reports are prepared and filed to appropriate regulatory authorities within the 
timelines required by pertinent national regulatory authorities.  
For details refer to the CoVPN 3008 Safety Data Process document.  
11.3 
Safety reviews 
11.3.1 
Prompt PSRT AE review 
If the trial is placed on safety pause, all enrollments and vaccinations with the 
product related to the event that triggered the pause will be held until further 
notice. 
Vaccinations may be suspended for safety concerns, if, in the judgment of the 
CoVPN 3008 (Ubuntu) PSRT, participant safety may be threatened. Criteria for an 
individual participant’s departure from the schedule of vaccinations are listed in 
Section 9.9. 
The following will result in a prompt PSRT AE review to consider a safety pause: 
x Any SAE determined to be related to study product 
x Any Grade 4 objective local reactogenicity sign or systemic reactogenicity sign 
or symptom 
These require notification by CRS staff within 24 hours of becoming aware of the 
event to the clinical safety staff for a prompt PSRT review; see CoVPN 3008 
(Ubuntu) SSP for details. 
If a prompt PSRT AE review is triggered, CoVPN safety staff or designee notifies 
the PSRT as soon as possible during working hours (local time) or, if the 
information was received during off hours, by the morning of the next workday. 
Once the trial is paused, the CoVPN clinical safety team notifies the CoVPN 
3008 (Ubuntu) PSRT, SAMRC Regulatory Affairs, CoVPN Regulatory 
Affairs, participating CoVPN CRSs and the OG. 
If the trial is paused, the CoVPN 3008 (Ubuntu) PSRT reviews safety data and 
decides whether the pause can be lifted or permanent discontinuation of 
vaccination is appropriate, consulting the OG if necessary. CoVPN Core notifies 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 86 of 169 
the participating CoVPN CRSs, SAMRC Regulatory Affairs, and CoVPN 
Regulatory Affairs of the decision regarding resumption or discontinuation of 
study vaccinations. 
The CoVPN requires that each CRS submit to its IRB/EC and any applicable RE 
protocol-related safety information (such as unanticipated problems involving risks 
to participants or others). CRSs must also follow all applicable RE reporting 
requirements. 
Based on the CoVPN 3008 (Ubuntu) PSRT assessment, SAMRC notifies 
SAHPRA. Other pertinent national and regional authorities will also be 
notified as appropriate (see Section 11.2.5). 
In addition, all other reportable AEs are reviewed routinely by the CoVPN 3008 
(Ubuntu) PSRT (see Sections 11.3.2 and 11.3.3). 
11.3.2 
Review of cumulative safety data 
Routine safety review occurs at the start of enrollment and then throughout the 
study. 
Reviews proceed from a standardized set of protocol-specific safety data reports. 
These reports are produced by the SDMC or designee and include queries to the 
CoVPN CRSs. Events are tracked by internal reports until resolution. 
11.3.3 
Weekly review 
The CoVPN 3008 (Ubuntu) PSRT reviews clinical safety reports weekly and 
conducts calls to review the data as appropriate, until 1 month post the initial set of 
injections (second injection) visits have been completed (Visit 7) are completed. 
Thereafter, less frequent reporting and safety reviews may be conducted at the 
discretion of the CoVPN 3008 (Ubuntu) PSRT. CoVPN LOC or designee reviews 
reports of clinical AEs. Events identified during the review that are considered 
questionable, inconsistent, or unexplained are referred to the CoVPN CRS clinic 
staff for verification. 
 
 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 87 of 169 
12 
Protocol conduct 
This protocol and all actions and activities connected with it will be conducted in 
compliance with the principles of GCP (ICH E6 (R2)), and according to NIAID 
and CoVPN policies and procedures as specified in the CoVPN 3008 SSP, NIAID 
Clinical Research Policies and Standard Procedures Documents including 
procedures for the following: 
x Protocol registration, activation, and implementation; 
x Informed consent, screening, and enrollment; 
x Study participant reimbursement; 
x Clinical and safety assessments; 
x Safety monitoring and reporting; 
x Data collection, documentation, transfer, and storage; 
x Participant confidentiality; 
x Study follow-up and close-out; 
x Unblinding of staff and participants; 
x Quality control; 
x Protocol monitoring and compliance; 
x Specimen collection, processing, and analysis; 
x Exploratory and ancillary studies and substudies, and 
x Destruction of specimens. 
Any policies or procedures that vary from CoVPN and/or NIAID standards or 
require additional instructions (eg, instructions for randomization specific to this 
study) will be described in the CoVPN 3008 (Ubuntu) SSP. 
12.1 
Study termination 
NIAID and the Study Sponsor reserve the right to terminate or curtail a clinical 
study for any reason, including but not limited to the following: 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 88 of 169 
x risk to subject safety 
x the scientific question is no longer relevant or the objectives will not be met 
(ie, slow accrual) 
x failure to comply with GCP, US. Federal regulations, or Terms and Conditions 
of Award 
x occurrence of unforeseen drug safety issues or data from preclinical studies 
indicate a presence of unanticipated toxicity 
x risks that cannot be adequately quantified 
x ethical concerns raised by the local community or local medical care/health 
care authorities 
x failure to remedy deficiencies identified through site monitoring 
x substandard data 
x reaching a major study endpoint substantially before schedule with persuasive 
statistical significance. 
This study may also be terminated early by the determination of the FDA, the 
United States Department of Health and Human Services Office for Human 
Research Protections (OHRP). In addition, the conduct of this study at an 
individual CRS may be terminated by the determination of the IRB/EC and any 
applicable RE. 
12.2 
Emergency communication with study participants 
As in all clinical research, this study may generate a need to reach participants 
quickly to avoid imminent harm, or to report study findings that may otherwise 
concern their health or welfare and their willingness to remain on study. 
When such communication is needed, the CRS will request that its IRB/EC and 
any applicable RE expedite review of the message. If this review cannot be 
completed in a timeframe consistent with the urgency of the required 
communication, the site can contact the participant without IRB/EC approval if 
such communication is necessary to avoid imminent harm to the study participant. 
The CRS must notify the IRB/EC and any applicable RE of the matter as soon as 
possible. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 89 of 169 
12.3 
Site monitoring 
Site monitoring is conducted by Hutchinson Centre Research Institute of South 
Africa (HCRISA) to ensure that the rights and well-being of trial participants are 
protected, that the reported trial data are accurate, complete, and verifiable, and 
that the conduct of the trial is in compliance with the currently approved 
protocol/amendment(s), Declaration of Helsinki, Guidelines for Good Practice in 
the Conduct of Clinical Trials in Human Participants, ICH, FDA regulations and 
with applicable regulatory requirement(s). Refer to CoVPN 3008 (Ubuntu) 
Clinical Trial Monitoring Plan for more information about monitoring schedule, 
reports, and virtual and onsite support. 
 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 90 of 169 
13 
Version history 
The Protocol Team may modify the original version of the protocol. Modifications 
are made to CoVPN protocols via clarification memos, letters of amendment, or 
full protocol amendments. 
The version history of, and modifications to, Protocol CoVPN 3008 (Ubuntu) are 
described below. 
Protocol history and modifications 
Date: June 28, 2023 
Protocol version:8.0 
Protocol modification: Full protocol amendment 7 
Item 1 
Revised in Section 1, Overview; Section 2.1.1, Overall study design ; Section 
6, Statistical considerations; Appendix B, Laboratory procedures table for 
Groups 1 and 3 (SARS-CoV-2 seronegative participants, main study), 
Appendix C, Laboratory procedures table for Groups 2 and 4 (SARS-CoV-2 
seropositive participants, main study); Appendix D, Laboratory procedures for 
PBMC immunogenicity subset, Groups 1 and 3; Appendix E, Laboratory 
procedures for PBMC immunogenicity subset, Groups 2 and 4; Appendix F, 
Laboratory procedures for the PBMC immunogenicity correlates (Group 1, 
HIV positive, SARS-CoV-2 seronegative participants); Appendix G, 
Laboratory procedures for the PBMC immunogenicity correlates (Group 2, 
HIV positive, SARS-CoV-2 seropositive participants); Appendix H,  Schedule 
of clinic procedures for Groups 1 and 3 (SARS-CoV-2 seronegative 
participants); Appendix I, Schedule of clinic procedures for Groups 2 and 4 
(SARS-CoV-2 seropositive participants); Appendix K, Visit windows and 
Appendix N, Addendum 3 to the sample informed consent form (SICF):  
harmonizing protocol language with the current study design 
Item 2 
Clarified in Section 6.1, Summary of statistical design: assignment and 
randomisation to study arms 
Item 3 
Clarified in Section 6.2, Definitions of study cohorts for analyses: SARS-CoV2 
seropositive and SARS-CoV-2 seronegative 
Item 4 
Updated in Title page; Section 13, Version history: Contents of this 
amendment 
Item 5 
Corrected throughout the Protocol: Minor errors in grammar, typography, 
formatting 
Item 6 
Updated throughout the Protocol: Section numbering and cross-references 
Item 7 
Updated per Protocol Version 7.0, Clarification Memo 1, dated April 17, 2023 
and Clarification Memo 2, dated June 20, 2023 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 91 of 169 
Date: June 20, 2023 
Protocol version: Version 7.0 
Protocol modification: Clarification Memo 2 
 
Clarified in Appendix H,  Schedule of clinic procedures for Groups 1 and 3 
(SARS-CoV-2 seronegative participants); Appendix I, Schedule of clinic 
procedures for Groups 2 and 4 (SARS-CoV-2 seropositive participants) and 
Appendix J, COVID-19 symptom visits: continue active COVID-19 
surveillance and symptomatic post-diagnosis schedule beyond Month 12 
Date: April 17, 2023 
Protocol version: Version 7.0 
Protocol modification: Clarification Memo 1 
 
Corrected in Appendix H,  Schedule of clinic procedures for Groups 1 and 3 
(SARS-CoV-2 seronegative participants): checkmark for vaccination visit 
 
Corrected in Appendix K, Visit windows: missing footnote indicator 
Date: February 27, 2023 
Protocol version:7.0 
Protocol modification: Full protocol amendment 6 
 
Item 1 
Revised in Section 1, Overview; Section 2, Background; Section ; Section 3, 
Objectives and Endpoints; Section 6, Statistical considerations; Section 9, 
Clinical procedures; Appendix B, Laboratory procedures table for Groups 1 
and 3 (SARS-CoV-2 seronegative participants, main study), Appendix C, 
Laboratory procedures table for Groups 2 and 4 (SARS-CoV-2 seropositive 
participants, main study), Appendix D, Laboratory procedures for PBMC 
immunogenicity subset, Groups 1 and 3; Appendix E, Laboratory procedures 
for PBMC immunogenicity subset, Groups 2 and 4; Appendix F, Laboratory 
procedures for the PBMC immunogenicity correlates (Group 1, HIV positive, 
SARS-CoV-2 seronegative participants); Appendix G, Laboratory procedures 
for the PBMC immunogenicity correlates (Group 2, HIV positive, SARS-CoV-2 
seropositive participants); Appendix H,  Schedule of clinic procedures for 
Groups 1 and 3 (SARS-CoV-2 seronegative participants); Appendix I, 
Schedule of clinic procedures for Groups 2 and 4 (SARS-CoV-2 seropositive 
participants), Appendix J, COVID-19 symptom visits; Appendix K, Visit 
windows and Appendix M, Addendum 2 to the sample informed consent form 
(SICF):  harmonizing protocol language with the changed study focus 
Item 2 
Revised in in Section 1, Overview; Section 3, Objectives and endpoints; 
Section 6.4.3, Analysis of relative risk between treatment arms: definitions to 
be considered for COVID-19 
Item 3 
Revised in Section 2, Background; Section 3, Objectives and endpoints and 
Section 6, Statistical considerations: roles of the DSMB, OG and the EAC; and 
Section 11, Safety monitoring and safety review 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 92 of 169 
Item 4 
Clarified in Section 9.4, Follow-up procedures: change in antiretroviral 
medication 
Item 5 
Clarified in Section 9.11, Early termination visit: operational guidance for 
early study termination 
Item 6 
Clarified in Section 9.12, Pregnancy: documentation of pregnancy outcome 
Item 7 
Updated in Section 11.2, 2, AE reporting: weblink for the CoVPN Member’s 
site 
Item 8 
 Clarified in Section 11.2.5, Reporting of AEs to pertinent national regulatory 
authorities and Section 12, Protocol conduct: reference documents mentioned 
in these sections refer to CoVPN3008 reference documents 
Item 9 
Updated in Title page; Section 13, Version history and Section 16, Literature 
cited: Contents of this amendment 
Item 10 
Corrected throughout the Protocol: Minor errors in grammar, typography, 
formatting 
Item 11 
Updated throughout the Protocol: Section numbering and cross-references 
Item 12 
Updated per Protocol Version 6.0, Clarification Memo 1, dated October 05, 
2022 
Date: October 05, 2022 
Protocol version: Version 6.0 
Protocol modification: Clarification memo 1 
Revised in Section 2.1.1, Overall study design and Section 8.1, Vaccine 
regimen: language related to injection volumes of the study vaccines 
        Corrected in Full protocol amendment 5 document: version number 
Date: September 27, 2022 
Protocol version:6.0 
Protocol modification: Full protocol amendment 5 
Item 1 
Revised in Section 1, Overview; Section 2, Background; Section 3, Objectives 
and Endpoints; Section 6, Statistical considerations; Section 8, Study Products; 
Section 9, Clinical procedures; Section 14, Document references (other than 
literature citations); Appendix K, Visit windows; Appendix L, Addendum to 
the sample informed consent form (SICF):  updated information/language 
related to the addition of the mRNA-1273.222 vaccine at Month 6 and the 
current schema. 
Item 2 
Clarified in Section 6.2, Definition of study cohorts for analysis: group 
assignment based on SARS-CoV-2 sero-status 
Item 3 
Added in Section 6.3.1, Power calculations for coprimary objectives 1-4 
(Efficacy): SARS-CoV-2 (re-infection) incidence rate among unvaccinated 
PLWH SARS-CoV-2 positive individua1. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 93 of 169 
Item 4 
Clarified in Section 6.4, Statistical analyses: analysis of coprimary efficacy 
endpoints 
Item 5 
Clarified in Section 8.4, Administration of study products: administration of 
intramuscular injections 
Item 6 
Added in Section 9.1.1, Protocol-specific consent form: addendum to informed 
consent form 
Item 7 
Updated in Appendix J, COVID-19 Symptom Visits: Laboratory 
Procedures Table: added footnote indicators for clarity and updated  
footnote #5 to correct an error 
Item 8 
Updated Section 1.1, Protocol Team: to reflect current team composition 
Item 9 
Updated in Title page; Section 13, Version history and Section 16, Literature 
cited: Contents of this amendment 
Item 10 
Corrected throughout the Protocol: Minor errors in grammar, typography, 
formatting 
Item 11 
Updated throughout the Protocol: Section numbering and cross-references 
Item 12 
Updated per Protocol Version 5.0, Claification Memo 1, dated May 19, 2022 
Item 13 
Updated per Protocol Version 5.0, Clarification Memo 2, dated June 
29, 2022 
Date: June 29, 2022 
Protocol version: Version 5.0 
Protocol modification: Clarification Memo 2 
Item 1 
Clarified in Appendix D, Laboratory Procedures for PBMC 
Immunogenicity subset, Groups 1 and 3; Appendix E, Laboratory 
Procedures for PBMC Immunogenicity subset, Groups 2 and 4; 
Appendix F, Laboratory Procedures for the PBMC Immune Correlates 
subset (Group 1, HIV positive, SARS-CoV-2 seronegative participants); 
Appendix G, Laboratory Procedures for the PBMC Immune Correlates 
subset (Group 2, HIV positive, SARS-CoV-2 seropositive participants) 
and Appendix J, Symptom visits: Laboratory procedures table: 
Alternative to ACD tubes for sample collection 
Item 2 
Corrected in Appendix E, Laboratory Procedures for PBMC 
Immunogenicity subset, Groups 2 and 4: missing ‘Cellular Assays’ row 
Date: May 19, 2022 
Protocol version: Version 5.0 
Protocol modification: Clarification Memo 1 
Item 1 
Clarified in Appendix J, COVID-19 Symptom visits: Clinic procedures and in 
Section 9.6, COVID-19 symptom visits and COVID-19 postdiagnosis schedule: 
symptom monitoring and SpO2 measurement by participants (if symptomatic) 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 94 of 169 
Item 2 
Clarified in Section 9.9, Delaying vaccinations for a participant; Appendix B, 
Laboratory procedures table for Groups 1 and 3 (SARS-CoV-2 seronegative 
participants, main study); Appendix C, Laboratory procedures table for 
Groups 2 and 4 (SARS-CoV-2 seropositive participants, main study); 
Appendix D, Laboratory procedures for PBMC immunogenicity subset, 
Groups 1 and 3; Appendix E,  Laboratory procedures for PBMC 
immunogenicity subset, Groups 2 and 4; Appendix F, Laboratory procedures 
for the PBMC immune correlates subset (Group 1, HIV positive, SARS-CoV-2 
seronegative participants) and Appendix G, Laboratory procedures for the 
PBMC immune Correlates subset (Group 2, HIV positive, SARS-CoV-2 
seropositive participants): change in the dosage of antiretroviral therapy. 
Item 3 
Revised in Section 2.1, Rational for trial concept and Appendix J, COVID-19 
Symptom visits: Clinic procedures: clarified that post diagnosis follow up is 
until symptoms improve. 
Item 4 
Clarified in Section 9.5, Active COVID-19 symptomatic surveillance: symptom 
visit after symptom resolution 
Item 5 
Clarified in Section 2.1, Rational for trial concept; Section 2.1.1, Overall study 
design; Section 2.4, Study schema and overview of trial design; Section 3, 
Objectives and endpoints; Section 6.4.3, Analyses of relative risk between 
treatment arms; Section 9.5, Active COVID-19 symptomatic surveillance; 
Section 9.6, COVID-19 symptom visits and COVID-19 postdiagnosis schedule 
and Appendix J, COVID-19 symptom visits: harmonized SARS-CoV-2 testing 
assay description for consistency 
Item 6 
Clarified in Section 3, Objectives and endpoints: randomized assignment to 
treatment arms 
Item 7 
Clarified in Appendix K, Adverse Events of Special Interest (AESI) and Section 
14, Document references (other than literature citations): comprehensive list 
of AESIs 
Item 8 
Clarified in Section 9.2, Pre-enrollment procedures: enrollment may be 
deferred if antiretroviral therapy needs to be initiated 
Item 9 
Corrected in Appendix H, Schedule of clinic procedures for Groups 1 and 3 
(SARS-CoV-2 seronegative participants) and Appendix I, Schedule of clinic 
procedures for Groups 2 and 4 (SARS-CoV-2 seropositive participants) : 
removed typographical error 
Date: March 6, 2022 
Protocol version:5.0 
Protocol modification: Full Protocol Amendment 4 
Item 1 
Revisions to Section 1, Overview: study schema, primary objectives, study 
duration, endpoint assay laboratories, protocol team 
Item 2 
Revised in Section 2, Background: study rationale, SARS-CoV-2 
epidemiology, study design, added Appendix G 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 95 of 169 
Item 3 
Revised in Section 3, Objectives and endpoints: primary, secondary, and 
exploratory objectives 
Item 4 
Updated Section 5, IRB/EC review considerations: Countermeasures 
Acceleration Group 
Item 5 
Revised Section 6, Statistical considerations: study groups, analysis cohorts, 
power calculations for vaccine efficacy analysis 
Item 6 
Revised in Section 7.1, Inclusion criteria: criteria 1 and 6 
Item 7 
Revised in Section 7.2, Exclusion criteria: previously, Criterion #3 
Item 8 
Revised in Section 8.1, Vaccine regimen; Section 8.3, Acquisition of study 
products and Section 8.4, Administration of study products : updated to align 
with current study design 
Item 9 
Revised in Section 9, Clinical procedures: procedures for pregnant 
participants, deleted randomization at enrollment, added blood collection for 
PLWH participants if there is a change in antiretroviral (ARV) medication, 
updated COVID-19 postdiagnosis schedule to monitor persistent shedding, 
updated Appendices B to J 
Item 10 
Clarified in Section 10, Laboratory Procedures: qualitative and quantitative 
reverse transcriptase PCRs 
Item 11 
Revisions to Appendix A, Sample Informed Consent Form: Key information, 
participants groups and procedures tables, blood volumes 
Item 12Updated in Title Page; Section 13, Version history; Section 16, Literature cited: 
Updates related to contents of this amendment 
Item 13Consistency in references to the Study, study product and participants 
Item 14 
Updated or corrected throughout the protocol: Section numbering, cross-
references, acronym list, and minor errors 
Item 15 
Updated per protocol version 4.0, Clarification Memo 2, dated February 9, 
2022 
Item 16 
Updated per protocol version 4.0, Clarification Memo 1, dated December 5, 
2021 
 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 96 of 169 
Date: February 9, 2022 
Protocol version:4.0 
Protocol modification: Clarification Memo 2 
 
Item 1 
Clarified in Section 9.6, COVID-19 Symptom Visits and COVID-19 post-
diagnosis schedule: participants testing positive for SARS-CoV-2 will follow 
procedures outlined in Appendix I 
Item 2 
Updated in Appendix I, COVID-19 symptom visits (Clinic Procedures and 
Laboratory procedures tables): avoid duplication of procedures and sample 
collections 
Item 3 
Clarified in Section 9.5, Active COVID-19 Symptomatic Surveillance, 
Appendix G, Schedule of clinic procedures for Groups 1 and 3 (SARS-CoV-2 
seronegative participants) and in Appendix H, Schedule of clinic procedures 
for Groups 2 and 4 (SARS-CoV-2 seropositive participants): elicit participant 
feedback approximately every two weeks. 
Date: December 5, 2021 
Protocol version:4.0 
Protocol modification: Clarification Memo 1 
Item 1 
Updated in Appendix B, Laboratory procedures table for Groups 1 and 3 
(SARS-CoV-2 seronegative participants, main study): nasal swab collection 
Date: October 1, 2021 
Protocol version:4.0 
Protocol modification: Full Protocol Amendment 3 
Item 1 
Revisions to Section 1, Overview: study schema, primary objectives, study 
duration, protocol team 
Item 2 
Updated in Section 2, Background: study rationale, SARS-CoV-2 
epidemiology, study design 
Item 3 
Revised in Section 3, Objectives and endpoints: primary, secondary, and 
exploratory objectives 
Item 4 
Revised in Section 4, Ethical considerations: updated language 
Item 5 
Revised Section 6, Statistical considerations: study groups, analysis cohorts, 
power calculations for vaccine efficacy analysis 
Item 6 
Revised in Section 7.1, Inclusion criteria: criteria 1 and 4 
Item 7 
Revised in Section 8.1, Vaccine regimen: updated vaccine regimen 
Item 8 
Revised in Section 9, Clinical procedures: schedule of procedures, added HIV 
diagnostic test at screening for all participants, revised vaccination and follow-
up procedures 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 97 of 169 
Item 9 
Added in Section 10, Laboratory Procedures: new sections to describe 
endpoint assays 
Item 10 
Reconciled in Section 11, Expedited reporting of adverse events: study product 
name 
Item 11 
Revisions to Appendix A, Sample Informed Consent Form: study questions, 
study duration, participants groups and procedures tables, blood volumes 
Item 12 
Revised Appendix B, added new Appendix C, Laboratory Procedures tables: 
reorganized, updated visit schedule, and sample collections 
Item 13 
Added Appendices D and E, Laboratory Procedures tables for PBMC 
Immunogenicity subset 
Item 14 
Added new Appendix F, Laboratory Procedures for the Cellular PBMC 
Immune Correlates subset (Group 1, HIV positive, SARS-CoV-2 seronegative 
participants) 
Item 15 
Revised Appendix G and H, Schedule of Clinic Procedures: added Visit 8, 
study group-specific schedule, procedures 
Item 16 
Revised Appendix I, COVID-19 symptom visits, Laboratory Procedures Table: 
blood volume, footnotes 
Item 17 
Revised Appendix J, Visit Windows: added Visit 8 and table for Groups 2 and 
4, revised visit windows for Visit 7 
Item 18 
Clarification Memo 1 to Version 3.0, dated August 25, 2021 
Item 19 
Updated, Section 13, Version history 
Item 20 
Cross-references, acronym list, and minor errors corrected 
Date: August 25, 2021 
Protocol version: Version 3.0 
Protocol modification: Clarification Memo 1 
Item 1 
Clarified in Section 9.2, Pre-enrollment procedures and Appendix B, 
Laboratory procedures table (main study and PBMC subset): SARS-CoV-2 
serology testing at screening 
Item 2 
Corrected in Appendix E, Visit windows: Vaccination 3 target window 
Date: August 11, 2021 
Protocol version:3.0 
Protocol modification: Full Protocol Amendment 2 
Item 1 
Revisions to Section 1, Overview, and Section 1.1, Protocol Team: vaccine 
administration and Protocol Team members 
Item 2 
Updated in Section 2, Background: clarified study design 
Item 3 
Revised in Section 3, Objectives and endpoints: Primary Endpoints 3, 
secondary endpoints 5, exploratory objectives 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 98 of 169 
Item 4 
Revised in Section 4, Ethical considerations: vaccine regimen 
Item 5 
Revised Section 6, Statistical considerations: statistical design, definitions, 
power calculations for vaccine efficacy, analysis 
Item 6 
Revised in Section 7.1, Inclusion criteria: criteria 1 and 6 
Item 7 
Clarified in Section 8.1, Vaccine regimen: updated vaccine regimen 
Item 8 
Clarified in Section 9.8, Assessments of reactogenicity for a subset of 
participants: timepoints for reactogenicity assessments 
Item 9 
Clarified in Section 11.2.2, AE reporting: timepoints for AE collection 
Item 10 
Revisions to Appendix A, SICF: revised language and reconciled clinic 
procedures and blood collection volumes 
Item 11 
Revised Appendix B, Laboratory Procedures tables: relabeled visits, revised 
visit schedule and sample collections 
Item 12 
Revised Appendix C, Schedule of Clinic Procedures 
Item 13 
Revised Appendix E, Visit Windows: visit target day and visit type 
Item 14 
Updated, Section 13, Version history 
Item 15 
Cross-references, acronym list, and minor errors corrected 
Date: July 15, 2021 
Protocol version:2.0 
Protocol modification: Full Protocol Amendment 1 
Item 1 
Revised the CoVPN 3008 protocol name to CoVPN 3008 (Ubuntu) 
Item 2 
Revisions to Section 1, Overview, and Section 1.1, Protocol Team: Protocol 
Team members and SDMC 
Item 3 
Updated in Section 2, Background: name of B.1.351 variant and clarified study 
design 
Item 4 
Revised in Section 3, Objectives and endpoints: Primary Endpoints 1, 
secondary endpoints 5, exploratory objectives and endpoints 
Item 5 
Revised in Section 4, Ethical considerations: optional unblinding for 
participants 
Item 6 
Removed in Section 5.7, Pregnant participants: reference to pregnant women 
as vulnerable population 
Item 7 
Added in Section 6.2, Definitions of Study Cohorts for Analysis, Section 6.5.1, 
Immunogenicity and Immune Correlates Analyses: timepoints for blood 
collection for cellular assays 
Item 8  
Clarified in Section 6.4.3, Vaccine Efficacy Analyses: use of statistical 
methods 
Item 9 
Added in Section 6.9, Roles of DSMB, OG and EAC: information about EAC 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 99 of 169 
Item 10 
Updated in Section 7.1, Inclusion criteria: added reference to CDC 
Item 11 
Revised in Section 7.2, Exclusion criteria: added criterion # 5, revised criteria # 
4, # 6, and #7 
Item 12 
Clarified in Section 8, Study products:  placebo and procedures for 
administration 
Item 13 
Revised Section 9, Clinical procedures: data entry into the study database, 
clarified study procedures 
Item 14 
Added to Section 10, Laboratory: blood collection for PBMC for pregnant 
women 
Item 15 
Revisions to Section 11, Safety monitoring and safety review: 
Item 16 
Added new section 12.3, Site monitoring 
Item 17 
Revisions to Appendix A, SICF: reconciled blood volumes collected from 
participants and revised language 
Item 18 
Revised Appendix B, Laboratory Procedures tables: blood volume for SARS-
CoV-2 Serology (main study and PBMC subset) and cellular assays (PBMC 
subset) 
Item 19 
Revised Appendix C, Schedule of Clinic Procedures 
Item 20 
Revised Appendix D, COVID-19 Symptom Visits, to reflect updates to Section 
9.6 and Laboratory procedures 
Item 21 
Revised Appendix E, Visit Windows: visit target day 
Item 22 
Updated, Section 13, Version history 
Item 23 
Cross-references, acronym list, and minor errors corrected 
Date: May 16, 2021 
Protocol version:1.0 
Protocol modification: Not applicable 
Original protocol 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 100 of 169 
14 
Document references (other than literature citations) 
Other documents referred to in this protocol and containing information relevant to 
the conduct of this study include: 
x Assessment of Understanding. Accessible through the CoVPN protocol-
specific website. 
x CDC COVID-19 Vaccination Program Provider Requirements and 
Support. Available at https://www.cdc.gov/vaccines/covid-19/vaccination-
provider-support.html 
x CoVPN 3008 (Ubuntu) Study Specific Procedures. Accessible through the 
CoVPN protocol-specific website. 
x Dangerous Goods Regulations (updated annually), International Air 
Transport Association. Available for purchase at 
https://www.iata.org/publications/dgr/Pages/index.aspx 
x International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) E6 (R2), Guideline for Good 
Clinical Practice: Section 4.8, Informed consent of trial subjects. Available 
at http://www.ich.org/page/efficacy-guidelines 
x Laboratory Center assay portfolio 
x Moderna COVID-19 Vaccine EUA Fact Sheet and Full PI for Vaccination 
Providers. Available at https://www.modernatx.com/covid19vaccine-
eua/.Participants’ Bill of Rights and Responsibilities. Accessible through 
the CoVPN protocol-specific website. 
x Moderna COVID-19 Vaccine Bivalent (Original and Omicron BA.4/.5) 
EUA Fact Sheet for Healthcare Providers Administering Vaccine. 
Available at https://www.fda.gov/media/161318/download. 
x NIH Policy on Reporting Race and Ethnicity Data: Subjects in Clinical 
Research. Available at https://grants.nih.gov/grants/guide/notice-
files/NOT-OD-01-053.html 
x Title 21, Code of Federal Regulations, Part 50. Available at 
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?C
FRPart=50 
x Title 45, Code of Federal Regulations, Part 46 (2018 requirements). 
Current requirements available at https://www.hhs.gov/ohrp/regulations-
and-policy/regulations/45-cfr-46/index.html 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 101 of 169 
x The Protection of Personal Information Act (POPIA, South Africa, 2013). 
Available at 
https://www.gov.za/sites/default/files/gcis_document/201409/3706726-
11act4of2013protectionofpersonalinforcorrect.pdf  
x Brighton Collaboration, COVID-19 AESI list. Available at 
https://brightoncollaboration.us/covid-19/. 
See Section 16 for literature cited in the background and statistics sections of this 
protocol. 
 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 102 of 169 
15 
Acronyms and abbreviations 
Ab 
 
antibody 
ACIP 
 
Advisory Committee on Immunization Practices 
AE 
 
adverse event 
AESI 
 
Adverse Events of Special Interest 
ART 
 
antiretroviral therapy 
BAMA 
 
binding antibody multiplex assay 
CAB 
 
Community Advisory Board 
CDC 
 
US Centers for Disease Control and Prevention 
CFR 
 
Code of Federal Regulations 
CI 
 
confidence interval 
COVID-19 
Coronavirus Disease 2019 
CoVPN 
 
COVID-19 Prevention Network 
CRF 
 
case report form 
CRS 
 
clinical research site 
DAIDS 
 
Division of AIDS (US NIH) 
DHHS 
 
US Department of Health and Human Services 
DSMB 
 
Data and Safety Monitoring Board 
EAC 
 
Endpoint Adjudication Committee 
EAE 
 
adverse event requiring expedited reporting  
EC 
 
Ethics Committee 
ELISA 
 
enzyme-linked immunosorbent assay 
EUA 
 
Emergency use authorization 
EUL 
 
Emergency use listing 
FAS 
 
Full analysis set 
FDA 
 
US Food and Drug Administration 
Fred Hutch 
Fred Hutchinson Cancer Center 
GCP 
 
Good Clinical Practice 
GMT 
 
geometric mean titer 
HCORE 
 
HHS Coordination Operations and Response Element 
HHS 
 
US Department of Health and Human Services 
HIV 
 
human immunodeficiency virus 
ICH 
 
International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use 
IQR 
 
Interquartile range 
IS 
 
Immunogenicity subset 
IM 
 
Intramuscular 
IRB 
 
Institutional Review Board 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 103 of 169 
JNJ 
 
Johnson and Johnson 
LC 
 
Laboratory Center 
LNP 
 
Lipid nanoparticle 
LOC 
 
Leadership and Operations Center 
mRNA 
 
Messenger ribonucleic acid 
nAb 
 
neutralizing antibody 
NAAT 
 
nucleic acid amplification testing 
NIAID 
 
National Institute of Allergy and Infectious Diseases (US NIH) 
NIH 
 
US National Institutes of Health 
OHRP 
 
US Office for Human Research Protections 
OG 
 
Oversight Group 
OWS 
 
Operation Warp Speed 
PCR 
 
polymerase chain reaction 
PI 
 
Principal Investigator 
PLWH 
 
People living with HIV 
PP 
 
per-protocol 
RE 
 
regulatory entity 
RT-PCR  
reverse transcription-polymerase chain reaction 
RVE 
 
relative vaccine efficacy 
SAE 
 
serious adverse event 
SAMRC  
South African Medical Research Council 
SAP 
 
Statistical Analysis Plan 
SCHARP  
Statistical Center for HIV/AIDS Research and Prevention 
SDMC 
 
statistical and data management center 
SS 
 
safety subset 
SSP 
 
Study specific procedures 
SOP 
 
Standard operating procedure 
UW-VL 
 
University of Washington Virology Laboratory 
VE 
 
Vaccine efficacy 
VL 
 
Viral load 
VOC 
 
Variants of Concern 
 
 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 104 of 169 
16 
Literature cited 
1. 
NBC C. Illinois Reports Highest Vaccine Numbers in Months Following Strong 
Demand for New COVID Booster Shots. 2022 September 16, 2022. 
2. 
Browning K. Covid Booster Rollout Begins in California With Little Fanfare. The 
NewYork Times. 2022 September 21, 2022. 
3. 
COVID data tracker [Internet]. US Department of Health and Human Services. 2003 
[cited February 13, 2023]. Available from: https://covid.cdc.gov/covid-data-
tracker/#vaccinations_vacc-%20people-booster-percent-pop5. 
4. 
Prevention CfDCa. Stay Up to Date with Your Vaccines 2022 [cited 2022 
01/16/2022]. Available from: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/stay-up-
to-date.html. 
5. 
FDA. January 31, 2022 Approval Letter - SPIKEVAX 2022 [cited 2022 01/31/2022]. 
Available from: https://www.fda.gov/media/155815/download. 
6. 
FDA. August 23, 2021 Approval Letter - Comirnaty 2021 [cited 2021 08/23/2021]. 
Available from: https://www.fda.gov/media/151710/download. 
7. 
SeyedAlinaghi S, Karimi A, Pashaei Z, Afzalian A, Mirzapour P, Ghorbanzadeh K, et 
al. Safety and Adverse Events Related to COVID-19 mRNA Vaccines; a Systematic Review. 
Arch Acad Emerg Med. 2022;10(1):e41. 
8. 
Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al. Efficacy and 
Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2021;384(5):403-16. 
9. 
Lopez Bernal J, Andrews N, Gower C, Gallagher E, Simmons R, Thelwall S, et al. 
Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant. New England 
Journal of Medicine. 2021;385(7):585-94. 
10. 
Hall VJ, Foulkes S, Saei A, Andrews N, Oguti B, Charlett A, et al. COVID-19 vaccine 
coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine 
against infection (SIREN): a prospective, multicentre, cohort study. 2021(1474-547X 
(Electronic)). 
11. 
Self WH, Tenforde MW, Rhoads JP, Gaglani M, Ginde AA, Douin DJ, et al. 
Comparative Effectiveness of Moderna, Pfizer-BioNTech, and Janssen (Johnson & Johnson) 
Vaccines in Preventing COVID-19 Hospitalizations Among Adults Without 
Immunocompromising Conditions — United States, March–August 2021. Morbidity and 
Mortality Weekly Report. 2021. 
12. 
El Sahly HM, Baden LR, Essink B, Doblecki-Lewis S, Martin JM, Anderson EJ, et al. 
Efficacy of the mRNA-1273 SARS-CoV-2 Vaccine at Completion of Blinded Phase. New 
England Journal of Medicine. 2021. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 105 of 169 
13. 
Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and 
Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. New England Journal of Medicine. 
2020;383(27):2603-15. 
14. 
Rosenblum HG, Gee J, Liu R, Marquez PL, Zhang B, Strid P, et al. Safety of mRNA 
vaccines administered during the initial 6 months of the US COVID-19 vaccination 
programme: an observational study of reports to the Vaccine Adverse Event Reporting 
System and v-safe. Lancet Infect Dis. 2022;22(6):802-12. 
15. 
Mellor MM, Bast AC, Jones NR, Roberts NW, Ordonez-Mena JM, Reith AJM, et al. 
Risk of adverse coronavirus disease 2019 outcomes for people living with HIV. AIDS. 
2021;35(4):F1-F10. 
16. 
Ssentongo P, Heilbrunn ES, Ssentongo AE, Advani S, Chinchilli VM, Nunez JJ, et al. 
Epidemiology and outcomes of COVID-19 in HIV-infected individuals: a systematic review 
and meta-analysis. Sci Rep. 2021;11(1):6283. 
17. 
CDC. COVID-19 Vaccines for People who are Moderately or Severely 
Immunocompromised 2022 [updated July 20, 2022. Available from: 
https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/immuno.html. 
18. 
Kamar N, Abravanel F, Marion O, Couat C, Izopet J, Del Bello A. Three Doses of an 
mRNA Covid-19 Vaccine in Solid-Organ Transplant Recipients. N Engl J Med. 
2021;385(7):661-2. 
19. 
Boyarsky BJ, Werbel WA, Avery RK, Tobian AAR, Massie AB, Segev DL, et al. 
Antibody Response to 2-Dose SARS-CoV-2 mRNA Vaccine Series in Solid Organ Transplant 
Recipients. JAMA. 2021;325(21):2204-6. 
20. 
Furer V, Eviatar T, Zisman D, Peleg H, Paran D, Levartovsky D, et al. 
Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in adult patients 
with autoimmune inflammatory rheumatic diseases and in the general population: a 
multicentre study. Ann Rheum Dis. 2021;80(10):1330-8. 
21. 
Roeker LE, Knorr DA, Thompson MC, Nivar M, Lebowitz S, Peters N, et al. COVID-
19 vaccine efficacy in patients with chronic lymphocytic leukemia. Leukemia. 
2021;35(9):2703-5. 
22. 
Levy I, Wieder-Finesod A, Litchevsky V, Biber A, Indenbaum V, Olmer L, et al. 
Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in people living 
with HIV-1. Clinical microbiology and infection : the official publication of the European 
Society of Clinical Microbiology and Infectious Diseases. 2021;27(12):1851-5. 
23. 
Lombardi A, Butta GM, Donnici L, Bozzi G, Oggioni M, Bono P, et al. Anti-spike 
antibodies and neutralising antibody activity in people living with HIV vaccinated with 
COVID-19 mRNA-1273 vaccine: a prospective single-centre cohort study. Lancet Reg Health 
Eur. 2022;13:100287. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 106 of 169 
24. 
Aledo MG, Canizares A, Vazquez-Rodriguez P, Castro A, Moldes L, Lopez S, et al. 
Safety and immunogenicity of SARS-CoV-2 mRNA-1273 and BNT162b2 vaccines in people 
living with HIV. AIDS. 2022. 
25. 
Frater J, Ewer KJ, Ogbe A, Pace M, Adele S, Adland E, et al. Safety and 
immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in HIV 
infection: a single-arm substudy of a phase 2/3 clinical trial. Lancet HIV. 2021;8(8):e474-e85. 
26. 
Heath PT, Galiza EP, Baxter DN, Boffito M, Browne D, Burns F, et al. Safety and 
Efficacy of NVX-CoV2373 Covid-19 Vaccine. New England Journal of Medicine. 
2021;385(13):1172-83. 
27. 
Cevik M, Grubaugh ND, Iwasaki A, Openshaw P. COVID-19 vaccines: Keeping pace 
with SARS-CoV-2 variants. Cell. 2021. 
28. 
Vaccines and Related Biological Products Advisory Committee Meeting. FDA 
Briefing Document, Janssen Ad26.COV2.S Vaccine 2021 [Available from: 
https://www.fda.gov/media/146217/download. 
29. 
Sadoff J, Gray G, Vandebosch A, Cardenas V, Shukarev G, Grinsztejn B, et al. Safety 
and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19. N Engl J Med. 
2021;384(23):2187-201. 
30. 
Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, Aley PK, et al. 
Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an 
interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. 
Lancet. 2021;397(10269):99-111. 
31. 
Tregoning JS, Flight KE, Higham SL, Wang Z, Pierce BF. Progress of the COVID-19 
vaccine effort: viruses, vaccines and variants versus efficacy, effectiveness and escape. Nature 
Reviews Immunology. 2021;21(10):626-36. 
32. 
Andrews N, Stowe J, Kirsebom F, Toffa S, Rickeard T, Gallagher E, et al. Covid-19 
Vaccine Effectiveness against the Omicron (B.1.1.529) Variant. N Engl J Med. 
2022;386(16):1532-46. 
33. 
Agency UHaS. COVID-19 vaccine surveillance report week 24 2022 [updated June 
16, 2022July 29, 2022]. Available from: 
https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/
file/1083443/Vaccine-surveillance-report-week-24.pdf. 
34. 
Tseng HF, Ackerson BK, Luo Y, Sy LS, Talarico CA, Tian Y, et al. Effectiveness of 
mRNA-1273 against SARS-CoV-2 Omicron and Delta variants. Nat Med. 2022;28(5):1063-
71. 
35. 
Collie S, Champion J, Moultrie H, Bekker LG, Gray G. Effectiveness of BNT162b2 
Vaccine against Omicron Variant in South Africa. N Engl J Med. 2022;386(5):494-6. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 107 of 169 
36. 
Chalkias S, Essink, B., Khetan, S., Nestorova, B. et al. Safety, Immunogenicity and 
Antibody Persistence of 
a Bivalent Beta-Containing Booster Vaccine. 2022. 
37. 
Mahase E. Covid-19: UK will roll out Moderna's omicron BA.1 vaccine as part of 
autumn booster programme. Bmj. 2022;378:o2038. 
38. 
Korber B FW, Gnanakaran S, Yoon H, Theiler J, et al. Spike mutation pipeline reveals 
the emergence of a more transmissible form of SARS CoV-2. 2020. 
39. 
Salleh MZ, Derrick JP, Deris ZZ. Structural Evaluation of the Spike Glycoprotein 
Variants on SARS-CoV-2 Transmission and Immune Evasion. Int J Mol Sci. 2021;22(14). 
40. 
Cai Y, Zhang J, Xiao T, Lavine CL, Rawson S, Peng H, et al. Structural basis for 
enhanced infectivity and immune evasion of SARS-CoV-2 variants. Science. 
2021;373(6555):642-8. 
41. 
Tarhini H, Recoing A, Bridier-Nahmias A, Rahi M, Lambert C, Martres P, et al. Long-
Term Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infectiousness 
Among Three Immunocompromised Patients: From Prolonged Viral Shedding to SARS-CoV-
2 Superinfection. J Infect Dis. 2021;223(9):1522-7. 
42. 
Aydillo T, Gonzalez-Reiche AS, Aslam S, van de Guchte A, Khan Z, Obla A, et al. 
Shedding of Viable SARS-CoV-2 after Immunosuppressive Therapy for Cancer. N Engl J 
Med. 2020;383(26):2586-8. 
43. 
Meiring S, Tempia S, Bhiman JN, Buys A, Kleynhans J, Makhasi M, et al. Prolonged 
shedding of SARS-CoV-2 at high viral loads amongst hospitalised immunocompromised 
persons living with HIV, South Africa. Clin Infect Dis. 2022. 
44. 
Leung WF, Chorlton S, Tyson J, Al-Rawahi GN, Jassem AN, Prystajecky N, et al. 
COVID-19 in an immunocompromised host: persistent shedding of viable SARS-CoV-2 and 
emergence of multiple mutations: a case report. Int J Infect Dis. 2022;114:178-82. 
45. 
Cele S, Karim F, Lustig G, San JE, Hermanus T, Tegally H, et al. SARS-CoV-2 
prolonged infection during advanced HIV disease evolves extensive immune escape. Cell 
Host Microbe. 2022;30(2):154-62 e5. 
46. 
Weigang S, Fuchs J, Zimmer G, Schnepf D, Kern L, Beer J, et al. Within-host 
evolution of SARS-CoV-2 in an immunosuppressed COVID-19 patient as a source of immune 
escape variants. Nat Commun. 2021;12(1):6405. 
47. 
UNAIDS. UNAIDS Global AIDS Update 2022 2022 [Available from: 
https://www.unaids.org/sites/default/files/media_asset/2022-global-aids-update_en.pdf. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 108 of 169 
48. 
Madhi SA, Kwatra G., Myers, J.E., Jassat, W., Dhar, N., Mukendi, C.K., Nana, A.J., 
Blumberg, L., Welch, R., Ngorima-Mabhena, N., and Mutevedzi, P.C. South African 
Population Immunity and Severe Covid-19 with Omicron Variant. 2022. 
49. 
Bingham J, Cable R, Coleman C, Glatt TN, Grebe E, Mhlanga L, et al. Estimates of 
prevalence of anti-SARS-CoV-2 antibodies among blood donors in South Africa in March 
2022. Res Sq. 2022. 
50. 
Crotty S. Hybrid immunity. COVID-19 vaccine responses provide insights 
into how the immune system perceives threats. Science. 2022;372(6549). 
51. 
Crotty S. Hybrid immunity. Science. 2021;372(6549):1392-3. 
52. 
Stamatatos L, Czartoski J, Wan Y-H, Homad LJ, Rubin V, Glantz H, et al. mRNA 
vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection. 
Science. 2021;372(6549):1413-8. 
53. 
Reynolds CJ, Pade C, Gibbons JM, Butler DK, Otter AD, Menacho K, et al. Prior 
SARS-CoV-2 infection rescues B and T cell responses to variants after first vaccine dose. 
Science. 2021;372(6549):1418-23. 
54. 
Saadat S, Rikhtegaran Tehrani Z, Logue J, Newman M, Frieman MB, Harris AD, et al. 
Binding and Neutralization Antibody Titers After a Single Vaccine Dose in Health Care 
Workers Previously Infected With SARS-CoV-2. JAMA. 2021;325(14):1467-9. 
55. 
Blain H, Tuaillon E, Gamon L, Pisoni A, Miot S, Picot M-C, et al. Spike Antibody 
Levels of Nursing Home Residents With or Without Prior COVID-19 3 Weeks After a Single 
BNT162b2 Vaccine Dose. JAMA. 2021;325(18):1898-9. 
56. 
Ebinger JE, Fert-Bober J, Printsev I, Wu M, Sun N, Prostko JC, et al. Antibody 
responses to the BNT162b2 mRNA vaccine in individuals previously infected with SARS-
CoV-2. Nature Medicine. 2021;27(6):981-4. 
57. 
Lin DY, Zeng D, Mehrotra DV, Corey L, Gilbert PB. Evaluating the Efficacy of 
COVID-19 Vaccines. Clin Infect Dis. 2020. 
58. 
Rid A, Saxena A, Baqui AH, Bhan A, Bines J, Bouesseau MC, et al. Placebo use in 
vaccine trials: recommendations of a WHO expert panel. Vaccine. 2014;32(37):4708-12. 
59. 
Wendler D, Ochoa J, Millum J, Grady C, Taylor HA. COVID-19 vaccine trial ethics 
once we have efficacious vaccines. Science. 2020;370(6522):1277-9. 
60. 
Rouchka EC, Chariker JH, Chung D. Variant analysis of 1,040 SARS-CoV-2 
genomes. PLoS One. 2020;15(11):e0241535. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 109 of 169 
61. 
Alam I, Radovanovic A, Incitti R, Kamau AA, Alarawi M, Azhar EI, et al. CovMT: an 
interactive SARS-CoV-2 mutation tracker, with a focus on critical variants. The Lancet 
Infectious Diseases. 2021;21(5):602. 
62. 
Hoffmann M, Arora P, Groß R, Seidel A, Hörnich BF, Hahn AS, et al. SARS-CoV-2 
variants B.1.351 and P.1 escape from neutralizing antibodies. (1097-4172 (Electronic)). 
63. 
McCallum M Fau - Bassi J, Bassi J Fau - Marco AD, Marco A Fau - Chen A, Chen A 
Fau - Walls AC, Walls Ac Fau - Iulio JD, Iulio Jd Fau - Tortorici MA, et al. SARS-CoV-2 
immune evasion by variant B.1.427/B.1.429. LID - 2021.03.31.437925 [pii] LID - 
10.1101/2021.03.31.437925 [doi]. 
64. 
Planas D, Veyer D, Baidaliuk AA-O, Staropoli I, Guivel-Benhassine F, Rajah MA-O, 
et al. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. (1476-
4687 (Electronic)). 
65. 
Wang P, Nair MA-O, Liu L, Iketani SA-O, Luo Y, Guo YA-OX, et al. Antibody 
resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. (1476-4687 (Electronic)). 
66. 
Wang P, Nair MS, Liu L, Iketani S, Luo Y, Guo Y, et al. Antibody resistance of 
SARS-CoV-2 variants B.1.351 and B.1.1.7. Nature. 2021;593(7857):130-5. 
67. 
Planas D, Veyer D, Baidaliuk A, Staropoli I, Guivel-Benhassine F, Rajah MM, et al. 
Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature. 
2021;596(7871):276-80. 
68. 
McCallum M, Bassi J, De Marco A, Chen A, Walls AC, Di Iulio J, et al. SARS-CoV-2 
immune evasion by the B.1.427/B.1.429 variant of concern. Science. 2021;373(6555):648-54. 
69. 
Hoffmann M, Arora P, Gross R, Seidel A, Hornich BF, Hahn AS, et al. SARS-CoV-2 
variants B.1.351 and P.1 escape from neutralizing antibodies. Cell. 2021;184(9):2384-93 e12. 
70. 
Wu K, Werner AP, Koch M, Choi A, Narayanan E, Stewart-Jones GBE, et al. Serum 
Neutralizing Activity Elicited by mRNA-1273 Vaccine. N Engl J Med. 2021;384(15):1468-
70. 
71. 
Boehm E, Kronig I, Neher RA, Eckerle I, Vetter P, Kaiser L. Novel SARS-CoV-2 
variants: the pandemics within the pandemic. Clin Microbiol Infect. 2021;27(8):1109-17. 
72. 
Korber B, Fischer WM, Gnanakaran S, Yoon H, Theiler J, Abfalterer W, et al. 
Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the 
COVID-19 Virus. Cell. 2020;182(4):812-27 e19. 
73. 
Tao K, Tzou PL, Nouhin J, Gupta RK, de Oliveira T, Kosakovsky Pond SL, et al. The 
biological and clinical significance of emerging SARS-CoV-2 variants. Nat Rev Genet. 
2021;22(12):757-73. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 110 of 169 
74. 
Davies NG, Abbott S, Barnard RC, Jarvis CI, Kucharski AJ, Munday JD, et al. 
Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England. Science. 
2021;372(6538). 
75. 
Davies NG, Jarvis CI, van Zandvoort K, Clifford S, Sun FY, Funk S, et al. Increased 
mortality in community-tested cases of SARS-CoV-2 lineage B.1.1.7. Nature. 
2021;593(7858):270-4. 
76. 
Graham MS, Sudre CH, May A, Antonelli M, Murray B, Varsavsky T, et al. Changes 
in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant 
B.1.1.7: an ecological study. Lancet Public Health. 2021;6(5):e335-e45. 
77. 
GSAID. Overview of Variants in Countries 2022 [updated August 25, 2022. Available 
from: https://covariants.org/per-country. 
78. 
Wilton T, Bujaki E, Klapsa D, Majumdar M, Zambon M, Fritzsche M, et al. Rapid 
Increase of SARS-CoV-2 Variant B.1.1.7 Detected in Sewage Samples from England between 
October 2020 and January 2021. mSystems. 2021;6(3):e0035321. 
79. 
Faria NR, Mellan TA, Whittaker C, Claro IM, Candido DDS, Mishra S, et al. 
Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil. Science. 
2021;372(6544):815-21. 
80. 
Moyo-Gwete T, Madzivhandila M, Makhado Z, Ayres F, Mhlanga D, Oosthuysen B, 
et al. Cross-Reactive Neutralizing Antibody Responses Elicited by SARS-CoV-2 501Y.V2 
(B.1.351). N Engl J Med. 2021;384(22):2161-3. 
81. 
Souza WM, Amorim MR, Sesti-Costa R, Coimbra LD, Brunetti NS, Toledo-Teixeira 
DA, et al. Neutralisation of SARS-CoV-2 lineage P.1 by antibodies elicited through natural 
SARS-CoV-2 infection or vaccination with an inactivated SARS-CoV-2 vaccine: an 
immunological study. Lancet Microbe. 2021;2(10):e527-e35. 
82. 
Liu Y, Liu J, Johnson BA, Xia H, Ku Z, Schindewolf C, et al. Delta spike P681R 
mutation enhances SARS-CoV-2 fitness over Alpha variant. Cell Rep. 2022;39(7):110829. 
83. 
Saito A, Irie T, Suzuki R, Maemura T, Nasser H, Uriu K, et al. Enhanced fusogenicity 
and pathogenicity of SARS-CoV-2 Delta P681R mutation. Nature. 2022;602(7896):300-6. 
84. 
Bolze A, Luo S, White S, Cirulli ET, Wyman D, Dei Rossi A, et al. SARS-CoV-2 
variant Delta rapidly displaced variant Alpha in the United States and led to higher viral loads. 
Cell Rep Med. 2022;3(3):100564. 
85. 
Dhar MS, Marwal R, Vs R, Ponnusamy K, Jolly B, Bhoyar RC, et al. Genomic 
characterization and epidemiology of an emerging SARS-CoV-2 variant in Delhi, India. 
Science. 2021;374(6570):995-9. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 111 of 169 
86. 
Sheikh A, McMenamin J, Taylor B, Robertson C. SARS-CoV-2 Delta VOC in 
Scotland: demographics, risk of hospital admission, and vaccine effectiveness. Lancet. 
2021;397(10293):2461-2. 
87. 
Callaway E. Heavily mutated Omicron variant puts scientists on alert. Nature. 
2021;600(7887):21. 
88. 
Martin DP, Lytras S, Lucaci AG, Maier W, Gruning B, Shank SD, et al. Selection 
analysis identifies unusual clustered mutational changes in Omicron lineage BA.1 that likely 
impact Spike function. bioRxiv. 2022. 
89. 
Harvey WT, Carabelli AM, Jackson B, Gupta RK, Thomson EC, Harrison EM, et al. 
SARS-CoV-2 variants, spike mutations and immune escape. Nat Rev Microbiol. 
2021;19(7):409-24. 
90. 
Cui Z, Liu P, Wang N, Wang L, Fan K, Zhu Q, et al. Structural and functional 
characterizations of infectivity and immune evasion of SARS-CoV-2 Omicron. Cell. 
2022;185(5):860-71.e13. 
91. 
Schmidt F, Muecksch F, Weisblum Y, Da Silva J, Bednarski E, Cho A, et al. Plasma 
Neutralization of the SARS-CoV-2 Omicron Variant. N Engl J Med. 2022;386(6):599-601. 
92. 
Dejnirattisai W, Huo J, Zhou D, Zahradnik J, Supasa P, Liu C, et al. SARS-CoV-2 
Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses. Cell. 
2022;185(3):467-84 e15. 
93. 
Mallapaty S. Where did Omicron come from? Three key theories. Nature. 
2022;602(7895):26-8. 
94. 
Today E. Egypt announces first Coronavirus infection. Egypt Today. 2020 February 
14, 2020. 
95. 
Reuters. Remote Lesotho becomes last country in Africa to record COVID-19 case. 
Reuters; 2020 May 13, 2020. 
96. 
Tegally H, Wilkinson E, Giovanetti M, Iranzadeh A, Fonseca V, Giandhari J, et al. 
Detection of a SARS-CoV-2 variant of concern in South Africa. Nature. 2021;592(7854):438-
43. 
97. 
Tessema SK, Nkengasong JN. Understanding COVID-19 in Africa. Nat Rev Immunol. 
2021;21(8):469-70. 
98. 
News U. Delta variant drives Africa COVID threat to ‘whole new level´: WHO warns; 
‘dominant’ in Europe by August. United Nations; 2021 July 01, 2021. 
99. 
Princewill N. Delta variant has spiked Covid-19 deaths in Africa by 80% in one 
month, WHO says. CNN2021. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 112 of 169 
100. 
Mamoon N, Rasskin, G. Covidvisualizer. 2021. 
101. 
Lab GCD. Our World in Data. 2021. 
102. 
VAERS. Vaccine Adverse Event Reporting System 2021 [Available from: 
https://vaers.hhs.gov/. 
103. 
Control ECfDPa. COVID-19 Vaccine Tracker 2021 [Available from: 
https://vaccinetracker.ecdc.europa.eu/public/extensions/COVID-19/vaccine-
tracker.html#distribution-tab. 
104. 
Mathieu E, Ritchie H, Ortiz-Ospina E, Roser M, Hasell J, Appel C, et al. A global 
database of COVID-19 vaccinations. Nat Hum Behav. 2021;5(7):947-53. 
105. 
Alliance GTV. Gavi and Moderna reach agreement for additional supply to COVAX 
Gavi2021 [updated December 10, 2021. Available from: https://www.gavi.org/news/media-
room/gavi-and-moderna-reach-agreement-additional-supply-covax. 
106. 
Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, Coler RN, et al. 
An mRNA Vaccine against SARS-CoV-2 - Preliminary Report. N Engl J Med. 2020. 
107. 
Anderson EJ, Rouphael NG, Widge AT, Jackson LA, Roberts PC, Makhene M, et al. 
Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults. N Engl J 
Med. 2020;383(25):2427-38. 
108. 
Vaccines and Related Biological Products Advisory Committee Meeting. FDA 
Briefing Document, Moderna COVID-19 Vaccine 2020 [Available from: 
https://www.fda.gov/media/144434/download. 
109. 
Vaccines and Related Biological Products Advisory Committee Meeting. Sponsor 
Briefing Document, Moderna COVID-19 Vaccine 2020 [Available from: 
https://www.fda.gov/media/144452/download. 
110. 
Products VaRB, Committee A. mRNA-1273 Sponsor Briefing Document Addendum: 
Moderna Tx; 2020 [updated 12/17/2020. Available from: 
https://www.fda.gov/media/144453/download. 
111. 
Ai J, Zhang H, Zhang Y, Lin K, Zhang Y, Wu J, et al. Omicron variant showed lower 
neutralizing sensitivity than other SARS-CoV-2 variants to immune sera elicited by vaccines 
after boost. Emerg Microbes Infect. 2022;11(1):337-43. 
112. 
Abu-Raddad LJ, Chemaitelly H, Ayoub HH, AlMukdad S, Yassine HM, Al-Khatib 
HA, et al. Effect of mRNA Vaccine Boosters against SARS-CoV-2 Omicron Infection in 
Qatar. N Engl J Med. 2022;386(19):1804-16. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 113 of 169 
113. 
Chalkias S, Harper C, Vrbicky K, Walsh SR, Essink B, Brosz A, et al. A Bivalent 
Omicron-containing Booster Vaccine Against Covid-19. medRxiv. 
2022:2022.06.24.22276703. 
114. 
CDC. Booster Doses of Moderna COVID-19 Vaccines in Adults, 
Adolescents & Children ACIP2022 [updated September 01, 2022. Available from: 
https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-09-01/06-COVID-
Miller-508.pdf. 
115. 
Miller JM, editor Booster doses of Moderna COVID-19 vaccines in adults, adolescents 
& children2022; Atlanta, GA. 
116. 
Statista. Number of COVID-19 vaccine doses administered in the United States as of 
August 24, 2022, by vaccine manufacturer 2022 [updated August 24, 2022. Available from: 
https://www.statista.com/statistics/1198516/covid-19-vaccinations-administered-us-by-
company/ Accessed 21 August 2022. 
117. 
Hause AM, Baggs J, Marquez P, Abara WE, Baumblatt JG, Thompson D, et al. Safety 
Monitoring of COVID-P51$9DFFLQH)LUVW%RRVWHU'RVHV$PRQJ3HUVRQV$JHG
Years with Presumed Immunocompromise Status - United States, January 12, 2022-March 28, 
2022. MMWR Morb Mortal Wkly Rep. 2022;71(28):899-903. 
118. 
González de Aledo M, Cañizares A, Vázquez-Rodríguez P, Castro Á, Moldes L, 
López S, et al. Safety and Immunogenicity of SARS-CoV-2 vaccines in people with HIV. 
Aids. 2022;36(5):691-5. 
119. 
Vergori A, Cozzi Lepri A, Cicalini S, Matusali G, Bordoni V, Lanini S, et al. 
Immunogenicity to COVID-19 mRNA vaccine third dose in people living with HIV. Nat 
Commun. 2022;13(1):4922. 
120. 
Klein NP, Lewis N, Goddard K, Fireman B, Zerbo O, Hanson KE, et al. Surveillance 
for Adverse Events After COVID-19 mRNA Vaccination. JAMA. 2021;326(14):1390-9. 
121. 
Niesen MJM, Pawlowski C, O'Horo JC, Challener DW, Silvert E, Donadio G, et al. 
Surveillance of Safety of 3 Doses of COVID-19 mRNA Vaccination Using Electronic Health 
Records. JAMA Netw Open. 2022;5(4):e227038. 
122. 
Hause AM, Baggs J, Marquez P, Myers TR, Su JR, Blanc PG, et al. Safety Monitoring 
of COVID-19 Vaccine Booster Doses Among Adults - United States, September 22, 2021-
February 6, 2022. MMWR Morb Mortal Wkly Rep. 2022;71(7):249-54. 
123. 
FDA. Coronavirus (COVID-19) Update: FDA Authorizes Moderna, Pfizer-BioNTech 
Bivalent COVID-19 Vaccines for Use as a Booster Dose FDA News Release2022 [updated 
August 31, 2022. Available from: https://www.fda.gov/news-events/press-
announcements/coronavirus-covid-19-update-fda-authorizes-moderna-pfizer-biontech-
bivalent-covid-19-vaccines-use. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 114 of 169 
124. 
Hause AM, Marquez P, Zhang B, Myers TR, Gee J, Su JR, et al. Safety Monitoring of 
Bivalent COVID-19 mRNA Vaccine Booster Doses Among Persons Aged >/=12 Years - 
United States, August 31-October 23, 2022. MMWR Morb Mortal Wkly Rep. 
2022;71(44):1401-6. 
125. 
Mueller BaL, S. Covid Vaccines Targeting Omicron Should Be Standard, Panel Says. 
The New York Times. 2023 January 26, 2023. 
126. 
Werbel WA, Boyarsky BJ, Ou MT, Massie AB, Tobian AAR, Garonzik-Wang JM, et 
al. Safety and Immunogenicity of a Third Dose of SARS-CoV-2 Vaccine in Solid Organ 
Transplant Recipients: A Case Series. Annals of Internal Medicine. 2021;174(9):1330-2. 
127. 
Westhoff TH, Seibert FS, Anft M, Blazquez-Navarro A, Skrzypczyk S, Zgoura P, et 
al. A third vaccine dose substantially improves humoral and cellular SARS-CoV-2 immunity 
in renal transplant recipients with primary humoral nonresponse. Kidney international. 
2021:S0085-2538(21)00850-4. 
128. 
A Trial of the Safety and Immunogenicity of the COVID-19 Vaccine (mRNA-1273) in 
Participants With Hematologic Malignancies and Various Regimens of Immunosuppression, 
and in Participants With Solid Tumors on PD1/PDL1 Inhibitor Therapy; NCT04847050 
[Internet]. 2021. Available from: https://clinicaltrials.gov/ct2/show/NCT04847050. 
129. 
A Study to Evaluate Safety and Immunogenicity of mRNA-1273 Vaccine to Prevent 
COVID-19 in Adult Organ Transplant Recipients and in Healthy Adult Participants; 
NCT04860297 [Internet]. 2021. Available from: 
https://clinicaltrials.gov/ct2/show/NCT04860297. 
130. 
Third Dose of Moderna COVID-19 Vaccine in Transplant Recipients;  NCT04885907 
[Internet]. 2021. Available from: https://www.clinicaltrials.gov/ct2/show/NCT04885907. 
131. 
Chapin-Bardales J, Myers T, Gee J, Shay DK, Marquez P, Baggs J, et al. 
Reactogenicity within 2 weeks after mRNA COVID-19 vaccines: Findings from the CDC v-
safe surveillance system. Vaccine. 2021;39(48):7066-73. 
132. 
Prevention CfDCa. Updates on myocarditis and pericarditis following Moderna 
COVID-19 vaccination 2022 [updated 04 February, 2022. Available from: 
https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-02-04/03-COVID-
Shimabukuro-508.pdf. 
133. 
Singer ME, Taub IB, Kaelber DC. Risk of Myocarditis from COVID-19 Infection in 
People Under Age 20: A Population-Based Analysis. medRxiv. 2021:2021.07.23.21260998. 
134. 
Choi A, Koch M, Wu K, Chu L, Ma L, Hill A, et al. Safety and immunogenicity of 
SARS-CoV-2 variant mRNA vaccine boosters in healthy adults: an interim analysis. Nat Med. 
2021;27(11):2025-31. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 115 of 169 
135. 
Chapin-Bardales J, Gee J, Myers T. Reactogenicity Following Receipt of mRNA-
Based COVID-19 Vaccines. JAMA. 2021. 
136. 
Hause AM BJ, Gee J, et al. Safety Monitoring of an Additional Dose of COVID-19 
Vaccine — United States, August 12–September 19, 2021.; 2021. 
137. 
Gray KJ, Bordt EA, Atyeo C, Deriso E, Akinwunmi B, Young N, et al. COVID-19 
vaccine response in pregnant and lactating women: a cohort study. Am J Obstet Gynecol. 
2021. 
138. 
Prevention CfDCa. v-safe COVID-19 Vaccine Pregnancy Registry 2021 [updated 
2021, March 15. Available from: https://www.cdc.gov/coronavirus/2019-
ncov/vaccines/safety/vsafepregnancyregistry.html. 
139. 
Shimabukuro TT, Kim SY, Myers TR, Moro PL, Oduyebo T, Panagiotakopoulos L, et 
al. Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons. N Engl J 
Med. 2021;384(24):2273-82. 
140. 
NIH. COVID-19 vaccination does not reduce chances of conception, study suggests 
2022 [updated January 20, 2022. Available from: https://www.nih.gov/news-events/news-
releases/covid-19-vaccination-does-not-reduce-chances-conception-study-suggests. 
141. 
Dandachi D, Geiger G, Montgomery MW, Karmen-Tuohy S, Golzy M, Antar AAR, et 
al. Characteristics, Comorbidities, and Outcomes in a Multicenter Registry of Patients with 
HIV and Coronavirus Disease-19. Clin Infect Dis. 2020. 
142. 
Geretti AM, Stockdale AJ, Kelly SH, Cevik M, Collins S, Waters L, et al. Outcomes 
of COVID-19 related hospitalization among people with HIV in the ISARIC WHO Clinical 
Characterization Protocol (UK): a prospective observational study. Clin Infect Dis. 2020. 
143. 
Hadi YB, Naqvi SFZ, Kupec JT, Sarwari AR. Characteristics and outcomes of 
COVID-19 in patients with HIV: a multicentre research network study. AIDS. 
2020;34(13):F3-F8. 
144. 
(CDC) CfDCaP. Symptoms of COVID-19 2022 [updated October 26, 2022. Available 
from: https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html. 
145. 
NIAID-RML. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines: National 
Institutes of Health (NIH); 2023 [updated January 30, 2023. Available from: 
https://www.covid19treatmentguidelines.nih.gov/. 
146. 
UNAIDS. Ethical considerations in biomedical HIV prevention trials. 2007 7/2007. 
147. 
The National Commission for the Protection of Human Subjects of Biomedical and 
Behavioral Research. The Belmont Report: Ethical Principles and Guidelines for the 
Protection of Human Subjects of Research. 1979 4/18/1979. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 116 of 169 
148. 
Council for International Organizations of Medical Sciences (CIOMS). International 
ethical guidelines for biomedical research involving human subjects. Bull Med Ethics. 
2002(182):17-23. 
149. 
Madhi SA, Baillie V, Cutland CL, Voysey M, Koen AL, Fairlie L, et al. Efficacy of 
the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant. N Engl J Med. 2021. 
150. 
Pulliam JRC, van Schalkwyk C, Govender N, von Gottberg A, Cohen C, Groome MJ, 
et al. Increased risk of SARS-CoV-2 reinfection associated with emergence of Omicron in 
South Africa. Science. 2022;376(6593):eabn4947. 
151. 
Nunes MC, Mbotwe-Sibanda S, Baillie VL, Kwatra G, Aguas R, Madhi SA, et al. 
SARS-CoV-2 Omicron Symptomatic Infections in Previously Infected or Vaccinated South 
African Healthcare Workers. Vaccines (Basel). 2022;10(3). 
152. 
Mallapaty S. COVID reinfections surge during Omicron onslaught. Nature. 2022. 
153. 
Altarawneh HN, Chemaitelly H, Hasan MR, Ayoub HH, Qassim S, AlMukdad S, et al. 
Protection against the Omicron Variant from Previous SARS-CoV-2 Infection. N Engl J Med. 
2022;386(13):1288-90. 
154. 
Datta S, Halloran ME, Longini IM, Jr. Efficiency of estimating vaccine efficacy for 
susceptibility and infectiousness: randomization by individual versus household. Biometrics. 
1999;55(3):792-8. 
155. 
Mehrotra DV, Heyse JF. Use of the false discovery rate for evaluating clinical safety 
data. Stat Methods Med Res. 2004;13(3):227-38. 
 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 117 of 169 
Appendix A 
Sample informed consent form 
Title: Multi-Center, Randomized, Efficacy Study of COVID-19 mRNA Vaccine in 
Regions with SARS-CoV-2 Variants of Concern 
Study number: CoVPN 3008 
Site: [Insert site name] 
 
Thank you for your interest in our research study. It is called CoVPN 3008 
(Ubuntu) or the Ubuntu Study. This informed consent form will tell you more 
about the study. Please read it carefully as you decide if you want to join. If you 
have questions, please ask us. At the end, we will ask you to answer a few 
questions to make sure we have explained everything clearly. 
If you decide to join this study, we will ask you to sign this form. We will offer 
you a copy of this form to keep. 
CoVPN 3008 (Ubuntu) is a research study testing the Moderna COVID-19 
vaccine. We already know that this vaccine reduces the symptoms and severity of 
COVID-19. It is widely used in the United States and many other countries. We 
want to know how many doses of vaccine are needed for protection against 
COVID-19 for adults living with HIV and adults with existing health conditions 
that may put them at risk for severe COVID-19. We also want to know if people 
who have already had COVID-19 (and likely have some immunity) need as many 
vaccine doses as other people to obtain strong protection from COVID-19. 
Research is not the same as medical care. The purpose of a research study is to 
answer scientific questions. We hope that what we learn will help people in the 
future. If you have access to a COVID-19 vaccine you should consider the risks 
and benefits of getting a COVID-19 vaccine as part of your government’s vaccine 
rollout or by joining a clinical trial.  
Key information 
x Joining this research study is voluntary. It is your choice. There may be other 
options for you, like joining your government national rollout. 
x Our scientific questions are: How many doses of vaccine are needed for 
protection against COVID-19 for adults living with HIV and adults with 
existing health conditions that may put them at risk of severe COVID-19? And 
do people who previously had COVID-19 need as many vaccine doses as other 
people to obtain good protection against COVID-19? 
x The vaccine we are using in this study has been approved by the United States 
Food and Drug Administration (FDA) and has an Emergency Use Listing 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 118 of 169 
(EUL) by the World Health Organization. More than 206 million doses of 
vaccine has been given to people in the United States and has been shown to 
work against the original strain of SARS-CoV-2. We are testing this vaccine in 
our countries to see how well it works against the variants that circulate in our 
region. These variants were not present in the US when the vaccine was first 
tested.  
x If you join, your participation in this study will last for about 18 months.  
x If you get a positive COVID-19 test result while in this study, we will monitor 
your health and help you get the care you need. You will need to self-isolate at 
home away from others. You may also need additional medical care including 
hospitalization. The clinic staff may come to your home to meet with you and 
collect the samples for this study as needed. 
x If you join, we will ask you to have injections, blood draws, and swabs of your 
nose. 
x Here are the risks of taking part: 
o  The most common risk of vaccination are symptoms such as muscle    
aches, fevers or headaches after getting the study vaccine.
o  There are other risks. We will tell you more about them later in this 
consent form.
x We know that some vaccines do not work as well in people living with HIV. 
We want to know if this vaccine will work well in people living with HIV. 
x We know that sometimes people who have been infected with a virus are 
protected against that virus if they get it again. We want to know if people with 
past COVID-19 infection need as many vaccine doses as other people to have 
good protection against COVID-19. 
x While you are in this study, you should still follow local COVID-19 prevention 
guidelines. 
About the study 
The COVID-19 Prevention Network (CoVPN) is doing a study to test a vaccine 
against SARS-CoV-2, the virus that causes COVID-19. This is the virus that 
causes the disease called COVID-19. Up to 15,600 people will take part in this 
study. We will recruit people from many clinics in Eastern and Southern Africa. 
The researcher in charge of this study at this clinic is [Insert name of site PI]. The 
US Government is paying for this study through funding from the National 
Institute of Allergy and Infectious Diseases (NIAID). 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 119 of 169 
The vaccine we will use in this study is the Moderna mRNA-1273 vaccine. From 
here on we will call it the study vaccine. 
The study vaccine used in this trial has been given to over 15,000 people in other 
research studies and over 206 million doses have been used to vaccinate people in 
the United States. More than 141 million doses have been given to people in 
Europe under Conditional Marketing Authorization (CMA). The study vaccine is 
on the Emergency Use Listing by the World Health Organization which 
recommends its use to prevent COVID-19 disease. More than 906 million doses of 
mRNA-1273 vaccine made by Pfizer/BioNTech, which is very similar to our study 
vaccine, has been given to more than 400 million people in the US and Europe. 
The person giving you the study vaccine can answer any questions you might have 
about it. 
We already know the study vaccine can prevent serious COVID-19 disease in 
people from the Unites States. It was found to be over 90% effective in preventing 
symptomatic Covid-19 illness caused by the initial strains of the virus in the US 
and Europe. We want to test the study vaccine in people who may have a higher 
chance of getting severe COVID-19 illness. For that reason, we are inviting people 
who are 18 years or older to join the study, and have HIV, or at least 1 existing 
health issue that puts them at risk for severe COVID-19 (for example diabetes, 
obesity, heart or kidney problems, cancer, etc.). 
The study vaccine was developed by ModernaTX, Inc. Typical vaccines for 
viruses are made from a weakened or killed virus, but the study vaccine is not 
made from the SARS-CoV-2 virus. The study vaccine includes a short segment of 
messenger ribonucleic acid (mRNA). The mRNA is a genetic code that tells cells 
how to make a protein. This mRNA is made in a laboratory. When injected into the 
body, the mRNA vaccine causes some cells to make that viral protein, which can 
trigger the immune system. Your immune system protects you from disease. If a 
person is later infected, their immune system remembers the protein from the 
vaccine which may help it to fight the virus. It is impossible for the vaccine to give 
you SARS-CoV-2 or COVID-19 infection.  
People living with HIV have higher risk of severe COVID-19. Data from earlier 
studies have shown that mRNA vaccines appear to be safe for people living with 
HIV. Current advice in the US is that people living with HIV should get the 
vaccine. We do not know if people living with HIV need more vaccine doses that 
other people to have good protection from COVID-19. And we do not know if 
people who previously had COVID-19 need as many vaccine doses as other people 
to obtain good protection from COVID-19.  
The safety of the mRNA vaccines in pregnant women and their babies is being 
looked at by health authorities in many countries. No safety problems have been 
reported so far in many thousands of pregnant women, and health authorities 
recommend vaccination of pregnant women to prevent COVID-19. Breastfeeding 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 120 of 169 
after vaccination has also been shown to be safe and may protect babies from 
COVID-19. 
Risks of the Moderna COVID-19 Vaccine: 
To date, millions of people have already received the study vaccine. In clinical 
trials, most people who got the study vaccine had some reaction after their 
injections, especially after the second injection. In most people the reaction to the 
study vaccine didn’t affect their daily lives and it went away after 2 or 3 days. 
Most of these people said they had pain in the arm where they got the injection. 
These people also felt tired, had headaches, muscle and joint pain, and chills. A 
much smaller number of these people said they had redness or swelling where the 
needle went in their arm. Some people also said they had nausea, fever, and 
swelling or pain in their arm pit. 
A small number of people who got the study vaccine had myocarditis 
(inflammation of the heart muscle) and pericarditis (inflammation of the lining 
outside the heart). The chance of having this occur is very low. It was seen more 
often in people less than 20 years of age. Symptoms began within a few days after 
getting the second dose. It did not last long and most people got better. You should 
tell us right away if you have chest pain, shortness of breath, or the feeling of a 
fast-beating, fluttering, or pounding heart, as you may need medical care. 
The side effects of the study vaccine seen so far are the same as what have been 
seen with most vaccines. Generally, vaccines can cause fever, chills, rash, aches 
and pains, nausea, headache, dizziness, and feeling tired. Vaccines can also cause 
pain, redness, swelling, or itching where you got the injection. Most people can 
still do their planned activities after getting a vaccine. Rarely, people have side 
effects that limit their normal activities or make them go to the doctor. 
Rarely, a vaccine can cause you to have an allergic reaction. You might have a 
rash, hives, or trouble breathing. Allergic reactions can be life-threatening. Tell us 
if you have ever had a bad reaction to any injection or vaccine. 
There may be other risks that we don’t yet know about, even serious ones. We will 
tell you if we learn about any new risks. 
Joining the study 
1. You will receive either 2 or 3 doses of the study vaccine. 
Everyone who joins the study will get the study vaccine. There are 4 groups in this 
study. The groups differ in the number of doses of study vaccine you will get. The 
groups are organized by whether or not people are living with HIV and whether or 
not people have evidence of prior SARS-CoV-2 infection in their blood. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 121 of 169 
Group 1 includes people living with HIV and Group 3 includes people who are not 
living with HIV. All people in Groups 1 and 3 will have no evidence of prior 
SARS-CoV-2 infection in their blood. If you are in these groups, you will get 3 
doses of the study vaccine.  
Group 2 includes people living with HIV and Group 4 includes people who are not 
living with HIV. All people in Groups 2 and 4 will have evidence of prior SARS-
CoV-2 infection in their blood. If you are in these groups, you will get 2 doses of 
the study vaccine.  
2. It is completely up to you whether or not to join this study. 
We know you may have access to other COVID-19 vaccines outside of this study 
(for example through a national rollout). If you do, we urge you to carefully think 
about whether joining this study is right for you. Take your time in deciding. If it 
helps, talk to people you trust, such as your doctor, friends or family. If you decide 
not to join this study, or if you leave it after you have joined, it will not change 
your healthcare. If you do join, you do not give up your legal rights.  
You cannot be in this study while you are in another study where you get a study 
product. Site: Modify or delete the following sentences as appropriate. We check 
to make sure that you are not in more than 1 study by taking your fingerprint on an 
electronic system. This information is only accessed by a few members of the 
clinic staff using a secure password. We might also check the government COVID-
19 vaccine rollout system to see if you have been vaccinated before. We may also 
be able to update the system with the vaccines you get in this study.  
If you choose not to join this study, you may be able to join another study. 
3. If you want to join this study, we will screen you to see if you are eligible. 
We will give you a physical exam. We will give you a coronavirus and an HIV 
test. And we will ask you about your health history, including any medications you 
are taking.  
If we find that you have HIV, we will refer you for treatment and care. We will 
check the level of HIV in your blood and the number of immune cells you have. 
If you are a person who could become pregnant, we will do a urine pregnancy test. 
If we find that you are pregnant or you become pregnant during the study, we will 
do an ultrasound to measure the age and status of your developing pregnancy. We 
will also contact you after your due date to ask some questions about outcome of 
your pregnancy, delivery, and the health of your baby.  
If you are pregnant, we will help you get advice on how to avoid getting HIV. If 
we find that you have HIV, we will refer you for treatment and care. We will check 
the level of HIV in your blood and the number of immune cells you have. We will 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 122 of 169 
also ask if you now have or ever had syphilis and any treatment for it. This is for 
your safety and could also affect the timing of your injections. 
Being in the study 
If you want to join and you are eligible, here is what will happen: 
4. You will come to the clinic for scheduled visits about 7 or 8 times over 18 
months depending on which group you are in. 
Site: Insert number of visits and range of visit lengths. (There is site-specific 
variation in screening protocols and in the number of possible follow-up visits 
between protocol-mandated visits.) 
Visits can be done in-person or remotely depending on the type of procedures that 
need to be done. Visits where you get injections must be done in person. Remote 
visits will be done whenever possible to reduce potential SARS-CoV-2 exposure. 
Visits can last from [#] to [#] hours. 
You may have to come for more visits if you have a lab or health issue. 
We will also ask you for the name of someone who can tell us how you are doing 
if we can’t reach you or if you are unable to talk. We may contact you after the 
main study ends (for example, to tell you about the study results). 
5. We will give you [Site: Insert compensation]for each study visit you complete. 
This amount is to cover the costs of [Site: Insert text] 
Site: Insert any covered costs to participants. 
You do not have to pay anything to be in this study. 
6. We will give you the study products on a schedule. 
You will be in 1 of 4 groups. 
All people in Group 1 and Group 3 will get 3 doses of the study vaccine. You will 
receive 1 injection into your upper arm at 3 separate visits during the study. The 
injections are given with a needle and syringe. 
All people in Group 2 and Group 4 will get 2 doses of the study vaccine. You will 
get 1 injection into your upper arm at 2 separate visits during the study. The 
injections are given with a needle and syringe.  

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 123 of 169 
At the visits where we give you the study products, we will need to make sure you 
do not have a bad reaction to it. For this reason, we will ask you to stay in the 
clinic for at least 15 minutes after your injection. You may have to wait longer if 
the rules in your local area require it. 
Site: If your site has been selected for the reactogenicity assessment then include 
this paragraph below. 
Then for that night and up to 7 more days, you will need to keep track of how you 
are feeling and if you have any symptoms. To help you do this, we can give you 
tools and show you how to use them. Contact the clinic staff if you have any issues 
or concerns after receiving an injection. If you have a problem, we will continue to 
check on you until it goes away. 
7. In addition to giving you the study products, we will do the procedures 
described and shown in the tables below: 
a. Do physical exams  
b. Do swabs of your nose 
c. Ask questions about your health, including medications you may be taking 
d. We will ask you to keep track of any symptoms of COVID-19 or any other 
problems you might develop. We will give you a thermometer and ask you to take 
your temperature if you have symptoms. We will ask you to record any symptoms 
you are having on a paper form. We will contact you about every 2 weeks to ask 
about this. We will ask you to contact us if you develop symptoms or are 
hospitalized. 
e. Take blood samples.  
When we take blood, the amount will depend on the lab tests we need to do. It will 
be some amount between 19 ½ mL and 114.5 mL (about 4 teaspoons to 7 ½ 
tablespoons). If you have HIV, some of this blood will be used to check the level 
of HIV and the number of immune cells you have. This is for your safety and 
could also affect the timing of your injections if you are started on HIV 
medications or have recently changed your HIV medications 
We will be looking for side effects. We will also be looking for any symptoms of 
COVID-19. If any of the results are important to your health, we will tell you. 
 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 124 of 169 
Procedures for Group 1 and Group 3 
Procedures  
Screenin
g visit 
First 
injectio
n visit 
1 
month  
2 
months 
6 
months  
7 
months  12 months 
18 
months 
Injection 
 
¥ 
¥ 
 
¥ 
 
 
 
Physical exam 
¥ 
 
 
 
 
 
 
¥ 
Medical 
history 
¥ 
¥ 
 
 
 
 
 
 
Interview 
/Questionnaire 
¥ 
¥ 
¥ 
¥ 
¥ 
¥ 
¥ 
¥ 
Pregnancy 
test* 
¥ 
 
 
 
 
 
 
 
Ultrasound* 
¥ 
 
 
 
 
 
 
 
HIV test 
¥ 
 
 
 
 
 
 
 
Blood drawn 
¥ 
¥ 
 
¥ 
¥ 
¥ 
¥ 
¥ 
Nasal swabs 
 
¥ 
¥ 
 
¥ 
 
 
 
* May be performed for pregnant participants at screening and as needed during the study. 
Procedures for Group 2 and Group 4 
Procedures  
Screening 
visit 
First 
injection 
visit 
1 month  
6 months  
7 months  
12 
months 
18 
months 
Injection 
 
¥ 
 
¥ 
 
 
 
Physical exam 
¥ 
 
 
 
 
 
¥ 
Medical history 
¥ 
¥ 
 
 
 
 
 
Interview/ 
Questionnaire 
¥ 
¥ 
¥ 
¥ 
¥ 
¥ 
¥ 
Pregnancy test* 
¥ 
 
 
 
 
 
 
Ultrasound* 
¥ 
 
 
 
 
 
 
HIV test 
¥ 
 
 
 
 
 
 
Blood drawn 
¥ 
¥ 
¥ 
¥ 
¥ 
¥ 
¥ 
Nasal swabs 
 
¥ 
 
¥ 
 
 
 
* May be performed for pregnant participants at screening and as needed during the study. 
8. The CoVPN will test your samples to see how your body, including your 
immune system, responds to the study products. 
We will send your samples to labs approved by the CoVPN. Your samples will not 
be labeled with your name or other identifying information. Researchers may also 
do genetic testing related to this study on your samples. Your genes are passed to 
you from your birth parents. Differences in people’s genes can help explain why 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 125 of 169 
some people get a disease while others do not. The genetic testing will only 
involve some of your genes, not all of your genes (your genome). The researchers 
will study only the genes related to the immune system and coronavirus, and genes 
that may affect how people get coronavirus. 
If you get SARS-CoV-2, the researchers may look at all of the virus’ genes that are 
in your samples. The researchers will use this information to learn more about 
SARS-CoV-2 and how the virus is impacted by the study vaccine. 
In some cases, researchers may take cells from your samples and grow more of 
them over time, so that they can continue to contribute to this study.  
The tests the researchers do on your samples are for research purposes, not to 
check your health. The labs will not give the results to you or this clinic because 
their tests are not approved for use in making health care decisions. These labs are 
only approved to do research tests. 
When your samples are no longer needed for this study, the CoVPN will continue 
to store them. 
9. We will do our best to protect your private information. 
Your study records and samples will be kept in a secure location. Clinic staff will 
label all of your samples and most of your records with a code number, not your 
name or other personal information. We will not share your name with anyone 
who does not need to know it. 
Your records may also be reviewed by groups who watch over this study. These 
groups include: 
x The Sponsor and its study monitors  
x The COVID-19 Prevention Network (CoVPN) and people who work for them, 
x Some government agencies: 
a) The US National Institutes of Health 
b) The US Food and Drug Administration 
c) The US Office for Human Research Protections 
d) [Insert name of local and/or national regulatory authority as appropriate] 
e) Any regulatory agency that reviews research studies 
x Some committees that make sure we protect your rights and keep you safe: 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 126 of 169 
a. The Data and Safety Monitoring Board 
b. Sites must include: [Insert name of local IRB/EC]  
All reviewers will take steps to keep your records private. 
We cannot guarantee absolute privacy. If you are found to have a medical 
condition that we are required to report by law, then some of your information may 
be shared. At this clinic, we have to report the following information:  
Site: Include any public health or legal reporting requirements. Bulleted examples 
should include all appropriate cases (reportable communicable disease, risk of 
harm to self or others, etc.)  
x SARS-CoV-2 
x Pneumonia 
x [Item 3] 
x [Item 4] 
We will not share your name or information that can identify you with the CoVPN. 
The CoVPN may share information from this study with other researchers. 
Researchers may publish the results of this study.  
Site: The text below may not be deleted or changed per FDA requirement.  
A description of this clinical trial will be available on 
http://www.ClinicalTrials.gov, as required by US. Law. This website will not 
include information that can identify you. At most, the website will include a 
summary of the results. You can search this website at any time. 
The study will also be listed in the Pan-African Clinical Trials registry.  
10. There are several reasons why we may stop your injections.  
We may stop your injections for a time if you get COVID-19. You can still take 
part in the other parts of the study. We will discuss your study options with you.  
We will stop your injections if you enroll in a different study where you get 
another study product. 
11. We may take you out of the study at any time.  
We may take you out of the study if: 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 127 of 169 
x you do not follow instructions, 
x we think that staying in the study might harm you, 
x the study is stopped for any reason. 
12. If you get COVID-19, we will monitor your health and help you get the care 
you need.  
If you have COVID-19 like symptoms or find out that you have COVID-19, you 
will be directed to contact the clinic, or we may visit you in your home. We will 
ask you to self-isolate per local guidelines. 
We will not give you any study injections until you no longer have symptoms of 
COVID-19. We will continue your study injections when your symptoms go away, 
and the study staff thinks you are well enough.  
Over a 4-week period, we will also: 
x Contact you every other day to find out how you are feeling 
x Ask you to keep track of your COVID-19 symptoms daily or until you test 
negative for COVID-19 
x Do physical exams 
x Ask questions about your health 
x Ask you to measure the oxygen level in your blood daily. We will give you a 
small device to do this (pulse oximeter). The clinic will teach you about the 
device and when to contact the clinic if you develop low oxygen levels. If at 
any time you need additional care, we will help you get the care you need, 
including if you need to be hospitalized.  
x Do swabs of your nose 
x Take blood  
x Do an HIV test 
x At the end of the 4-week period, if you had a test that confirmed you had 
COVID-19, we will ask you to come to the clinic for a visit 
When we take blood, the amount will depend on the lab tests we need to do. It will 
be some amount between 5 to 114.5 mL (about 1 teaspoon to 7 ½ tablespoons) 
each time. We will be looking for how your body reacts to infection and the study 
product. If any of the results are important to your health, we will tell you.  

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 128 of 169 
After the 4-week period, if you still have a test that confirms COVID-19, we will 
do swabs of your nose about every 2 weeks until you test negative for COVID-19. 
Some people with COVID-19 develop severe symptoms and must be hospitalized. 
This can include being put on a ventilator to help you breathe. In the event you are 
not able to communicate and give consent for the study procedures to continue, we 
will pause your participation. It is unlikely that you will be hospitalized, but to 
prepare for this, we will ask you to sign and date a medical release of information 
so we can get records from your doctor or view your hospital records. When you 
are released from the hospital, please let us know. We will ask if you would like to 
continue participating in the study. We will only resume the study procedures if 
you give us permission to do so. 
13. If you plan to get another available COVID-19 vaccine outside the study, we 
will stop your in-study vaccinations but you may continue in the study. 
If you have plans to get another available COVID-19 vaccine outside the study, 
please let us know. We will ask you to tell us what vaccine you plan to get and 
when you will get it. You may continue to participate in follow-up visits. Your 
continued participation is important to help us meet our study goals. 
Other Risks 
14. There are other risks to being in this study.  
This section describes the other risks and restrictions we know about. There may 
also be unknown risks, even serious ones. We will tell you if we learn anything 
new that may affect your willingness to stay in the study. 
Risks of routine medical procedures: 
In this study, we will do some routine medical procedures. These are taking blood 
and giving injections. These procedures can cause bruising, pain, fainting, 
soreness, redness, swelling, itching, a sore, bleeding, and (rarely) muscle damage 
or infection where you got the injection. Taking blood can cause a low blood cell 
count (anemia), making you feel tired. 
Risks of swabs of your nose: 
You may feel some discomfort from the swabs we put into your nose. Rarely, 
swabs can cause nosebleeds. 
Risks to your personal information: 
We will take several steps to protect your personal information. Although the risk 
is very low, it is possible that your personal information could be given to someone 
who should not have it. If that happened, you could have stress or anxiety.  

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 129 of 169 
Risks of genetic testing: 
It is unlikely, but the genetic tests done on your samples could show you may be at 
risk for certain diseases. If others found out, it could lead to discrimination or other 
problems.  
Risk of anxiety/emotional stress: 
You may feel anxiety or emotional stress if you experience any of the risks 
described here. You may feel worried if tests show that you have SARS-CoV-2. 
Some of the questions we will ask you may make you feel uncomfortable.  
Unknown risks: 
The study vaccine has been shown to prevent adults from getting COVID-19 for at 
least 6 months after their injection, but we do not know if it will protect them for 
any longer. If you get COVID-19, we know that the study vaccine did not make 
the disease worse. It is also unknown if the study vaccine will prevent you from 
giving the virus to someone else if you become infected.  
We do not know if getting this study vaccine will affect how you respond to any 
future SARS-CoV-2 vaccines. 
Benefits 
15. This study may not benefit you. 
Although this study vaccine was shown to protect people from COVID-19 disease 
in other countries, we do not know how much the study vaccine will benefit you. 
However, being in the study might still help you in some ways. The lab tests and 
physical exams that you get while in this study might detect health problems you 
don’t yet know about. 
This study may help in the search for a vaccine to prevent SARS-CoV-2 that 
works for all people around the world.  
If you decide not to join this study, you may be able to get another COVID-19 
vaccine in your community. You should continue to follow local guidelines for 
SARS-CoV-2 infection. 
Your rights and responsibilities 
16. If you join the study, you have rights and responsibilities. 
You have many rights that we will respect. You also have responsibilities. We list 
these in the Bill of Rights and Responsibilities for Research. We will give you a 
copy of it. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 130 of 169 
Leaving the study 
17. Tell us if you decide to leave the study. 
You are free to leave the study at any time and for any reason. If you want to 
leave, you will need to tell us. Your care at this clinic and your legal rights will not 
be affected. We may ask you to come back to the clinic one last time, and we may 
ask to take some more samples. We believe this is important to protecting your 
health, but it is up to you whether you do this. 
Injuries 
Sites: Please do not make any changes to this section (other than those specified). 
If your institution requires changes, then you must consult CoVPN Regulatory 
Affairs (at CoVPN.core.reg@fredhutch.org). 
18. If you get sick or injured during the study, contact us immediately. 
Your health is important to us. We will tell you about the care that we can give 
here. For the care that we cannot provide, we will explain how we will help you 
get care elsewhere. 
In this study, our clinic has insurance to cover your medical treatment in the case 
of a study-related injury. The Medical Research Council of South Africa have not 
provided for any payment if you are harmed as a result of taking part in this study. 
(Sites outside of South Africa: remove the rest of the language in this paragraph. 
Sites in South Africa only: keep the rest of the language in this paragraph.) We 
will follow the Association of the British Pharmaceutical Industry guidelines for 
payment of study-related injury. We can give you a copy of these guidelines.  
Some injuries are not physical. For example, you might be harmed emotionally by 
being in this study. Or you might lose wages because you cannot go to work. 
However, there are no funds to pay for these kinds of injuries, even if they are 
study related.  
You always have the right to use the court system if you are not satisfied. 
Site: Delete next section if using separate consent for use of samples and 
information in other studies 
19. When samples are no longer needed for this study, the CoVPN wants to use 
them in other studies and share them with other researchers.  
The CoVPN calls these samples “extra samples”. The CoVPN will only allow your 
extra samples to be used in other studies if you agree to this. You will mark your 
decision at the end of this form.  

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 131 of 169 
Do I have to agree? No. You are free to say yes or no, or to change your mind 
after you sign this form. At your request, the CoVPN will destroy all extra samples 
that it has. Your decision will not affect your being in this study. 
Where are the samples stored? Extra samples are stored in a secure central place 
called a repository. Your samples will be stored in the CoVPN repository in South 
Africa.  
How long will the samples be stored? There is no limit on how long your extra 
samples will be stored. [Site: Revise the previous sentence to insert limits if your 
regulatory authority imposes them.] 
Will I be paid for the use of my samples? No. Researchers may make scientific 
discoveries or products using your samples. If this happens, there is no plan to 
share any money with you.  
Will I benefit from allowing my samples to be used in other studies? Probably not. 
Results from these other studies are not given to you, this clinic, or your doctor. 
They may help other people in the future.  
Will the CoVPN sell my samples and information? No, but the CoVPN may share 
your samples with other researchers. Once the CoVPN shares your samples and 
information, it may not be able to get them back. 
How do other researchers get my samples and information? When a researcher 
wants to use your samples and information, their research plan must be approved 
by the CoVPN. Also, the researcher’s institutional review board (IRB) or ethics 
committee (EC) will review their plan. [Site: If review by your institution’s 
IRB/EC/RE is also required, insert a sentence stating this.] IRBs/ECs protect the 
rights and well-being of people in research. If the research plan is approved, the 
CoVPN will send your samples to the researcher’s location. 
What information is shared with researchers? The samples and information will be 
labeled with a code number which will not be removed. The key to the code will 
stay at this clinic. However, some information that the CoVPN shares may be 
personal, such as your race, ethnicity, sex, and health information from the study.  
What kind of studies might be done with my extra samples and information? The 
studies will be related to vaccines, the immune system, coronavirus, HIV, and 
other diseases. 
In some cases, researchers may take cells from your samples and grow more of 
them over time, so that they can continue to do research with them. 
Researchers may also do genetic testing on your samples. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 132 of 169 
If you agree, researchers may compare all of your genes (your genome) to the 
genomes of many other people. Researchers look for common patterns of genes to 
help them understand diseases. The researchers may put the information into a 
protected database so that other researchers can access it. Your name and other 
personal information will not be included.  
Usually, no one could connect your genome to you as a person. There are rules 
against this. It’s also really difficult to do. But there is a risk that someone could 
combine information from your genome and other public information about you 
and identify you. If others found out, it could lead to discrimination or other 
problems. The risk of this happening is very small.  
Who will have access to my information in studies using my extra samples? 
People who may see your information are: 
x Researchers who use your extra samples and information for other research 
x Government agencies that fund or monitor the research using your extra 
samples and information 
x The researcher’s Institutional Review Board or Ethics Committee 
x Any regulatory agency that reviews research studies 
x The people who work with the researcher 
All of these people will do their best to protect your information. If they publish 
their research, they will not use your name or identify you personally. 
Questions  
20. If you have questions or problems at any time during your participation in 
this study, use the following important contacts. 
If you have questions about this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
If you have any symptoms that you think may be related to this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
This study has been reviewed and approved by a committee called the 
[name of local IRB/EC]. If you have questions about your rights as a research 
participant, or problems or concerns about how you are being treated in this study, 
contact [name or title and telephone number of person on IRB/EC] , at the 
committee. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 133 of 169 
Paragraph for South African sites. The study has been structured in accordance 
with the Declaration of Helsinki (last updated October 2013) which deals with the 
recommendations guiding doctors in biomedical research involving human 
participants, the Ethics in Health Research: Principles, Structures and Processes 
Second Edition 2015, and Guidelines for Good Practice in the Conduct of Clinical 
Trials in Human Participants in South Africa. We can provide you with copies of 
these guidelines if you wish to review them. In addition, the recent Protection of 
Personal Information Act (POPIA) ensures that all South African institutions 
conduct themselves in a responsible manner when collecting, processing, storing 
and sharing another entity’s personal information by holding them accountable 
should they abuse or compromise your personal information in any way. 
If you want to leave this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
Remainder of section for South African sites only.  
You can reach a study staff member 24 hours a day at [telephone number]. 
If you have questions about this trial you should first discuss them with your 
doctor or the ethics committee (contact details as provided on this form). After you 
have consulted your doctor or the ethics committee and if they have not provided 
you with answers to your satisfaction, you should write to the South African 
Healthcare Products Regulatory Authority (SAHPRA) at: 
The Chief Executive Officer 
Dr Boitumelo Semete-Makokotlela 
South African Health Products Regulatory Authority Private Bag X828 
PRETORIA 
0001 
Tel: (012) 501 0410/13 
e-mail: Boitumelo.Semete@sahpra.org.za 
Your permissions and signature  
Site: Delete this section if using a separate consent for use of samples and 
information in other studies 
21. We told you above about possible other uses of your extra samples and 
information outside this study. Please choose only 1 of the options below and 
write your initials in the box next to it. Whatever you choose, the CoVPN 
keeps track of your decision about how your samples and information can be 
used. You can change your mind after signing this form. 
 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 134 of 169 
I allow my extra samples and information to be used for other studies related to vaccines, the immune 
system, coronavirus, HIV, and other diseases. This may include genetic testing and keeping my cells 
growing over time.  
OR 
I agree to the option above and also to allow my extra samples and information to be used in studies that 
look at my whole genome. 
OR 
I do not allow my extra samples to be used in any other studies. This includes not allowing genetic testing, 
growing more of my cells, or studies that look at my whole genome.  
22. If you agree to join this study, you will need to sign below. Before you sign,
make sure of the following:
x
You have read this consent form, or someone has read it to you.
x
You feel that you understand what the study is about and what will happen to
you if you join. You understand what the possible risks and benefits are.
x
You have had your questions answered and know that you can ask more.
x
You agree to join this study.
You will not be giving up any of your rights by signing this consent form. 
Participant’s name (print) 
Participant’s signature 
Date 
Time 
Clinic staff conducting consent 
discussion (print) 
Clinic staff signature 
Date 
Time 
For participants who are unable to read or write, a witness should complete the 
signature block below: 
Witness’s name (print) 
Witness’s signature 
Date 
Time 
*Witness is impartial and was present for the entire discussion of this consent form.

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 135 of 169 
Appendix B 
Laboratory procedures table for Groups 1 and 3 (SARS-CoV-2 
seronegative participants, main study) 
1BARC = Bio Analytical Research Corporation South Africa (Pty) Ltd (Johannesburg, South Africa). 
2 HVTN Laboratories include: Bio Analytical Research Corporation South Africa (Pty) Ltd (Johannesburg, South Africa); Duke University Medical Center (Durham, North Carolina, 
USA); KwaZulu-Natal Research and Innovation Sequencing Platform (KRISP, Durban, South Africa). 
3 Screening may occur over the course of several contacts/visits up to and including Day 1 prior to study product administration.  
4 Local labs may assign appropriate alternative specimen type, tube and volume for locally performed tests.  
5 HIV diagnostic test will be performed for all participants at screening and as clinically indicated. 
6 HIV Viral Load and CD4+ T Cell Count will be performed at screening or at any visit for participants with newly diagnosed HIV infection, at enrollment for known PLWH, 
approximately 4-6 weeks after any change in antiretroviral therapy (other than just dosage) for PLWH, at visit 5 for PLWH, and as clinically indicated. (see Sections 9.2, 9.3, 9.4and 
9.9). HIV Viral Load and CD4+ T Cell Count do not need to be recollected if they were collected and the results available within the past 14 days. 
7 Nasal swab sample will only be sent to site processing lab for processing and storage if local testing results at the same visit return as SARS-CoV-2 infected.  
8 Pregnancy test will be performed at screening for all participants who were assigned female sex at birth and are of reproductive potential. A pregnancy test will be performed at other 
visits if the participant reports a new pregnancy and / or as clinically indicated. 
Visit:
01
02
03
04
05
106
107
108
109
110
111
112
113
114
115
116
117
Day:
-56 to 1
D1
D29
D57
D169
D197
D231
D265
D299
D333
D365
D396
D426
D456
D486
D516
D547
Week:
W0
W4
W8
W24
W28
W33
W38
W43
W48
W52
W56
W61
W65
W69
W74
W78
Month:
M0
M1
M2
M6
M7
M8
M9
M10
M11
M12
M13
M14
M15
M16
M17
M18
Procedure
Ship to1
Tube4
Tube size
(vol. 
capacity)4
Vac 1
Vac 2
Vac 3 
BLOOD COLLECTION
Screening/Diagnostic
HIV test5
Local Lab
Local Lab
EDTA
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
HIV Viral Load6
Local Lab
Local Lab
EDTA
5mL
56
56
—
—
56
—
—
—
—
—
—
—
—
—
—
—
—
CD4+ T Cell Count6
Local Lab
Local Lab
EDTA
5mL
56
56
—
—
56
—
—
—
—
—
—
—
—
—
—
—
—
SARS-CoV-2 POC Serology
Local Lab
Local Lab
EDTA
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
SARS-CoV-2 Serology
BARC
HVTN Labs
SST
5mL
—
5
—
5
5
5
—
—
—
—
5
—
—
—
—
—
5
Immunogenicity assays
     Humoral assays
BARC
HVTN Labs
SST
8.5mL
—
8.5
—
8.5
8.5
8.5
—
—
—
—
8.5
—
—
—
—
—
8.5
Gene Expression
BARC
HVTN Labs
Tempus
3mL
—
6
—
6
6
6
—
—
—
—
6
—
—
—
—
—
6
Visit total
20.0
29.5
0.0
19.5
29.5
19.5
0.0
0.0
0.0
0.0
19.5
—
—
—
—
—
19.5
56-Day total
20.0
49.5
49.5
69.0
29.5
49.0
19.5
19.5
0.0
0.0
19.5
—
—
—
—
—
19.5
NASAL SWAB SAMPLE COLLECTION4
SARS-CoV-2  PCR
Local Lab
Local Lab
—
X
X
—
X
X
X
X
X
X
X
X
X
X
X
X
X
SARS-CoV-2  Viral Sequencing7
BARC
HVTN Labs
—
X7
X7
—
X7
X7
X7
X7
X7
X7
X7
X7
X7
X7
X7
X7
X7
URINE COLLECTION
Pregnancy Test8
Local Lab
Local Lab
X
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
Screening 
visit 3
Assay 
Location2

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 136 of 169 
Appendix C 
Laboratory procedures table for Groups 2 and 4 (SARS-CoV-2 
seropositive participants, main study) 
Greyed out visit (4) does not apply to this groups. 
1 BARC = Bio Analytical Research Corporation South Africa (Pty) Ltd (Johannesburg, South Africa) 
2 HVTN Laboratories include: Bio Analytical Research Corporation South Africa (Pty) Ltd (BARC) (Johannesburg, South Africa); Duke University Medical Center (Durham, North 
Carolina, USA); KwaZulu-Natal Research and Innovation Sequencing Platform (KRISP, Durban, South Africa) 
3 Screening may occur over the course of several contacts/visits up to and including Day 1 prior to study product administration.  
4 Local labs may assign appropriate alternative specimen type, tube and volume for locally performed tests.  
5 HIV diagnostic test will be performed for all participants at screening and as clinically indicated. 
6 HIV Viral Load and CD4+ T Cell Count will be performed at screening or at any visit for participants with newly diagnosed HIV infection, at enrollment for known PLWH, 
approximately 4-6 weeks after any change in antiretroviral therapy (other than just dosage) for PLWH, at visit 5 for PLWH, and as clinically indicated (see Sections 9.2, 9., 9. and 
9.9). HIV Viral Load and CD4+ T Cell Count do not need to be recollected if they were collected and the results available within the past 14 days. 
7 Nasal swab sample will only be sent to site processing lab for processing and storage if local testing results at the same visit return as SARS-CoV-2 infected.  
8 Pregnancy test will be performed at screening for all participants who were assigned female sex at birth and are of reproductive potential. A pregnancy test will be performed at other 
visits if the participant reports a new pregnancy and / or as clinically indicated. 
Visit:
01
02
03
04
05
106
107
108
109
110
111
112
113
114
115
116
117
Day:
-56 to 1
D1
D29
D57
D169
D197
D231
D265
D299
D333
D365
D396
D426
D456
D486
D516
D547
Week:
W0
W4
W8
W24
W28
W32
W38
W43
W48
W52
W56
W61
W65
W69
W74
W78
Month:
M0
M1
M2
M6
M7
M8
M9
M10
M11
M12
M13
M14
M15
M16
M17
M18
Procedure
Ship to1
Tube4
Tube size
(vol. capacity)4
Vac 1
Vac 2 
BLOOD COLLECTION
Screening/Diagnostic
HIV test5
Local Lab
Local Lab
EDTA
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
HIV Viral Load6
Local Lab
Local Lab
EDTA
5mL
56
56
—
—
56
—
—
—
—
—
—
—
—
—
—
—
—
CD4+ T Cell Count6
Local Lab
Local Lab
EDTA
5mL
56
56
—
—
56
—
—
—
—
—
—
—
—
—
—
—
—
SARS-CoV-2 POC Serology
Local Lab
Local Lab
EDTA
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
SARS-CoV-2 Serology
BARC
HVTN Labs
SST
5mL
—
5
5
—
5
5
—
—
—
—
5
—
—
—
—
—
5
Immunogenicity assays
     Humoral assays
BARC
HVTN Labs
SST
8.5mL
—
8.5
8.5
—
8.5
8.5
—
—
—
—
8.5
—
—
—
—
—
8.5
Gene Expression
BARC
HVTN Labs Tempus
3mL
—
6
6
—
6
6
—
—
—
—
6
—
—
—
—
—
6
Visit total
20.0
29.5
19.5
0.0
29.5
19.5
0.0
0.0
0.0
0.0
19.5
—
—
—
—
—
19.5
56-Day total
20.0
49.5
69.0
29.5
49.0
19.5
19.5
0.0
0.0
19.5
—
—
—
—
—
19.5
NASAL SWAB SAMPLE COLLECTION4
SARS-CoV-2  PCR
Local Lab
Local Lab
—
X
—
—
X
X
X
X
X
X
X
X
X
X
X
X
X
SARS-CoV-2  Viral Sequencing7
BARC
HVTN Labs
—
X7
—
—
X7
X7
X7
X7
X7
X7
X7
X7
X7
X7
X7
X7
X7
URINE COLLECTION
Pregnancy Test8
Local Lab
Local Lab
X
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
Screenin
g visit 3
Assay 
Location2

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 137 of 169 
Appendix D 
Laboratory Procedures for PBMC Immunogenicity subset, Groups 1 and 3 
1BARC = Bio Analytical Research Corporation South Africa (Pty) Ltd (Johannesburg, South Africa) 
2HVTN Laboratories include: Bio Analytical Research Corporation South Africa (Pty) Ltd (BARC) (Johannesburg, South Africa); Fred Hutchinson Cancer Center (Seattle, Washington, 
USA); Duke University Medical Center (Durham, North Carolina, USA); Cape Town Immunology Laboratory (CHIL, Cape Town, South Africa); KwaZulu-Natal Research and 
Innovation Sequencing Platform (KRISP, Durban, South Africa). 
3Screening may occur over the course of several contacts/visits up to and including Day 1 prior to study product administration.  
4Local labs may assign appropriate alternative specimen type, tube and volume for locally performed tests.  
5HIV diagnostic test will be performed for all participants at screening and as clinically indicated. 
6 HIV Viral Load and CD4+ T Cell Count will be performed at screening or at any visit for participants with newly diagnosed HIV infection, at enrollment for known PLWH, 
approximately 4-6 weeks after any change in antiretroviral therapy (other than just dosage) for PLWH, at visit 5 for PLWH, and as clinically indicated (see Sections 9.2, 9., 9., 
and 9.9). HIV Viral Load and CD4+ T Cell Count do not need to be recollected if they were collected and the results available within the past 14 days. 
7 Nasal swab sample will only be sent to site processing lab for processing and storage if local testing results at the same visit return as SARS-CoV-2 infected.  
8 Pregnancy test will be performed at screening for all participants who were assigned female sex at birth and are of reproductive potential. A pregnancy test will be performed at other 
visits if the participant reports a new pregnancy and / or as clinically indicated. 
98x10mL NaHep tubes may be used if ACD tubes are not available 
Visit:
01
02
03
04
05
106
107
108
109
110
111
112
113
114
115
116
117
Day:
-56 to 1
D1
D29
D57
D169
D197
D231
D265
D299
D333
D365
D396
D426
D456
D486
D516
D547
Week:
W0
W4
W8
W24
W28
W32
W38
W43
W48
W52
W56
W61
W65
W69
W74
W78
Month:
M0
M1
M2
M6
M7
M8
M9
M10
M11
M12
M13
M14
M15
M16
M17
M18
Procedure
Ship to1
Tube4
Tube size
(vol. 
capacity)4
Vac 1
Vac 2
Vac 3 
BLOOD COLLECTION
Screening/Diagnostic
HIV test5
Local Lab
Local Lab
EDTA
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
HIV Viral Load6
Local Lab
Local Lab
EDTA
5mL
56
56
—
—
56
—
—
—
—
—
—
—
—
—
—
—
—
CD4+ T Cell Count6
Local Lab
Local Lab
EDTA
5mL
56
56
—
—
56
—
—
—
—
—
—
—
—
—
—
—
—
SARS-CoV-2 POC Serology
Local Lab
Local Lab
EDTA
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
SARS-CoV-2 Serology
BARC
HVTN Labs
SST
5mL
—
5
—
5
5
—
—
—
—
—
5
—
—
—
—
—
5
Immunogenicity assays
     Cellular assays9
BARC
HVTN Labs
ACD
8.5mL
—
85
—
85
85
85
—
—
—
—
85
—
—
—
—
—
85
     Humoral assays
BARC
HVTN Labs
SST
8.5mL
—
8.5
—
8.5
8.5
8.5
—
—
—
—
8.5
—
—
—
—
—
8.5
Gene Expression
BARC
HVTN Labs
Tempu
3mL
—
6
—
6
6
6
—
—
—
—
6
—
—
—
—
—
6
Visit total
20.0
114.5
0.0
104.5
114.5
99.5
0.0
0.0
0.0
0.0
104.5
—
—
—
—
—
104.5
56-Day total
20.0
134.5
134.5
239.0
114.5
99.5
99.5
99.5
0.0
0.0
104.5
—
—
—
—
—
104.5
NASAL SWAB SAMPLE COLLECTION4
SARS-CoV-2  PCR
Local Lab
Local Lab
—
X
X
—
X
X
X
X
X
X
X
X
X
X
X
X
X
SARS-CoV-2  Viral Sequencing7
BARC
HVTN Labs
—
X7
X7
—
X7
X7
X7
X7
X7
X7
X7
X7
X7
X7
X7
X7
X7
URINE COLLECTION
Pregnancy Test8
Local Lab
Local Lab
X
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
Assay 
Location2
Screeining 
visit 3

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 138 of 169 
Appendix E 
Laboratory Procedures for PBMC Immunogenicity subset, Groups 2 and 4 
Greyed out Visit 4 does not apply to this group. 
1BARC = Bio Analytical Research Corporation South Africa (Pty) Ltd (Johannesburg, South Africa) 
2HVTN Laboratories include: Bio Analytical Research Corporation South Africa (Pty) Ltd (BARC) (Johannesburg, South Africa); Fred Hutchinson Cancer Center (Seattle, Washington, 
USA); Duke University Medical Center (Durham, North Carolina, USA); Cape Town Immunology Laboratory (CHIL, Cape Town, South Africa); KwaZulu-Natal Research and 
Innovation Sequencing Platform (KRISP, Durban, South Africa) 
3Screening may occur over the course of several contacts/visits up to and including Day 1 prior to study product administration.  
4Local labs may assign appropriate alternative specimen type, tube and volume for locally performed tests.  
5HIV diagnostic test will be performed for all participants at screening and as clinically indicated. 
6 HIV Viral Load and CD4+ T Cell Count will be performed at screening or at any visit for participants with newly diagnosed HIV infection, at enrollment for known PLWH, 
approximately 4-6 weeks after any change in antiretroviral therapy (other than just dosage) for PLWH, at visit 5 for PLWH, and as clinically indicated (see Sections 9.2, 9., 9. and 
9.9). HIV Viral Load and CD4+ T Cell Count do not need to be recollected if they were collected and the results available within the past 14 days. 
7 Nasal swab sample will only be sent to site processing lab for processing and storage if local testing results at the same visit return as SARS-CoV-2 infected.  
8 Pregnancy test will be performed at screening for all participants who were assigned female sex at birth and are of reproductive potential. A pregnancy test will be performed at other 
visits if the participant reports a new pregnancy and / or as clinically indicated. 
98x10mL NaHep tubes may be used if ACD tubes are not available 
Visit:
01
02
03
04
05
106
107
108
109
110
111
112
113
114
115
116
117
Day:
-56 to 1
D1
D29
D57
D169
D197
D231
D265
D299
D333
D365
D396
D426
D456
D486
D516
D547
Week:
W0
W4
W8
W24
W28
W32
W38
W43
W48
W52
W56
W61
W65
W69
W74
W78
Month:
M0
M1
M2
M6
M7
M8
M9
M10
M11
M12
M13
M14
M15
M16
M17
M18
Procedure
Ship to1
Tube4
Tube size
(vol. 
capacity)4
Vac 1
Vac 2 
BLOOD COLLECTION
Screening/Diagnostic
HIV test5
Local Lab
Local Lab
EDTA
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
HIV Viral Load6
Local Lab
Local Lab
EDTA
5mL
56
56
—
—
56
—
—
—
—
—
—
—
—
—
—
—
—
CD4+ T Cell Count6
Local Lab
Local Lab
EDTA
5mL
56
56
—
—
56
—
—
—
—
—
—
—
—
—
—
—
—
SARS-CoV-2 POC Serology
Local Lab
Local Lab
EDTA
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
SARS-CoV-2 Serology
BARC
HVTN Labs
SST
5mL
—
5
5
—
5
—
—
—
—
—
5
—
—
—
—
—
5
Immunogenicity assays
     Cellular assays9
BARC
HVTN Labs
ACD
8.5mL
—
85
85
—
85
85
—
—
—
—
85
—
—
—
—
—
85
     Humoral assays
BARC
HVTN Labs
SST
8.5mL
—
8.5
8.5
—
8.5
8.5
—
—
—
—
8.5
—
—
—
—
—
8.5
Gene Expression
BARC
HVTN Labs
Tempus
3mL
—
6
6
—
6
6
—
—
—
—
6
—
—
—
—
—
6
Visit total
20.0
114.5
104.5
0.0
114.5
99.5
0.0
0.0
0.0
0.0
104.5
—
—
—
—
—
104.5
56-Day total
20.0
134.5
239.0
114.5
214.0
214.0
99.5
0.0
0.0
104.5
—
—
—
—
—
104.5
NASAL SWAB SAMPLE COLLECTION4
SARS-CoV-2  PCR
Local Lab
Local Lab
—
X
—
—
X
X
X
X
X
X
X
X
X
X
X
X
X
SARS-CoV-2  Viral Sequencing7
BARC
HVTN Labs
—
X7
—
—
X7
X7
X7
X7
X7
X7
X7
X7
X7
X7
X7
X7
X7
URINE COLLECTION
Pregnancy Test8
Local Lab
Local Lab
X
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
Screeining 
visit 3
Assay 
Location2

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 139 of 169 
Appendix F 
Laboratory Procedures for the PBMC Immune Correlates subset (Group 
1, HIV positive, SARS-CoV-2 seronegative participants) 
1BARC = Bio Analytical Research Corporation South Africa (Pty) Ltd (Johannesburg, South Africa) 
2HVTN Laboratories include: Bio Analytical Research Corporation South Africa (Pty) Ltd (BARC) (Johannesburg, South Africa); Fred Hutchinson Cancer Center (Seattle, Washington, 
USA); Duke University Medical Center (Durham, North Carolina, USA); Cape Town Immunology Laboratory (CHIL, Cape Town, South Africa); KwaZulu-Natal Research and 
Innovation Sequencing Platform (KRISP, Durban, South Africa) 
3Screening may occur over the course of several contacts/visits up to and including Day 1 prior to study product administration.  
4Local labs may assign appropriate alternative specimen type, tube and volume for locally performed tests.  
5HIV diagnostic test will be performed for all participants at screening and as clinically indicated. 
6 HIV Viral Load and CD4+ T Cell Count will be performed at screening or at any visit for participants with newly diagnosed HIV infection, at enrollment for known PLWH, 
approximately 4-6 weeks after any change in antiretroviral therapy (other than just dosage) for PLWH, at visit 5 for PLWH, and as clinically indicated (see Sections 9.2, 9., 9. 
and 9.9). HIV Viral Load and CD4+ T Cell Count do not need to be recollected if they were collected and the results available within the past 14 days. 
7 Nasal swab sample will only be sent to site processing lab for processing and storage if local testing results at the same visit return as SARS-CoV-2 infected.  
8 Pregnancy test will be performed at screening for all participants who were assigned female sex at birth and are of reproductive potential. A pregnancy test will be performed at other 
visits if the participant reports a new pregnancy and / or as clinically indicated. 
98x10mL NaHep tubes may be used if ACD tubes are not available 
Visit:
01
02
03
04
05
106
107
108
109
110
111
112
113
114
115
116
117
Day:
-56 to 1
D1
D29
D57
D169
D197
D231
D265
D299
D333
D365
D396
D426
D456
D486
D516
D547
Week:
W0
W4
W8
W24
W28
W32
W38
W43
W48
W52
W56
W61
W65
W69
W74
W78
Month:
M0
M1
M2
M6
M7
M8
W41
M10
M11
M12
M13
M14
M15
M16
M17
M18
Procedure
Ship to1
Tube4
Tube size
(vol. 
capacity)4
Vac 1
Vac 2
Vac 3 
BLOOD COLLECTION
Screening/Diagnostic
HIV test5
Local Lab
Local Lab
EDTA
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
HIV Viral Load6
Local Lab
Local Lab
EDTA
5mL
56
56
—
—
56
—
—
—
—
—
—
—
—
—
—
—
—
CD4+ T Cell Count6
Local Lab
Local Lab
EDTA
5mL
56
56
—
—
56
—
—
—
—
—
—
—
—
—
—
—
—
SARS-CoV-2 POC Serology
Local Lab
Local Lab
EDTA
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
SARS-CoV-2 Serology
BARC
HVTN Labs
SST
5mL
—
5
—
5
5
—
—
—
—
—
5
—
—
—
—
—
5
Immunogenicity assays
     Cellular assays9
BARC
HVTN Labs
ACD
8.5mL
—
85
—
85
—
85
—
—
—
—
—
—
—
—
—
—
—
     Humoral assays
BARC
HVTN Labs
SST
8.5mL
—
8.5
—
8.5
8.5
8.5
—
—
—
—
8.5
—
—
—
—
—
8.5
Gene Expression
BARC
HVTN Labs Tempus
3mL
—
6
—
6
6
6
—
—
—
—
6
—
—
—
—
—
6
Visit total
20.0
114.5
0.0
104.5
29.5
99.5
0.0
0.0
0.0
0.0
19.5
—
—
—
—
—
19.5
56-Day total
20.0
134.5
134.5
239.0
29.5
99.5
99.5
99.5
0.0
0.0
19.5
—
—
—
—
—
19.5
NASAL SWAB SAMPLE COLLECTION4
SARS-CoV-2  PCR
Local Lab
Local Lab
—
X
X
—
X
X
X
X
X
X
X
X
X
X
X
X
X
SARS-CoV-2  Viral Sequencing7
BARC
HVTN Labs
—
X7
X7
—
X7
X7
X7
X7
X7
X7
X7
X7
X7
X7
X7
X7
X7
URINE COLLECTION
Pregnancy Test8
Local Lab
Local Lab
X
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
Screeining 
visit 3
Assay 
Location2

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 140 of 169 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 141 of 169 
Appendix G 
Laboratory Procedures for the PBMC Immune Correlates subset (Group 
2, HIV positive, SARS-CoV-2 seropositive participants) 
Greyed out Visit 4 does not apply to this group. 
1BARC = Bio Analytical Research Corporation South Africa (Pty) Ltd (Johannesburg, South Africa) 
2HVTN Laboratories include: Bio Analytical Research Corporation South Africa (Pty) Ltd (BARC) (Johannesburg, South Africa); Duke University Medical Center (Durham, North 
Carolina, USA); KwaZulu-Natal Research and Innovation Sequencing Platform (KRISP, Durban, South Africa) 
3Screening may occur over the course of several contacts/visits up to and including day 1 prior to study product administration.  
4Local labs may assign appropriate alternative specimen type, tube and volume for locally performed tests.  
5 HIV diagnostic test will be performed for all participants at screening and as clinically indicated. 
6 HIV Viral Load and CD4+ T Cell Count will be performed at screening or any visit for participants with newly diagnosed HIV infection, at enrollment for known PLWH, 
approximately 4-6 weeks after any change in antiretroviral therapy (other than just dosage) for PLWH, at visit 5 for PLWH, and as clinically indicated (see Sections 9.2, 9.3, 9.4 and 
9.9). HIV Viral Load and CD4+ T Cell Count do not need to be recollected if they were collected and the results available within the past 14 days. 
7 Nasal swab sample will be only be sent to site processing lab for processing and storage if local testing results at the same visit return as SARS-CoV-2 infected.  
8 Pregnancy test will be performed at screening for all participants who were assigned female sex at birth and are of reproductive potential. A pregnancy test will be performed at other 
visits if the participant reports a new pregnancy and / or as clinically indicated. 
98x10mL NaHep tubes may be used if ACD tubes are not available 
Visit:
01
02
03
04
05
106
107
108
109
110
111
112
113
114
115
116
117
Day:
-56 to 1
D1
D29
D57
D169
D197
D231
D265
D299
D333
D365
D396
D426
D456
D486
D516
D547
Week:
W0
W4
W8
W24
W28
W32
W38
W43
W48
W52
W56
W61
W65
W69
W74
W78
Month:
M0
M1
M2
M6
M7
M8
M9
M10
M11
M12
M13
M14
M15
M16
M17
M18
Procedure
Ship to1
Tube4
Tube size
(vol. 
capacity)4
Vac 1
Vac 2 
BLOOD COLLECTION
Screening/Diagnostic
HIV test5
Local Lab
Local Lab
EDTA
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
HIV Viral Load6
Local Lab
Local Lab
EDTA
5mL
56
56
—
—
56
—
—
—
—
—
—
—
—
—
—
—
—
CD4+ T Cell Count6
Local Lab
Local Lab
EDTA
5mL
56
56
—
—
56
—
—
—
—
—
—
—
—
—
—
—
—
SARS-CoV-2 POC Serology
Local Lab
Local Lab
EDTA
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
SARS-CoV-2 Serology
BARC
HVTN Labs
SST
5mL
—
5
5
—
5
—
—
—
—
—
5
—
—
—
—
—
5
Immunogenicity assays
Cellular assays9
BARC
HVTN Labs
ACD
8.5mL
—
85
85
—
—
85
—
—
—
—
—
—
—
—
—
—
—
     Humoral assays
BARC
HVTN Labs
SST
8.5mL
—
8.5
8.5
—
8.5
8.5
—
—
—
—
8.5
—
—
—
—
—
8.5
Gene Expression
BARC
HVTN Labs
Tempus
3mL
—
6
6
—
6
6
—
—
—
—
6
—
—
—
—
—
6
Visit total
20.0
114.5
104.5
0.0
29.5
99.5
0.0
0.0
0.0
0.0
19.5
—
—
—
—
—
19.5
56-Day total
20.0
134.5
239.0
29.5
99.5
99.5
99.5
0.0
0.0
19.5
—
—
—
—
—
19.5
NASAL SWAB SAMPLE COLLECTION4
SARS-CoV-2  PCR
Local Lab
Local Lab
—
X
—
—
X
X
X
X
X
X
X
X
X
X
X
X
X
SARS-CoV-2  Viral Sequencing7
BARC
HVTN Labs
—
X7
—
—
X7
X7
X7
X7
X7
X7
X7
X7
X7
X7
X7
X7
X7
URINE COLLECTION
Pregnancy Test8
Local Lab
Local Lab
X
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
Screenin
g visit 3
Assay 
Location2

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 142 of 169 
Appendix H 
Schedule of clinic procedures for Groups 1 and 3 (SARS-CoV-2 
seronegative participants) 
Visit Number 
01 
02 
03 
04 
05 
106 
107 
108 
109 
110 
111 
112 
113 
114 
115 
116 
117 
Study Week 
0 
4 
8 
24 
28 
33 
38 
43 
48 
52 
56 
61 
65 
69 
74 
78 
Study Month 
0 
1 
2 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
Study Day 
-56 to
1
1 
29 
57 
169 
197 
231 
265 
299 
333 
365 
396 
426 
456 
486 
516 
547 
Procedure 
Screen 
Vac 
1 
Vac 
2 
Follow 
up 
Vac 
3 
Follow up 
Study procedures 
Assessment of Understanding 
я 
Informed consent 
я 
Medical history1 
я 
Physical exam2 
я 
я 
я 
Obtain demographics 
я 
Risk assessment questionnaire 
я 
Targeted concomitant 
medications3 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
Vaccination4 
я 
я 
я 
Ultrasound for gestational age5 
я 
 COVID-19 surveillance6 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
SAEs, AESIs7 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
Safety Subset participants 7 
Reactogenicity assessment 
я 
я 
я 
AEs for 28 days postvaccination 
я 
я 
я 
Specimen Collections 
Pregnancy test8  
я 
HIV diagnostic test9 
я 
Blood draw10 
я11
я 
я 
я 
я 
я 
я 
Nasal swab12 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
1 Medical history: Targeted medical history is performed during screening. At enrollment and at subsequent visits, an interim medical history may be performed. 
2 Abbreviated physical exam will be performed at screening, at the month 12 visit and at the last visit. At other clinic visits a physical exam will be performed as needed, based 
on participant self-reported symptoms or indications of illness. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 143 of 169 
3 Targeted concomitant medication will be assessed for high-risk conditions. 
4 Vaccination (in clinic assessments): At least 15 minutes after each vaccination and prior to clinic discharge, the injection site will be assessed, and systemic symptoms will be 
assessed (see Section 9.3 for detail).  
5 Ultrasound to evaluate gestational age and for presence of fetal anomalies will be performed for all participants confirmed to be pregnant at enrollment or any other visit, and 
as clinically indicated, if the participant intends to continue with the pregnancy.  
6 COVID-19 surveillance: prespecified symptoms that meet the criteria for suspicion of COVID-19 will be elicited approximately every 2 weeks from the participant (see 
Section 9.5). (Note: All participants who have not exited the study will be contacted as specified, regardless of where they are in the post-enrollment follow-up.) 
7 Solicited and unsolicited AEs collected for a subset of study participants. Serious adverse events and adverse events of special interest (see Appendix L) collected for all 
participants throughout the study.  
8 Pregnancy test will be performed at screening for all participants who were assigned female sex at birth and are of reproductive potential. A pregnancy test will be performed 
at other visits if the participant reports a new pregnancy and / or as clinically indicated.  
9 HIV diagnostic test will be performed for all participants at screening and as clinically indicated. Participants with a positive HIV status will be offered HIV counseling. They 
will also be referred for care and treatment according to local guidelines. 
10 For details on blood draws see Appendix B, Appendix D and Appendix F. 
11 Blood sample will be drawn to determine SARS-CoV-2 serostatus (see Section 9.2). 
12 Two nasal swabs will be collected at each indicated visit. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 144 of 169 
Appendix I 
Schedule of clinic procedures for Groups 2 and 4 (SARS-CoV-2 
seropositive participants) 
Visit Number 
01 
02 
03 
04 
05 
106 
107 
108 
109 
110 
111 
112 
113 
114 
115 
116 
117 
Study Week 
 
0 
4 
8 
24 
28 
33 
38 
43 
48 
52 
56 
61 
65 
69 
74 
78 
Study Month 
 
0 
1 
2 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
Study Day 
-56 to 
1 
1 
29 
57 
169 
197 
231 
265 
299 
333 
365 
396 
426 
456 
486 
516 
547 
Procedure 
Screen 
Vac 
1 
 
 
Vac 
2 
Follow up 
Study procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assessment of Understanding 
я 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
я 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history1 
я 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical exam2 
я 
 
 
 
 
 
 
 
 
 
я 
 
 
 
 
 
я 
Obtain demographics 
я 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Risk assessment questionnaire 
 
я 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Targeted concomitant medications3 
я 
я 
я 
 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
Vaccination4 
 
я 
 
 
я 
 
 
 
 
 
 
 
 
 
 
 
 
Ultrasound for gestational age5 
я 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COVID-19 surveillance6 
 
я 
я 
 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
SAEs, AESIs7 
 
я 
я 
 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
Safety Subset participants7 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reactogenicity assessment 
 
я 
 
 
я 
 
 
 
 
 
 
 
 
 
 
 
 
AEs for 28 days postvaccination 
 
я 
 
 
я 
 
 
 
 
 
 
 
 
 
 
 
 
Specimen Collections 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test8 
я 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV diagnostic test9 
я 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood draw10 
я11 
я 
я 
 
я 
я 
 
 
 
 
я 
 
 
 
 
 
я 
Nasal swab12 
 
я 
 
 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
я 
Grayed out Visit 4 does not apply for this group. 
1 Medical history: Targeted medical history is performed during screening. At enrollment and at subsequent visits, an interim medical history may be performed. 
2 Abbreviated physical exam will be performed at screening, at the month 12 visit and at the last visit. At other clinic visits a physical exam will be performed as needed, based 
on participant self-reported symptoms or indications of illness.   

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 145 of 169 
3 Targeted concomitant medication will be assessed for high-risk conditions. 
4 Vaccination (in clinic assessments): At least 15 minutes after each vaccination and prior to clinic discharge, the injection site will be assessed, and systemic symptoms will be 
assessed (see Section 9.3 for detail).  
5 Ultrasound to evaluate gestational age and for presence of fetal anomalies will be performed for all participants confirmed to be pregnant at enrollment or any other visit, and 
as clinically indicated, if the participant intends to continue with the pregnancy.  
6 COVID-19 surveillance: prespecified symptoms that meet the criteria for suspicion of COVID-19 will be elicited approximately every 2 weeks from the participant (see 
Section 9.5). (Note: All participants who have not exited the study will be contacted as specified, regardless of where they are in the post-enrollment follow-up.) 
7 Solicited and unsolicited AEs collected for a subset of study participants. Serious adverse events and adverse events of special interest (see Appendix L) collected for all 
participants throughout the study.  
8 Pregnancy test will be performed at screening for all participants who were assigned female sex at birth and are of reproductive potential. A pregnancy test will be performed 
at other visits if the participant reports a new pregnancy and / or as clinically indicated. 
9 HIV diagnostic test will be performed for all participants at screening and as clinically indicated. Participants with a positive HIV status will be offered HIV counseling. They 
will also be referred for care and treatment according to local guidelines. 
10 For details on blood draws see Appendix C, Appendix E and Appendix G. 
11 Blood sample will be drawn to confirm SARS-CoV-2 serostatus (see Section 9.2). 
12 Two nasal swabs will be collected at each indicated visit. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 146 of 169 
Appendix J 
COVID-19 symptom visits 
COVID-19 Symptom Visits: Clinic Procedures 
Procedure5 
[visit allowance] 
Day 1 
(clinic visit) 
Day 3 
(blood 
collection) 
[-2, + 2] 
Day 2-14 
(phone 
call) 
Day 14 
(swab collection) 
[-3, + 3] 
Day 28 
(clinic visit) 
[-3, +3] 
Day 42+ 
(swab collection if 
indicated7,8) 
[-3, +3] 
Day 56+ (swab and 
blood collection, if 
indicated) 
History & Physical 
Exam 
X1 
 
 
X 
 
X 
Symptom and SpO2 
monitoring by 
participant2 
Daily through 14 days or until a negative SARS-CoV-2 NAAT test is obtained, 
whichever is longer 
 
Symptom 
monitoring by CRS3 
Every other day through 14 days or until symptoms improve (if symptomatic), 
whichever is longer 
 
Sample collections6 
 
 
 
Nasal swabs (two)4 
X 
 
X 
X7 
X7 
X7 
Blood collection 
X 
X 
 
X 
 
X8 
1 Participant history and physical exam on Day 1. 
2 On Day 1 participant will receive the Memory Aid 2 and will be instructed to record symptoms (if any) and their maximum daily severity if determined to have a SARS-CoV-2 
positive NAAT test. Participant will also receive pulse oximeter and will be instructed on how to use it at rest and after mild exercise and how to record these O2 saturations in 
the Memory Aid 2. Participants will be instructed to record daily symptoms (if any) and O2 saturations through Day 14 or until a negative SARS-CoV-2 NAAT test result, 
whichever is longer. They will be instructed to contact the clinic if symptoms worsen.  (See Section 9.6.) Recorded symptoms and their severity will be entered into the 
appropriate CRF by CRS staff. 
3 Participants will be contacted by the CRS staff every other day, at a minimum, by phone (or alternative contact method) through Day 14 or until symptom improvement (if 
symptomatic), whichever is longer. 
4 Two nasal swabs will be collected at indicated timepoints (1 swab will be sent for local SARS-CoV-2 NAAT testing to confirm diagnosis and the other one will be shipped to 
the central laboratory). Local tests can be repeated at the investigator’s discretion. Symptom history will be collected at this visit and consolidated information will be entered 
into the appropriate CRF by CRS staff. 
5 Day 1 and Day 3 procedures can be combined in a single visit if participants have been diagnosed with SARS-CoV-2 and all required COVID-19 Visit procedures for Day 1 
and Day 3 can be done in 1 visit. 
6 Specimens previously collected during a routine visit do not need to be recollected if it was within the visit window. HIV Viral Load and CD4+ T Cell Count do not need to be 
recollected if they were collected and the results available within the past 14 days. See CoVPN 3008 (Ubuntu) SSP for further guidance. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 147 of 169 
7 If nasal swab at day 14 is positive, nasal swabs will be collected approximately every 2 weeks until a negative result is received (1 swab will be sent for local SARS-CoV-2 
NAAT testing to confirm diagnosis and the other one will be shipped to the central laboratory). Local tests can be repeated at the investigator’s discretion. 
8 If nasal swab at day 42 is positive, blood samples will be collected on day 56 and every 8 weeks thereafter until a negative swab result is received (Note: Participants who 
continue to test positive will not exit the study even if otherwise anticipated, they will continue with post-diagnosis follow-up, as specified.) 
 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 148 of 169 
COVID-19 Symptom Visits: Laboratory Procedures Table 
 
 
1 BARC = Bio Analytical Research Corporation South Africa (Pty) Ltd (Johannesburg, South Africa); 
2 HVTN Laboratories include: Bio Analytical Research Corporation South Africa (Pty) Ltd (BARC) (Johannesburg, South Africa); Fred Hutchinson Cancer Center (Seattle, 
Washington, USA); Duke University Medical Center (Durham, North Carolina, USA); Cape Town Immunology Laboratory (CHIL, Cape Town, South Africa); KwaZulu-
Natal Research and Innovation Sequencing Platform (KRISP, Durban, South Africa). 
3 Local labs may assign appropriate alternative specimen type, tube and volume for locally performed tests.  
4 Visit #.X indicates a Symptom visit for participants where they were confirmed SARS-CoV-2 positive by NAAT, which can be an interim or scheduled visit. See protocol 
Section 9.5 and 9.6. 
5 Visit #.Y, #.S and #.Z indicates a Symptom follow-up visit for participants with confirmed SARS-CoV-2 infection which can be an interim or scheduled visit. See protocol 
Section 9.6. 
6 HIV test will not be performed for known PLWH. 
7 HIV Viral Load and CD4+ T Cell Count do not need to be recollected for PLWH if they were collected and the results available within the past 14 days. 
8 CPT tubes may be collected at predetermined sites. 
9 Samples for immunogenicity and gene expression do not need to be recollected if they have already been collected within the visit window. 
10 If nasal swab at day 14 is positive, nasal swabs will be collected approximately every two weeks until a negative result is received. 
118x10mL NaHep tubes may be collected if ACD tubes are not available 
12If nasal swab on day 42 is positive, blood samples will be collected on day 56 and approximately every 8 weeks thereafter until a negative swab result is received. 
 
 
 
Visit:
#.X4
#.Y5
#.S5
#.Z5
#.S5,10
#.S5,10
Days relative to Symptom Visit:
D1
D3
D14
D28
D42
D56+12
Procedure
Ship to1
Tube3
Tube size
(vol. capacity)3
Symptom 
visit 
BLOOD COLLECTION
HIV test
Local Lab
Local Lab
EDTA
5mL
56
—
—
—
—
—
HIV Viral Load
Local Lab
Local Lab
EDTA
5mL
—
57
—
—
—
57
CD4+ T Cell Count
Local Lab
Local Lab
EDTA
5mL
—
57
57
SARS-CoV-2 Serology
BARC
HVTN Labs
SST
5mL
—
5
5
Immunogenicity Assays9 
Cellular Assays11
BARC
HVTN Labs
ACD8
8.5mL
—
85
—
85
—
85
Humoral Assays
BARC
HVTN Labs
SST
8.5mL
—
8.5
—
8.5
—
8.5
Gene Expression
BARC
HVTN Labs
Tempus
3mL
—
6
—
6
—
—
Visit total
5.0
114.5
0.0
104.5
0.0
103.5
56-Day total
5.0
119.5
119.5
224.0
224.0
327.5
NASAL SWAB SAMPLE COLLECTION3
SARS-CoV-2  NAAT
Local Lab
Local Lab
X
—
X
X10
X10
X10
SARS-CoV-2  Viral Sequencing
BARC
HVTN Labs
X
—
X
X10
X10
X10
Assay Location2

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 149 of 169 
Appendix K 
Visit windows 
Groups 1 and 3 
Visit 
Number 
Visit Type 
Lower 
Allowable 
Window  
Lower 
Target 
Window 
Target 
Day1 
Upper 
Target 
Window 
Upper 
Allowable 
Window  
01 
Screening 
-56 
- 
 
- 
0 
02 
Vaccination 1 
- 
-0 
1 
+0 
0 
03 
Vaccination 2 
 
-3 
29 
+7 
+14 
04 
Follow-up2 
 
-3 
57 
+7 
+14 
05 
Vaccination 3 
-28 
-7 
169 
+14 
+28 
106 
Follow-up2  
 
-7 
197 
+7 
+16 
107 
Follow-up2 
-17 
-7 
231 
+7 
+16 
108 
Follow-up2 
-17 
-7 
265 
+7 
+16 
109 
Follow-up2 
-17 
-7 
299 
+7 
+16 
110 
Follow-up2 
-17 
-7 
333 
+7 
+16 
111 
Follow-up2 
-15 
-7 
365 
+7 
+15 
112 
Follow-up2 
-15 
-7 
396 
+7 
+14 
113 
Follow-up2 
-15 
-7 
426 
+7 
+14 
114 
Follow-up2 
-15 
-7 
456 
+7 
+14 
115 
Follow-up2 
-15 
-7 
486 
+7 
+14 
116 
Follow-up2 
-15 
-7 
516 
+7 
+14 
117 
Follow-up2 
-16 
-7 
547 
+7 
+14 
1. Target dates are relative to Visit 2 (Enrollment/Randomization), except for cases described in footnote 2. 
2. Target dates are relative to the vaccination visit before. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 150 of 169 
Groups 2 and 4 
Visit 
Number 
Visit Type 
Lower 
Allowable 
Window  
Lower 
Target 
Window 
Target 
Day1 
Upper 
Target 
Window 
Upper 
Allowable 
Window  
01 
Screening 
-56 
- 
 
- 
0 
02 
Vaccination 1 
- 
-0 
1 
+0 
0 
03 
Follow-up 
 
-3 
29 
+7 
+14 
043 
 
 
 
 
 
 
05 
Vaccination 2 
-28 
-7 
169 
+14 
+28 
106 
Follow-up2  
 
-7 
197 
+7 
+16 
107 
Follow-up2 
-17 
-7 
231 
+7 
+16 
108 
Follow-up2 
-17 
-7 
265 
+7 
+16 
109 
Follow-up2 
-17 
-7 
299 
+7 
+16 
110 
Follow-up2 
-17 
-7 
333 
+7 
+16 
111 
Follow-up2 
-15 
-7 
365 
+7 
+15 
112 
Follow-up2 
-15 
-7 
396 
+7 
+14 
113 
Follow-up2 
-15 
-7 
426 
+7 
+14 
114 
Follow-up2 
-15 
-7 
456 
+7 
+14 
115 
Follow-up2 
-15 
-7 
486 
+7 
+14 
116 
Follow-up2 
-15 
-7 
516 
+7 
+14 
117 
Follow-up2 
-16 
-7 
547 
+7 
+14 
1. Target dates are relative to Visit 2 (Enrollment/Randomization), except for cases described in footnote 2. 
2. Target dates are relative to the vaccination visit before. 
3. Grayed out Visit 4 does not apply for these groups.  
 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 151 of 169 
Appendix L 
Addendum to the sample informed consent 
form 
Title: Multi-Center, Randomized, Efficacy Study of COVID-19 mRNA Vaccine in 
Regions with SARS-CoV-2 Variants of Concern 
Study number: CoVPN 3008 (Ubuntu) 
Site: [Insert site name] 
Key information 
x Enrollment in this study is now complete with over 14,000 participants. About 
half of the participants have completed their injections visits. Injection visits are 
ongoing for the rest. 
x We are adding Moderna’s updated bivalent vaccine to this study. Bivalent 
means it contains components of the original strain of SARS-CoV-2 and the 
Omicron subvariants BA.4 and BA.5. 
x Participants will need to sign this consent form. They will have the same study 
procedures as were described in the original consent form, but the version of 
study product given at their last injection may change.  
x We do not expect there to be any additional risks from the updated study 
vaccine, but we do not know for sure. 
1. Review of study information 
You are a participant in CoVPN 3008 (Ubuntu), a research study that tests the 
Moderna COVID-19 vaccine in adults living with HIV and adults with existing 
health conditions that may put them at risk of severe COVID-19. The study is fully 
enrolled with over 14,000 participants. About half of the participants have 
completed their injections visits. Injection visits are ongoing for the rest. We are 
making an update to the study that we want to share with you. 
Please review this information carefully. We also suggest that you review 
information in the main study consent form. You are free to ask questions at any 
time.  
To show that you have received and understand this information, we will ask you 
to sign this form. You will get a copy to keep. 
2. What is changing in this study? 
Until now everyone in this study has gotten the first version of Moderna’s vaccine 
(Moderna mRNA-1273). An updated version of this vaccine is now available 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 152 of 169 
(Moderna mRNA-1273.222). This updated version was made to target the newer 
Omicron subvariants, BA.4 and BA.5, as well as the original strain of SARS-CoV-
2. This version was made to give better protection against these newer variants of 
the virus. 
We want to test whether there a difference between the two study vaccines in their 
ability to protect against COVID-19 and the newer strains of the virus. To do this, 
at your last dose we will now either give you Moderna mRNA-1273 or the updated 
vaccine version.  
If you have already completed all of your injection visits, you will not get the 
updated study vaccine. 
3. What do I need to know about the updated study vaccine? 
The updated study vaccine, Moderna mRNA-1273.222, was made by a similar 
approach to how influenza vaccine is made each year. It uses the Moderna mRNA-
1273 vaccine and adds better coverage against current variants. Because the 
process for making the vaccine did not change, it does not need to be tested in 
large studies like the original vaccine. There are some smaller studies in progress. 
As of September 2022, the updated vaccine has been given to over 500 people as 
part of a study that is still ongoing. So far there have been no safety concerns. 
Studies done in mice showed that the updated vaccine worked well against both 
older and newer variants and we expect it will be the same in humans. Earlier 
versions of the updated study vaccine were given to over 700 people and there 
have been no safety concerns. We think that the risks of this updated study vaccine 
will be similar. But we do not know for sure. 
In the United States (US), the updated study vaccine Moderna mRNA-1273.222 
has been authorized for use in people by the Food and Drug Administration (FDA) 
and hundreds of thousands of previously vaccinated Americans have already 
received booster doses of it or a similar bivalent vaccine by Pfizer-BioNTech. 
We will be using the new vaccine version authorized in the US. In this study, we 
will be giving it to you at a higher dose than the dose that is currently authorized in 
the US. This is because in the US the new version is currently being given as a 
booster vaccination, meaning an extra vaccination given to people already fully 
vaccinated to enhance or restore protection against COVID-19, which may 
decrease over time. In the US the booster vaccination dose for Moderna vaccines is 
half the dose of the vaccinations normally given at first to people to get them fully 
vaccinated. Because this study is evaluating potential ways of initially vaccinating 
people to get them fully vaccinated, this study is using a higher dose than the 
booster dose. The older version of the Moderna vaccine has already been approved 
and widely used at the higher dose, while the newer version has not yet.        

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 153 of 169 
4. We will give you the study products on the same schedule, but the version of 
the study product you get at your last dose may change. 
All people in Group 1 and Group 3 will still get 3 doses of the study vaccines. The 
first 2 doses will be of the Moderna mRNA-1273 study vaccine. For the last dose, 
you will get either Moderna mRNA-1273 or the updated study vaccine.  
All people in Group 2 and Group 4 will still get 2 doses of the study vaccines. The 
first dose will be of the Moderna mRNA-1273 study vaccine. For the last dose, 
you will get either Moderna mRNA-1273 or the updated study vaccine.  
For all groups, which version of the study vaccine you get in the last dose is 
completely random, like flipping a coin. We have no say and will not know which 
version you get, and neither will you. Only the pharmacist and the person injecting 
you at this clinic will have this information while the study is going on. The 
updated study vaccine comes in a different volume. To keep you from knowing 
which version you are getting, we may ask you to turn you head away when you 
get your injection.  
Because this is also the first time the updated study vaccine is being given to 
people at  this dose, the study has a planned safety pause where safety information 
will be reviewed to decide if it is safe to continue. The pause will be after about 
120 participants get the updated study vaccine and will determine if other 
participants should get it, too.  
5. You are free to choose to continue or to leave the study.  
You are still free to leave the study at any time and for any reason. If you want to 
leave, you will need to tell us. Your care at this clinic and your legal rights will not 
be affected. We may ask you to come back to the clinic one last time, and we may 
ask to take some more samples. We believe this is important to protecting your 
health, but it is up to you whether you do this. 
6. Most things described in the informed consent form you signed previously 
remain the same. 
These include: 
x The study procedures we will do; 
x The length of time you will be in the study; 
x The potential risks and benefits of being in the study; 
x Your rights and responsibilities in the study; 
x How your samples will be used; 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 154 of 169 
x What we will do if we find you have a health problem or you get COVID-19; 
x How we will protect your private information and who can access your study 
records; 
x Reasons we might take you out of the study; 
x What will happen if you get sick or injured during the study. 
As before, there is no cost to you for being in the study. We will give you [Site: 
Insert compensation] for each study visit you complete. 
In the consent form you signed when you joined this study, you chose whether the 
CoVPN could use your extra samples and information in other studies. The 
CoVPN will continue to honor the choice you made in that consent form. You can 
change your mind if you want. Your decision will not affect your being in this 
study or have any negative consequences here. 
7. If you have questions or problems at any time during this study, use the 
following important contacts. 
If you have questions about this study, contact [name or title and telephone number 
of the investigator or other study staff]. 
If you have any symptoms that you think may be related to this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
This study has been reviewed and approved by a committee called the [name of 
local IRB/EC]. If you have questions about your rights as a research participant, or 
problems or concerns about how you are being treated in this study, contact [name 
or title and telephone number of person on IRB/EC], at the committee. 
Paragraph for South African sites. The study has been structured in accordance 
with the Declaration of Helsinki (last updated October 2013) which deals with the 
recommendations guiding doctors in biomedical research involving human 
participants, the Ethics in Health Research: Principles, Structures and Processes 
Second Edition 2015, and Guidelines for Good Practice in the Conduct of Clinical 
Trials in Human Participants in South Africa. We can provide you with copies of 
these guidelines if you wish to review them. In addition, the recent Protection of 
Personal Information Act (POPIA) ensures that all South African institutions 
conduct themselves in a responsible manner when collecting, processing, storing 
and sharing another entity’s personal information by holding them accountable 
should they abuse or compromise your personal information in any way. 
If you want to leave this study, contact [name or title and telephone number of the 
investigator or other study staff]. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 155 of 169 
You can reach a study staff member 24-hours a day at [telephone number]. 
Remainder of section for South African sites only.  
If you have questions about this trial you should first discuss them with your 
doctor or the ethics committee (contact details as provided on this form). After you 
have consulted your doctor or the ethics committee and if they have not provided 
you with answers to your satisfaction, you should write to the South African 
Healthcare Products Regulatory Authority (SAHPRA) at: 
The Chief Executive Officer 
Dr Boitumelo Semete-Makokotlela 
South African Health Products Regulatory Authority Private Bag X828 
PRETORIA 
0001 
Tel: (012) 501 0410/13 
e-mail: Boitumelo.Semete@sahpra.org.za 
8. If you agree to continue in this study, you will need to sign or make your mark 
below. Before you sign or make your mark on this consent form, make sure of 
the following: 
x You have read this consent form, or someone has read it to you. 
x You feel that you understand what the study is about and what will happen to 
you if you continue. You understand what the possible risks and benefits are. 
x You have had your questions answered and know that you can ask more. 
x You agree to stay in this study. 
You will not be giving up any of your rights by signing this consent form. 
 
 
 
 
 
 
 
Participant’s name 
(print) 
 
Participant’s 
signature or mark 
 
Date 
 
Time 
 
 
 
 
 
 
 
Clinic staff 
conducting consent 
discussion (print) 
 
Clinic staff 
signature 
 
Date 
 
Time 
For participants who are unable to read or write, a witness should complete the 
signature block below: 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 156 of 169 
 
 
 
 
 
 
 
Witness’s name (print) 
 
Witness’s signature  
 
Date 
 
Time 
*Witness is impartial and was present for the consent process. 
 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 157 of 169 
Appendix M 
Addendum 2 to the sample informed consent 
form for additional procedures 
Title: Multi-Center, Randomized, Efficacy Study of COVID-19 mRNA Vaccine in 
Regions with SARS-CoV-2 Variants of Concern 
Study number: CoVPN 3008 (Ubuntu) 
Site: [Insert site name] 
Key information 
x Enrollment in this study is now complete with 14,237 participants.  
x Some participants will be ending their participation earlier than others.  
x For people staying in the study, we are changing the schedule of procedures to 
include monthly nasal swabs through your month 12 visit.  
x We are decreasing the duration of per participant follow-up from 18 months to 
12 months  
x Participants will need to sign this addendum consent form. 
1. Review of study information 
You are a participant in CoVPN 3008 (Ubuntu), a research study that tests the 
Moderna COVID-19 vaccine in adults living with HIV and adults with existing 
health conditions that may put them at risk of severe COVID-19. The study is 
fully enrolled with 14,237 participants.  
As you were informed recently, the study sponsors have done an early review of 
the study data and have made several observations. The mRNA vaccinations 
appear safe and well tolerated by study participants, including people living with 
HIV. Participants across all sites have rarely gotten seriously ill from COVID-19, 
especially if they previously had COVID-19. Testing has shown that quite a few 
participants across sites have gotten COVID-19 during the study but without 
symptoms, and some people have had infections for weeks or months, particularly 
some people living with HIV with low CD4 counts. 
These observations, along with the fact that the pandemic and vaccine availability 
have changed since the Ubuntu study began, have led us to make some changes to 
the study as described below.  
Please review this information carefully. We also suggest that you review 
information in the main study consent form and the first addendum to the consent 
form. You are free to ask questions at any time.  

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 158 of 169 
To show that you have received and understand this information, we will ask you 
to sign this form. You will get a copy to keep.  
2. What is changing in this study? 
We are making the following changes to the study: 
x Most participants who received or will receive their final vaccination under 
version 5 of the study protocol will have a final visit as soon as possible (but 
at least a month after the final vaccination).   
x About 400 participants in this group will be asked to remain in the study for 
further monitoring until approximately 12 months after enrolment.  
x Participants who received their final vaccination under version 6 of the 
protocol (about 4000) will be asked to remain in the study until approximately 
12 months after enrolment.  
x All participants who remain in the study until month 12 after enrolment will 
also be asked to provide some additional nasal samples for COVID-19 testing.  
x If you test positive for COVID-19 you will follow the same procedures in the 
main consent form, except for the following: 
If you are still testing positive for COVID-19 at your Day 42 swab, we will 
ask you to come to the clinic for a blood draw, and again every 8 weeks 
thereafter as long as you continue to test positive for COVID-19. 
You are being asked to stay in the study to continue to provide valuable 
information. We will continue to do most of the same procedures that are 
described in the original consent form you signed that include: 
x Doing physical exams  
x Doing swabs of your nose 
x Asking questions about your health, including medications you may be taking 
x Asking you to keep track of any symptoms of COVID-19 or any other 
problems you might develop.  
x Taking blood samples 
In addition to the procedures above, we would like you to do monthly nasal swabs 
from month 6 through month 12. This means you will have additional swabs 
done, but the amount varies depending on where you are in the study. The 
updated schedule of procedures is shown below:  

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 159 of 169 
 
Procedures for Group 1 and Group 3 
Procedures  
Screening 
visit 
First 
injection 
visit 
1 month  
2 months 
6 months  
7 months  
8 months 
9 months 
10 months 
11 months 
12 months 
Injection 
 
¥ 
¥ 
 
¥ 
 
 
 
 
 
 
Physical exam 
¥ 
 
 
 
 
 
 
 
 
 
¥ 
Medical history 
¥ 
¥ 
 
 
 
 
 
 
 
 
 
Interview 
/Questionnaire 
¥ 
¥ 
¥ 
¥ 
¥ 
¥ 
¥* 
¥* 
¥* 
¥* 
¥ 
Pregnancy test 
¥ 
 
 
 
 
 
 
 
 
 
 
Ultrasound 
¥ 
 
 
 
 
 
 
 
 
 
 
HIV test 
¥ 
 
 
 
 
 
 
 
 
 
 
Blood drawn 
¥ 
¥ 
 
¥ 
¥ 
¥ 
 
 
 
 
¥ 
Nasal swabs 
 
¥ 
¥ 
 
¥ 
¥* 
¥* 
¥* 
¥* 
¥* 
¥* 
* Additional procedure/timepoint 
Procedures for Group 2 and Group 4 
Procedures  
Screening 
visit 
First 
injection 
visit 
1 month  
6 months  
7 months  
8 months 
9 months 
10 months  
11 months 
12 months 
Injection 
 
¥ 
 
¥ 
 
 
 
 
 
 
Physical exam 
¥ 
 
 
 
 
 
 
 
 
¥ 
Medical history 
¥ 
¥ 
 
 
 
 
 
 
 
 
Interview/ 
Questionnaire 
¥ 
¥ 
¥ 
¥ 
¥ 
¥* 
¥* 
¥* 
¥* 
¥ 
Pregnancy test 
¥ 
 
 
 
 
 
 
 
 
 
Ultrasound* 
¥ 
 
 
 
 
 
 
 
 
 
HIV test 
¥ 
 
 
 
 
 
 
 
 
 
Blood drawn 
¥ 
¥ 
¥ 
¥ 
¥ 
 
 
 
 
¥ 
Nasal swabs 
 
¥ 
 
¥ 
¥* 
¥* 
¥* 
¥* 
¥* 
¥* 
* Additional procedure/timepoint 
If you are testing positive for COVID-19 at Month 12, we will connect you with 
appropriate follow up as needed to support your care. 
 
 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 160 of 169 
3. You are free to choose to continue or to leave the study.  
You are still free to leave the study at any time and for any reason. If you want to 
leave, you will need to tell us. Your care at this clinic and your legal rights will 
not be affected. We may ask you to come back to the clinic one last time, and we 
may ask to take some more samples. We believe this is important to protecting 
your health, but it is up to you whether you do this. 
4. Most things described in the informed consent form and first addendum to 
the consent form you signed previously remain the same. 
These include: 
x The potential risks and benefits of being in the study; 
x Your rights and responsibilities in the study; 
x How your samples will be used; 
x How we will protect your private information and who can access your study 
records; 
x Reasons we might take you out of the study; 
x What will happen if you get sick or injured during the study. 
5. If you have questions or problems at any time during this study, use the 
following important contacts. 
If you have questions about this study, contact [name or title and telephone 
number of the investigator or other study staff]. 
If you have any symptoms that you think may be related to this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
This study has been reviewed and approved by a committee called the [name of 
local IRB/EC]. If you have questions about your rights as a research participant, 
or problems or concerns about how you are being treated in this study, contact 
[name or title and telephone number of person on IRB/EC], at the committee. 
Paragraph for South African sites. The study has been structured in accordance 
with the Declaration of Helsinki (last updated October 2013) which deals with the 
recommendations guiding doctors in biomedical research involving human 
participants, the Ethics in Health Research: Principles, Structures and Processes 
Second Edition 2015, and Guidelines for Good Practice in the Conduct of Clinical 
Trials in Human Participants in South Africa. We can provide you with copies of 
these guidelines if you wish to review them. In addition, the recent Protection of 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 161 of 169 
Personal Information Act (POPIA) ensures that all South African institutions 
conduct themselves in a responsible manner when collecting, processing, storing 
and sharing another entity’s personal information by holding them accountable 
should they abuse or compromise your personal information in any way. 
If you want to leave this study, contact [name or title and telephone number of the 
investigator or other study staff]. 
You can reach a study staff member 24-hours a day at [telephone number]. 
Remainder of section for South African sites only.  
If you have questions about this trial you should first discuss them with your 
doctor or the ethics committee (contact details as provided on this form). After 
you have consulted your doctor or the ethics committee and if they have not 
provided you with answers to your satisfaction, you should write to the South 
African Healthcare Products Regulatory Authority (SAHPRA) at: 
The Chief Executive Officer 
Dr Boitumelo Semete-Makokotlela 
South African Health Products Regulatory Authority Private Bag X828 
PRETORIA 
0001 
Tel: (012) 501 0410/13 
e-mail: Boitumelo.Semete@sahpra.org.za 
6. If you agree to continue in this study, you will need to sign or make your 
mark below. Before you sign or make your mark on this consent form, make 
sure of the following: 
x You have read this consent form, or someone has read it to you. 
x You feel that you understand what the study is about and what will happen to 
you if you continue. You understand what the possible risks and benefits are. 
x You have had your questions answered and know that you can ask more. 
x You agree to stay in this study. 
You will not be giving up any of your rights by signing this consent form. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 162 of 169 
 
 
 
 
 
 
 
Participant’s name (print) 
 
Participant’s signature or mark 
 
Date 
 
Time 
 
 
 
 
 
 
 
Clinic staff conducting consent 
discussion (print) 
 
Clinic staff signature 
 
Date 
 
Time 
For participants who are unable to read or write, a witness should complete the 
signature block below: 
 
 
 
 
 
 
 
Witness’s name (print) 
 
Witness’s signature  
 
Date 
 
Time 
*Witness is impartial and was present for the consent process. 
 
 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 163 of 169 
Appendix N 
Addendum 3 to the sample informed consent 
form for additional procedures 
Title: Multi-Center, Randomized, Efficacy Study of COVID-19 mRNA Vaccine in 
Regions with SARS-CoV-2 Variants of Concern 
Study number: CoVPN 3008 (Ubuntu) 
Site: [Insert site name] 
Key information 
x For people currently remaining in the study, we are increasing the duration of 
per participant follow-up from 12 months to 18 months. 
x We are changing the schedule of procedures to continue monthly nasal swabs 
through the month 18 visit.  
x Blood samples will also be collected at the month 18 visit. 
x Participants will need to sign this addendum consent form. 
1. Review of study information 
You are a participant in CoVPN 3008 (Ubuntu), a research study that tests the 
Moderna COVID-19 vaccine in adults living with HIV and adults with existing 
health conditions that may put them at risk of severe COVID-19. The study fully 
enrolled in September 2022 with 14,237 participants.  
A few months ago, you were asked to stay in the study but shorten your 
participation from 18 months to 12 months. You were also asked to provide nasal 
swabs every month. We are now requesting that you stay in the study for 18 
months, as originally intended, and continue to provide monthly swabs. This is 
because we are learning much more information about COVID-19 infections 
from the monthly swabs than we had expected, and this will help us achieve the 
final study objectives.   
Please review this information carefully. We also suggest that you review 
information in the main study consent form and the first addendum to the 
consent form. You are free to ask questions at any time.  
To show that you have received and understand this information, we will ask you 
to sign this form. You will get a copy to keep.  
2. What is changing in this study? 
We are making the following changes to the study: 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 164 of 169 
x All participants currently in the study are being asked to continue follow-up 
until month 18 after enrolment.  
x Monthly nasal swabs for COVID-19 testing will continue until the end of 
follow-up. This means you will have additional swabs done, but the total 
amount varies depending on where you are in the study. 
x Blood samples will also be collected at the month 18 visit. 
You are being asked to stay in the study to continue to provide valuable 
information. We will continue to do most of the same procedures that are 
described in the original consent form you signed that include: 
x Doing physical exams  
x Doing swabs of your nose 
x Asking questions about your health, including medications you may be 
taking 
x Asking you to keep track of any symptoms of COVID-19 or any other 
problems you might develop.  
x Taking blood samples 
The updated schedule of procedures is shown below:  
 
Procedures for Group 1 and Group 3 
Procedures  
Scr. 
visit 
First 
inj. 
visit 
1 month  
2 months 
6 months  
7 months  
8 months 
9 months 
10 months 
11 months 
12 months 
13 months 
14 months 
15 months 
16 months 
17 months 
18 months 
Injection 
 
¥ 
¥ 
 
¥ 
 
 
 
 
 
 
 
 
 
 
 
 
Physical exam 
¥ 
 
 
 
 
 
 
 
 
 
¥ 
 
 
 
 
 
¥* 
Medical history 
¥ 
¥ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Interview 
/Questionnaire 
¥ 
¥ 
¥ 
¥ 
¥ 
¥ 
¥ 
¥ 
¥ 
¥ 
¥ 
¥* 
¥* 
¥* 
¥* 
¥* 
¥* 
Pregnancy test 
¥ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ultrasound 
¥ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV test 
¥ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood drawn 
¥ 
¥ 
 
¥ 
¥ 
¥ 
 
 
 
 
¥ 
 
 
 
 
 
¥* 
Nasal swabs 
 
¥ 
¥ 
 
¥ 
¥ 
¥ 
¥ 
¥ 
¥ 
¥ 
¥* 
¥* 
¥* 
¥* 
¥* 
¥* 
* Additional procedure/timepoint 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 165 of 169 
Procedures for Group 2 and Group 4 
Procedures  
Scr. 
visit 
First 
inj. 
visit 
1 month  
6 months  
7 months  
8 months 
9 months 
10 months  
11 months 
12 months 
13 months 
14 months 
15 months 
16 months 
17 months 
18 months 
Injection 
 
¥ 
 
¥ 
 
 
 
 
 
 
 
 
 
 
 
 
Physical exam 
¥ 
 
 
 
 
 
 
 
 
¥ 
 
 
 
 
 
¥* 
Medical history 
¥ 
¥ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Interview/ 
Questionnaire 
¥ 
¥ 
¥ 
¥ 
¥ 
¥ 
¥ 
¥ 
¥ 
¥ 
¥* 
¥* 
¥* 
¥* 
¥* 
¥* 
Pregnancy test 
¥ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ultrasound 
¥ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV test 
¥ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood drawn 
¥ 
¥ 
¥ 
¥ 
¥ 
 
 
 
 
¥ 
 
 
 
 
 
¥* 
Nasal swabs 
 
¥ 
 
¥ 
¥ 
¥ 
¥ 
¥ 
¥ 
¥ 
¥* 
¥* 
¥* 
¥* 
¥* 
¥* 
* Additional procedure/timepoint 
If you are testing positive for COVID-19 at Month 18, we may continue offering 
testing or other follow-up appropriate to support your care. 
3. You are free to choose to continue or to leave the study.  
You are still free to leave the study at any time and for any reason. If you want to 
leave, you will need to tell us. Your care at this clinic and your legal rights will 
not be affected. We may ask you to come back to the clinic one last time, and we 
may ask to take some more samples. We believe this is important to protecting 
your health, but it is up to you whether you do this. 
4. Most things described in the informed consent form and first addendum to 
the consent form you signed previously remain the same. 
These include: 
x The potential risks and benefits of being in the study; 
x Your rights and responsibilities in the study; 
x How your samples will be used; 
x How we will protect your private information and who can access your study 
records; 
x Reasons we might take you out of the study; 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 166 of 169 
x What will happen if you get sick or injured during the study. 
5. If you have questions or problems at any time during this study, use the 
following important contacts. 
If you have questions about this study, contact [name or title and telephone 
number of the investigator or other study staff]. 
If you have any symptoms that you think may be related to this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
This study has been reviewed and approved by a committee called the [name of 
local IRB/EC]. If you have questions about your rights as a research participant, 
or problems or concerns about how you are being treated in this study, contact 
[name or title and telephone number of person on IRB/EC], at the committee. 
Paragraph for South African sites. The study has been structured in accordance 
with the Declaration of Helsinki (last updated October 2013) which deals with the 
recommendations guiding doctors in biomedical research involving human 
participants, the Ethics in Health Research: Principles, Structures and Processes 
Second Edition 2015, and Guidelines for Good Practice in the Conduct of Clinical 
Trials in Human Participants in South Africa. We can provide you with copies of 
these guidelines if you wish to review them. In addition, the recent Protection of 
Personal Information Act (POPIA) ensures that all South African institutions 
conduct themselves in a responsible manner when collecting, processing, storing 
and sharing another entity’s personal information by holding them accountable 
should they abuse or compromise your personal information in any way. 
If you want to leave this study, contact [name or title and telephone number of the 
investigator or other study staff]. 
You can reach a study staff member 24-hours a day at [telephone number]. 
Remainder of section for South African sites only.  
If you have questions about this trial you should first discuss them with your 
doctor or the ethics committee (contact details as provided on this form). After 
you have consulted your doctor or the ethics committee and if they have not 
provided you with answers to your satisfaction, you should write to the South 
African Healthcare Products Regulatory Authority (SAHPRA) at: 
 
The Chief Executive Officer 
South African Health Products Regulatory Authority 
Loftus Park 
Building A 
402 Kirkness Street 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 167 of 169 
Arcadia PRETORIA 
0083 
e-mail: Boitumelo.Semete@sahpra.org.za 
Tel: (012) 501 0413 
 
6. If you agree to continue in this study, you will need to sign or make your 
mark below. Before you sign or make your mark on this consent form, make 
sure of the following: 
x You have read this consent form, or someone has read it to you. 
x You feel that you understand what the study is about and what will happen to 
you if you continue. You understand what the possible risks and benefits are. 
x You have had your questions answered and know that you can ask more. 
x You agree to stay in this study. 
You will not be giving up any of your rights by signing this consent form. 
 
 
 
 
 
 
 
Participant’s name (print) 
 
Participant’s signature or mark 
 
Date 
 
Time 
 
 
 
 
 
 
 
Clinic staff conducting consent 
discussion (print) 
 
Clinic staff signature 
 
Date 
 
Time 
For participants who are unable to read or write, a witness should complete the 
signature block below: 
 
 
 
 
 
 
 
Witness’s name (print) 
 
Witness’s signature  
 
Date 
 
Time 
*Witness is impartial and was present for the consent process. 
 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 168 of 169 
Appendix O 
Adverse Events of Special Interest AESIs 
Nonexhaustive list of examples of AEs of Special Interest (AESI) for this protocol, derived 
in large part from the Brighton Collaboration COVID-19 Updated AESI list (section 14): 
1. Anosmia, Ageusia 
2. Subacute thyroiditis 
3. Acute pancreatitis 
4. Appendicitis 
5. Rhabdomyolysis 
6. Acute respiratory distress syndrome (ARDS) 
7. Coagulation disorders 
8. Acute cardiovascular injury 
9. Acute kidney injury 
10. Acute liver injury 
11. Dermatologic findings 
12. Multisystem inflammatory disorders 
13. Thrombocytopenia (platelet counts < 125 ×109 per mm3) 
14. Acute aseptic arthritis 
15. New onset of or worsening of neurologic disease 
16. Anaphylaxis 
17. Fibromyalgia 
18. Postural Orthostatic Tachycardia Syndrome 
19. Chronic Fatigue Syndrome (includes myalgic encephalomyelitis and postviral fatigue syndrome) 
20. Myasthenia gravis 
Note: SARS-CoV-2 symptomatic or asymptomatic infections / COVID-19 events are study 
endpoints and will not be reported as AEs or AESIs unless SAE criteria are met. 

CoVPN 3008 (Ubuntu) Version 8.0 / June 28, 2023 
CoVPN3008_v8.0_Final_28June23 / Page 169 of 169 
Appendix P 
Protocol signature page 
Multi-Center, Randomized, Efficacy Study of COVID-19 mRNA Vaccine in Regions with 
SARS-CoV-2 Variants of Concern 
I will conduct the study in accordance with the provisions of this protocol and all 
applicable protocol-related documents. I agree to conduct this study in 
compliance with United States (US.) Health and Human Service regulations (45 
CFR 46); applicable US. Food and Drug Administration regulations; standards of 
the International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) Guideline for Good Clinical Practice (E6) 
(R2); Institutional Review Board/Ethics Committee determinations; all applicable 
in-country, state, and local laws and regulations; and other applicable 
requirements (eg, US. National Institutes of Health, Division of AIDS) and 
institutional policies. 
 
 
 
 
 
 
 
 
 
Investigator of Record Name (print) 
 
Investigator of Record Signature 
 
Date 
 
 
Protocol Number: CoVPN 3008 (Ubuntu) 
Protocol Version: Version 8.0 
Protocol Date: June 28, 2023