A Comparison of Immunogenicity of Licensed RSV Vaccines in Residents of Long-Term Care Facilities (LTCF) to Community-dwelling Older Adults
Phase: PHASE4
Conditions: Respiratory Syncytial Virus (RSV)
Sponsor: University of Rochester

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Title: An Assessment of Immunogenicity of Respiratory Syncytial Virus (RSV) vaccines in residents of Long-Term Care 
Facilities (LTCF) and community-dwelling older adults receiving RSV vaccine as part of standard medical care 
 
 
 
 
 
NCT06077149 
 
 
 
 
Document Date: 01-03-2024 
 
 

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An Assessment of Immunogenicity of licensed RSV vaccines in residents of Long-Term Care 
Facilities (LTCF) and community-dwelling older adults planning Respiratory Syncytial Virus 
(RSV) vaccination as part of medical care 
 
 
 
 
 
 
 
Investigators:  
Ann R. Falsey, M.D. 
Edward E. Walsh, MD 
Angela R. Branche, MD 
 
 
University of Rochester School of Medicine and Dentistry 
Rochester, NY 
 
 
 
 
 
 
 
 
Version Number 4.0 
 
 
03 JAN 2024 
 
 
 
 
 
 
 
 
 
 
 
 

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STATEMENT OF COMPLIANCE 
This study will be carried out in accordance with Good Clinical Practice (GCP) as required by the U.S. Code of 
Federal Regulations applicable to clinical studies (45 CFR 46), and the International Commission on 
Harmonization (ICH) guidelines for Good Clinical Practice (GCP) E6.  Investigators will complete and remain 
current with appropriate Human Subjects Protection Training. The study will be conducted in accordance with 
HHS-regulatory compliance for the Federal Wide Assurance and Institutional Review Boards (IRB). 
 
 

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SIGNATURE PAGE 
The signature below constitutes the approval of this protocol and the attachments and provides the necessary 
assurances that this trial will be conducted according to all stipulations of the protocol, including all statements 
regarding confidentiality, and according to local legal and regulatory requirements and applicable US federal 
regulations and ICH guidelines. 
The University of Rochester Institutional Review Board will be guided by the ethical principles described in the 
Belmont Report and by the regulations of the U.S. Food and Drug Administration (21 CFR 50 and 56) and the 
U.S. Department of Health and Human Services (45 CFR 46). The University of Rochester maintains an 
Assurance of Compliance with the Office for Human Research Protection (OHRP).  
 
 
Primary Investigator:  Ann R. Falsey, M.D. 
 
 
Signed: 
 
 
 
 
Date: 
 
 
Ann R. Falsey, MD 
Professor of Medicine 
 
 
 
 
 
 
 
 
 

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Protocol Summary 
 
 
Title: 
An Assessment of immunogenicity of licensed Respiratory Syncytial Virus (RSV) 
vaccines in residents of Long-Term Care Facilities (LTCF) and community-dwelling older 
adults planning to receive RSV vaccination as part of medical care. 
 
 
Population: 
Adults > 60 years of age: 76 residents of LTCF and 76 participants from community-
dwelling adults. Adults living in the community will serve as the control group to reflect 
the study population enrolled in the Phase 3 Trials of the Pfizer and GSK RSV vaccines. 
 
Number of Sites: 
The study will be conducted at 3 sites (URMC and 2 local LTCF).  
 
Study Duration: 
6 months  
  
Participant Duration: The protocol requires a participant to remain in the study for 1 month. 
 
Objectives:   
The primary objective of this study is to compare the neutralizing antibody response at 
one-month post-vaccination with a licensed RSV vaccine in adults > 60 years of age 
living in skilled nursing facilities with adults living in the community. A secondary 
objective will be to evaluate the binding antibody responses to RSV preF proteins at 1 
month.  
 
Study Design 
The study will be conducted at URMC and 2 local LTCFs. Approximately 76 persons ≥ 
60 years of age who live in LTCF and an equal number of older adults living 
independently in the community who are planning to receive one of the licensed RSV 
vaccines as part of standard of care (SOC) will be recruited for participation in the study.  
 
 
Study procedures: Visits will occur at the LTCF for residents of LTCF or in the research 
clinic for community-dwelling older adults. After informed consent by the participant or 
legally authorized representative (LAR), demographic and medical history will be 
collected and a symptom-targeted physical exam will be performed. A 10 cc blood 
sample will be collected prior to vaccination. Following vaccine administration, 
individuals will be monitored for 15 minutes for immediate adverse events. One 
additional visit will occur at 1 month post vaccination at which time 10 cc of blood will be 
collected, the participant will be interviewed and medical records reviewed. Subjects will 
be queried about any intervening respiratory illnesses and persons testing positive for 
RSV infection as part of the standard of care (SOC) after vaccination or by a non-
vaccine RSV protein by ELISA and before the 1-month blood draw will not be included in 
the immunogenicity analysis. Serum samples will be tested for binding (RSV A and RSV 
B PreFusion F, Attachment (G) protein) and neutralizing antibodies to RSV A and RSV B 
in the URMC research laboratory.  
 
 

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BACKGROUND and RATIONALE 
 
RSV is a major cause of respiratory infection in all ages, which can result in severe illness in 
both infants and older adults.1-4  Like influenza, RSV infection follows a seasonal pattern, causing yearly 
wintertime epidemics in temperate climates. Although most well recognized as a pediatric pathogen, RSV was 
first acknowledged as a serious threat to adults when outbreaks of acute respiratory infection (ARI) with high 
pneumonia and mortality rates were reported in nursing homes settings in the 1980s.5,6  Since the initial 
reports, prospective studies demonstrate infection rates in LTCF ranging from 1-12%.7-10  RSV infection is 
particularly problematic for very elderly adults and those with underlying medical conditions, particularly heart 
and lung disease.1,11-13 RSV not only causes respiratory tract infection but can also trigger exacerbations of 
underlying comorbid conditions such as COPD and CHF.14 RSV infection has been associated with up to 22% 
of acute COPD exacerbations in prospective cohort studies and 11% of wintertime hospitalizations for COPD 
exacerbations.1,15 
 
Current epidemiology shows that RSV is responsible for approximately 100,000-177,000 hospitalizations and 
9,000-14,000 deaths annually in US adults 65 years of age and older.4,16,17   Morbidity is significant among 
adults hospitalized with RSV disease, with 18% requiring intensive care, 31% needing home health services at 
discharge, and 26% dying within 1 year of hospitalization. In some studies, the risk of poor outcomes and 
death is higher among patients hospitalized for RSV compared to influenza.13,18  In addition to the acute 
morbidity, longer term functional loss has been demonstrated following RSV hospitalization and the group most 
severely affected are residents of LTCFs.19 The overall burden of adult RSV disease is likely underestimated 
since testing for RSV is less common in older adults than in children and RSV is more difficult to detect due to 
low levels of virus in the upper airways.20,21 
 
Presently there is no specific antiviral treatment for RSV disease and management in adults is limited to 
supportive therapies such as hydration and oxygenation. Thus, a major unmet public health need has been to 
prevent RSV infection in at risk adults through vaccination. Two adult RSV vaccines (produced by GSK and 
Pfizer) are now licensed by the FDA, and are available in the fall of 2023 for use in adult populations age 60 
years or older. The current vaccines are both based on the RSV prefusion F protein.  The RSV F glycoprotein 
facilitates fusion of the virion and host cell membranes through a transition from an unstable but highly 
immunogenic prefusion conformation to a more stable post-fusion state.22 Preclinical studies show that 
prefusion F elicits much higher neutralizing antibody titers than post-fusion F and that the most potent 
neutralizing antibodies from post-infection human sera target the prefusion form. 23,24 The vaccine 
manufactured by Pfizer is a bivalent RSV prefusion F subunit vaccine (RSVpreF) and is marketed under the 
brand name ABRYSVO. The vaccine manufactured by GSK is a monovalent RSV prefusion F with the 
adjuvant AS01E and is marketed under the brand name AREXVY. 
 
Although the placebo-controlled randomized phase 3 studies of the Pfizer and GSK RSV vaccines each 
demonstrated >80% efficacy to prevent lower respiratory tract disease (LRTD), the trials have been criticized 
because the populations were relatively healthy older adults and not representative of individuals who are at 
highest risk for poor outcomes, including residents of LTCF.26,27 Conducting large efficacy vaccine studies in 
LTCF residents is particularly challenging, and therefore this population was not well assessed in the clinical 
trials. For example, only 1.2 % resided in LTCF in the GSK RSV vaccine trial and LTCF residence was not 
reported in the Pfizer trial. Although a valid criticism, given the high efficacy demonstrated in the clinical trials, 
randomized clinical trials with a placebo is no longer ethical in high-risk populations. Concern about the lack of 
representation has resulted in the AMDA (American Medical Directions Association for Post-Acute and Long-
Term Care Medicine) and the American Geriatric Society’s reluctance to make strong recommendations for 
RSV vaccine use in this very high-risk population. RSV vaccines are to be prescribed in LTCFs using shared 
clinical decision making per ACIP recommendations, despite clear evidence that the general medical 
community is not familiar with the risks of RSV disease and the risks and benefits of RSV vaccine.  Although 
there is no precise correlate of immunity to RSV, the high efficacy of the current pre-F vaccines that stimulate 

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robust neutralizing antibodies against RSV suggests that a significant vaccine-induced antibody response in 
residents of LTCF would likely be protective. This study will assess the antibody response to the current RSV  
vaccines in the vulnerable population of LTCF residents and compare the immune response to a concurrently 
enrolled group of community-dwelling adults ≥60 years that reflect the phase 3 trial population. These data will 
be important to help support the likely benefit of RSV vaccination in LTCF populations.  
 
STUDY DESIGN and OBJECTIVES 
 
This is an open label non-inferiority study where all participants will receive either the licensed Pfizer RSV 
Vaccine (ABRYSVO) or the GSK RSV Vaccine (AREXVY) as part of Standard of Care (SOC) and immune 
responses will be compared between adults living in the community and adults living in LTCF. The vaccines 
available at the participating LTCF as part of SOC will direct what product is administered at the individual 
LTCF and the community cohort will be matched for similar proportions of ABRYSVO and AREXVY. 
 
Primary Objectives:  
 
Demonstrate that the peak immune response at 1 month post vaccination of adults 60 years and older residing 
in LTCF is non-inferior to community-dwelling adults 60 years and older as measured by: 
• 
Serum neutralizing antibody against RSV A & B 
 
Secondary Objectives: 
 
Demonstrate that the peak immune response at 1-month post vaccination of adults 60 years and older residing 
in LTCF is non-inferior to community-dwelling adults 60 years and older as measured by: 
• 
Serum binding antibody to RSV prefusion F protein against RSV A & B 
 
 
Study Period and Sites:  
The study will be conducted at the University of Rochester Medical Center (URMC) in collaboration with 2 local 
LTCFs and include the Highlands at Brighton and St. Ann’s Home. These LTCFs are located geographically 
close to URMC and have expressed a high interest in participating in this study. The study period will be from 
November 2023 to April 2024. There will be 1 month of direct participant involvement and 6 months for 
completion of the immune assays and data analysis. 
 
Participant Recruitment:  
For the cohort of LTCF residents, participant recruitment will be coordinated with the staff of the participating 
LTCF. At Highlands of Brighton the LTCF will identify individuals who express interest in the study. The LTCF 
staff contact individuals and legally authorized representatives to obtain consent for influenza, RSV, and 
COVID vaccination during the annual vaccination campaigns. During the conversation regarding SOC RSV 
vaccination with an FDA-approved RSV vaccine, LTCF staff will also assess potential interest in participating in 
the clinical study related to RSV vaccination for residents accepting the RSV vaccine as part of SOC. Those 
individuals who express interest in both receiving a licensed RSV vaccine as SOC and also participating in a 
research study will be directed to a member of the study team who will provide more detailed information about 
the study and if appropriate provide an IRB-approved consent form for review and consideration. St Ann’s 
Home uses an opt-out approach when communicating with residents and LAR about vaccines. If residents or 
LAR’s do not opt-out they will be scheduled for RSV vaccination. St Ann’s will include in the opt-out letter a 
statement that a member of the research team will contact them about the study if they do not opt-out of RSV 
vaccination. Included in the communication will be the ability to-opt out of contact with the research team.  
The major source for recruitment for the community cohort at URMC will be our RedCap Database Registry 
(STUDY00000413) of participants who have previously agreed to be contacted for future research 

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opportunities. We will send them an email to ascertain interest in the proposed study if RSV vaccination is 
planned as part of routine medical care. Potential participants will be provided the clinic phone number and the 
web-based registry to express interest (https://www.urmc.rochester.edu/idrc-research-studies.aspx). We will 
include all genders, races, and ethnicities in the study. We will use our IRB-approved screening protocol 
(STUDY00000484) to perform an initial pre-screening for basic inclusion and exclusion criteria after which, for 
those interested and meeting study criteria, we will set up a screening/enrollment appointment in the clinic. We 
will e-mail information on their scheduled appointment and a copy of the IRB-approved consent for the 
participant to review. Questions about the study will be answered prior to or during the enrollment visit.   
 
Inclusion and Exclusion: 
Inclusion criteria are intended to be broad with relatively few exclusions to reflect a real-life population in LTCF. 
Inclusion:  
• 
≥60 years of age who live in skilled nursing facilities or reside independently in the community  
• 
Life expectancy of >6 months, as assessed by the investigator 
• 
Able to sign informed consent or to provide consent via a legally authorized representative (LAR) 
• 
Planning to receive an RSV vaccine as part of standard medical care 
 
Exclusion criteria:  
• 
History of a current immunosuppressive condition or receipt of chemotherapy or other 
immunosuppressive or cytotoxic therapy, including chronic prednisone use of ≥ 20 mg/day for more 
than 14 days within 3 months of study vaccination 
• 
History of hypersensitivity or reaction to any vaccine component 
• 
Simultaneous administration of another vaccine (influenza, SARS-CoV-2) or within a 14-day 
window before or after intervention 
• 
Previous receipt or intended receipt of an RSV vaccine outside the study 
• 
Receipt of blood/plasma products or immunoglobulin within 60 days before study intervention 
administration. 
• 
Documented RSV infection within 2 months prior to study intervention (enrollment). 
 
Criteria for Temporarily Delaying Enrollment/Administration of Study Intervention: 
The following conditions may allow a participant to be enrolled once the conditions have been resolved and the 
participant is otherwise eligible. Participants meeting these criteria at Visit 1 will be considered screen failures if 
enrollment has closed once the condition(s) has/have resolved. 
• 
Current febrile illness (temperature ≥38.0°C [≥100.4°F]) or other acute illness within 48 hours before 
study intervention administration 
• 
Receipt of any vaccine (including COVID-19 vaccines authorized for temporary or emergency use) 
within 14 days before study intervention administration 
• 
Anticipated receipt of any non-study vaccine within 14 days after study intervention administration 
• 
Receipt of short-term (<14 days) systemic corticosteroids (the equivalent of ≥20 mg/day of prednisone) 
• 
Study intervention administration should be delayed until systemic corticosteroid use has been 
discontinued for at least 28 days. 
Note: Systemic corticosteroids administered at a dose of <20 mg/day of prednisone or equivalent are 
permitted. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted. 
 
 

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Study Procedures:  
 
For residents of LTCF all procedures will be conducted on-site at the LTCF and for the community cohort, all 
procedures will be conducted in the research clinic. No study procedures will be performed prior to consent.  
 
 
It is anticipated that most LTCF residents will have a screening/enrollment visit and that vaccination will occur 
separately as per the LTCF vaccination plans. In most cases, the community cohort will have screening and 
vaccination on the same visit.  
 
Schedules of Activities are listed below.  
 
Schedule of Activities  
 
 
Category of Activity 
Research 
Standard of 
Care 
Research 
Visit Number 
V0a 
V1a 
V2 
Visit Type 
Screening and 
Enrollment 
Vaccination 
1-month (D28) 
Visit Window 
up to -21 days before 
vaccination 
 
D21-42 after 
vaccination/infection 
Visit Location 
LTCF/clinic 
LTCF/clinic 
LTCF/clinic 
Informed Consent 
up to -21 days before 
vaccination 
 
 
I/E 
X 
 
 
Medical History 
X 
 
X 
Vaccine History 
X 
 
X 
Prohibited Medication Review 
X 
 
X 
Vital Signs 
X 
Xc 
 
Targeted PEb 
X 
Xc 
 
Collect 10cc serum 
X 
 
X 
Vaccinate 
 
X 
 
15-minute Observation (post vaccination) 
 
Xc 
 
Review ARI history and test results 
 
 
X 
SAE review 
 
 
X 
 
 
a Informed consent and screening activities can be separate or combined with Visit 1.   
b Targeted physical exam will be performed on screening and before vaccination only as clinically indicated based on the presence of 
signs or symptoms warranting further investigation. 
c Vaccination related procedures will be guided by SOC at each location 
 
 

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CONSENT PROCESS 
Research Clinic: Consent and HIPAA Authorization will be documented by signing of an approved Informed 
Consent Form. Consent will be obtained utilizing the procedures outlined in the IDRC Research Group (SOP 
1.1, version 6) by either the study investigator, research nurse, or a study coordinator. In brief, an IRB-
approved consent describing the study will be provided to participants to review in the clinic. After adequate 
time to review the form, an informed consent discussion will take place in a room in the Infectious Diseases 
Research Clinic. During the visit, the document will be reviewed with the participant and all questions will be 
answered. Brief questioning of the participant will be completed after reading the forms to ensure 
understanding. At all times, we will ensure that all concerns are fully addressed and no procedures will be 
performed prior to obtaining informed consent. After signing the consent, the participant will be provided with a 
copy of the form, with the original copy filed with source documentation. A Consent Checklist is employed at 
the end of the visit to ensure that all essential tasks have been completed.   
LTCF: Since it is anticipated that many residents of the LTCF will have some degree of cognitive impairment 
and be unable to sign the Informed Consent Form we will use one of two methods for consent. If the potential 
subject has mental capacity and autonomy, we will utilize the same consent process described above in the 
Research Clinic. If, however, the subject does not have the mental capacity to sign their own consent we will 
obtain consent from their Legally Authorized Representative (LAR). When feasible this will also use the same 
process described in the Research Clinic. Alternatively, this will be performed by obtaining a verbal consent 
by phone from the LAR that documents consent for subjects to participate in the study and addresses Privacy 
Protection described in HIPAA Authorization statements (see under Privacy and Confidentiality section). We 
request a waiver of documentation of consent and alteration of elements of consent for the verbal 
consent process. This is considered reasonable as it is not practical to carry out this minimal risk study without 
a waiver. For many LARs it may be inconvenient and a hardship to appear in-person due to work or family 
commitments, living out of town, or health reasons. Consent will be obtained utilizing the procedures outlined in 
the IDRC standard operating procedures (SOP 1.1, version 6.0) by either the study investigators, research 
nurse, or a study coordinator. SOP 1.6, version 1.0 specifically outlines the procedures to be used for remote 
consent by LAR. By phone or tele-visit, the consent will be reviewed with the LAR by research personnel and 
the LAR will be provided time for questions. The consent form will indicate that results of the study, and 
additional information if appropriate, will be provided to the LAR once the study has been completed. The LAR 
will indicate their consent and the consent will then be signed by study personnel. A signed copy of the 
informed consent will be mailed back to the LAR.  
If after LAR consent is obtained, it is clear that the participant does not wish to participate, the participant will 
be withdrawn. 
 
PRIVACY AND CONFIDENTIALITY OF PARTICIPANTS AND RESEARCH DATA 
We have requested an alteration of HIPAA Authorization in the verbal consenting process (described 
above). Elements of the authorization will not be altered. The disclosure of Protected Health Information (HPI) 
is necessary in order to accurately enroll eligible subjects and for verification of medical conditions that would 
make a subject ineligible for this minimal risk study. PHI will not be reused or shared except as required by law, 
such as with the IRB for oversight of the study, and potentially the FDA who may evaluate results of the study, 
or for other research for which the use or disclosure of PHI would be permitted by the HIPAA Privacy Rule. 
This information sharing is included in the standard and verbal ICFs. All source data will be maintained in a 
locked office in a locked file cabinet, with all electronic data maintained on a password-protected University 
computer. All transmitted data inputted into the eCRF (Redcap) will be identified by only a study ID. All 
samples will be identified with only a sample ID.  Future analyses of these samples may be performed in-
house or in collaboration with other research groups  
 
 

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Standard of Care Vaccines Offered 
Name 
RSVpreF (ABRYSVO) 
Type 
Vaccine 
Formulation 
The active ingredients in RSVpreF are 2 stabilized RSV prefusion 
F antigens, in equal amounts from virus subgroups A and B, in a 
lyophilized dosage form for reconstitution.  
Dose 
120ug of the RSV prefusion F antigen 
Route of Administration 
IM in non-dominant deltoid muscle 
Source 
Pfizer 
 
Name 
RSVpreF (AREXVY) 
Type 
Vaccine 
Formulation 
The active ingredient is RSVpreF stored in single use 
lyophilized form requiring reconstitution. The adjuvant AS01E is composed 
of MPL and QS-21 combined in a phosphate buffered solution and water 
for reconstituting RSVpreF. 
Dose 
120ug of the RSV prefusion F antigen 
Route of Administration 
IM in non-dominant deltoid muscle 
Source 
GSK 
 
Study Procedures 
No study-specific procedure will be conducted before informed consent is obtained. Visits 0 and 1 may be 
performed on the same day, where feasible.  
 
Visit 0 (Research Procedures) 
• 
Obtain informed consent from the participant or LAR before performing any study-specific procedures 
• 
Assign a single participant identifier 
• 
Ensure and document that all of the inclusion criteria and none of the exclusion are met 
• 
Obtain and record the participant's demography (including complete date of birth, sex, race, racial 
designation, and ethnicity)  
• 
Obtain and record medical history 
• 
Obtain and record details of any non-study vaccinations, and prohibited concomitant medications and 
treatments 
• 
Perform a clinical assessment including vital signs (Blood pressure, heart rate and oxygen saturation) 
and symptom-targeted physical exam 
*Note: Height and weight will be recorded as by participant report or medical record in LTCF. 
• 
Collect 10 cc of serum 
• 
Confirm contact and alternate contact information with participant and LTCF staff 
• 
Schedule visit 2. 
 
 
 

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Visit 1 (Standard of Care) [Vaccination: For LTCF this will be performed by LTCF staff per their facility 
protocol and for Community Cohort this will be performed in the clinic] 
• 
Perform a clinical assessment including vital signs (Blood pressure, heart rate and temperature) and 
symptom-targeted physical exam as dictated by location of vaccination standard procedures. 
• 
Vaccinate with ABRYSVO or AREXVY and in non-dominant arm and document product, time and 
location. 
• 
15 minutes of observation in the clinic, in LTCF standard practice will be followed 
If a person has an intercurrent RSV infection and is not vaccinated as part of SOC, visit 2 will be scheduled 28 
-42 days after infection was documented.  
 
Visit 2 (Research Procedures) [1-month] 
• 
Verbally confirm the participant wishes to continue in the study 
• 
Obtain and record any new medical history 
• 
Inquire about any respiratory illnesses and record results any viral testing performed. 
• 
Collect information on AEs, SAEs related to study procedures 
• 
Obtain and record details of any non-study vaccinations, and prohibited concomitant medications and 
treatments 
• 
Perform a symptom-targeted clinical assessment and physical exam   
• 
Collect 10 cc of serum. 
 
Individuals who do not meet the criteria for participation in the study (screen failure) can be rescreened if the 
exclusionary condition is considered to be temporary in nature by the investigator.  
Only the following information will be collected on screen failures: demographics (age, screen number, sex, 
ethnicity, and race) and reason for ineligibility. Participants who are found to be ineligible will be told the reason 
for ineligibility. 
LABORATORY METHODS: 
 
RSV PCR will be performed as standard of care in the LTCF. 
 
Enzyme Immunoassay (EIA): Serum IgG titers to RSV F (prefusion) protein of group A and B RSV will be 
determined by enzyme immunoassay using established methods.28 Briefly, purified RSV proteins are coated to 
96-well EIA plates to which serum 2-fold dilutions are added in duplicate. Bound antibody is detected with 
alkaline phosphatase-conjugated goat anti-human IgG antibody and substrate. 
 
Microneutralization Assay (MNA): Serum neutralizing titers will be performed using an established 
microneutralization method for RSV A and B strains.28 Briefly, 2-fold serum dilutions are incubated with 75 
plaque forming units of RSV for 30 min at room temperature followed by the addition of 104 HEp-2cells in 96-
well culture plates. After 3 days, the quantity of RSV antigen is determined by enzyme immunoassay using a 
monoclonal antibody to the RSV F protein. The neutralization titer is defined as the serum dilution that results 
in a 50% reduction in color development. 
 
ANALYTICAL AND STATISTICAL METHODS 
 
The primary immunogenicity analysis will include persons vaccinated but without documented RSV infection 
(PCR or G ELISA. The immune response to infection alone or combined infection and vaccination will be 
analyzed descriptively and separate from the primary analysis.  This study is designed to demonstrate non-
inferiority to within a 1.5-fold difference in the 1-month titer level, adjusting for baseline titer level. Since the 
distribution of titer levels is strongly positively skewed, and we are interested in relative changes, all titer levels 

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will be log transformed to help symmetrize the distribution while simultaneously stabilizing the variance. 
Exponentiating arithmetic mean log(titer), and their differences, thus results in geometric mean titer levels, and 
relative changes therein, which are the desired metrics. A linear model will be used to model log (1-month titer) 
as a function of an indicator for population, adjusted for continuous log (baseline titer). This model is equivalent 
to modeling log (relative change in titer), 1-month vs baseline, as a function of an indicator for population, 
adjusted for continuous log (baseline titer). The adjustment for log (baseline titer) improves statistical efficiency 
compared with using a 2-sample t-test to compare either (a) log (relative change in titer) or (b) log (1-month 
titer) by population, while obviating the choice between them. The focal parameter is the regression coefficient 
on population, whose antilog represents the ratio (test population vs reference population) of the adjusted 
geometric mean titer level (and, equivalently, the ratio of the adjusted relative geometric mean 1-month change 
in titer level). If the 1-sided 95% lower bound for this ratio exceeds 2/3, indicating with 95% confidence that the 
geometric mean titer level for the test population is at least 2/3 as high as that of the reference population (i.e. 
that the geometric mean titer level for the reference population is at most 1.5 times that of the test population), 
then we will conclude non-inferiority of the test population relative to the reference population.  
 
Power and Sample Size Considerations:  
Based on data from 52 participants in a prior study of the Pfizer RSV vaccine, the geometric mean titer level 
was estimated to be 2218 (95% CI: 1822-2699) at baseline, and 22,510 (17,003-29,799) at 1-month, 
corresponding with a relative change of 10.15-fold (95% CI: 7.39-13.95). From this data we estimate the 
Standard Deviation (SD) of log(titer) to be 0.71 at baseline and 1.01 at 1-month, while the SD of the 1-month 
change in log(titer) is 1.14 –larger than SD (log (1-month titer), indicating that a 2-sample t-test of the change 
in log(titer) would be less efficient than a t-test of the 1-month log(titer). Since we plan to adjust for baseline 
log(titer), our residual SD < min (SD (log (1-month titer), SD (log (relative change in titer) = min (1.01, 1.14) = 
1.01. But not much less, since the prior data suggests the correlation between baseline and 1-month log(titer) 
is very weak (r=0.14), with log (baseline titer) explaining only 2% of the variability in log (1-month titer). In 
particular, we estimate residual SD = 1, suggesting that a 2-sample t-test of log (1-month titer) would be nearly 
as efficient as our linear model-based test adjusting for log (baseline titer). Given this estimate of variability 
(SD=1), a sample size of 76, 89, or 105 per group provides 80%, 85%, or 90% power to demonstrate non-
inferiority to within a relative non-inferiority margin of 1.5-fold using a 1-sided 0.05 level linear model-based t-
test comparing log (1-month titer) by population, adjusted for log (baseline titer). We have chosen a sample 
size of 76 in each group which will provide 80% power to demonstrate non-inferiority.  
 
 
POTENTIAL RISKS AND BENEFITS 
This study may be associated with risk due to sample collection or loss of privacy. 
Sample Collection:  
• 
Blood draws: A blood draw may cause faintness, inflammation of the vein, pain, bruising, or bleeding 
at the site of the puncture. There is also a slight chance of infection. 
Loss of Confidentiality: Basic demographic and health information will be collected on participants in this 
study; therefore, there is a possibility of breach of confidentiality. Participant confidentiality will be maintained 
using study numbers on all data collection forms and keeping personal health information (PHI) separate. 
These documents are available to study personnel only and are kept under double-locked secure areas at 
URMC. Only study numbers are written on the data collection forms. All data are entered into Redcap and 
stored on the University of Rochester’s Server. This server requires two authentications and specific training 
and documentation for access by investigators and staff.  
Potential Benefits 
There are no benefits to subjects for participating in the study 
Costs/Payments 

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• 
The participant or their insurance company will not incur any additional costs for being in the study; any 
additional research testing will be paid for by the study 
• 
Subjects will receive a $100 check for visit 1 (this may be split into two $50 payments if screening and 
vaccination occur on separate days) and $50 for visit 2. 
Participant Status 
• 
Participants will be free to withdraw at any time without providing a reason  
• 
A participant may be withdrawn from the study if the investigator feels it is unsafe for them to continue 
• 
New findings that might influence a participant’s decision to participate will be made known to potential 
participants. 
Safety 
SAEs will be monitored from the time of consent to the final visit. Any SAE related to a study procedure will be 
reported to the IRB within 24 hours. 
 
Definitions: 
A serious adverse event (SAE) is any AE that: 
• 
Results in death 
• 
Is life-threatening (i.e., causes an immediate risk of death) 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization 
• 
Results in persistent or significant disability or incapacity (i.e., substantial disruption of the ability to conduct 
normal life functions) 
• 
Results in a congenital anomaly or birth defect 
• 
Considered to be an important medical event.   
 
Reporting Responsibilities: 
 
A medically qualified investigator will provide a causality assessment for each SAE. The Principal 
Investigator should provide a rationale and medical justification for this determination.  This assessment 
is to be recorded on the CRF and the SAE Report Form (for SAEs) along with a description of the SAE that 
is sufficiently detailed to allow for a complete medical assessment of the case and determination of 
possible causality. All SAEs will be followed until resolution, until the event is considered stable, or until a 
non-study causality is assigned. 
 
FUTURE USE OF SAMPLES 
 
The purpose of allowing future testing of samples obtained as part of the current protocol is to maximize value 
for biomedical research. Specimens to be used for future use will be blood. Samples will be stored in the 
University of Rochester Infectious Diseases Unit laboratories at URMC (Biorepository IRB 00008473). The 
samples will be maintained in locked freezers in secure locations in the medical center. All freezers have 
temperature monitors and are alarmed if temperatures deviate from the control range. Only the investigators 
listed on the protocol will maintain this repository and will have access to these samples. Samples will not be 
stored with any personal identifiers and will be labeled only with a coded study number. Data linked to the 
samples will be kept in a separate secure location on password protected computers.  Investigators outside 
the investigative team or at other institutions may request permission to use the samples only with the 
permission of the primary investigators. Samples will be de-identified and coded anonymously if 
tested outside the University. Analyses of these future use of samples may be performed in-house or 
in collaboration with other research groups.  
 
 
Genetic testing that might result in health consequences for an individual will not be permitted as part of this 
protocol. No samples will be sold for commercial development.  
 
Samples will be kept indefinitely in the repository. Participants may withdraw from future use at any time by 

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contacting the investigators. Samples will be located and destroyed at that time.  
 
No future contact with participants will be sought regarding health conditions or related to the stored samples. 
 
 
 

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