A Randomized, Double-blind, Placebo-controlled Phase 3 Study to Evaluate the Safety and Immunogenicity of an Ad26.RSV.preF-based Vaccine in Adults Aged 18 to 59 Years, Including Those at High-risk for Severe RSV
Phase: PHASE3
Conditions: Respiratory Syncytial Virus Infection Prevention
Sponsor: Janssen Vaccines & Prevention B.V.

CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
1
Status: Approved,  Date: 30 November 2021
Janssen Vaccines & Prevention B.V.*
Clinical Protocol
A Randomized, Double-blind, Placebo-controlled Phase 3 Study to Evaluate the Safety and
Immunogenicity of an Ad26.RSV.preF-based Vaccine in Adults Aged 18 to 59Years,
Including Those at High-risk for Severe RSV
Protocol VAC18193RSV3006; Phase 3
Amendment 2
VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
* Janssen Vaccines & Prevention B.V. is a Janssen pharmaceutical company of Johnson & Johnson and is
hereafter referred to as the sponsor of the study. The sponsor is identified on the Contact Information page
that accompanies the protocol.
Studies conducted at sites in the United States (US)will be conducted under US Food & Drug
Administration Investigational New Drug (IND) regulations (21 CFR Part 312).
Regulatory Agency Identifier Number:
EudraCT NUMBER: 2021‐001909‐77
Status: 
Approved
Date: 
30 November 2021
Prepared by: 
Janssen Vaccines & Prevention B.V.
EDMS number: 
EDMS-RIM-319564, 3.0
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory
requirements.
Confidentiality Statement
The information provided herein contains Company trade secrets, commercial or financial information that the Company
customarily holds close and treats as confidential.  The information is being provided under the assurance that the recipient
will maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or
otherwise.
NCT05070546

VAC18193 (JNJ-64400141/ JNJ-64213175)
Clinical Protocol VAC18193RSV3006 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
2
Status: Approved, Date: 30 November 2021
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document 
Date
Amendment 2 
This document
Amendment 1 
25 August 2021
Original Protocol 
12 May 2021
Amendment 2 (30 November 2021)
Overall Rationale for the Amendment: In response to feedback from Health Authorities,
additional guidance is being provided in Appendix to the protocol for inclusion of participants in
Cohort 2, with examples of chronic cardiac and pulmonary comorbidities eligible for participation
in this Cohort.
Furthermore, additional language referring to laboratory diagnostic tests that may be performed
for the follow-up and assessment of potential adverse events of special interest (AESIs) was added.
Clarifications were made with regards to co-participation in the observational phase of
interventional studies and the use of immunoglobulins expected to have an impact on immune
response. Clarifications have also been made to the schedule of activities with regard to recording
of medical history  and the possibility to split screening and vaccination into two visits.
Additionally, a few minor updates were made in alignment with the latest Janssen protocol
template.
The changes made to the clinical protocol VAC18193RSV3006 as part of Protocol Amendment 2
are listed below, including the rationale of each change and a list of all applicable sections. The
changes do not impact the objectives and endpoints, study conduct, scientific integrity of the study,
or the safety of the participants.
Changes made in the previous protocol amendment are listed in Section 10.11 Appendix 11:
Protocol Amendment History.
Section Number 
and Name
Description of Change 
Brief Rationale
5.1 Inclusion Criteria 
10.10 Appendix 10: 
Guidance on Eligible 
Chronic Heart and
Lung Conditions for
Cohort 2
Additional guidance was provided on
eligible chronic heart and long conditions
for Cohort 2.
Upon Health Authority request
1.3 Schedule of 
Activities 
8.3.6.1 Thrombosis 
with 
Thrombocytopenia
Syndrome
Additional language referring to
laboratory diagnostic tests for the
assessment of potential AESIs was
added.
To facilitate and simplify the local site
management of follow-up testings in the
event of potential AESIs.
5.2 Exclusion Criteria 
It was clarified in Exclusion Criterion 7
that the exclusion oftreatment with
Clarification

VAC18193 (JNJ-64400141/ JNJ-64213175)
Clinical Protocol VAC18193RSV3006 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
3
Status: Approved, Date: 30 November 2021
Section Number 
and Name
Description of Change 
Brief Rationale
immunoglobulins applies to those
immunoglobulins expected to impact the
vaccine-induced immune response.
5.2 Exclusion Criteria 
Footnote for Exclusion Criterion 14 was 
updated to clarify that co-participation in
the observational phase of interventional
studies may be allowed during the
current study, if approved by the sponsor
or its delegate.
Clarification
1.3 Schedule of 
Activities 
It was clarified that risk factors for blood 
clotting events and thrombocytopenia are
to be collected and documented as part of
the medical history at screening.
Clarification
1.1 Synopsis 
1.2 Schema 
1.3 Schedule of 
Activities 
4.1 Overall Design
5 STUDY
POPULATION
5.5 Criteria for
Temporarily Delaying
Study Vaccine
Administration
It was clarified that screening and 
vaccination may be split into 2 visits in 
consultation with the sponsor or its 
delegate.
To allow more flexibility in timing of
screening and vaccination in the best
interest of participants.
1.1 Synopsis 
4.1 Overall Design  
It was clarified that enrollment in Spain 
will be limited to Cohorts 2 and 3. 
Enrollment in Cohort 1 has been
completed in other participating countries.
4.4 End of Study 
Definition  
8.3.1 Time Period and 
Frequency for
Collecting AE, SAE,
and AESI Information
8.3.3 Follow-up of
AEs, SAEs, and AESIs
10.2.4 Special
Reporting Situations
10.2.6 PQC Handling
10.3.14 Study and Site
Start and Closure
10.8 Appendix 8:
Guidance on Study
Conduct During a
Natural Disaster
A few minor updates were made in 
alignment with the latest Janssen 
protocol template.
To align with the most recent Janssen
protocol template.
Throughout the 
protocol 
Minor grammatical, formatting, or 
spelling changes were made.
Minor errors were noted

VAC18193 (JNJ-64400141/ JNJ-64213175)
Clinical Protocol VAC18193RSV3006 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
4
Status: Approved, Date: 30 November 2021
TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................................... 2
TABLE OF CONTENTS ............................................................................................................................... 4
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 6
1. 
PROTOCOL SUMMARY..................................................................................................................... 7
1.1. 
Synopsis........................................................................................................................................... 7
1.2. 
Schema.......................................................................................................................................... 16
1.3. 
Schedule of Activities..................................................................................................................... 17
2. 
INTRODUCTION................................................................................................................................ 20
2.1. 
Study Rationale.............................................................................................................................. 20
2.2. 
Background .................................................................................................................................... 21
2.3. 
Benefit-Risk Assessment............................................................................................................... 23
2.3.1. 
Risks Related to Study Participation .......................................................................................... 23
2.3.2. 
Benefits of Study Participation.................................................................................................... 25
2.3.3. 
Benefit-Risk Assessment of Study Participation ........................................................................ 25
3. 
OBJECTIVES AND ENDPOINTS ..................................................................................................... 26
4. 
STUDY DESIGN ................................................................................................................................ 29
4.1. 
Overall Design................................................................................................................................ 29
4.2. 
Scientific Rationale for Study Design............................................................................................. 31
4.2.1. 
Study-Specific Ethical Design Considerations ........................................................................... 31
4.3. 
Justification for Dose...................................................................................................................... 32
4.4. 
End of Study Definition................................................................................................................... 32
5. 
STUDY POPULATION ...................................................................................................................... 32
5.1. 
Inclusion Criteria............................................................................................................................ 33
5.2. 
Exclusion Criteria........................................................................................................................... 35
5.3. 
Lifestyle Considerations................................................................................................................. 38
5.4. 
Screen Failures.............................................................................................................................. 38
5.5. 
Criteria for Temporarily Delaying Study Vaccine Administration ................................................... 38
6. 
STUDY VACCINE(S) AND CONCOMITANT THERAPY ................................................................. 39
6.1. 
Study Vaccine Administration ........................................................................................................ 39
6.2. 
Preparation/Handling/Storage/Accountability ................................................................................ 39
6.3. 
Measures to Minimize Bias: Randomization and Blinding............................................................. 41
6.4. 
Study Vaccination Compliance ...................................................................................................... 42
6.5. 
Dose Modification........................................................................................................................... 42
6.6. 
Continued Access to Study Vaccine After the End of the Study ................................................... 42
6.7. 
Treatment of Overdose .................................................................................................................. 43
6.8. 
Concomitant Therapy..................................................................................................................... 43
7. 
DISCONTINUATION OF STUDY VACCINATION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL............................................................................................... 44
7.1. 
Discontinuation of Study Vaccination............................................................................................. 44
7.2. 
Participant Discontinuation/Withdrawal From the Study................................................................ 44
7.2.1. 
Withdrawal From the Use of Research Samples ....................................................................... 45
7.3. 
Lost to Follow-up............................................................................................................................ 45
8. 
STUDY ASSESSMENTS AND PROCEDURES ............................................................................... 46
8.1. 
Immunogenicity Assessments ....................................................................................................... 47
8.2. 
Safety Assessments....................................................................................................................... 48
8.2.1. 
Physical Examinations................................................................................................................ 49

VAC18193 (JNJ-64400141/ JNJ-64213175)
Clinical Protocol VAC18193RSV3006 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
5
Status: Approved, Date: 30 November 2021
8.2.2. 
Vital Signs................................................................................................................................... 49
8.2.3. 
Pregnancy Testing...................................................................................................................... 49
8.3. 
AEs, SAEs, AESIs and Other Safety Reporting ............................................................................ 49
8.3.1. 
Time Period and Frequency for Collecting AE, SAE, and AESI Information.............................. 50
8.3.2. 
Method of Detecting AEs, SAEs, and AESIs.............................................................................. 51
8.3.3. 
Follow-up of AEs, SAEs, and AESIs .......................................................................................... 52
8.3.4. 
Regulatory Reporting Requirements for SAEs........................................................................... 52
8.3.5. 
Pregnancy................................................................................................................................... 52
8.3.6. 
Adverse Events of Special Interest............................................................................................. 53
8.3.6.1. 
Thrombosis with Thrombocytopenia Syndrome...................................................................... 53
8.4. 
Medical Resource Utilization.......................................................................................................... 55
9. 
STATISTICAL CONSIDERATIONS.................................................................................................. 55
9.1. 
Statistical Hypotheses.................................................................................................................... 55
9.2. 
Sample Size Determination ........................................................................................................... 55
9.2.1. 
Immunogenicity........................................................................................................................... 55
9.2.2. 
Safety.......................................................................................................................................... 56
9.3. 
Populations for Analysis Sets ........................................................................................................ 57
9.4. 
Statistical Analyses ........................................................................................................................ 58
9.4.1. 
General Considerations.............................................................................................................. 58
9.4.2. 
Participant Information................................................................................................................ 58
9.4.3. 
Immunogenicity Analyses........................................................................................................... 58
9.4.3.1. 
Primary Endpoints ................................................................................................................... 58
9.4.3.2. 
Secondary/Exploratory Immunogenicity Endpoints................................................................. 59
9.4.4. 
Safety Analyses.......................................................................................................................... 60
9.5. 
Planned Analyses .......................................................................................................................... 60
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ............................ 61
10.1. 
Appendix 1: Abbreviations ............................................................................................................. 61
10.2. 
Appendix 2: AEs, SAEs, AESIs, PQCs, and Other Safety Reporting: Definitions and
Procedures for Recording, Evaluating, Follow-up, and Reporting................................................. 62
10.2.1. 
AE Definitions and Classifications.............................................................................................. 62
10.2.2. 
Attribution Definitions.................................................................................................................. 63
10.2.3. 
Severity Criteria.......................................................................................................................... 63
10.2.4. 
Special Reporting Situations ...................................................................................................... 64
10.2.5. 
Procedures ................................................................................................................................. 64
10.2.6. 
PQC Handling............................................................................................................................. 66
10.2.7. 
Contacting Sponsor Regarding Safety, Including Product Quality............................................. 66
10.3. 
Appendix 3: Regulatory, Ethical, and Study Oversight Considerations......................................... 67
10.3.1. 
Regulatory and Ethical Considerations ...................................................................................... 67
10.3.2. 
Financial Disclosure.................................................................................................................... 70
10.3.3. 
Informed Consent Process ......................................................................................................... 70
10.3.4. 
Data Protection........................................................................................................................... 71
10.3.5. 
Long-Term Retention of Samples for Additional Future Research ............................................ 72
10.3.6. 
Committees Structure................................................................................................................. 72
10.3.7. 
Publication Policy/Dissemination of Clinical Study Data............................................................ 72
10.3.8. 
Data Quality Assurance.............................................................................................................. 73
10.3.9. 
Case Report Form Completion................................................................................................... 74
10.3.10. Source Documents ..................................................................................................................... 74
10.3.11. Monitoring ................................................................................................................................... 75
10.3.12. On-Site Audits............................................................................................................................. 75
10.3.13. Record Retention........................................................................................................................ 76
10.3.14. Study and Site Start and Closure ............................................................................................... 76
10.4. 
Appendix 4: Contraceptive and Barrier Guidance ......................................................................... 78
10.5. 
Appendix 5: New York Heart Association Classification of Cardiac Disease ................................ 79
10.6. 
Appendix 6: Toxicity Grading Scale For Use in Cohorts 1 and 2 (Adults Aged 18 to 59
Years)............................................................................................................................................. 80

VAC18193 (JNJ-64400141/ JNJ-64213175)
Clinical Protocol VAC18193RSV3006 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
6
Status: Approved, Date: 30 November 2021
10.7. 
Appendix 7: Toxicity Grading Scale For Use in Cohort 3 (Adults Aged 60 Years and
Older) ............................................................................................................................................. 83
10.8. 
Appendix 8: Guidance on Study Conduct During a Natural Disaster ............................................ 86
10.9. 
Appendix 9: Thrombotic Events to be Reported as Potential AESIs ............................................. 88
10.10. Appendix 10: Guidance on Eligible Chronic Heart and Lung Conditions for Cohort 2 .................. 89
10.11. Appendix 11: Protocol Amendment History................................................................................... 90
11. REFERENCES................................................................................................................................... 93
INVESTIGATOR AGREEMENT................................................................................................................. 95
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1: 
Overview of the Cohorts, Groups, and Targeted Number of Participants................................ 30
Table 2: 
Summary of Immunogenicity Assays (Humoral) ...................................................................... 48
Table 3: 
Summary of Immunogenicity Assays (Cellular)........................................................................ 48
Table 4: 
Laboratory Tests That May Be Performed Upon Sponsor Request on Immunogenicity
Samples Collected on Day 1, Day 15 and/or Day 183 ............................................................. 54
Table 5: 
Laboratory Tests That May Be Requested by the Sponsor to be Performed at the
Central Laboratory After Potential AESI Reporting .................................................................. 54
Table 6: 
Probability to Observe at Least One AE by Given True AE Rates........................................... 57
FIGURES
Figure 1: Schematic Overview of the Study............................................................................................. 16
Figure 2: Upper-Limit of the One-sided 95% CI around the Proportion if no Events are
Observed by Number of Participants........................................................................................ 57

VAC18193 (JNJ-64400141/ JNJ-64213175)
Clinical Protocol VAC18193RSV3006 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
7
Status: Approved, Date: 30 November 2021
1. 
PROTOCOL SUMMARY
1.1. 
Synopsis
A Randomized, Double-blind, Placebo-controlled Phase 3 Study to Evaluate the Safety and
Immunogenicity of an Ad26.RSV.preF-based Vaccine in Adults Aged 18 to 59 Years, Including Those
at High-risk for Severe RSV
The respiratory syncytial virus (RSV) vaccine that will be investigated in the current study, the
Ad26/protein preF RSV vaccine (VAC18193), is a combination of 2 vaccine components, administered as
a single intramuscular (IM) injection:
 
Ad26.RSV.preF (JNJ-64400141), a replication-incompetent adenovirus serotype 26 (Ad26)
containing a DNA transgene that encodes the prefusion conformation-stabilized F protein (pre-F)
derived from the RSV A2 strain.
 
RSV preF protein (JNJ-64213175), a recombinant pre-F protein derived from the RSV A2 strain.
The aim of this study is to demonstrate the safety and immunogenicity of the Ad26/protein preF RSV
vaccine in adults aged 18 to 59 years, who are in stable health as well as individuals with existing chronic
heart or lung conditions who are at higher risk for severe RSV disease. The World Health Organization
(WHO) Guidelines on Clinical Evaluation of Vaccines recommend obtaining safety and immunogenicity
in the vaccine target population, which may include people with comorbidities predisposing to the
development of severe RSV disease. Additionally, vaccination of healthcare workers and
caregivers/educators of children or adults living with or caring for individuals at higher risk for severe
disease and complications may be beneficial. Besides the known substantial disease burden in adults aged
65 years and older and in the population with specific comorbidities (increased risk), a recent modelling
estimate of disease burden in adults in the UK shows comparable burden of RSV attributable outcomes
(medical visit, hospitalization) in 50 to 64-year-olds at low risk and 18 to 49 -year-olds at increased risk. In
this study, vaccine immunogenicity in the 18 to 59-year-olds and in high-risk adults aged 18 to 59 years
will be assessed relative to adults aged 65 years and older, an age group in which efficacy has been
demonstrated in study VAC18193RSV2001. Successful demonstration of comparable immune responses
in these 2 populations, both  relative to adults aged 65 years and older will allow to bridge efficacy
demonstrated in the latter population.
The virus neutralizing antibody assay (VNA) against RSV A2 strain  will be used as the primary
immunogenicity assay to demonstrate non-inferiority of immunogenicity in terms of neutralizing antibody
geometric mean titers (GMTs) and seroresponse rates in adults aged 18 to 59 years and in high-risk adults
aged 18 to 59 years, both relative to adults 65 years of age and above. This immunogenicity measure was
selected upon request from  the FDA to use a functional immune marker for immunobridging and
extrapolation of the vaccine efficacy to another population. In the absence of a defined immune correlate
of protection, the preF binding antibody titers will also be evaluated as a secondary endpoint in this study
in a descriptive fashion. The preliminary findings from the correlate of protection analysis based on data
from VAC18193RSV2001 showed that both VNA and preF ELISA absolute titers have strong correlation
with protection from RSV disease.

VAC18193 (JNJ-64400141/ JNJ-64213175)
Clinical Protocol VAC18193RSV3006 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
8
Status: Approved, Date: 30 November 2021
OBJECTIVES AND ENDPOINTS
Objectives 
Endpoints
Primary
 
To assess the safety and reactogenicity of 
Ad26.RSV.preF-based RSV vaccine in healthy 
adults aged 18 to 59 years 
 
Solicited local (injection site) and systemic
AEs for 7 days after vaccination
 
Unsolicited AEs for 28 days after
vaccination
 
Serious adverse events (SAEs) and adverse
events of special interest (AESIs) until
6 months after vaccination
 
To assess the safety and reactogenicity of 
Ad26.RSV.preF-based RSV vaccine in adults 
aged 18 to 59 years at high-risk of severe RSV 
disease 
 
Solicited local (injection site) and systemic
AEs for 7 days after vaccination
 
Unsolicited AEs for 28 days after
vaccination
 
SAEs and AESIs until 6 months after
vaccination
 
To demonstrate the non-inferiority of the 
humoral response to the administration of 
Ad26.RSV.preF-based vaccine in adults aged 
18 to 59 years versus in adults aged 65 years 
and older 
 
Neutralizing antibody titers against RSV
A2 strain at 14 days after vaccination
 
Seroresponse rate* at 14 days after
vaccination as determined by neutralization
assay (VNA-A2).
 
If non-inferiority is demonstrated in adults: 
To demonstrate the non-inferiority of the 
humoral response to the administration of 
Ad26.RSV.preF-based vaccine in high-risk 
adults aged 18 to 59 years versus in adults 
aged 65 years and older
 
Neutralizing antibody titers against RSV
A2 strain at 14 days after vaccination
 
Seroresponse rate* at 14 days after
vaccination as determined by neutralization
assay (VNA-A2).
* Seroresponse is defined as a 4 fold increase from baseline in Day 15 antibody titers.
Secondary
 
Investigate the vaccine-induced immune 
responses post-vaccination 
 
Pre-F ELISA antibody titers at 14 days
after vaccination
Exploratory
 
To assess the persistence of immune response 
post-vaccination 
 
Pre-F ELISA antibody titers at 6 months
after vaccination
 
Neutralizing antibody titers against RSV A2
strain at 6 months after vaccination
 
To further explore the humoral immune 
responses elicited by the Ad26.RSV.preF- 
based vaccine 
 
Neutralizing antibody titers against RSV B
strains and other RSV A strains
 
Neutralizing antibody titers against Ad26
 
Molecular and functional antibody
characterization including antibody avidity,
Fc-mediated effector function, subtyping
and isotyping, glycosylation patterns,
antibody sequencing for repertoire†

VAC18193 (JNJ-64400141/ JNJ-64213175)
Clinical Protocol VAC18193RSV3006 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
9
Status: Approved, Date: 30 November 2021
Objectives 
Endpoints
 
To explore the cellular immune responses 
elicited by the Ad26.RSV.preF-based vaccine 
in a subset of participants (ie, the Cellular 
Immuno Subset) 
 
RSV-F specific interferon gamma (IFN-γ)
enzyme-linked immunospot (ELISpot) and
detailed immunoprofiling which may
include analysis of T-cell and B-cell
responses to RSV F protein peptide-
stimulated peripheral blood mononuclear
cell (PBMC) (including, but not limited to,
CD4+/CD8+, Th1/Th2, IL-2, IFN-γ, TNF-
α, activation markers and memory markers)
using flow cytometry or mass cytometry
† Exploratory endpoints are optional. Exploratory assessments are based on the outcome of ongoing testing in
other studies. Some testing may not be performed or reported.
Hypotheses
To demonstrate the non-inferiority ofthe humoral immune response to Ad26/protein preF RSV vaccine in
all adults aged 18 to 59 years (Group 1+3) versus in adults aged 65 years and older (Group 5) and in
high-risk adults aged 18 to 59 years (Group 3) versus in adults aged 65 years and older (Group 5)in terms
of neutralizing antibody GMTs and seroresponse rates.
The following hypotheses will be tested sequentially:
Null Hypothesis 1:
 
Ad26/protein preF RSV vaccine induces inferior humoral immune response in terms of VNA A2
antibody GMTs at Day 15 in adults aged 18 to 59 years (Groups 1 and 3) versus in adults aged 65 years
and older (Group 5).
OR
 
Ad26/protein preF RSV vaccine induces inferior humoral immune response in terms of seroresponse
rates of VNA A2 antibody titers at Day 15 in adults aged 18 to 59 years (Groups 1 and 3) versus in
adults aged 65 years and older (Group 5).
Alternative Hypothesis 1:
 
Ad26/protein preF RSV vaccine induces non-inferior humoral responses in terms of VNA A2 antibody
GMTs at Day 15 in adults aged 18 to 59 years (Groups 1 and 3) versus in adults aged 65 years and
older (Group 5).
AND
 
Ad26/protein preF RSV vaccine induces non-inferior humoral responses in terms ofseroresponse rates
of VNA A2 antibody titers at Day 15 in adults aged 18 to 59 years (Groups 1 and 3) versus in adults
aged 65 years and older (Group 5).
Success Criterion 1 (All Adults):
Non-inferiority of immune response in all adults is demonstrated:
 
if the lower limit of the 2-sided 95% confidence interval (CI) for the VNA A2 GMT ratio of all adults
aged 18 to 59 years versus in adults aged 65 years and older (GMTGroup 1+3/GMTGroup 5) is >0.67.
AND

VAC18193 (JNJ-64400141/ JNJ-64213175)
Clinical Protocol VAC18193RSV3006 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
10
Status: Approved, Date: 30 November 2021
 
if the lower limit of the 2-sided 95% CI for the seroresponse rate difference of all adults aged 18 to
59 years versus in adults aged 65 years and older (Seroresponse Rate Group 1+3 –Seroresponse Rate Group
5) based on the VNA A2 antibody titers is >-0.1
If non-inferiority is demonstrated in all adults for both neutralizing antibody GMTs and seroresponse rates,
then the following hypothesis will be tested:
Null Hypothesis 2:
 
Ad26/protein preF RSV vaccine induces inferior humoral response in terms of VNA A2 antibody
GMTs at Day 15 in high-risk adults aged 18 to 59 years (Groups 3) versus in adults aged 65 years and
older (Group 5).
OR
 
Ad26/protein preF RSV vaccine induces inferior humoral response in terms of seroresponse rates of
VNA A2 antibody titers at Day 15 in high-risk adults aged 18 to 59 years (Group 3) versus in adults
aged 65 years and older (Group 5).
Alternative Hypothesis 2:
 
Ad26/protein preF RSV vaccine induces non-inferior humoral response in terms of VNA A2 antibody
GMTs at Day 15 in high-risk adults aged 18 to 59 years (Groups 3) versus in adults aged 65 years and
older (Group 5)
AND
 
Ad26/protein preF RSV vaccine induces non-inferior humoral response in terms of seroresponse rates
of VNA A2 antibody titers at Day 15 in high-risk adults aged 18 to 59 years (Groups 3) versus in adults
aged 65 years and older (Group 5).
Success Criterion 2 (High-risk Adults):
Non-inferiority of immune response in high-risk adults is demonstrated:
 
if the lower limit of the 2-sided 95% CI for the VNA A2 GMT ratio of high-risk adults aged 18 to
59 years versus in adults aged 65 years and older (GMTGroup 3/GMTGroup 5) is >0.67.
AND
 
if the lower limit of the 2-sided 95% CI for the seroresponse rate difference of high-risk adults aged
18 to 59 years versus in adults aged 65 years and older (Seroresponse Rate Group 3 –Seroresponse Rate
Group 5) based on the VNA A2 antibody titers is >-0.1.
OVERALL DESIGN
This is a randomized, double-blind, placebo-controlled, multicenter, interventional Phase 3 study to
evaluate the safety and immunogenicity of the Ad26/protein preF RSV vaccine in adults aged 18 to
59 years, including those who are at high-risk of severe RSV disease. A cohort of adults aged 65 years and
older will also be included (see table below). The study vaccine will be administered as a single IM
injection.
Participants will be stratified for COVID-19 vaccine administration (3 categories: 1. Janssen COVID-19
vaccine, 2. Vaxzevria® (Oxford/AstraZeneca), 3. other vaccine, or no vaccine).

VAC18193 (JNJ-64400141/ JNJ-64213175)
Clinical Protocol VAC18193RSV3006 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
11
Status: Approved, Date: 30 November 2021
Table: 
Overview of the Cohorts, Groups, and Targeted Number of Participants
Cohort 
Group  N 
Day 1 (Vaccination)
1 
healthy adults, 18 to 59 years 
1 
315 
Ad26.RSV.preF 1×1011 vp + RSV preF protein
150 μg
2 
70 
Placebo
2 
high-risk adults, 18 to 59 years a 
3 
315 
Ad26.RSV.preF 1×1011 vp + RSV preF protein
150 μg
4 
70 
Placebo
3 
adults, 65 years and older 
5 
315 
Ad26.RSV.preF 1×1011 vp + RSV preF protein
150 μg
6 
28 
Placebo
N = number of participants, vp = virus particles.
In all cohorts, participants will be stratified for COVID-19 vaccine administration.
All cohorts will be enrolled in parallel. Enrollment in Spain will be limited to Cohorts 2 and 3.
Safety and humoral immunogenicity assessments will be performed for all participants.
For a subset of the participants, additional cellular immunogenicity assessments will be performed. This
subset will be referred to as the Cellular Immuno Subset and will consist of approximately 63 active study
vaccine participants and approximately 7 placebo participants per cohort. The Cellular Immuno Subset will
be recruited in specific study sites.
After vaccination, participants will remain under observation at the study site for at least 30 minutes for
presence of any acute reactions and solicited events. Any unsolicited AEs, solicited local (injection site) or
systemic AEs, and vital signs (sitting systolic and diastolic blood pressure, heart rate, respiratory rate, and
body temperature) will be documented by study site personnel following this observation period. In
addition, participants will record temperature and solicited signs and symptoms in a participant diary
beginning on the evening of the day of vaccination and on a daily basis for 7 days post-vaccination.
Blood will be collected from all participants to assess humoral immune responses pre-vaccination and at
14 days and 6 months post-vaccination. Additional blood will be collected from the Cellular Immuno Subset
to assess cellular immune responses pre-vaccination and at 14 days and 6 months post-vaccination.
Safety issues that might arise from this study may be escalated to an Independent Data Monitoring
Committee, as needed.
The end of the study is defined as the last participant’s last visit.
NUMBER OF PARTICIPANTS
A target of 1,113 participants will be enrolled: 385 healthy adults aged 18 to 59 years will be enrolled in
Cohort 1 and randomized in a 9:2 ratio to receive Ad26/protein preF RSV vaccine or placebo; 385 high-
risk adults aged 18 to 59 years will be enrolled in Cohort 2 and randomized in a 9:2 ratio to receive
Ad26/protein preF RSV vaccine or placebo, 343 adults aged 65 years and older will be enrolled in Cohort
3 and randomized in a 45:4 ratio to receive Ad26/protein preF RSV vaccine or placebo.
VACCINATION GROUPS AND DURATION
The study duration will be approximately 6 months per participant. The study comprises screening (pre-
vaccination) and vaccination for each participant on Day 1, and a 6-month safety and immunogenicity
follow-up period.

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Study Vaccine Administration
The active study vaccine to be used in this study is Ad26/protein preF RSV vaccine, composed of
Ad26.RSV.preF and RSV preF protein, to be administered as a single injection (1.0 mL) in the deltoid
muscle:
 
Ad26.RSV.preF (JNJ-64400141) will be used at a dose level of 1×1011 virus particles (vp).
 
RSV preF protein (JNJ-64213175) will be used at a dose level of 150 μg.
Placebo for Ad26/protein preF RSV vaccine will be 0.9% saline (1.0 mL).
IMMUNOGENICITY EVALUATIONS
All Participants
For all participants (N=1,113), venous blood samples of approximately 20 mL will be collected for the
determination of humoral immune responses at Day 1, Day 15 and Month 6 visits.
Humoral immunogenicity evaluations are summarized in the table below. These include exploratory
assays that may be performed based on the outcome of other ongoing clinical studies.
Assay 
Purpose
Primary endpoint
RSV A neutralizing assay (VNA A2) 
Analysis of neutralizing antibodies against the RSV A2 strain
Secondary endpoint
RSV A pre-F binding antibody preF 
ELISA)
Analysis of antibodies binding to RSV A F protein in pre-fusion form
Exploratory endpoints
RSV strain cross neutralization 
Analysis of cross-neutralizing antibodies to RSV B and/or a different
RSV A strain(s) using virus neutralization assays and/or other
surrogate antibody-binding assays
Adenovirus neutralization assay  
Analysis of neutralizing antibodies to Ad26
Molecular and functional antibody 
characterization  
Analysis of antibody characteristics including, but not limited to,
ADCC, ADCP, avidity, Ig isotype, functional VNAs and binding
antibodies to other respiratory viruses, and antibody assessments for
antibody repertoire
ADCC = antibody-dependent cell-mediated cytotoxicity; ADCP = antibody-dependent cellular phagocytosis; ELISA
= enzyme-linked immunosorbent assay; Ig = immunoglobulin; VNA = virus neutralization assay.
Cellular Immuno Subset
For a subset of the participants, ie, the Cellular Immuno Subset (N=210), additional venous blood samples
of approximately 40 mL will be collected for the determination of cellular immune responses at Day 1,
Day 15 and Month 6 visits.
Cellular immunogenicity evaluations are summarized in the table below.
Assay 
Purpose
Exploratory endpoint
IFN-γ ELISpot 
T-cell IFN-γ responses to RSV F protein peptides
Detailed immunoprofiling 
Analysis of T-cell responses to RSV F protein peptide-stimulated
PBMC (including, but not limited to, CD4+/CD8+, IL-2, IFN-γ,
TNF-α, activation markers and memory) using ICS/cytoF
cytoF = flow cytometry; ELISpot = enzyme-linked immunospot; ICS = intracellular cytokine staining; IFN  =
interferon; IL = interleukin; PBMC = peripheral blood mononuclear cell; TNF = tumor necrosis factor.

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SAFETY EVALUATIONS
Safety assessments will include the monitoring of AEs, physical examinations, and vital signs.
AEs and special reporting situations, whether serious or non-serious, that are related to study procedures or
that are related to non-investigational sponsor products will be reported from the time a signed and dated
informed consent form (ICF) is obtained until the end of the study/early withdrawal. Solicited AEs,
collected through a participant diary, will be recorded from the time of vaccination until 7 days post-
vaccination. All other unsolicited AEs and special reporting situations, whether serious or non-serious, will
be reported from the time of vaccination until 28 days post-vaccination. All SAEs, AESIs, and AEs leading
to discontinuation from the study (regardless of the causal relationship) are to be reported from the moment
of vaccination until completion of the participant’s last study-related procedure, which may include contact
for safety follow-up. All AEs will be followed until resolution or until clinically stable.
STATISTICAL METHODS
Sample Size Determination
Humoral Immunogenicity Analysis
Immunogenicity assessments will be performed in all participants.
Sample size calculations for the immunogenicity objectives are performed under the following assumptions.
For the humoral immune response in terms of neutralizing antibody GMTs:
 
no difference between all adults aged 18 to 59 years (Groups 1 and 3) and adults aged 65 years and
older (Group 5) and no difference between high-risk adults aged 18 to 59 years and adults aged
65 years and older (ie, assuming a true GMT ratio of Day 15 [ie, 14 days after vaccination] RSV A2
neutralizing antibody titers equal to 1 for those comparisons, and similar standard deviation)
 
a standard deviation of 1.5 at the log2 scale for VNA A2 on Day 15*
 
non-inferiority limit of 0.67 (2/3)
 
1-sided α of 2.5%
For the humoral immune response in terms of neutralizing antibody seroresponse rates (defined as a 4-fold
increase from baseline in Day 15 antibody titers):
 
Seroresponse rates are assumed to be 85% in all adults aged 18 to 59 years, high risk adults aged 18 to
59 years and adults aged 65 years and older, based on available data from Phase 1/2 clinical studies,
 
Non-inferiority margin of 10%
 
1-sided α of 2.5%
In addition:
 
a ratio of 1:1:1 for the active groups in Cohorts 1, 2, and 3
 
hierarchical testing (ie, test first Group 1+3 versus Group 5, if non-inferiority is demonstrated: test
Group 3 versus Group 5)
Simulations show that a total of 285 evaluable participants per active group in each cohort are needed to
have 90% power to demonstrate non-inferiority in terms of neutralizing antibody GMT and seroresponse
* Based on Day 15 VNA A2 results obtained from Cohort 2, Group 14 in study VAC18193RSV1004.

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rates between high-risk adults aged 18 to 59 years and adults aged 65 years and older. With this sample
size, the power to demonstrate non-inferiority in terms of neutralizing antibody GMT and seroresponse
rates between all adults aged 18 to 59 years and adults aged 65 years and older is >95%. The power to
demonstrate non-inferiority for the high-risk adults aged 18 to 59 years and adults aged 65 years and older
is approximately  90%, taking into account the testing strategy (sequential testing). To account for
exclusions from the Per-protocol Immunogenicity (PPI) Set, drop-outs, and missing samples,
approximately 315 participants per active group should be enrolled.
Safety Analysis
Solicited AEs, unsolicited AEs, SAEs and AESIs will be collected in all participants.
In Cohorts 1 and 2, a placebo group (Groups 2 and 4) of approximately 70 high-risk adults aged 18 to
59 years and of approximately 70 healthy adults aged 18 to 59 years is added for blinding purposes. In
Cohort 3, a placebo group (Group 6) of approximately 28 adults aged 65 years and older is added for
blinding purposes.
Populations for Analysis Sets
The Full Analysis (FA) Set will include all participants who received study vaccine, regardless of the
occurrence of protocol deviations and vaccine type (study vaccine or placebo). All safety and participant
information analyses will be based on the FA Set.
The PPI Set will include all randomized participants who received study vaccine and for whom
immunogenicity data are available. Samples taken after a participant experienced a major protocol deviation
expected to impact the immunogenicity outcomes will be excluded from the PPI Set.
The list of major protocol deviations that would lead to elimination from the immunogenicity analysis will
be specified in the Statistical Analysis Plan (SAP) or major protocol violation criteria document, which will
be finalized before database lock and unblinding.
The primary analysis set for analyses related to RSV immunogenicity is the PPI Set. As a sensitivity
analysis, key tables may also be based on the FA Set.
Immunogenicity Analyses
The primary immunogenicity objectives will be assessed sequentially.
To assess non-inferiority in terms of GMTs, 2-sided CIs will be calculated for the difference in log2-
transformed VNA A2 antibody titers at 14 days after active vaccination between all adults aged 18 to 59
years (Groups 1 and 3) and adults aged 65 years and older (Group 5) and between high-risk adults aged 18
to 59 years (Group 3) and adults aged 65 years and older (Group 5). The GMT ratio and CIs for the
neutralizing antibody GMT objectives will be calculated via an analysis of variance (ANOVA) including
all active groups (ie, Groups 1, 3, and 5) with Day 15 (ie, 14 days after vaccination) VNA A2 antibody
titers as dependent variable and group as independent variable and COVID-19 vaccination as astratification
factor (3 categories: 1. Janssen COVID-19 vaccine, 2. Vaxzevria (Oxford/AstraZeneca), 3. other vaccine,
or no vaccine). The CIs around the difference will be back-transformed (by exponentiation) to CIs around
a GMT ratio (GMTGroup x/GMTGroup 5,with x=1+3 or x=3) and compared to the non-inferiority limit of 0.67
(2/3).
To assess non-inferiority in terms of seroresponse rates (co-primary objective), 2-sided CIs will be
calculated for the difference in seroresponse rates 14 days after active vaccination for the same comparisons.
Seroresponse based on VNA A2 antibody titers is defined as a 4-fold increase from baseline on Day 15.
The Newcombe (Score) with continuity correction method will be used to calculate the CIs for the
difference in seroresponse rates (Seroresponse Rate Group x –Seroresponse Rate Group 5, with x=1+3 or x=3)

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and compared with the non-inferiority margin of -0.1. This analysis will be stratified for COVID-19
vaccination.
Non-inferiority of the humoral immune response to Ad26/protein preF RSV vaccine in all adults aged 18 to
59 years (Groups 1 and 3) versus in adults aged 65 years and older (Group 5) is demonstrated if the lower
limit of the 2-sided 95% CI of the estimated GMT ratio is >0.67 and if the lower limit of the 2-sided 95%
CI of the estimated difference in seroresponse rates is >-0.1.
If non-inferiority in all adults aged 18 to 59 years (Groups 1 and 3) is not demonstrated for both neutralizing
antibody GMTs and seroresponse rates, the study fails. If non-inferiority in all adults aged 18 to 59 years
is demonstrated for both neutralizing antibody GMTs and seroresponse rates, then non-inferiority in high-
risk adults aged 18 to 59 years (Group 3) can be tested; similarly, non-inferiority of the humoral immune
response to Ad26/protein preF RSV vaccine in high-risk adults aged 18 to 59 years (Group 3) versus in
adults aged 65 years and older (Group 5) is demonstrated if the lower limit of the 2-sided 95% CI of the
estimated GMT ratio is >0.67 and if the lower limit of the 2-sided 95% CI of the estimated difference in
seroresponse rates is >-0.1.
As a sensitivity analysis to assess the impact of baseline titers, the neutralizing antibody GMT primary
endpoint will also be evaluated adjusting for the respective baseline titers. For immunogenicity, baseline is
considered as the last assessment pre-vaccination. In a second sensitivity analysis, different variances
between the groups will be allowed. Therefore, the CIs will be calculated via Welch’s ANOVA.
Baseline is considered as the last available assessment before the vaccination.
The percentage of participants with a seroresponse (and corresponding 2-sided 95% CI) at Day 15 will be
tabulated for VNA A2 antibody titers. Seroresponse is defined as a 4-fold increase from baseline in Day 15
antibody titers. For pre-F ELISA, the percentages of participants with 2- and 4-fold increase from baseline
will also be tabulated.
Descriptive statistics (such as geometric mean and 95% CI for preF ELISA antibody titers and VNA A2,
and median and quartiles for IFN-γ and ELISpot) will be calculated for continuous immunogenicity
parameters at all available timepoints. For the humoral assays, geometric mean fold rises from baseline
with 95% CIs will be calculated additionally.
Graphical representations of immunogenicity parameters will be created as applicable. For categorical
variables, frequency tables will be presented and corresponding CIs may be calculated where appropriate.
Safety Analyses
No formal statistical testing of safety data is planned.
Safety data (including solicited and unsolicited AEs) will be analyzed descriptively by cohort and group.
All safety analyses will be based on the FA Set.

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1.2. 
Schema
Figure 1: 
Schematic Overview of the Study
* Screening and vaccination may be split into 2 visits in consultation with the sponsor or its delegate.
** By telephone.
Safety - 7 days after study vaccination**
1 
2
3
4
5
VISIT
Immunogenicity and Safety - 14 days after study vaccination
Safety - 28 days after study vaccination**
Safety and Immunogenicity - 6 months after study vaccination
Screening and Vaccination: Day 1*

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i. 
Blood for cellular immune responses at the time points indicated will be drawn only from Cellular Immuno Subset participants.
j. 
After vaccination, participants will remain under observation at the study site for at least 30 minutes for presence of any acute reactions and solicited events. Any
unsolicited AEs, solicited local (injection site)or systemic AEs, and vital signs (systolic and diastolic blood pressure [sitting], heart rate, respiratory rate after at
least 5 minutes rest, and body temperature) will be documented by study-site personnel following this observation period.
k. 
AESIs, including potential AESIs, are to be reported to the sponsor from the moment of vaccination until 6 months after the vaccination. See Section 8.3.6.
l. 
Concomitant therapies will be collected from the time of study vaccination through 28 days post-vaccination when associated with an AE, and from ICF signature
until 6 months post-vaccination when associated with an SAE or AESI.
m. Any history of SARS-COV-2 vaccination (name/manufacturer of the vaccine and date of administration, whenever possible) prior to and during the study will be
collected in the eCRF.
n. 
Rulers and thermometers will be distributed at Visit 1.
o. 
Participants will be contacted by telephone 2 to 4 days post-vaccination to remind them to fill in the participant diaries and to check that they are entering
information correctly.
p. 
Screening and vaccination may be split into 2 visits in consultation with the sponsor or its delegate. Every effort should be made for split visits to occur preferably
within 3 to 5 days and no later than 10 days, and pre-vaccination vital signs should be repeated on the day of vaccination if this visit is split.
q. 
As part of the medical history, the investigator must collect and document risk factors for blood clotting events and thrombocytopenia at screening. As done for
any other medical history events, the information must be entered on the relevant eCRF pages such as Medical History page or Concomitant Medication page.
r. 
Aliquots of serum samples collected for immunogenicity tests can be reconverted for participant’s safety purposes upon sponsor request. Please refer to Table 4 for
a non-exhaustive list of tests that may be requested to be performed on these samples in case of potential AESI reporting.

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2. 
INTRODUCTION
The respiratory syncytial virus (RSV) vaccine that will be investigated in the current study, the
Ad26/protein preF RSV vaccine (VAC18193), is a combination of 2 vaccine components,
administered as a single intramuscular (IM) injection:
 
Ad26.RSV.preF (JNJ-64400141), a replication-incompetent adenovirus serotype 26 (Ad26)
containing a DNA transgene that encodes the prefusion conformation-stabilized F protein
(pre-F) derived from the RSV A2 strain.
 
RSV preF protein (JNJ-64213175), a recombinant pre-F protein derived from the RSV A2
strain.
For the most comprehensive nonclinical and clinical information regarding the Ad26/protein preF
RSV vaccine, refer to the latest version of the Investigator’s Brochure (IB) for Ad26/protein preF
RSV vaccine (IB Ad26/protein preF RSV vaccine 2021).
The term “study vaccine” used throughout the protocol, refers to the Ad26/protein preF RSV
vaccine or placebo as defined in Section 6.1.
The term “sponsor” used throughout this document refers to the entities listed in the Contact
Information page(s), which will be provided as a separate document.
2.1. 
Study Rationale
The World Health Organization (WHO) Guidelines on Clinical Evaluation of Vaccines
(WHO 2017) recommend obtaining safety and immunogenicity in the vaccine target population,
which may include people with comorbidities predisposing to the development of severe RSV
disease. Individuals with certain medical conditions are at high-risk of severe sequelae from RSV
infection. These conditions can be broadly classified as either chronic heart or lung conditions (eg,
asthma, COPD, congestive heart failure) or immunologic (eg, human immunodeficiency virus
infection, post-transplant immunosuppression) (CDC 2020; Falsey 2005, 2006; Walsh 2004).
Chronic heart and lung conditions are unlikely to interfere with the immune response to the
Ad26/protein preF RSV vaccine. In the ongoing study VAC18193RSV2001, 334 participants
(167 received Ad26/protein preF RSV vaccine, 167 received placebo) aged 65 years and older
with non-severe chronic cardiac and/or pulmonary disease were included in the safety subset.
Based on preliminary data of this safety subset, adults with these conditions are not considered to
be at increased risk of adverse events (AEs) due to the Ad26/protein preF RSV vaccine itself. The
Immuno Subset of this study consisted of 24 participants at increased risk for severe RSV disease
in the Ad26/protein preF RSV vaccine group. The preliminary data of this immune subset suggest
a similar immune response for the participants aged 65 years and older who are at increased risk
for severe RSV disease in comparison to the healthy participants in the same age range.
This study is designed to evaluate the immunogenicity of the Ad26/protein preF RSV vaccine in
the 18- to 59-year-old population with the focus on the medical need for prevention of RSV in
adults who are at risk for a severe RSV burden. Similar to the population above the age of 65 years,

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chronic heart and lung conditions are comorbidities that place the 18- to 59-year-old population at
risk for severe RSV and its complications. Additionally, vaccination of healthcare workers and
caregivers/educators of children or adults living with or caring for individuals at higher risk for
severe disease and complications may be beneficial. Besides the known substantial disease burden
in adults aged 65 years and olderand in the population with specific comorbidities (increased risk),
a recent modelling estimate of disease burden in adults in the United Kingdom shows comparable
burden of RSV attributable outcomes (medical visit, hospitalization) in 50 to 64-year-olds at low
risk and 18 to 49 -year-olds at increased risk (Fleming 2015).
In alignment with the Phase 2b proof-of-concept study (VAC18193RSV2001) and the planned
Phase 3 efficacy study (VAC18193RSV3001), the current study will enroll participants with
chronic heart and/or lung conditions in the high-risk cohort. Vaccine immunogenicity in the
healthy 18 to 59-year-olds and in high-risk adults aged 18 to 59 years will be assessed relative to
adults aged 65 years and older, an age group in which efficacy has been demonstrated in study
VAC18193RSV2001. The primary objective is to demonstrate non-inferior immune responses in
the pooled cohorts of healthy and high-risk adult cohorts relative to the ≥65 years and older cohort.
If successful, non-inferiority of immune responses in the high-risk adult cohort alone relative to
≥65 years and older cohort will be assessed.
Successful demonstration of comparable immune responses in these 2 populations, both relative
to adults aged 65 years and olderwill allow to bridge efficacy demonstrated in the latter population
(WHO 2017). The study results should guide decisions around vaccine indication as well as
recommendation for use in adults younger than 60 years of age aged less than 60 years old.
The virus neutralizing antibody assay (VNA) against RSV A2 strain will be used as the primary
immunogenicity assay to demonstrate non-inferiority immunogenicity in terms of neutralizing
antibody geometric mean titers (GMTs) and seroresponse rates in adults aged 18 to 59 years and
in high-risk adults aged 18 to 59 years, both relative to adults 65 years of age and above. This
immunogenicity measure was selected upon request from the FDA to use a functional immune
marker for immunobridging and extrapolation of the vaccine efficacy to another population. In the
absence of a defined immune-correlate of protection, the preF binding antibody titers will also be
evaluated as a secondary endpoint in this study in a descriptive fashion. The preliminary findings
from the correlate of protection analysis based on data from VAC18193RSV2001 showed that
both VNA and preF ELISA absolute titers have strong correlation with protection from RSV
disease.
2.2. 
Background
RSV is an important cause of serious respiratory infections in adults aged 60 years and older,
immunocompromised individuals, and those with underlying chronic cardiopulmonary conditions
(Falsey 2005). Exact numbers on the burden of RSV disease in adults aged 60 years and older are
limited. In long-term care facilities, RSV is estimated to infect 5% to 10% of the residents per year
with significant rates of pneumonia (10%  to 20%) and death (2%  to 5%) as a consequence
(Falsey 2000). In the United States (US), approximately 177,000 hospital admissions and
approximately 10,000 to 14,000 deaths per year are due to severe RSV infections in adults aged

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65 years and older (Falsey 2005). These data support the importance of developing a safe and
effective vaccine for certain adult populations, such as older adults and adults with conditions that
pre-disposes them to severe RSV disease. In addition, healthcare workers and caregivers/educators
of children or adults living with or caring for individuals at higher risk for severe disease and
complications could also benefit. Currently, there are no vaccines or specific treatments available
for RSV.
Several studies have indicated that high serum neutralizing antibody levels are associated with
reduced risk of severe RSV infection in older adults (Falsey 1998; Walsh 2004). There is some
indication that decreased protection against RSV in older adults could be attributed to an age-
related decline in RSV-specific T-cell function (de Bree 2005; Looney 2002). The Ad26.RSV.preF
vaccine component evaluated in this study is based on the AdVac® platform, which has been
shown to promote strong humoral and cellular responses (Barouch 2013; Barouch 2018; Data on
file; Milligan 2016).
Nonclinical Studies
For the most comprehensive nonclinical information regarding the Ad26/protein preF RSV
vaccine, refer to the latest version of the IB for Ad26/protein preF RSV vaccine (IB Ad26/protein
preF RSV vaccine 2021).
Clinical Studies
For the most comprehensive clinical information regarding the Ad26/protein preF RSV vaccine,
refer to the latest version of the IB for Ad26/protein preF RSV vaccine (IB Ad26/protein preF
RSV vaccine 2021).
Clinical Safety Experience With Ad26-based Vaccines
Safety data of Ad26-vectored vaccines from the adenoviral vaccine safety database (AdVac Safety
Database 2021), including vaccines against Ebola virus (Ad26.ZEBOV), HIV (Ad26.ENVA.01,
Ad26.Mos.HIV, and Ad26.Mos4.HIV), malaria (Ad26.CS.01), RSV (Ad26.RSV.FA2 and
Ad26.RSV.preF), filovirus (Ad26.Filo), Zikavirus (Ad26.ZIKV.001), and HPV (Ad26.HPV16
and Ad26.HPV18) have been evaluated in adults.
All the above Ad26-based vaccines were found to be well tolerated in adults, without significant
safety issues identified. Several other studies are currently ongoing, and no safety concerns have
been raised to date.
Thrombosis With Thrombocytopenia Syndrome
Thrombosis in combination with thrombocytopenia (thrombosis with thrombocytopenia syndrome
[TTS]), in some cases accompanied by internal bleeding, has been observed very rarely following
vaccination with the Janssen COVID-19 (Ad26.COV2.S) vaccine. Reports include severe cases of
venous thrombosis at unusual sites such as cerebral venous sinus thrombosis (CVST), splanchnic
vein thrombosis and arterial thrombosis, in combination with thrombocytopenia. The associated
symptoms began approximately 1 to 2 weeks after vaccination, mostly in women under 60 years
of age. Thrombosis in combination with thrombocytopenia can be fatal. The exact

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pathophysiology  of TTS is unclear. This event has not been observed to date with any other
Janssen Ad26-based vaccines. Participants should be instructed to seek immediate medical
attention if they develop symptoms such as shortness of breath, chest pain, leg swelling, persistent
abdominal pain, severe or persistent headaches, blurred vision, skin bruising or petechiae beyond
the site of vaccination.
2.3. 
Benefit-Risk Assessment
More detailed information about the known and expected benefits and risks of the Ad26/protein
preF RSV vaccine may be found in the IB for Ad26/protein preF RSV vaccine (IB Ad26/protein
preF RSV vaccine 2021).
2.3.1. 
Risks Related to Study Participation
The following potential risks for the Ad26/protein preF RSV vaccine will be monitored during the
study:
Risks Related to Ad26/protein preF RSV Vaccine
The Ad26/protein preF RSV vaccine is being studied in 4 ongoing studies in more than
6500 participants aged 60 years and above, including participants with comorbidities, to assess
safety and immunogenicity, and to investigate whether the vaccine prevents RSV disease. In these
studies, the most commonly reported solicited local AEs were injection site pain/tenderness and
swelling (mild to moderate). The most frequently reported solicited systemic AEs were fatigue,
muscle pain, headache, chills, joint pain and nausea, which were mild to moderate in severity.
These solicited AEs were short-lived and resolved within a few days. Overall, available results
from these studies show the vaccine to be well-tolerated with no safety concerns.
General Risks Related to Vaccination
In general, IM injection may cause local itching, warmth, pain, tenderness, erythema/redness,
induration, swelling, arm discomfort, or bruising of the skin. Participants may exhibit general signs
and symptoms associated with IM injection of a vaccine and/or placebo, including fever, chills,
rash, myalgia, nausea/vomiting, headache, dizziness, arthralgia, general itching, and fatigue. These
side effects will be monitored, but are generally short-term and do not require treatment.
Syncope can occur in association with administration of injectable vaccines. Syncope can be
accompanied by falls. Procedures should be in place to avoid falling injury. If syncope develops,
participants should be observed until the symptoms resolve. Fear of injection might lead to fainting
and fast breathing.
Participants may have an allergic reaction to the vaccination. An allergic reaction may cause a
rash, urticaria, or even anaphylaxis. Severe reactions are rare. Participants with a known or
suspected allergy, or history of anaphylaxis or other serious adverse reactions to vaccines or their
excipients (including specifically the excipients of the study vaccine) will be excluded from the
study.

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After vaccination, participants will remain at the study site for at least 30 minutes and will be
closely observed by study staff. Necessary emergency equipment and medications must be
available in the clinic to treat severe allergic reactions.
Pregnancy and Birth Control
The effect of the Ad26/protein preF RSV vaccine on a fetus or nursing baby is unknown.
Participants of childbearing potential will be required to agree to practice an acceptable effective
method of contraception and agree to remain on such a method of contraception from providing
consent until 3 months after receiving study vaccine (see Section 5.1). Participants who are
pregnant will be excluded from the study. Participants who become pregnant during the study will
remain in the study and will continue to undergo all procedures for surveillance and all safety
follow-up as outlined in the protocol for all participants. Follow-up information regarding the
outcome of the pregnancy will be required.
Because the effect on sperm is unknown, participants must inform the study-site personnel if their
partner becomes pregnant during the study. Follow-up information regarding the outcome of the
pregnancy will be requested upon the consent provided by the partner.
Participants with Immunosuppression/Reduced Immune Response
Participants with abnormal function of the immune system will be excluded from the study.
Limited evidence indicates that inactivated vaccines (or nonreplicating viral vaccines) generally
have the same safety profile in immunocompromised patients as in immunocompetent individuals.
However, the magnitude, breadth, and persistence of the immune response to vaccination may be
reduced or absent in immunocompromised persons.
Risks from Blood Draws
Blood draws may cause pain, tenderness, bruising, bleeding, dizziness, vasovagal response,
syncope, and rarely, infection at the site where the blood is taken. Participants with
contraindications to IM injections and blood draws (eg, bleeding disorders) will be excluded.
Concomitant Vaccination
Concomitant vaccination might have an influence on both the safety profile and immunogenicity
of the Ad26/protein preF RSV vaccine. Likewise, the Ad26/protein preF RSV vaccine might have
an influence on both the safety profile and immunogenicity of any concomitant vaccination. As a
result, licensed live attenuated vaccines should be given at least 28 days before or after vaccination.
Other licensed (not live) vaccines (eg, influenza, tetanus, hepatitis A, hepatitis B, rabies) should
be given at least 14 days before or after vaccination to avoid potential confusion of adverse
reactions and potential immune interference. If a vaccine is indicated in a postexposure setting (eg,
rabies or tetanus), it must take priority over the study vaccine.

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For SARS-COV-2 vaccines either licensed or available under Emergency Use Authorization: live
attenuated vaccines should be given at least 28 days before or after vaccination; non-live vaccines
should be given at least 14 days before or after vaccination.
A viral-vectored SARS-COV-2 vaccine is not to be given within 28 days prior to randomization
or during the study period until 28 days after the study vaccination.
Unknown Risks
There may be other risks that are not known. If any significant new risks are identified, the
investigators and participants will be informed.
2.3.2. 
Benefits of Study Participation
Participants may benefit from clinical testing and physical examination.
The clinical benefits of the Ad26/protein preF RSV vaccine have yet to be confirmed.
The Ad26/protein preF RSV vaccine is under development for prophylaxis of RSV and vaccine
efficacy is being evaluated in ongoing studies. Results from the primary analysis of study
VAC18193RSV2001 with approximately 5,800 participants showed the potential for the vaccine
to prevent lower respiratory tract disease caused by RSV in participants 65 years and older.
2.3.3. 
Benefit-Risk Assessment of Study Participation
Based on the available data and proposed safety measures, the overall benefit-risk assessment for
this clinical study is considered acceptable for the following reasons:
 
The dose levels for Ad26.RSV.preF and RSV preF protein used in the current study were
determined from the primary analysis of Cohort 2 in study VAC18193RSV1004 and are
currently under further evaluation in studies VAC18193RSV1004 and VAC18193RSV2001.
Available safety data from all studies show the vaccine to be well-tolerated with no safety
concerns. Based on these data, the dose levels of Ad26.RSV.preF and RSV preF protein
selected for the present study are 1×1011 vp and 150 µg, respectively (Section 4.3). In the
primary analysis of study VAC18193RSV2001, vaccine efficacy was demonstrated for these
dose levels in adults aged 65 years and above, for the prevention of LRTD caused by RSV.
 
Only participants who meet all inclusion criteria and none of the exclusion criteria (specified
in Section 5) will be allowed to participate in this study. The selection criteria include adequate
provisions to minimize the risk and protect the well-being of participants in the study.
 
Safety will be closely monitored throughout the study:
 
In general, safety evaluations will be performed at scheduled visits during the study, as
indicated in the Schedule of Activities.
 
After vaccination, participants will remain at the study site for at least 30 minutes and
will be closely observed by study staff. Necessary emergency equipment and medications
must be available in the clinic to treat severe allergic reactions. Participants will use a
participant diary  to document solicited signs and symptoms. Details are provided in
Section 8.2.

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The investigator or the designee will document unsolicited AEs, SAEs, and (potential)
adverse events of special interest (AESIs) as indicated in Sections 8.2 and 8.3 and
Appendix 2.
 
Any clinically significant abnormalities will be followed by the investigator until
resolution or until clinically stable.
 
After vaccination, participants will enter a 6-month safety follow-up period for collection
of serious adverse events (SAEs)and AESIs.
 
All AEs, SAEs, and AESIs will be followed by the investigator until clinical resolution
or until a clinically stable condition is reached, or until the participant has been deemed
lost to follow-up after demonstration of due diligence of follow-up efforts. An early exit
visit will be conducted for those participants who are unable to continue participation in
the study and withdraw from the study before Day 183, but who do not withdraw consent.
Participants who wish to withdraw consent from participation in the study will be offered
an early exit visit (prior to formal withdrawal of consent) (Section 7.2).
 
Several safety measures are included in this protocol to minimize the potential risk to
participants, including the following:
 
Safety issues that might arise from this study may be escalated to an Independent Data
Monitoring Committee, as needed.
 
Study vaccinations will be discontinued in participants for the reasons described in
Section 7.
 
Temporary contraindications to study vaccination are included in Section 5.5.
3. 
OBJECTIVES AND ENDPOINTS
Objectives 
Endpoints
Primary
 
To assess the safety and reactogenicity of
Ad26.RSV.preF-based RSV vaccine in healthy
adults aged 18 to 59 years
 
Solicited local (injection site) and systemic
AEs for 7 days after vaccination
 
Unsolicited AEs for 28 days after
vaccination
 
Serious adverse events (SAEs) and adverse
events of special interest (AESIs) until
6 months after vaccination
 
To assess the safety and reactogenicity of
Ad26.RSV.preF-based RSV vaccine in adults
aged 18 to 59 years at high-risk of severe RSV
disease
 
Solicited local (injection site) and systemic
AEs for 7 days after vaccination
 
Unsolicited AEs for 28 days after
vaccination
 
SAEs and AESIs until 6 months after
vaccination

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Objectives 
Endpoints
 
If non-inferiority is demonstrated in adults: 
To demonstrate the non-inferiority of the 
humoral response to the administration of 
Ad26.RSV.preF-based vaccine in high-risk 
adults aged 18 to 59 years versus in adults 
aged 65 years and older
 
Neutralizing antibody titers against RSV
A2 strain at 14 days after vaccination
 
Seroresponse rate* at 14 days after
vaccination as determined by neutralization
assay (VNA-A2).
* Seroresponse is defined as a 4 fold increase from baseline in Day 15 antibody titers.
Secondary
 
Investigate the vaccine-induced immune 
responses post-vaccination 
 
Pre-F ELISA antibody titers at 14 days
after vaccination
Exploratory
 
To assess the persistence of immune response 
post-vaccination 
 
Pre-F ELISA antibody titers at 6 months
after vaccination
 
Neutralizing antibody titers against RSV A2
strain at 6 months after vaccination
 
To further explore the humoral immune 
responses elicited by the Ad26.RSV.preF- 
based vaccine 
 
Neutralizing antibody titers against RSV B
strains and other RSV A strains
 
Neutralizing antibody titers against Ad26
 
Molecular and functional antibody
characterization including antibody avidity,
Fc-mediated effector function, subtyping
and isotyping, glycosylation patterns,
antibody sequencing for repertoire†
 
To explore the cellular immune responses 
elicited by the Ad26.RSV.preF-based vaccine 
in a subset of participants (ie, the Cellular 
Immuno Subset) 
 
RSV-F specific interferon gamma (IFN-γ)
enzyme-linked immunospot (ELISpot) and
detailed immunoprofiling which may
include analysis of T-cell and B-cell
responses to RSV F protein peptide-
stimulated peripheral blood mononuclear
cell (PBMC) (including, but not limited to,
CD4+/CD8+, Th1/Th2, IL-2, IFN-γ, TNF-
α, activation markers and memory markers)
using flow cytometry or mass cytometry
† Exploratory endpoints are optional. Exploratory assessments are based on the outcome of ongoing testing in
other studies. Some testing may not be performed or reported.
Refer to Section 8 for evaluations related to endpoints.
HYPOTHESES
To demonstrate the non-inferiority of the humoral immune response to Ad26/protein preF RSV
vaccine in all adults aged 18 to 59 years (Group 1+3) versus in adults aged 65 years and older
(Group 5) and in high-risk adults aged 18 to 59 years (Group 3) versus in adults aged 65 years and
older (Group 5) in terms of neutralizing antibody GMTs and seroresponse rates.

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The following hypotheses will be tested sequentially:
Null Hypothesis 1:
 
Ad26/protein preF RSV vaccine induces inferior humoral response in terms of VNA A2
antibody GMTs at Day 15 in adults aged 18 to 59 years (Groups 1 and 3) versus in adults aged
65 years and older (Group 5).
OR
 
Ad26/protein preF RSV vaccine induces inferior humoral immune response in terms of
seroresponse rates of VNA A2 antibody titers at Day 15 in adults aged 18 to 59 years
(Groups 1 and 3) versus in adults aged 65 years and older (Group 5).
Alternative Hypothesis 1:
 
Ad26/protein preF RSV vaccine induces non-inferior humoral responses in terms of VNA A2
antibody GMTs at Day 15 in adults aged 18 to 59 years (Groups 1 and 3) versus in adults aged
65 years and older (Group 5).
AND
 
Ad26/protein preF RSV vaccine induces non-inferior humoral responses in terms of
seroresponse rates of VNA A2 antibody titers at Day 15 in adults aged 18 to 59 years
(Groups 1 and 3) versus in adults aged 65 years and older (Group 5).
Success Criterion 1 (All Adults):
Non-inferiority of immune response in all adults is demonstrated:
 
if the lower limit of the 2-sided 95% confidence interval (CI) for the VNA A2 GMT ratio of
all adults aged 18 to 59 years versus in adults aged 65 years and older
(GMTGroup 1+3/GMTGroup 5) is >0.67.
AND
 
ifthe lower limit of the 2-sided 95% CI for the seroresponse rate difference of all adults aged
18 to 59 years versus in adults aged 65 years and older (Seroresponse Rate Group 1+3 
Seroresponse Rate Group 5) based on the VNA A2 antibody titers is >-0.1
If non-inferiority is demonstrated in all adults for both neutralizing antibody GMTs and
seroresponse rates, then the following hypothesis will be tested:
Null Hypothesis 2:
 
Ad26/protein preF RSV vaccine induces inferior humoral response in terms of VNA A2
antibody GMTs at Day 15 in high-risk adults aged 18 to 59 years (Group 3) versus in adults
aged 65 years and older (Group 5).
OR
 
Ad26/protein preF RSV vaccine induces inferior humoral response in terms of seroresponse
rates of VNA A2 antibody titers at Day 15 in high-risk adults aged 18 to 59 years (Group 3)
versus in adults aged 65 years and older (Group 5).

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Alternative Hypothesis 2:
 
Ad26/protein preF RSV vaccine induces non- inferior humoral response in terms of VNA A2
antibody GMTs at Day 15 in high-risk adults aged 18 to 59 years (Group 3) versus in adults
aged 65 years and older (Group 5).
AND
 
Ad26/protein preF RSV vaccine induces non-inferior humoral response in terms of
seroresponse rates of VNA A2 antibody titers at Day 15 in high-risk adults aged 18 to 59 years
(Groups 3) versus in adults aged 65 years and older (Group 5).
Success Criterion 2 (High-risk Adults):
Non-inferiority of immune response in high-risk adults is demonstrated:
 
if the lower limit of the 2-sided 95% CI for the VNA A2 GMT ratio of high-risk adults aged
18 to 59 years versus in adults aged 65 years and older (GMTGroup 3/GMTGroup 5) is >0.67.
AND
 
if the lower limit of the 2-sided 95% CI for the seroresponse rate difference of high-risk adults
aged 18 to 59 years versus in adults aged 65 years and older (Seroresponse Rate Group 3 
Seroresponse Rate Group 5) based on the VNA A2 antibody titers is >-0.1.
4. 
STUDY DESIGN
4.1. 
Overall Design
This is a randomized, double-blind, placebo-controlled, multicenter, interventional Phase 3 study
to evaluate the safety and immunogenicity of the Ad26/protein preF RSV vaccine in adults aged
18 to 59 years, including those who are at high-risk of severe RSV disease. A cohort of adults aged
65 years and older will also be included. A target of 1,113 participants will be enrolled: 385 healthy
adults aged 18 to 59 years will be enrolled in Cohort 1 and randomized in a 9:2 ratio to receive
Ad26/protein preF RSV vaccine or placebo; 385 high-risk adults aged 18 to 59 years will be
enrolled in Cohort 2 and randomized in a 9:2 ratio to receive Ad26/protein preF RSV vaccine or
placebo, 343 adults aged 65 years and older will be enrolled in Cohort 3 and randomized in a 45:4
ratio to receive Ad26/protein preF RSV vaccine or placebo (see Table 1). The study vaccine will
be administered as a single IM injection.
Participants will be stratified for COVID-19 vaccine administration (3 categories: 1. Janssen
COVID-19 vaccine, 2. Vaxzevria® [Oxford/AstraZeneca], 3. other vaccine, or no vaccine).

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Table 1: 
Overview of the Cohorts, Groups, and Targeted Number of Participants
Cohort 
Group  
N 
Day 1 (Vaccination)
1 
healthy adults, 18 to 59 years 
1 
315 
Ad26.RSV.preF 1×1011 vp + RSV preF protein 150 μg
2 
70 
Placebo
2 high-risk adults, 18 to 59 years a 
3 
315 
Ad26.RSV.preF 1×1011 vp + RSV preF protein 150 μg
4 
70 
Placebo
3 
adults, 65 years and older 
5 
315 
Ad26.RSV.preF 1×1011 vp + RSV preF protein 150 μg
6 
28 
Placebo
N = number of participants, vp = virus particles.
In all cohorts, participants will be stratified for COVID-19 vaccine administration.
All cohorts will be enrolled in parallel. Enrollment in Spain will be limited to Cohorts 2 and 3.
Safety and humoral immunogenicity assessments will be performed for all participants (see
Section 9.2.1 for the sample size determination).
Fora subset of the participants, additional cellular immunogenicity assessments will be performed.
This subset will be referred to as the Cellular Immuno Subset and will consist of approximately
63 active study vaccine participants and approximately 7 placebo participants per cohort. The
Cellular Immuno Subset will be recruited in specific study sites.
After vaccination, participants will remain under observation at the study site for at least
30 minutes for presence of any acute reactions and solicited events. Any unsolicited AEs, solicited
local (injection site)orsystemic AEs, and vital signs (systolic and diastolic blood pressure [sitting],
heart rate, respiratory rate, and body temperature) will be documented by study-site personnel
following this observation period. In addition, participants will record solicited signs and
symptoms in a participant diary beginning on the evening of the day of vaccination and on a daily
basis for 7 days post-vaccination (Section 8).
The reporting periods of AEs, SAEs, and AESIs are detailed in Section 8.3. Reporting periods for
concomitant therapy are outlined in Section 6.8.
Blood will be collected from all participants to assess humoral immune responses pre-vaccination
and at 14 days and 6 months post-vaccination. Additional blood will be collected from the Cellular
Immuno Subset to assess cellular immune responses pre-vaccination and at 14 days and 6 months
post-vaccination.
Safety issues that might arise from this study may be escalated to an Independent Data Monitoring
Committee, as needed.
The study duration will be approximately 6 months per participant. The study comprises screening
(pre-vaccination) and vaccination for each participant on Day 1, and a 6-month safety and
immunogenicity follow-up period. The end of the study is defined as the last participant’s last visit.
Over the entire study, approximately 60 mL blood will be collected from each participant to assess
humoral immune responses. In addition, approximately 120 mL will be collected from each

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participant in the Cellular Immuno Subset to assess cellular immune responses. The total blood
volume to be collected from participants in the Cellular Immuno Subset will be approximately
180 mL.
Unscheduled study visits may be performed based on investigator’s clinical judgment and may
include further evaluations, as needed.
A diagram of the study design is provided in Section 1.2 (Figure 1). Further details are provided
in the Schedule of Activities.
4.2. 
Scientific Rationale for Study Design
For the rationale for performing this study, refer to Section 2.1.
Blinding and Control
A placebo control will be used to establish the frequency and magnitude of changes in clinical
endpoints that may occur in the absence of active study vaccine in Cohorts 1 and 2. Safety of the
vaccine in older adults has been established in the VAC18193RSV2001 study, therefore only a
small placebo control group is added for blinding purposes. Within a cohort, randomization will
be used to minimize bias in the assignment of participants to vaccination groups (active or
placebo), to increase the likelihood that known and unknown participant attributes
(eg, demographic and baseline characteristics) are evenly balanced across vaccination groups.
Blinded vaccine will be used to reduce potential bias during data collection and evaluation of safety
endpoints.
Vaccination Groups
The dose of each vaccine will be identical in the active groups (Groups 1, 3 and 5). Groups 2, 4
and 6 will receive placebo.
Vaccine Component Selection
The rationale behind the selection of the Ad26/protein preF RSV vaccine is described in
Section 2.2 and in the IB for Ad26/protein preF RSV vaccine (IB Ad26/protein preF RSV vaccine
2021).
Dose Level Selection
The rationale behind the dose level selection for the Ad26/protein preF RSV vaccine is described
in Section 4.3.
4.2.1. 
Study-Specific Ethical Design Considerations
Potential participants will be fully informed of the risks and requirements of the study and, during
the study, participants will be given any new information that may affect their decision to continue
participation. They will be told that their consent to participate in the study is voluntary and may be
withdrawn at any time with no reason given and without penalty or loss of benefits to which they
would otherwise be entitled. Only participants who are fully able to understand the risks, benefits,
and potential AEs of the study, and provide their consent voluntarily will be enrolled.

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The primary ethical concern is that this study will be performed in adult participants who will receive
no benefit from participation in the study, except for compensation for the time and inconveniences
that may arise from participation in the study.
See Section 2.3 for Benefit-Risk Assessment.
The total blood volume to be collected is considered to be an acceptable amount of blood to be
collected over this time period from the population in this study based upon the standard of the US
Department of Health and Human Services Office for Human Research Protections, and US Food
and Drug Administration (FDA) guidelines of 550 mL in any 8-week period (OHRP 2016;
FDA 1998).
The results of this study may be made available to all participants through a plain language
summary at the conclusion of the study according to local standards/restrictions.
4.3. 
Justification for Dose
The dose level for the Ad26/protein preF RSV vaccine used in the current study was determined
from the primary analysis of Cohort 2 in study VAC18193RSV1004. From the primary analysis,
a significant increase in humoral immune responses including virus neutralizing antibodies (virus
neutralization assay) and pre-F  antibody titers were observed in the groups combining
Ad26.RSV.preF (5×1010 or 1×1011 vp) and RSV preF protein (50 or 150 µg) compared to
Ad26.RSV.preF 1×1011 vp alone. No relevant differences between the combination groups and
Ad26.RSV.preF alone were noted for cellular immune responses. All regimens had acceptable
safety and reactogenicity profiles, which were similar across groups. Additionally, in the primary
analysis of study VAC18193RSV2001, vaccine efficacy was demonstrated for these dose levels.
Based on these data, the dose levels of Ad26.RSV.preF and RSV preF protein selected for the
present study are 1×1011 vp and 150 µg, respectively.
4.4. 
End of Study Definition
End of Study Definition
The end of study is considered as the last visit (on Day 183) for the last participant in the study.
The final data from the study site will be sent to the sponsor (or designee) after completion of the
final participant visit at that study site, in the time frame specified in the Clinical Trial Agreement.
Participant Study Completion Definition
A participant will be considered to have completed the study if the participant has completed
assessments at the Day 183 visit.
5. 
STUDY POPULATION
Screening for eligible participants will be performed pre-vaccination on Day 1. Screening and
vaccination may be split into 2 visits in consultation with the sponsor or its delegate. Refer to
Section 5.4 for conditions under which the repeat of any screening procedures are allowed.

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The inclusion and exclusion criteria for enrolling participants in this study are described below. If
there is a question about these criteria, the investigator must consult with the appropriate sponsor
representative and resolve any issues before enrolling a participant in the study. Waivers are not
allowed.
For a discussion of the statistical considerations of participant selection, refer to Section 9.2.
5.1. 
Inclusion Criteria
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
1. 
must sign an informed consent form (ICF) indicating that the participant understands
the purpose, procedures and potential risks and benefits of the study, and is willing to
participate in the study.
2. 
willing and able to adhere to the prohibitions and restrictions specified in this protocol.
3. 
contraceptive (birth control) use should be consistent with local regulations regarding
the acceptable methods of contraception for those participating in clinical studies.
Before randomization, participants must be either (as defined in Appendix 4):
a. not of childbearing potential
b. of childbearing potential and practicing an acceptable effective method of
contraception and agrees to remain on such a method of contraception from signing
the ICF until 3 months after study vaccination. Use of hormonal contraception
should start at least 28 days before study vaccination. The investigator should
evaluate the potential for contraceptive method failure (eg, noncompliance, recently
initiated) in relationship to the study vaccination. Acceptable effective methods for
this study include:
1) hormonal contraception;
2) intrauterine device;
3) intrauterine hormone-releasing system;
4) condom with or without spermicide;
5) cap, diaphragm, or sponge with a vaginal spermicide;
6) bilateral tubal occlusion/ligation procedure;
7) vasectomized partner (the vasectomized partner should be the sole partner
for that participant);
8) sexual abstinencea.
a Sexual abstinence is considered an effective method only if defined as refraining from heterosexual intercourse from
signing the ICF until 3 months after study vaccination. The reliability of sexual abstinence needs to be evaluated in
relation to the duration of the study and the preferred and usual lifestyle of the participant.

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Note: If the childbearing potential changes after start of the study (eg, a premenarchal
participant experiences menarche) or the risk of pregnancy changes (eg, a participant
who is not heterosexually active becomes active), a participant must begin an acceptable
effective method of contraception, as described throughout the inclusion criteria.
4. 
all participants of childbearing potential must:
a. have a negative highly sensitive urine β-human chorionic gonadotropin (β-
hCG) pregnancy test at screening.
b. have a negative highly sensitive urine β-hCG pregnancy test immediately prior
to study vaccination (if screening and vaccination are not performed on the
same day).
5. 
in the investigator’s clinical judgment, participant must be in stable health at the time
of vaccination. Participants will be included on the basis of physical examination,
medical history, and vital signsa performed between ICF signature and vaccination.
6. 
must be willing to provide verifiable identification, has means to be contacted and to
contact the investigator during the study.
For Participants in Cohort 1 only:
7. 
participant is aged 18 to 59 years (inclusive) on the day of signing the ICF and expected
to be available for the duration of the study.
8. 
in the investigator’s clinical judgment, participant must be either in good or stable
health.
For Participants in Cohort 2 only:
9. 
participant is aged 18 to 59 years (inclusive) on the day of signing the ICF and expected
to be available for the duration of the study.
10. 
Criterion modified per Amendment 2:
10.1 
has an existing chronic heart or lung condition, without hospitalizations or
major medication class change (ie, new or stopped medications) within 30 days
prior to screening, meeting the following criteria (based on Falsey et al. [2005]):
 
Cardiac disease: at least Class II symptoms per New York Heart
Association classification (Criteria Committee of the New York Heart
Association 1994, see Appendix 5)or similar guidelines according to local
practice.
a Participants can be enrolled with Grade 1 or Grade 2 values for vital signs measurements (refer to Appendix 6 [for
Cohorts 1 and 2] and Appendix 7 [for Cohort 3]).

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 
Pulmonary disease: activity-restricting symptoms or use of long-term
medications.
Note: The investigator’s judgment for inclusion in the study is based on the
participant’s medical history (see Appendix 10 for guidance on eligible chronic
heart and lung conditions for Cohort 2).
11. 
participant may have other underlying illnesses as long as their symptoms and signs are
stable at the time of vaccination, and these conditions receive routine follow-up by the
participant’s healthcare provider.
For Participants in Cohort 3 only:
12. 
participant is aged 65 years or older on the day of signing the ICF and expected to be
available for the duration of the study.
13. 
participant may have underlying illnesses such as hypertension, congestive heart failure,
COPD, type 2 diabetes, hyperlipoproteinemia, or hypothyroidism, as long as their
symptoms and signs are stable at the time of vaccination, and these conditions receive
routine follow-up by the participant’s healthcare provider.
5.2. 
Exclusion Criteria
Any potential participant who meets any of the following criteria will be excluded from
participating in the study:
1. 
history of malignancy within 5 years before screening not in the following categories:
a. participant with squamous and basal cell carcinomas of the skin and carcinoma in
situ of the cervix may be enrolled at the discretion of the investigator.
b. participant with a history of malignancy within 5 years before screening, which is
considered cured with minimal risk of recurrence per investigator’s judgment, can
be enrolled.
2. 
known or suspected allergy or history of anaphylaxis or other serious adverse reactions
to vaccines or their excipients (including specifically the excipients of the study
vaccine)(IB Ad26/protein preF RSV vaccine 2021).
Note: participants with egg allergies can be enrolled.
3. 
abnormal function of the immune system resulting from:
a. Clinical conditions (eg, autoimmune disease or immunodeficiency) expected to
have an impact on the immune response elicited by the study vaccine. Participants
with autoimmune disease (eg, autoimmune-mediated thyroid disease, autoimmune
inflammatory rheumatic disease such as rheumatoid arthritis, and type 1 diabetes)
that is stable and inactive without the use of systemic immunomodulators and
glucocorticoids may be enrolled at the discretion of the investigator.

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b. Use of systemic corticosteroids within 30 days before administration of study
vaccine until 14 days after study vaccination.
Note: Ocular, topical, or inhaled steroids are allowed.
c. Administration of antineoplastic and immunomodulating agents, eg, cancer
chemotherapeutic agents, or radiotherapy within 6 months before administration of
study vaccine until 14 days after study vaccination.
4. 
per medical history, participant has chronic active hepatitis B or hepatitis C infection.
5. 
per medical history, participant has HIV type 1 or type 2 infection.
6. 
history of acute polyneuropathy (eg, Guillain-Barré syndrome) or chronic idiopathic
demyelinating polyneuropathy.
7. 
Criterion modified per Amendment 2:
7.1 
received hematopoietic stem cell transplant in medical history, treatment with
immunoglobulins expected to impact the vaccine-induced immune response
(including monoclonal antibodies for chronic underlying conditions) in the 2
months, immunoglobulins specific to RSV, human metapneumovirus, or
parainfluenza viruses in the 12 months, apheresis therapies in the 4 months, or
blood products in the 4 months before the planned administration of the study
vaccine or has any plans to receive such treatment during the study.
Note: The investigator is encouraged to contact the sponsor to discuss
eligibility of participants on immunoglobulin treatment.
8. 
history of TTS or heparin-induced thrombocytopenia and thrombosis (HITT).
9. 
participant who is pregnant, breastfeeding or planning to become pregnant while
enrolled in the study.
10. 
received or plans to receive:
a. Licensed live attenuated vaccines within 28 days before or after planned
administration of the study vaccine.
b. Other licensed (not live) vaccines within 14 days before or after planned
administration of the study vaccine.
11. 
received or plans to receive a SARS-COV-2 vaccine (licensed or used under Emergency
Use Authorization):
a. Live attenuated SARS-COV-2 vaccine within 28 days before or after planned
administration of the study vaccine.
b. Non-live SARS-COV-2 vaccine within 14 days before or after planned
administration of the study vaccine.
c. A viral-vectored SARS-COV-2 vaccine within 28 days prior to randomization
or during the study period until 28 days after the study vaccination.

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12. 
received an RSV vaccine in a previous RSV vaccine study.
13. 
received or plans to receive an Ad26-vectored vaccine at any time prior to
randomization until 28 days after the last study vaccination  (for exclusion criteria
related to SARS-COV-2 vaccines; please refer to Exclusion Criterion 11).
14. 
Criterion modified per Amendment 2:
14.1 
received an investigational drug or used an invasive investigational medical
device within 30 days or received an investigational vaccine within 6 months
before the planned administration of the study vaccine or is currently enrolled
or plans to participate in another investigational study during this study.
Note: Participation in an observational clinical study (ie, without intervention)
or in the observational phase of interventional studies is allowed upon approval
of the sponsor or its delegate.
15. 
has a serious chronic disorder, eg, end-stage renal disease with or without dialysis,
clinically unstable cardiac disease, Alzheimer’s disease, or has any condition for which,
in the opinion of the investigator, participation would not be in the best interest of the
participant (eg, compromise the well-being) or that could prevent, limit, or confound
the protocol-specified assessments.
Note: In Cohort 3, participants with severe chronic obstructive pulmonary disease or
severe congestive heart failure will be excluded.
16. 
has had major surgery (per the investigator’s judgment) within 4 weeks before
administration of the study vaccine or will not have recovered from surgery per the
investigator’s judgment at time of vaccination, or has major surgery planned during the
time the participant is expected to participate in the study.
17. 
contraindication to IM injections and blood draws (eg, bleeding disorders).
18. 
employee of the investigator or study site, with direct involvement in the proposed study
or other studies under the direction of that investigator or study site, as well as family
members of the employees or the investigator, or an employee of the sponsor.
19. 
has had major psychiatric illness and/or drug or alcohol abuse which in the
investigator’s opinion would compromise the participant’s safety and/or compliance
with the study procedures.
20. 
cannot communicate reliably with the investigator.
21. 
who, in the opinion of the investigator, is unlikely to adhere to the requirements of the
study, or is unlikely to complete the full course of vaccination and observation.
22. 
who has significant scarring, tattoos, abrasions, cuts, or infections over the deltoid
region of both arms that, in the investigator’s opinion, could interfere with evaluation
ofinjection site local reactions.

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NOTE: Investigators should ensure that all study enrollment criteria have been met prior to
vaccination. If a participant’s clinical status changes (including any available laboratory results or
receipt of additional medical records) after screening but before the study vaccine is given such
that the participant no longer meets all eligibility criteria, then the participant should be excluded
from participation in the study. Section  5.4 describes options for rescreening. The required
documentation to support meeting the enrollment criteria is described under Source Documents in
Appendix 3.
5.3. 
Lifestyle Considerations
Potential participants must be willing and able to adhere to the following lifestyle restrictions
during the study to be eligible for participation:
1. 
refer to Section 6.8, Concomitant Therapyfor details regarding prohibited and restricted
therapy during the study.
2. 
agree to follow all requirements that must be met during the study as noted in the
Inclusion and Exclusion Criteria.
5.4. 
Screen Failures
Participant Identification, Enrollment, and Screening Logs
The investigator agrees to complete a participant identification and enrollment log to permit easy
identification of each participant during and after the study. This document will be reviewed by
the sponsor study-site contact for completeness.
The participant identification and enrollment log will be treated as confidential and will be filed
by the investigator in the study file. To ensure participant confidentiality, no copy will be made.
All reports and communications relating to the study will identify participants by participant
identification and age at initial informed consent. In cases where the participant is not randomized
into the study, the date seen and age at initial informed consent will be used.
Rescreening is allowed only for resolution of an acute condition or meeting a time window (eg, for
a prohibited medication). Only 1 rescreening per participant is permitted. Rescreened participants
will be assigned a new participant number, undergo the informed consent process, and then restart
a new screening phase.
5.5. 
Criteria for Temporarily Delaying Study Vaccine Administration
The following events constitute a temporary contraindication to study vaccination:
 
Clinically significant acute illness at the time of vaccination. This does not include minor
illnesses, such as diarrhea or mild upper respiratory tract infection.
 
Fever (body temperature ≥38.0°C [≥100.4°F]) within 24 hours prior to the planned time of
vaccination.

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If any of these events occur at the scheduled time for vaccination, randomization at a later date
within the screening window (allowed window up to 10 days)is permitted at the discretion of the
investigator and after consultation with the sponsor. In this case, screening and vaccination can be
split over 2 visits. If randomization cannot occur within the screening window, rescreening is
required. Note that the pregnancy test must be repeated prior to vaccination.
If the vaccination visit cannot be rescheduled within the allowed window or the contraindications
to vaccination persist, the sponsor should be contacted for further guidance.
6. 
STUDY VACCINE(S) AND CONCOMITANT THERAPY
6.1. 
Study Vaccine Administration
The investigational medicinal products (IMPs) to be administered to participants in this study are
Ad26.RSV.preF, RSV preF protein and placebo. The Ad26/protein preF RSV vaccine to be used
in this study is composed of Ad26.RSV.preF and RSV preF protein, to be administered as a single
injection (1.0 mL) in the deltoid muscle:
 Ad26.RSV.preF (JNJ-64400141) will be used at a dose level of 1×1011 vp.
 RSV preF protein (JNJ-64213175) will be used at a dose level of 150 μg.
Ad26.RSV.preF and RSV preF protein will be manufactured and provided under the responsibility
of the sponsor. Labels will contain information to meet the applicable regulatory requirements.
Note that RSV preF protein clinical trial material will be labeled as “RSV-F Vaccine”.
Refer to the IB for Ad26/protein preF RSV vaccine for details of the components and a list of
excipients (IB Ad26/protein preF RSV vaccine 2021).
Placebo for Ad26/protein preF RSV vaccine will be 0.9% saline (1.0 mL).
Participants will be vaccinated at the study site according to the schedule shown in Table 1. On
Day 1, each participant will receive an IM injection of study vaccine (Ad26/protein preF RSV
vaccine or placebo).
Study vaccine administration must be captured in the source documents and the electronic case
report form (eCRF).
For a definition of study vaccine overdose, refer to Section 6.7.
6.2. 
Preparation/Handling/Storage/Accountability
Preparation/Handling/Storage
Vials must be stored in a secured location under controlled temperature with no access for
unauthorized personnel. The study refrigerator/freezer must be equipped with a continuous
temperature monitor and alarm and should be equipped with back-up power systems. If the study
vaccine components are exposed to temperatures outside the specified temperature range, all
relevant data will be sent to the sponsor to determine if the affected study vaccine components can

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be used or will be replaced. The affected study vaccine components must be quarantined and not
used until further instruction from the sponsor is received.
An unblinded study-site pharmacist, or other qualified individual will prepare the appropriate vials
and syringes, labeled with the participant’s identification number, and provide the syringes for
Ad26/protein preF RSV vaccine and placebo in a blinded manner to the blinded study vaccine
administrator who will perform the injection.
Refer to the Investigational Product Preparation Instructions and Study Site Investigational
Product and Procedures Manual for additional guidance on study vaccine preparation, handling,
and storage.
Accountability
The investigator is responsible for ensuring that all study vaccine received at the site is inventoried
and accounted for throughout the study. The study vaccine administered to the participant must be
documented on the vaccine accountability form. All study vaccine will be stored and disposed of
according to the sponsor’s instructions.
Study vaccine must be handled in strict accordance with the protocol and the container label, and
must be stored at the study site in a limited-access area or in a locked cabinet under appropriate
environmental conditions. Unused study vaccine must be available for verification by the
sponsor’s study-site monitor during on-site monitoring visits. The return to the sponsor of unused
study vaccine will be documented on the vaccine return form. When the study site is an authorized
destruction unit and study vaccine supplies are destroyed on site, this must also be documented on
the vaccine return form.
Potentially hazardous materials containing hazardous liquids, such as used ampules, needles,
syringes, and vials, should be disposed of immediately in a safe manner and therefore will not be
retained for vaccine accountability purposes.
Study vaccine should be dispensed under the supervision of the investigator or a qualified member
of the study-site personnel. Study vaccine will be supplied only to participants participating in the
study. Study vaccine may not be relabeled or reassigned for use by other participants. The
investigator agrees neither to dispense the study vaccine from, nor store it at, any site other than
the study sites agreed upon with the sponsor.
Refer to the Investigational Product Preparation Instructions and Study Site Investigational
Product and Procedures Manual for additional guidance on the final disposition of unused study
vaccines.

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6.3. 
Measures to Minimize Bias: Randomization and Blinding
Study Vaccine Allocation
Procedures for Randomization
Central randomization will be implemented in this study. Participants will be randomly assigned
to a vaccination group based on a computer-generated randomization schedule prepared before the
study by or under the supervision of the sponsor. The randomization will be balanced by using
randomly permuted blocks.
The randomization will be stratified based on the COVID-19 administration vaccine (3 categories:
1. Janssen Covid-19 vaccine, 2. Vaxzevria (Oxford/AstraZeneca), 3. other vaccine or no vaccine).
Sites will be split into 2 categories based on their PBMC collection capabilities for enrolment in
the Cellular Immuno Subset.
For Cohorts 1 and 2, sites collecting PBMC samples will initially randomize participants in the
Cellular Immuno Subset of the respective cohort according to a 9:1 ratio (active: placebo). When
the Cellular Immuno Subset has been completed for a cohort (70 participants per cohort), the sites
will keep randomizing the remaining participants of that cohort according to a 4:1 ratio (active:
placebo). Sites with no PBMC sample collection capabilities will randomize participants that are
not part of the Cellular Immuno Subset (from whom only humoral samples will be collected) of
the respective cohort according to a 4:1 ratio (active: placebo).
For Cohort 3, sites collecting PBMC samples will initially randomize participants in the Cellular
Immuno Subset according to a 9:1 ratio (active: placebo). When the Cellular Immuno Subset has
been completed (70 participants), the sites will keep randomizing the remaining participants of
that cohort according to a 12:1 ratio (active: placebo). Sites with no PBMC sample collection
capabilities will only randomize participants that are not part of the Cellular Immuno Subset (from
whom only humoral samples will be collected) according to a 12:1 ratio (active: placebo).
In this way, the overall randomization ratio in Cohorts 1 and 2 is 9:2 (active:placebo) and
45:4 (active:placebo) in Cohort 3.
The interactive web response system (IWRS) will assign a unique study vaccine allocation code,
for all participants which will dictate the study vaccine assignment and matching study vaccine kit
for the participant. The requestor must use their own user identification and personal identification
number when contacting the IWRS and will then give the relevant participant details to uniquely
identify the participant.
Blinding
The investigator will not be provided with randomization codes until database lock of the final
analysis. The participants remain blinded until database lock of the final analysis. The codes will
be maintained within the IWRS, which has the functionality to allow the investigator to break the
blind for an individual participant.

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For the sponsor, unblinding (at the participant level) will occur at the time of the primary analysis
(Section 9.5). From the primary analysis onwards, group level results may be shared as needed,
however, efforts will be made to preserve the blinding to the individual participant allocation.
Data that may potentially unblind the randomization group assignment (eg, immunogenicity data,
study vaccine preparation/accountability data, study vaccine allocation) will be handled with
special care to ensure that the integrity of the blind is maintained and the potential for bias is
minimized. This can include making special provisions, such as segregating the data in question
from view by the investigators, clinical team, or others as appropriate until the time of database
lock and unblinding.
The investigator may in an emergency determine the identity of the randomization group by
contacting the IWRS. While the responsibility to break the study vaccine allocation code in
emergency situations resides solely with the investigator, it is recommended that the investigator
contacts the sponsor or its designee if possible, to discuss the particular situation, before breaking
the blind. Telephone contact with the sponsor or its designee will be available 24 hours per day,
7 days per week. In the event the blind is broken, the sponsor must be informed as soon as possible.
The date, time, and reason for the unblinding must be documented by the IWRS, in the appropriate
section of the eCRF, and in the source document. The documentation received from the IWRS
indicating the code break must be retained with the participant’s source documents in a secure
manner.
The study-site pharmacist or qualified individual with primary responsibility for study vaccine
preparation and dispensing will be unblinded to study vaccine allocation.
Participants who have had their randomization group assignment unblinded should continue to
return for scheduled evaluations.
Participants who withdraw will not be replaced.
6.4. 
Study Vaccination Compliance
Ad26/protein preF RSV vaccine or placebo will be administered IM by blinded qualified study-
site personnel at the study site. Details of the administration will be recorded in the eCRF
(including date and time of injection, and site of administration). For blinding procedures, see
Section 6.3.
6.5. 
Dose Modification
Not applicable.
6.6. 
Continued Access to Study Vaccine After the End of the Study
Participants will be instructed that study vaccine will not be made available to them after they have
completed/discontinued study vaccination.

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6.7. 
Treatment of Overdose
For this study, any dose ofthe Ad26/protein preF RSV vaccine greater than the protocol-specified
dose will be considered an overdose. The sponsor does not recommend specific treatment for an
overdose.
In the event of an overdose, the investigator or treating physician should:
 
Contact the Medical Monitor immediately.
 
Closely monitor the participant for AEs/SAEs/AESIs until resolution.
 
Document the quantity of the excess dose in the eCRF.
 
Report as a special reporting situation.
6.8. 
Concomitant Therapy
Prestudy therapies administered within the 30 days before administration of the study vaccine must
be recorded on Day 1. Additionally, any history of SARS-CoV-2 vaccination (name/manufacturer
of the vaccine and date of administration, whenever possible) prior to and during the study will be
collected in the eCRF.
Concomitant therapies associated with solicited AEs will be collected by the participants in the
participant diary from the time of study vaccination through 7 days after vaccination. Concomitant
therapies associated with unsolicited AEs will be collected and recorded in the eCRF from the time
of study vaccination through 28 days after vaccination. Concomitant therapies associated with
SAEs or AESIs will be collected and recorded in the eCRF from ICF signature until 6 months after
vaccination.
Analgesic/antipyretic medications and non-steroidal anti-inflammatory drugs may be used post-
vaccination only in cases of medical need (eg, fever or pain) and their use must be documented.
Use of these medications as routine prophylaxis prior to study vaccination is discouraged.
Information on concomitant use of herbal supplements or vitamins will not be collected.
Use of any experimental medication (including experimental vaccines other than the study
vaccine) during the study is not allowed.
Vaccination with licensed live attenuated vaccines within 28 days of a study vaccination (ie, before
or after) is prohibited. Other licensed (not live) vaccines (eg, influenza, tetanus, hepatitis A,
hepatitis B, rabies) should be given at least 14 days before (or at least 14 days after) administration
of study vaccine in order to avoid potential confusion of adverse reactions and potential immune
interference. If a vaccine is indicated in a postexposure setting (eg, rabies or tetanus), it must take
priority over the study vaccine.

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For SARS-COV-2 vaccines either licensed or available under Emergency Use Authorization: live
attenuated vaccines should be given at least 28 days before or after vaccination; non-live vaccines
should be given at least 14 days before or after vaccination.
A viral-vectored SARS-COV-2 vaccine is not to be given within 28 days prior to randomization
or during the study period until 28 days after the study vaccination.
Use of systemic corticosteroidsa must be documented until 14 days after study vaccination.
Antineoplastic and immunomodulating agents, eg, cancer chemotherapeutic agents, or systemic
corticosteroids, or radiotherapy are prohibited until 14 days after study vaccination. If the use of
systemic corticosteroids, antineoplastic or immunomodulating agents or any therapy described in
exclusion criterion 7 becomes medically indicated during the study for any participant, the sponsor
should be notified.
The sponsor must be notified in advance (or as soon as possible thereafter) of any instances in
which prohibited therapies are administered.
7. 
DISCONTINUATION OF STUDY VACCINATION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL
7.1. 
Discontinuation of Study Vaccination
A participant’s study vaccination must be discontinued if:
 
The participant withdraws consent to receive study vaccination.
 
The investigator believes that for safety reasons or reactogenicity reasons (eg, AE) it is in the
best interest of the participant to discontinue study vaccination.
Study vaccine assigned to the participant who discontinued study vaccination may not be assigned
to another participant. Discontinuation of study vaccination is only possible between screening
and vaccination.
7.2. 
Participant Discontinuation/Withdrawal From the Study
A participant will be withdrawn from the study for any of the following reasons:
 
Lost to follow-up
 
Withdrawal of consent
 
Death
 
AnyAE that requires discontinuation from the study
 
Repeated failure to comply with protocol requirements
a Note: Ocular, topical, or inhaled steroids are allowed.

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When a participant withdraws before study  completion, the reason for withdrawal is to be
documented in the eCRF and in the source document. If the reason for withdrawal from the study
is withdrawal ofconsent, then no additional assessments are allowed.
An early exit visit (by telephone) will be conducted for those participants who are unable to
continue participation in the study and withdraw from the study before Day 183, but who do not
withdraw consent (see Schedule of Activities). Participants who wish to withdraw consent from
participation in the study will be offered an early exit visit (prior to formal withdrawal of consent;
by telephone). They have the right to refuse.
Withdrawal of Consent
A participant declining to return for scheduled visits does not necessarily constitute withdrawal of
consent. Alternate follow-up mechanisms that the participant agreed to when signing the ICF apply
(eg, consult with family members, contacting the participant’s other physicians, medical records,
database searches, use of locator agencies at study completion)as local regulations permit.
7.2.1. 
Withdrawal From the Use of Research Samples
Withdrawal From the Use of Samples in Future Research
The participant may withdraw consent for use of samples for future research (refer to Long-Term
Retention of Samples for Additional Future Research in Appendix 3). In such a case, samples will
be destroyed after they are no longer needed for the clinical study. Details of the sample retention
for research are presented in the main ICF.
7.3. 
Lost to Follow-up
A participant will be considered lost to follow-up if the participant repeatedly fails to return for
scheduled visits and is unable to be contacted by the study site. A participant cannot be deemed
lost to follow-up until all reasonable efforts made by the study-site personnel to contact the
participant are deemed futile. The following actions must be taken if a participant fails to return to
the study site for a required study visit:
 
The study-site personnel must attempt to contact the participant to reschedule the missed visit
as soon as possible, to counsel the participant on the importance of maintaining the assigned
visit schedule, to ascertain whether the participant wishes to or should continue in the study.
 
Before a participant is deemed lost to follow-up, the investigator or designee must make every
reasonable effort to regain contact with the participant (where possible, 3 telephone calls,
e-mails, fax, and, if necessary, a certified letter to the participant’s last known mailing address,
or local equivalent methods. These contact attempts should be documented in the participant’s
medical records.
 
Should the participant continue to be unreachable, they will be considered to have withdrawn
from the study.
Should a study site close, eg, for operational, financial, or other reasons, and the investigator cannot
reach the participant to inform them, their contact information will be transferred to another study
site.

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8. 
STUDY ASSESSMENTS AND PROCEDURES
Overview
The Schedule of Activities summarizes the frequency and timing of study visits and of
immunogenicity and safety measurements applicable to this study.
If multiple assessments are scheduled for the same timepoint, it is recommended that procedures
be performed in the following sequence: vital signs, other safety assessments, blood draws. If
needed, assessments may be performed at another day within the applicable visit window. Actual
dates and times of assessments will be recorded in the source document and/or in the eCRF.
Participants will be provided a thermometer (to measure body temperature), ruler (to measure local
injection site reactions), and participant diary to record body temperature and solicited local
(injection site) and systemic signs and symptoms.
The participant diary includes instructions on how to capture the data and grading scales to assess
severity of the signs and symptoms. The study staff is responsible for providing appropriate
training to the participant to avoid missing or incorrect data. The participant diary will be reviewed
by the study-site personnel at the visit indicated in the Schedule of Activities.
Over the entire study, approximately 60 mL blood will be collected from each participant to assess
humoral immune responses. In addition, approximately 120 mL will be collected from each
participant in the Cellular Immuno Subset to assess cellular immune responses. The total blood
volume to be collected from participants in the Cellular Immuno Subset will be approximately
180 mL.
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the
samples.
Visit Windows
For the following visits, windows will be allowed as indicated:
Clinic Visit # 
Visit Day  
Visit Window  Primary Purpose
2 
8 
± 2 days 
7 days after study vaccination, Safety visit, by telephone
3 
15 
± 3 days 
14 days after study vaccination, Immunogenicity and Safety visit
4 
29 
± 5 days 
28 days after study vaccination, Safety visit, by telephone
5 
183 
± 14 days
6 months after study vaccination, Immunogenicity and Safety
visit
The timings of the post-vaccination visits will be determined relative to the actual day of
vaccination.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the eCRF or laboratory
requisition form.

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Refer to the Schedule of Activities for the timing and frequency of all sample collections.
Instructions for the collection, handling, storage, and shipment of samples are found in the
laboratory manual that will be provided. Collection, handling, storage, and shipment of samples
must be under the specified, and where applicable, controlled temperature conditions as indicated
in the laboratory manual.
Study-Specific Materials
The investigator will be provided with the following supplies:
 
IB for Ad26/protein preF RSV vaccine (IB Ad26/protein preF RSV vaccine 2021)
 
Study Site Investigational Product and Procedures Manual
 
Laboratory manual
 
Investigational Product Preparation Instructions
 
Participant diary and instructions for use
 
Ruler (to measure diameter of any erythema and swelling)
 
Thermometer
 
Laboratory kits
 
Contact Information page(s)
 
Study protocol
 
IWRS Manual
 
Electronic data capture (eDC) Manual/eCRF completion guidelines
 
Wallet card
 
Sample ICF
8.1. 
Immunogenicity Assessments
All Participants
For all participants(N 1,113), venous blood samples of approximately 20 mL will be collected for
the determination of humoral immune responses at the time points indicated in the Schedule of
Activities. Sample collection and processing will be performed by the study-site personnel
according to current versions of approved standard operating procedures.
Humoral immunogenicity evaluations are summarized in Table 2. These include exploratory
assays that may be performed based on the outcome of other ongoing clinical studies.

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Table 2: 
Summary of Immunogenicity Assays (Humoral)
Assay 
Purpose
Primary endpoint
RSV A neutralizing assay (VNA A2) 
Analysis of neutralizing antibodies against the RSV A2 strain
Secondary endpoint
RSV A pre-F binding antibody (preF 
ELISA)
Analysis of antibodies binding to RSV A F protein in pre-fusion form
Exploratory endpoints
RSV strain cross neutralization 
Analysis of cross-neutralizing antibodies to RSV B and/or a different
RSV A strain(s) using virus neutralization assays and/or other
surrogate antibody-binding assays
Adenovirus neutralization assay  
Analysis of neutralizing antibodies to Ad26
Molecular and functional antibody 
characterization  
Analysis of antibody characteristics including, but not limited to,
ADCC, ADCP, avidity, Ig isotype, functional VNAs and binding
antibodies to other respiratory viruses, and antibody assessments for
antibody repertoire
ADCC = antibody-dependent cell-mediated cytotoxicity; ADCP = antibody-dependent cellular phagocytosis; ELISA
= enzyme-linked immunosorbent assay; Ig = immunoglobulin; VNA = virus neutralization assay.
Cellular Immuno Subset
For a subset of the participants, ie, the Cellular Immuno Subset (N 210), additional venous blood
samples of approximately 40 mL will be collected for the determination of cellular immune
responses at the time points indicated in the Schedule of Activities. Sample collection and
processing will be performed by the study-site personnel according to current versions of approved
standard operating procedures.
Cellular immunogenicity evaluations are summarized in Table 3.
Table 3: 
Summary of Immunogenicity Assays (Cellular)
Assay 
Purpose
Exploratory endpoint
IFN-γ ELISpot 
T-cell IFN-γ responses to RSV F protein peptides
Detailed immunoprofiling 
Analysis of T-cell responses to RSV F protein peptide-stimulated
PBMC (including, but not limited to, CD4+/CD8+, IL-2, IFN-γ,
TNF-α, activation markers and memory)using ICS/cytoF
cytoF = flow cytometry; ELISpot = enzyme-linked immunospot; ICS = intracellular cytokine staining; IFN =
interferon; IL = interleukin; PBMC = peripheral blood mononuclear cell; TNF = tumor necrosis factor.
8.2. 
Safety Assessments
Safety assessments will include the monitoring of AEs, physical examinations, and vital signs.
AEs will be reported and followed by the investigator as specified in Section 8.3 and Appendix 2.
Any clinically significant abnormalities will be followed by the investigator until clinical
resolution (return to baseline) or until a clinically stable condition  is reached, or until the
participant has been deemed lost to follow-up after demonstration of due diligence of follow-up
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The study will include the following evaluations of safety and reactogenicity according to the time
points provided in the Schedule of Activities.
8.2.1. 
Physical Examinations
A physical examination, including height and body weight, will be carried out pre-vaccination on
Day 1. At any other clinic visit, an abbreviated, symptom-directed examination may be performed
if deemed necessary by the investigator based on any clinically relevant issues, clinically relevant
symptoms, and medical history.
Physical examinations will be performed by the investigator or appropriately trained delegate. Any
clinically relevant abnormalities or changes in severity noted during the review of body systems
should be documented in the eCRF as an AE or SAE if it meets the criteria for an AE or SAE
according to the protocol reporting requirements.
8.2.2. 
Vital Signs
Vital signs will be measured pre- and post-dose on Day 1. At non-vaccination visits, vital signs
will be measured if deemed necessary by the investigator. Body temperature (oral route preferred),
heart rate (beats per minute), respiratory rate (breaths per minute), and systolic and diastolic blood
pressure (mmHg) will be assessed.
Blood pressure and heart rate measurements will be assessed, if possible, with a completely
automated device. Manual techniques will be used only if an automated device is not available.
Sitting systolic and diastolic blood pressure and heart and respiratory rate measurements should
be preceded by at least 5 minutes of rest in a quiet setting without distractions (eg, television, cell
phones).
Confirmatory vital signs measurement can be performed if inconsistent with a prior measurement.
Any abnormalities or changes in severity noted during the review of vital signs should be
documented in the eCRF.
8.2.3. 
Pregnancy Testing
A urine pregnancy test for participants of childbearing potential will be performed at screening.
Additional urine pregnancy tests may be performed, as determined necessary by the investigator
or required by local regulation, to establish the absence of pregnancy at any time during the
participation in the study.
8.3. 
AEs, SAEs, AESIs and Other Safety Reporting
Timely, accurate, and complete reporting and analysis of safety information, including AEs, SAEs,
AESIs (including potential AESIs, refer to Section 8.3.6)and Product Quality Complaints (PQCs),
from clinical studies are crucial for the protection of participants, investigators, and the sponsor,
and are mandated by regulatory agencies worldwide. The sponsor has established standard
operating procedures in conformity with regulatory requirements worldwide to ensure appropriate

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reporting of safety information; all clinical studies conducted by the sponsor or its affiliates will
be conducted in accordance with those procedures.
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or the
participant’s legally acceptable representative) for the duration of the study.
Further details on AEs, SAEs, AESIs, and PQCs can be found in Appendix 2.
8.3.1. 
Time Period and Frequency for Collecting AE, SAE, and AESI
Information
All AEs
AEs and special reporting situations, whether serious or non-serious, that are related to study
procedures or that are related to non-investigational sponsor products will be reported from the
time a signed and dated ICF is obtained until the end of the study/early withdrawal.
Clinically relevant medical events not meeting the above criteria and occurring between signing
of ICF and moment of vaccination will be collected on the Medical History eCRF page as
pre-existing conditions.
Solicited AEs, collected through a participant diary, will be recorded from the time of vaccination
until 7 days post-vaccination.
All other unsolicited AEs and special reporting situations, whether serious or non-serious, will be
reported from the time of vaccination until 28 days post-vaccination.
All SAEs and AEs leading to discontinuation from the study (regardless of the causal relationship)
are to be reported from the moment of vaccination until completion of the participant’s last study-
related procedure, which may include contact for safety follow-up. The sponsor will evaluate any
safety information that is spontaneously reported by an investigator beyond the time frame
specified in the protocol.
See Section 7.2 for procedures associated with withdrawal of consent.
All AEs will be followed until resolution or until clinically stable.
SAEs
All SAEs occurring during the study must be reported to the appropriate sponsor contact person
by study-site personnel immediately, but no later than 24 hours of their knowledge of the event.
Information regarding SAEs will be transmitted to the sponsor using the SAE Form and Safety
Report Form of the eCRF, which must be completed and reviewed by a physician from the study
site, and transmitted to the sponsor immediately, but no later than within 24 hours. The initial and
follow-up reports of an SAE should be transmitted electronically or by facsimile (fax). Telephone
reporting should be the exception and the reporter should be asked to complete the appropriate
form(s) first.

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AESIs
TTS is considered to be an AESI. Thrombotic events and/or thrombocytopenia (defined as platelet
count below the lower limit of normal [LLN] range for the testing lab) are considered to be
potential AESIs. All AESIs, including potential AESIs, will be reported to the sponsor from the
moment of study vaccination until 6 months after the study vaccination (see Section 8.3.6).
8.3.2. 
Method of Detecting AEs, SAEs, and AESIs
Care will be taken not to introduce bias when detecting AEs, SAEs, or AESIs. Open-ended and
nonleading verbal questioning of the participant is the preferred method to inquire about AE
occurrence.
Solicited AEs
Solicited AEs are used to assess the reactogenicity of the study vaccine and are predefined local
(injection site) and systemic events for which the participant is specifically questioned and which
are noted by participants in their participant diary.
After vaccination, participants will remain under observation at the study site for at least
30 minutes for presence of any acute reactions and solicited events.
In addition, participants will record solicited signs and symptoms in a participant diary for 7 days
post-vaccination. All participants will be provided with a participant diary and instructions on how
to complete the participant diary(see Overview in Section 8). If a paper diary is used for this study,
the study staff will transcribe the information provided by the participant into the relevant sections
of the eCRF. If an e-diary is used, diary information will be transferred to the sponsor. After review
and verbal discussion of the initial diary entries with the participant, the investigator will complete
their own assessment in the relevant sections of the eCRF. Once a solicited sign or symptom from
a participant diaryis considered to be of severity Grade 1 or above, it will be recorded as a solicited
AE.
Solicited Local (Injection Site) AEs
Participants will be asked to note in the participant diary  occurrences of injection site
pain/tenderness, erythema and swelling at the study vaccine injection site daily for 7 days post-
vaccination (day of vaccination and the subsequent 7 days). The extent (largest diameter) of any
erythema and swelling should be measured (using the ruler supplied) and recorded daily. The case
definitions for solicited injection site events can be found in the references (Gidudu 2012;
Kohl 2007).
Solicited Systemic AEs
Participants will be instructed on how to record daily temperature using a thermometer provided
for home use. Participants should record the temperature (oral route preferred) in the participant
diary in the evening of the day of vaccination, and then daily for the next 7 days approximately at
the same time each day. If more than 1 measurement is made on any given day, the highest
temperature of that day will be used in the eCRF.

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Fever is defined as endogenous elevation of body temperature ≥38.0°C (≥100.4°F), as recorded in
at least 1 measurement (Marcy 2004).
Participants will also be instructed on how to note signs and symptoms in the participant diary on
a daily basis for 7 days post-vaccination (day of vaccination and the subsequent 7 days), for the
following events: fatigue, headache, nausea, and myalgia.
Unsolicited AEs
Unsolicited AEs are all AEs for which the participant is not specifically questioned in the
participant diary.
For details regarding AESIs, refer to Section 8.3.6.
8.3.3. 
Follow-up of AEs, SAEs, and AESIs
The investigator is obligated to perform or arrange for the conduct of supplemental measurements
and evaluations as medically indicated to elucidate the nature and causality of the AE, SAE, AESI,
or PQC as fully as possible. This may include additional laboratory tests or investigations,
histopathological examinations, or consultation with other health care professionals.
AEs and the special reporting situation of pregnancy will be followed by the investigator as
specified in Appendix 2.
8.3.4. 
Regulatory Reporting Requirements for SAEs
The sponsor assumes responsibility for appropriate reporting of AEs to the regulatory authorities.
The sponsor will also report to the investigator (and the head of the investigational institute where
required) all suspected unexpected serious adverse reactions (SUSARs). The investigator (or
sponsor where required) must report SUSARs to the appropriate IEC/IRB that approved the
protocol unless otherwise required and documented by the IEC/IRB. A SUSAR will be reported to
regulatory authorities unblinded. Participating investigators and IEC/IRB will receive a blinded
SUSAR summary, unless otherwise specified.
8.3.5. 
Pregnancy
All initial reports of pregnancy in participants or partners of male participants must be reported to
the sponsor by the study-site personnel within 24 hours of their knowledge of the event using the
appropriate pregnancy notification form. Abnormal pregnancy outcomes (eg, spontaneous
abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are considered SAEs and
must be reported using an SAE reporting form.
Follow-up information regarding the outcome of the pregnancy will be required.
If the partner of a male participant becomes pregnant during the study, follow-up information
regarding the outcome of the pregnancy will be requested upon the consent provided by the partner.

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8.3.6. 
Adverse Events of Special Interest
AESIs (including potential AESIs) are significant AEs that are judged to be of special interest
because of clinical importance, known or suspected class effects, or based on nonclinical signals.
AESIs and potential AESIs will be carefully monitored during the study by the sponsor.
AESIs and potential AESIs must be reported to the sponsor within 24 hours of awareness
irrespective of seriousness (ie, serious and nonserious AEs) or causality following the procedure
described above for SAEs.
AESIs must be reported using the AESI form in the eCRF using the eCRF completion guidelines.
Specific requirements for the AESI are described below.
8.3.6.1. 
Thrombosis with Thrombocytopenia Syndrome
As described in Section 2.2, TTS has been observed very rarely following vaccination with Janssen
COVID vaccine and is considered to be an AESI in this study. TTS is a syndrome characterized
by a combination of both a thrombotic event and thrombocytopenia. (American Society of
Hematology 2021; Brighton Collaboration 2021)
Because this syndrome is rare and not completely understood, all cases of thrombosis and/or
thrombocytopenia will be considered a potential case of TTS and should be reported to the sponsor
within 24 hours of awareness using the AESI form. Each potential AESI will be reviewed to
identify a TTS case. A potential TTS case is defined as:
 
Thrombotic events: suspected deep vessel venous or arterial thrombotic events as detailed in
Section 10.9, Appendix 9,
and/or
 
Thrombocytopenia, defined as platelet count below LLN for the testing lab
Symptoms, signs, or conditions suggestive of a thrombotic event or thrombocytopenia should be
recorded and reported as a potential AESI even if the final or definitive diagnosis has not yet been
determined, and alternative diagnoses have not yet been eliminated or shown to be less likely.
Follow-up information and final diagnoses, if applicable, should be submitted to the sponsor as
soon as they become available.
In the event of thrombocytopenia, study site personnel should report the absolute value for the
platelet count and the reference range for the laboratory test used.
For either a thrombotic event or thrombocytopenia, complete blood count including platelet count
and a coagulation profile available from participant’s medical records should be entered in the
eCRF. In case these results are not available at the time of the event report in the eCRF, the study
site is recommended to obtain a complete blood count including platelet count and a coagulation
profile (to be performed at the local laboratory). Repeat testing at the local laboratory may be
requested for confirmation upon sponsor discretion.

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Aliquots of serum samples collected for immunogenicity tests can be reconverted for participant’s
safety purposes upon sponsor request (Table 4).
Table 4 provides non-exhaustive list(s) of laboratory tests that may be performed (upon sponsor
request).
In addition, the sponsor may request additional laboratory tests on additional blood samples
obtained as soon as possible after the potential AESI onset, either during an ad hoc unscheduled
visit or the next scheduled visit, whichever comes first. Table 5 provides a non-exhaustive list of
laboratory tests that may be requested by the sponsor in case of potential AESI reporting, for which
additional samples may be needed.
Table 4: 
Laboratory Tests That May Be Performed Upon Sponsor Request on Immunogenicity Samples
Collected on Day 1, Day 15 and/or Day 183
Parameters 
Timepoints
 Serum samples for assay such as but not limited to:
o Heparin Induced Thrombocytopenia (HIT)/PF4 Ab, IgG·(HIT assay)
If the above test is positive, also consider:
 Anti-cardiolipin antibody
 Beta-2 glycoprotein
 Days 1, 15 and 183 visits
(aliquots of serum samples
collected for immunogenicity
test can be reconverted for
participant’s safety purposes).
Ab = antibody, IgG = immunoglobulin G, PF4 = platelet factor 4.
Note: results of the test should be reported in the narrative of the event and/or in the TTS AESI pages of the eCRF.
Table 5: 
Laboratory Tests That May Be Requested by the Sponsor to be Performed at the Central
Laboratory After Potential AESI Reporting
Parameters 
Timepoints
 Serum/plasma/whole blood samples for coagulation-related assays such as 
but not limited to: 
o Fibrinogen 
o D-dimer· 
o Lupus anticoagulant· 
o Anti-cardiolipin antibody 
o Beta-2 glycoprotein·
o Heparin Induced Thrombocytopenia (HIT)/PF4 Ab, IgG·(HIT assay)
o Platelet activation assay (if HIT/PF4 is positive)
o Homocysteine·
o COVID-19 serological test
 As soon as possible after the
potential AESI onset upon
sponsor request (during an ad
hoc unscheduled visit or the
next scheduled visit, whichever
comes first).
Ab = antibody, AESI = adverse event of special interest; COVID-19 = Coronavirus Disease 2019, IgG =
immunoglobulin G, PF4 = platelet factor 4.
Note: results of the test should be reported in the narrative of the event and/or in the TTS AESI pages of the eCRF.
Irrespective on samples for central laboratory tests collection, relevant data for TTS assessment reported in the
medical records of the participant should be reported in eCRF narrative of the event and/or in the TTS AESI pages
of the eCRF.
AESIs, including potential AESIs, will require enhanced data collection and evaluation. Every
effort should be made to report as much information as possible about the event to the sponsor in

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a reasonable timeframe. Relevant laboratory results can be entered on the AESI form in the eCRF,
using the eCRF completion guidelines.
If the investigator is not the treating physician, every effort should be made to collect the
information requested in the form from the treating physician and enter the available information
in the eCRF.
If an event meets the criteria for an SAE (Section 10.2.1), it should be reported using the same
process as for other SAEs.
Treatment and Follow-up Recommendation
The medical management of thrombotic events with thrombocytopenia is different from the
management of isolated thromboembolic diseases. Study site personnel and/or treating physicians
should follow available guidelines for treatment of thrombotic thrombocytopenia (eg, American
Society of Hematology 2021; British Society for Haematology 2021; CDC  2021). The use of
heparin may be harmful and alternative treatments may be needed. Consultation with a
hematologist is strongly recommended.
8.4. 
Medical Resource Utilization
Medical Resource Utilization parameters are not evaluated in this study.
9. 
STATISTICAL CONSIDERATIONS
Statistical analysis will be done by the sponsor or under the authority of the sponsor. A general
description of the statistical methods to be used to analyze the immunogenicity and safety data is
outlined below. Specific details will be provided in the SAP.
9.1. 
Statistical Hypotheses
For a description of the hypotheses, see Section 3.
9.2. 
Sample Size Determination
9.2.1. 
Immunogenicity
Immunogenicity assessments will be performed in all participants (N 1,113).
Sample size calculations for the immunogenicity objectives are performed under the following
assumptions.
For the humoral immune response in terms of neutralizing antibody GMTs:
 
no difference between high-risk adults aged 18 to 59 years and adults aged 65 years and older
and no difference between high-risk adults aged 18 to 59 years and adults aged 65 years and
older (ie, assuming a true GMT ratio of Day 15 [ie, 14 days after vaccination] RSV A2
neutralizing antibody titers equal to 1 for those comparisons, and similar standard deviation)

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 
a standard deviation of 1.5 at the log2 scale for VNA A2 on Day 15a
 
non-inferiority limit of 0.67 (2/3)
 
1-sided α of 2.5%
For the humoral immune response in terms of neutralizing antibody seroresponse rates (defined as
a 4-fold increase from baseline in Day 15 antibody titers):
 
Seroresponse rates are assumed to be 85% in all adults aged 18 to 59 years, high risk adults
aged 18 to 59 years and adults aged 65 years and older, based on available data from Phase 1/2
clinical studies,
 
Non-inferiority margin of 10%
 
1-sided α of 2.5%
In addition:
 
a ratio of 1:1:1 for the active groups in Cohorts 1, 2, and 3
 
hierarchical testing (ie, test first Group 1+3 versus Group 5, if non-inferiority is demonstrated:
test Group 3 versus Group 5)
Simulations show that a total of 285 evaluable participants per active group in each cohort are
needed to have 90% power to demonstrate non-inferiority in terms of neutralizing antibody GMT
and seroresponse rates between high-risk adults aged 18 to 59 years and adults aged 65 years and
older. With this sample size, the power to demonstrate non-inferiority in terms of neutralizing
antibody GMT and seroresponse rates between all adults aged 18 to 59 years and adults aged
65 years and older is >95%. The power to demonstrate non-inferiority for the high-risk adults aged
18 to 59 years and adults aged 65 years and older is approximately 90%, taking into account the
testing strategy (sequential testing). To account for exclusions from the Per-protocol
Immunogenicity Set (see Section 9.3), drop-outs, and missing samples, approximately
315 participants per active group should be enrolled.
9.2.2. 
Safety
Solicited AEs, unsolicited AEs SAEs, and AESIs will be collected in all participants (N 1,113).
Figure 2 shows that with 315 active participants per group (Groups 1 and 3), the observation of 0
events in the database would be associated with 95% confidence that the true rate is less than 1%.
When pooling Groups 1 and 3, the observations of 0 events would be associated with 95%
confidence that the true rate is less than 0.5%.
Table 6 indicates that with 315 active participants per group (Groups 1 and 3), the probability to
observe at least one AE is 96% if the true AE rate at least 1%. When pooling both groups, the
probability to observe at least 1 AE is 96% if the true AE rate is at least 0.5%. For Group 5 (active
a Based on Day 15 VNA A2 results obtained from Cohort 2, Group 14 in study VAC18193RSV1004.

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participants of the older adults group), safety data is already collected in other studies. Therefore,
no additional participants are added on top of what is needed to assess immunogenicity.
Figure 2: 
Upper-Limit of the One-sided 95% CI around the Proportion if no Events are Observed by
Number of Participants
Table 6: 
Probability to Observe at Least One AE by Given True AE Rates
True AE Rate 
N=315 
N=630
0.5%  
79% 
96%
1% 
96% 
100%
2.5% 
100%  
100%
In Cohorts 1 and 2, a placebo group (Groups 2 and 4) of approximately 70 high-risk adults aged
18 to 59 years and of approximately 70 healthy adults aged 18 to 59 years is added for blinding
purposes. In Cohort 3, a placebo group (Group 6) of approximately 28 adults aged 65 years and
older is added for blinding purposes. This results in a total sample size of approximately 1,113
participants.
9.3. 
Populations for Analysis Sets
Vaccination assignment will follow the as-treated principle.
The Full Analysis (FA)Set will include all participants who received study vaccine, regardless of
the occurrence of protocol deviations and vaccine type (study vaccine or placebo). All safety and
participant information analyses will be based on the FA Set.
The Per-protocol Immunogenicity (PPI)Set will include all randomized participants who received
study vaccine and for whom immunogenicity data are available. Samples taken after a participant
experienced a major protocol deviation expected to impact the immunogenicity outcomes will be
excluded from the PPI Set.

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The list of major protocol deviations that would lead to elimination from the immunogenicity
analysis will be specified in the SAP or major protocol violation criteria document, which will be
finalized before database lock and unblinding.
The primary analysis set for analyses related to RSV immunogenicity is the PPI Set. As a
sensitivity analysis, key tables may also be based on the FA Set.
9.4. 
Statistical Analyses
The SAP will be finalized prior to database lock of the primary analysis and it will include a more
technical and detailed description of the statistical analyses described in this section. This section
is a summary of the planned statistical analyses of all endpoints.
9.4.1. 
General Considerations
The primary analysis will be performed when all participants have completed the visit 28 days
post-vaccination or discontinued earlier.
The significance level (α) is 5% (2-sided). No multiplicity adjustments are neededsince the cohorts
are tested sequentially in the overall 18 to 59 years group (Groups 1 and 3) followed by the high
risk 18 to 59 years group (Group 3) and since non-inferiority based on GMTs and seroresponse
rate both need to be met for each comparison, and as no interim analyses are planned before the
primary analysis.
Refer to Section 9.3 for the choice of populations for the different analyses.
9.4.2. 
Participant Information
For all participants, demographic characteristics (eg, age, height, body weight, BMI, race, and
gender) and other baseline characteristics will be tabulated and summarized descriptively  by
cohort and group.
9.4.3. 
Immunogenicity Analyses
9.4.3.1. 
Primary Endpoints
The primary immunogenicity objectives will be assessed sequentially.
To assess non-inferiority in terms of GMTs, 2-sided CIs will be calculated for the difference in
log2-transformed VNA A2 antibody titers at 14 days after active vaccination between all adults
aged 18 to 59 years (Groups 1 and 3) and adults aged 65 years and older (Group 5) and between
high-risk adults aged 18 to 59 years (Group 3) and adults aged 65 years and older (Group 5). The
GMT ratio and CIs for the neutralizing antibody GMT objectives will be calculated via an analysis
of variance (ANOVA) including both active groups (ie, Groups 1, 3, and 5) with Day 15 (ie,
14 days after vaccination) VNA A2 antibody titers as dependent variable and group as independent
variable and COVID-19 vaccination as a stratification factor (3 categories: 1. Janssen COVID-19
vaccine, 2. Vaxzevria (Oxford/AstraZeneca), 3. other vaccine, or no vaccine). The CIs around the
difference will be back-transformed (by exponentiation) to CIs around a GMT ratio

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(GMTGroup x/GMTGroup 5, with x 1+3 or x 3) and compared to the non-inferiority limit of 0.67
(2/3).
To assess non-inferiority in terms of seroresponse rates (co-primary objective), 2-sided CIs will
be calculated for the difference in seroresponse rates 14 days after active vaccination for the same
comparisons. Seroresponse based on VNA A2 antibody titers is defined as a 4-fold increase from
baseline on Day 15. The Newcombe (Score) with continuity correction method will be used to
calculate the CIs for the difference in seroresponse rates (Seroresponse Rate Group x Seroresponse
Rate Group 5,with x 1+3 or x 3) and compared with the non-inferiority margin of -0.1. This analysis
will be stratified for COVID-19 vaccination.
Non-inferiority of the humoral immune response to Ad26/protein preF RSV vaccine in all adults
aged 18 to 59 years (Groups 1 and 3) versus in adults aged 65 years and older (Group 5) is
demonstrated if the lower limit of the 2-sided 95% CI of the estimated GMT ratio is >0.67 and if
the lower limit of the 2-sided 95% CI of the estimated difference in seroresponse rates is >-0.1.
If non-inferiority in all adults aged 18 to 59 years (Groups 1 and 3) is not demonstrated for both
neutralizing antibody GMTs and seroresponse rates, the study fails. If non-inferiority in all adults
aged 18 to 59 years is demonstrated for both neutralizing antibody GMTs and seroresponse rates,
then non-inferiority in high-risk adults aged 18 to 59 years (Group 3) can be tested;similarly, non-
inferiority of the humoral immune response to Ad26/protein preF RSV vaccine in high-risk adults
aged 18 to 59 years (Group 3) versus in adults aged 65 years and older (Group 5) is demonstrated
if the lower limit of the 2-sided 95% CI of the estimated GMT ratio is >0.67 and if the lower limit
of the 2-sided 95% CI of the estimated difference in seroresponse rates is >-0.1.
As a sensitivity analysis to assess the impact of baseline titers, the neutralizing antibody GMT
primary endpoint will also be evaluated adjusting for the respective baseline titers. For
immunogenicity, baseline is considered as the last assessment pre-vaccination. In a second
sensitivity analysis, different variances between the groups will be allowed. Therefore, the CIs will
be calculated via Welch’s ANOVA.
9.4.3.2. 
Secondary/Exploratory Immunogenicity Endpoints
Descriptive statistics (such as geometric mean and 95% CI for preF ELISA antibody titers and
VNA A2, and median and quartiles for IFN-γ and ELISpot) will be calculated for continuous
immunogenicity parameters at all available timepoints. For the humoral assays, geometric mean
fold rises from baseline with 95% CIs will be calculated additionally. For pre-F ELISA, the
percentages of participants with 2- and 4-fold increase from baseline will also be tabulated.
Graphical representations of immunogenicity parameters will be created as applicable. For
categorical variables, frequency tables will be presented and corresponding CIs may be calculated
where appropriate.

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9.4.4. 
Safety Analyses
No formal statistical testing of safety data is planned. Safety data (including solicited and
unsolicited AEs) will be analyzed descriptively by cohort and group. All safety analyses will be
based on the FA Set.
AEs
The verbatim terms used in the eCRF by investigators to identify AEs will be coded using the
Medical Dictionary for Regulatory Activities (MedDRA). All reported AEs with onset during the
active phase (ie, AEs occurring from the time ofvaccination up to 28 days post-vaccination), and
all SAEs and AESIs will be included in the analysis. For each AE, the number and percentage of
participants who experience at least 1 occurrence of the given event will be summarized by group.
Summaries, listings, datasets, or participant narratives may be provided, as appropriate, for those
participants who die, who discontinue study vaccination due to an AE, or who experience a severe
AE, an SAE, or an AESI.
Summaries and/or listings may be provided separately for AEs with onset outside the above
defined timeframe (ie, beyond 28 days post-vaccination).
Solicited local (injection site) and systemic AEs will be summarized descriptively. The overall
frequencies per group as well as frequencies according to severity and duration will be calculated
for solicited AEs. In addition, the number and percentages of participants with at least 1 solicited
local (injection site) or systemic AE will be presented. Frequencies of unsolicited AEs, separately
for all and vaccination-related only, will be presented by System Organ Class and preferred term.
Vital Signs
Baseline and emerging vital signs abnormalities will be listed.
9.5. 
Planned Analyses
The following analyses are planned:
 
Primary analysis: 28 days post-vaccination  safety analysis and 14 days post-vaccination
immunogenicity analysis. This analysis will be performed based on sponsor unblinded data
(study-site personnel and participants will remain blinded until the end of the study). The goal
of this analysis will be to evaluate the primary objectives.
 
Final analysis: including 6 months post-vaccination immunogenicity analysis and SAE data
up to study end. This analysis will be performed on unblinded data.

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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Abbreviations
Ad26 
adenovirus serotype 26
AE 
adverse event
AESI 
adverse event of special interest
ANOVA  
analysis of variance
β-hCG  
beta human chorionic gonadotropin
CI 
confidence interval
COPD  
chronic obstructive pulmonary disease
COVID-19 
coronavirus disease-2019
CVST  
cerebral venous sinus thrombosis
DNA  
deoxyribonucleic acid
eCRF  
electronic case report form
eDC  
electronic data capture
ELISA  
enzyme-linked immunosorbent assay
ELISpot 
enzyme-linked immunospot
FA 
Full Analysis
FDA  
Food and Drug Administration
FOIA  
Freedom of Information Act
GCP  
Good Clinical Practice
GMT  
geometric mean titer
HITT  
heparin-induced thrombocytopenia and thrombosis
IB  
Investigator’s Brochure
ICF  
informed consent form
ICH  
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for
Human Use
ICMJE 
International Committee of Medical Journal Editors
IEC  
Independent Ethics Committee
IFN-γ 
interferon gamma
IL 
interleukin
IM  
intramuscular
IMP  
investigational medicinal product
IRB  
Institutional Review Board
IWRS  
interactive web response system
MedDRA  
Medical Dictionary for Regulatory Activities
post-F 
post-fusion
PPI 
Per-protocol Immunogenicity
PQC  
Product Quality Complaint
pre-F 
prefusion conformation-stabilized F protein
RSV  
respiratory syncytial virus
SAE 
serious adverse event
SAP  
statistical analysis plan
SUSAR  
suspected unexpected serious adverse reaction
TNF-α 
tumor necrosis factor alpha
TTS  
thrombosis with thrombocytopenia syndrome
US  
United States
VNA  
virus neutralization assay
vp 
virus particles
WHO  
World Health Organization

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10.2. Appendix 2: AEs, SAEs, AESIs, PQCs, and Other Safety Reporting:
Definitions and Procedures for Recording, Evaluating, Follow-up, and
Reporting
10.2.1. 
AE Definitions and Classifications
AE
An AE is any untoward medical occurrence in a clinical study participant administered a
pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have
a causal relationship with the study vaccine. An AE can therefore be any unfavorable and
unintended sign (including an abnormal finding), symptom, or disease temporally associated with
the use of a medicinal (investigational or non-investigational) product, whether or not related to
that medicinal (investigational or non-investigational) product. (Definition per International
Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use [ICH])
This includes any occurrence that is new in onset or aggravated in severity or frequency from the
baseline condition, or abnormal results of diagnostic procedures, including laboratory test
abnormalities.
Note: For time period of sponsor’s AE collection, see All AEs under Section 8.3.1, Time Period
and Frequency for Collecting AE and SAE Information.
SAE
An SAE based on ICH and European Union  Guidelines on Pharmacovigilance for Medicinal
Products for Human Use is any untoward medical occurrence that at any dose:
 
Results in death
 
Is life-threatening
(The participant was at risk of death at the time of the event. It does not refer to an event that
hypothetically might have caused death if it were more severe.)
 
Requires inpatient hospitalization or prolongation of existing hospitalization
 
Results in persistent or significant disability/incapacity
 
Is a congenital anomaly/birth defect
 
Is a suspected transmission of any infectious agent via a medicinal product
 
Is Medically Important*
*Medical and scientific judgment should be exercised in deciding whether expedited reporting is
also appropriate in other situations, such as important medical events that may not be immediately
life threatening or result in death or hospitalization but may jeopardize the participant or may
require intervention to prevent one of the other outcomes listed in the definition above. These
should usually be considered serious.
If a serious and unexpected AE occurs for which there is evidence suggesting a causal relationship
between the study vaccine and the event (eg, death from anaphylaxis), the event must be reported

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as a SUSAR by the sponsor to health authorities and by the investigator to the IEC/IRB according
to regulatory and local requirements.
Unlisted (Unexpected) AE/Reference Safety Information
An AE is considered unlisted if the nature or severity is not consistent with the applicable product
reference safety information. For the Ad26/protein preF RSV vaccine, the expectedness of an AE
will be determined by whether or not it is listed in the IB (IB Ad26/protein preF RSV vaccine
2021).
10.2.2. 
Attribution Definitions
Assessment of Causality
The causal relationship to study vaccine is determined by the investigator. The following selection
should be used to assess all AEs.
Related
There is a reasonable causal relationship between study vaccine administration and the AE.
Not Related
There is not a reasonable causal relationship between study vaccine administration and the AE.
The term "reasonable causal relationship" means there is evidence to support a causal relationship.
By definition, all solicited AEs at the injection site (local) will be considered related to the study
vaccine administration.
10.2.3. 
Severity Criteria
All AEs will be coded for severity using a modified version of the FDA grading table, based on
version of September 2007 (FDA 2007), included in Appendix 6, Toxicity Grading Scale For Use
in Cohorts 1 and 2 (Adults Aged 18 to 59 Years) and Appendix 7, Toxicity Grading Scale For Use
in Cohort 3 (Adults Aged 60 Years and Older).

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For adverse events not identified in the grading table, the following guidelines will be applied:
Grade 1 
Mild 
Symptoms causing no or minimal interference with usual social
and functional activities
Grade 2 
Moderate 
Symptoms causing greater than minimal interference with usual
social and functional activities
Grade 3 
Severe 
Symptoms causing inability to perform usual social and
functional activities and requires medical intervention
Grade 4 
Potentially 
life- 
threatening 
Symptoms causing inability to perform basic self-care functions
OR medical or operative intervention indicated to prevent
permanent impairment, persistent disability OR ER visit or
hospitalization
The severity of solicited signs and symptoms will be graded in the diary by the participant based
on the severity assessment provided in the diary and then verified by the investigator using the
toxicity grading scale in Appendix 6, Toxicity Grading Scale For Use in Cohorts 1 and 2 (Adults
Aged 18 to 59 Years) and Appendix 7, Toxicity Grading Scale For Use in Cohort 3 (Adults Aged
60 Years and Older). (Note: severity of the measured events will be derived from the diameter [for
erythema and swelling] and the temperature measurements [for fever])
10.2.4. 
Special Reporting Situations
Safety events of interest for a sponsor study vaccine in an interventional study that may require
expedited reporting or safety evaluation include, but are not limited to:
 
Overdose of a sponsor study vaccine
 
Suspected abuse/misuse of a sponsor study vaccine
 
Accidental or occupational exposure to a sponsor study vaccine
 
Medication error, intercepted medication error, or potential medication error involving a
Johnson & Johnson medicinal product (with or without patient exposure to the Johnson &
Johnson medicinal product, eg, product name confusion, product label confusion, intercepted
prescribing or dispensing errors)
 
Exposure to a sponsor study vaccine from breastfeeding
 
Reporting of participant pregnancy or participant partner(s) pregnancy
Special reporting situations should be recorded in the eCRF. Any special reporting situation that
meets the criteria of an SAE should be recorded on the SAE page of the eCRF.
10.2.5. 
Procedures
All AEs
All AEs, regardless of seriousness, severity, or presumed relationship to study vaccine, must be
recorded using medical terminology in the source document and the eCRF. Whenever possible,
diagnoses should be given when signs and symptoms are due to a common etiology (eg, cough,

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runny nose, sneezing, sore throat, and head congestion should be reported as “upper respiratory
infection”). Investigators must record in the eCRF their opinion concerning the relationship of the
AE to study vaccine. All measures required for AE management must be recorded in the source
document and reported according to sponsor instructions.
For all studies with an outpatient phase, including open-label studies, the participant must be
provided with a "wallet (study) card" and instructed to carry this card with them for the duration
of the study indicating the following:
 
Study number
 
Statement, in the local language(s), that the participant is participating in a clinical study
 
Investigator’s name and 24-hour contact telephone number
 
Local sponsor’s name and 24-hour contact telephone number (for medical personnel only)
 
Site number
 
Participant number
 
Any other information that is required to do an emergency breaking of the blind
SAEs
All SAEs that have not resolved by the end of the study, or that have not resolved upon the
participant’s discontinuation from the study, must be followed until any of the following occurs:
 
The event resolves
 
The event stabilizes
 
The event returns to baseline, if a baseline value/status is available
 
The event can be attributed to agents other than the study vaccine or to factors unrelated to
study conduct
 
It becomes unlikely that any additional information can be obtained (participant or health care
practitioner refusal to provide additional information, lost to follow-up after demonstration of
due diligence with follow-up efforts)
Any event requiring hospitalization (or prolongation of hospitalization) that occurs during
participation in the study must be reported as an SAE, except hospitalizations for the following:
 
Hospitalizations not intended to treat an acute illness or AE (eg, social reasons such as pending
placement in long-term care facility).
 
Surgery or procedure planned before entry into the study (must be documented in the eCRF).
Note: Hospitalizations that were planned before the signing of the ICF, and where the
underlying condition for which the hospitalization was planned has not worsened, will not be
considered SAEs. Any AE that results in a prolongation of the originally planned
hospitalization is to be reported as a new SAE.
The cause of death of a participant in a study during the entire study period, whether or not the
event is expected or associated with the study vaccine, is considered an SAE and must be reported.

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Information regarding SAEs will be transmitted to the sponsor using an SAE reporting form and
safety report form of the eCRF, which must be completed and reviewed by a physician from the
study site, and transmitted in a secure manner to the sponsor within 24 hours. The initial and
follow-up reports of an SAE should be transmitted in a secure manner electronically or by
facsimile (fax). Telephone reporting should be the exception and the reporter should be asked to
complete the appropriate form(s) first.
Adverse Events of Special Interest
AESIs, including potential AESIs, will be carefully monitored during the study by the sponsor and
must be reported to the sponsor within 24 hours of awareness irrespective of seriousness (ie,
serious and nonserious AEs) or causality assessment, following the procedure described above for
SAEs and will require enhanced data collection.
10.2.6. 
PQC Handling
Definition
A PQC is defined as any suspicion of a product defect related to manufacturing, labeling, or
packaging, ie, any dissatisfaction relative to the identity, quality, durability, reliability, or
performance of a distributed product, including its labeling, drug delivery system, or package
integrity. A PQC may have an impact on the safety and efficacy of the product. In addition, it
includes any technical complaints, defined as any complaint that indicates a potential quality issue
during manufacturing, packaging, release testing, stability monitoring, dose preparation, storage
or distribution of the product or the drug delivery system.
All complaints related to ANY part of the Ad26/protein preF RSV vaccine must be reported within
1 business day. In the event of public holiday, measures must be taken to ensure reporting no later
than calendar day 3.
Procedures
All initial PQCs must be reported to the sponsor by the study-site personnel within 24 hours after
being made aware of the event.
A sample of the suspected product should be maintained under the correct storage conditions until
a shipment request is received from the sponsor.
10.2.7. 
Contacting Sponsor Regarding Safety, Including Product Quality
The names (and corresponding telephone numbers) of the individuals who should be contacted
regarding safety issues, PQCs, or questions regarding the study are listed in the Contact
Information page(s), which will be provided as a separate document.

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10.3. Appendix 3: Regulatory, Ethical, and Study Oversight Considerations
10.3.1. 
Regulatory and Ethical Considerations
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the
protocol, current ICH guidelines on Good Clinical Practice (GCP), and applicable regulatory and
country-specific requirements.
GCPis an international ethical and scientific quality standard for designing, conducting, recording,
and reporting studies that involve the participation of human participants. Compliance with this
standard provides public assurance that the rights, safety, and well-being of study participants are
protected, consistent with the principles that originated in the Declaration of Helsinki, and that the
study data are credible.
Protocol Clarification Communications
If text within a final approved protocol requires clarification (eg, current wording is unclear or
ambiguous) that does not change any aspect of the current study conduct, a protocol clarification
communication (PCC) may be prepared. The PCC Document will be communicated to the
Investigational Site, Site Monitors, Local Trial Managers (LTMs), Clinical Trial Managers
(CTMs), and/or Contract Research Organizations (CROs) who will ensure that the PCC
explanations are followed by the investigators.
The PCC Document may be shared by the sites with Independent Ethics Committees/Institutional
Review Boards (IECs/IRBs) per local regulations.
The PCC Documents must NOT be used in place of protocol amendments, but the content of the
PCC Document must be included in any future protocol amendments.
Protocol Amendments
Neither the investigator nor the sponsor will modify this protocol without a formal amendment by
the sponsor. All protocol amendments must be issued by the sponsor, and signed and dated by the
investigator. Protocol amendments must not be implemented without prior IEC/IRB approval, or
when the relevant competent authority has raised any grounds for non-acceptance, except when
necessary to eliminate immediate hazards to the participants, in which case the amendment must
be promptly submitted to the IEC/IRB and relevant competent authority. Documentation of
amendment approval by the investigator and IEC/IRB must be provided to the sponsor. When the
change(s) involve only logistic or administrative aspects of the study, the IEC/IRB (where
required) only needs to be notified.
During the study, in situations where a departure from the protocol is unavoidable, the investigator
or other physician in attendance will contact the appropriate sponsor representative listed in the
Contact Information page(s), which will be provided as a separate document. Except in emergency
situations, this contact should be made before implementing any departure from the protocol. In
all cases, contact with the sponsor must be made as soon as possible to discuss the situation and

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agree on an appropriate course of action. The data recorded in the eCRF and source documents
will reflect any departure from the protocol, and the source documents will describe this departure
and the circumstances requiring it.
Regulatory Approval/Notification
This protocol and any amendment(s) must be submitted to the appropriate regulatory authorities
in each respective country, if applicable. A study may not be initiated until all local regulatory
requirements are met.
Required Prestudy Documentation
The following documents must be provided to the sponsor before shipment of study vaccine to the
study site:
 
Protocol and amendment(s), if any, signed and dated by the principal investigator
 
A copy of the dated and signed (or sealed, where appropriate per local regulations), written
IEC/IRB approval of the protocol, amendments, ICF, any recruiting materials, and if
applicable, participant compensation programs. This approval must clearly identify the
specific protocol by title and number and must be signed (or sealed, where appropriate per
local regulations) by the chairman or authorized designee.
 
Name and address of the IEC/IRB, including a current list of the IEC/IRB members and their
function, with a statement that it is organized and operates according to GCP and the
applicable laws and regulations. If accompanied by a letter of explanation, or equivalent, from
the IEC/IRB, a general statement may be substituted for this list. If an investigator or a
member of the study-site personnel is a member of the IEC/IRB, documentation must be
obtained to state that this person did not participate in the deliberations or in the vote/opinion
of the study.
 
Regulatory authority approval or notification, if applicable
 
Signed and dated statement of investigator (eg, Form FDA 1572), if applicable
 
Documentation of investigator qualifications (eg, curriculum vitae)
 
Completed investigator financial disclosure form from the principal investigator, where
required
 
Signed and dated Clinical Trial Agreement, which includes the financial agreement
 
Any other documentation required by local regulations
The following documents must be provided to the sponsor before enrollment of the first
participant:
 
Completed investigator financial disclosure forms from all sub-investigators
 
Documentation of sub-investigator qualifications (eg, curriculum vitae)
 
Name and address of any local laboratory conducting tests for the study, and a dated copy of
current laboratory normal ranges for these tests, if applicable

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 
Local laboratory documentation demonstrating competence and test reliability
(eg, accreditation/license), if applicable
IEC or IRB
Before the start of the study, the investigator (or sponsor where required)will provide the IEC/IRB
with current and complete copies of the following documents (as required by local regulations):
 
Final protocol and, if applicable, amendments
 
Sponsor-approved ICF (and any other written materials to be provided to the participants)
 
IB (or equivalent information) and amendments/addenda
 
Sponsor-approved participant recruiting materials
 
Information on compensation for study-related injuries or payment to participants for
participation in the study, if applicable
 
Investigator’s curriculum vitae or equivalent information (unless not required, as documented
by the IEC/IRB)
 
Information regarding funding, name of the sponsor, institutional affiliations, other potential
conflicts of interest, and incentives for participants
 
Any other documents that the IEC/IRB requests to fulfill its obligation
This study will be undertaken only after the IEC/IRB has given full approval of the final protocol,
amendments (if any, excluding the ones that are purely administrative, with no consequences for
participants, data or study conduct, unless required locally), the ICF, applicable recruiting
materials, and participant compensation programs, and the sponsor has received a copy of this
approval. This approval letter must be dated and must clearly identify the IEC/IRB and the
documents being approved.
During the study the investigator (or sponsor where required) will send the following documents
and updates to the IEC/IRB for their review and approval, where appropriate:
 
Protocol amendments (excluding the ones that are purely administrative, with no
consequences for participants, data or study conduct)
 
Revision(s) to ICF and any other written materials to be provided to participants
 
If applicable, new or revised participant recruiting materials approved by the sponsor
 
Revisions to compensation for study-related injuries or payment to participants for
participation in the study, if applicable
 
New edition(s) of the IB and amendments/addenda
 
Summaries of the status of the study at intervals stipulated in guidelines of the IEC/IRB (at
least annually)
 
Reports of AEs that are serious, unlisted/unexpected, and associated with the study vaccine
 
New information that may adversely affect the safety of the participants or the conduct of the
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 
Deviations from or changes to the protocol to eliminate immediate hazards to the participants
 
Report of deaths of participants under the investigator’s care
 
Notification if a new investigator is responsible for the study at the site
 
Development Safety Update Report and Line Listings, where applicable
 
Any other requirements of the IEC/IRB
For all protocol amendments (excluding the ones that are purely administrative, with no
consequences for participants, data or study conduct), the amendment and applicable ICF revisions
must be submitted promptly to the IEC/IRB for review and approval before implementation of the
change(s).
At least once a year, the IEC/IRB will be asked to review and reapprove this study, where required.
At the end of the study, the investigator (or sponsor where required) will notify the IEC/IRB about
the study completion.
Country Selection
This study will only be conducted in those countries where the intent is to launch or otherwise help
ensure access to the developed product if the need for the product persists, unless explicitly
addressed as a specific ethical consideration in Section 4.2.1, Study-Specific Ethical Design
Considerations.
Other Ethical Considerations
For study-specific ethical design considerations, refer to Section 4.2.1.
10.3.2. 
Financial Disclosure
Investigators and sub-investigators will provide the sponsor with sufficient, accurate financial
information in accordance with local regulations to allow the sponsor to submit complete and
accurate financial certification or disclosure statements to the appropriate regulatory authorities.
Investigators are responsible for providing information on financial interests during the study and
for 1 year after completion of the study.
Refer to Required Prestudy Documentation (above) for details on financial disclosure.
10.3.3. 
Informed Consent Process
Each participant must give written consent according to local requirements after the nature of the
study has been fully explained. The ICF(s) must be signed before performance of any study-related
activity. The ICF(s) that is/are used must be approved by both the sponsor and by the reviewing
IEC/IRB and be in a language that the participant can read and understand. The informed consent
should be in accordance with principles that originated in the Declaration of Helsinki, current ICH
and GCP guidelines, applicable regulatory requirements, and sponsor policy.

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Before enrollment in the study, the investigator or an authorized member of the study-site
personnel must explain to potential participants the aims, methods, reasonably anticipated benefits,
and potential hazards of the study, and any discomfort participation in the study may entail.
Participants will be informed that their participation is voluntary and that they may withdraw
consent to participate at any time. They will be informed that choosing not to participate will not
affect the care the participant will receive. Finally, they will be told that the investigator will
maintain a participant identification register for the purposes of long-term follow-up if needed and
that their records may be accessed by health authorities and authorized sponsor personnel without
violating the confidentiality of the participant, to the extent permitted by the applicable law(s) or
regulations. By signing the ICF the participant is authorizing such access. It also denotes that the
participant agrees to allow their study physician to recontact the participant for the purpose of
obtaining consent for additional safety evaluations, if needed.
The participant will be given sufficient time to read the ICF and the opportunity to ask questions.
After this explanation and before entry into the study, consent should be appropriately recorded by
means of the participant’s personally dated signature. After having obtained the consent, a copy of
the ICF must be given to the participant.
Participants who are rescreened are required to sign a new ICF.
If the participant is unable to read or write, an impartial witness should be present for the entire
informed consent process (which includes reading and explaining all written information) and
should personally date and sign the ICF after the oral consent of the participant is obtained.
10.3.4. 
Data Protection
Privacy of Personal Data
The collection and processing of personal data from participants enrolled in this study will be
limited to those data that are necessary to fulfill the objectives of the study.
These data must be collected and processed with adequate precautions to ensure confidentiality
and compliance with applicable data privacy protection laws and regulations. Appropriate
technical and organizational measures to protect the personal data against unauthorized disclosures
or access, accidental or unlawful destruction, or accidental loss or alteration must be put in place.
Sponsor personnel whose responsibilities require access to personal data agree to keep the identity
of participants confidential.
The informed consent obtained from the participant includes explicit consent for the processing of
personal data and for the investigator/institution to allow direct access to their original medical
records (source data/documents) for study-related monitoring, audit, IEC/IRB review, and
regulatory inspection. This consent also addresses the transfer of the data to other entities and to
other countries.
The participant has the right to request through the investigator access to their personal data and
the right to request rectification of any data that are not correct or complete. Reasonable steps will

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be taken to respond to such a request, taking into consideration the nature of the request, the
conditions of the study, and the applicable laws and regulations.
10.3.5. 
Long-Term Retention of Samples for Additional Future Research
Samples collected in this study may be stored for up to 15 years (or according to local regulations)
for additional research. Samples will only be used to understand Ad26.RSV.preF and RSV preF
protein, to understand RSV and other respiratory pathogens, and to develop tests/assays related to
Ad26.RSV.preF, RSV preF protein, and RSV disease. The research may begin at any time during
the study or the post-study storage period. Included are samples from participants who were
screened but not randomized, and which may also be used to develop tests/assays related to
Ad26.RSV.preF, RSV preF protein, and RSV disease.
Stored samples will be coded throughout the sample storage and analysis process and will not be
labeled with personal identifiers. Participants may withdraw their consent for their samples to be
stored for research (refer to Section 7.2.1, Withdrawal From the Use of Research Samples).
10.3.6. 
Committees Structure
Safety issues that might arise from this study may be escalated to an Independent Data Monitoring
Committee, as needed.
All potential AESI cases will be reviewed to determine if they meet the definition of TTS (see
Section 10.3.6). A Charter will be developed to describe the roles and responsibilities of the
Committee appointed to perform this review.
10.3.7. 
Publication Policy/Dissemination of Clinical Study Data
All information, including but not limited to information regarding the Ad26/protein preF RSV
vaccine or the sponsor’s operations (eg, patent application, formulas, manufacturing processes,
basic scientific data, prior clinical data, formulation information) supplied by the sponsor to the
investigator and not previously published, and any data, generated as a result of this study, are
considered confidential and remain the sole property of the sponsor. The investigator agrees to
maintain this information in confidence and use this information only to accomplish this study and
will not use it for other purposes without the sponsor’s prior written consent.
The investigator understands that the information developed in the study will be used by the
sponsor in connection with the continued development ofthe Ad26/protein preF RSV vaccine, and
thus may be disclosed as required to other clinical investigators or regulatory agencies. To permit
the information derived from the clinical studies to be used, the investigator is obligated to provide
the sponsor with all data obtained in the study.
The results of the study will be reported in a clinical study report generated by the sponsor and
will contain data from all study sites that participated in the study as per protocol. Recruitment
performance or specific expertise related to the nature and the key assessment parameters of the
study will be used to determine a coordinating investigator for the study. Results of analyses

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performed after the clinical study report has been issued will be reported in a separate report and
will not require a revision of the clinical study report.
Study participant identifiers will not be used in publication of results. Any work created in
connection with performance of the study and contained in the data that can benefit from copyright
protection (except any publication by the investigator as provided for below)shall be the property
of the sponsor as author and owner of copyright in such work.
Consistent with Good Publication Practices and International Committee of Medical Journal
Editors (ICMJE) guidelines, the sponsor shall have the right to publish such primary (multicenter)
data and information without approval from the investigator. The investigator has the right to
publish study site-specific data after the primary data are published. If an investigator wishes to
publish information from the study, a copy of the manuscript must be provided to the sponsor for
review at least 60 days before submission for publication or presentation. Expedited reviews will
be arranged for abstracts, poster presentations, or other materials. If requested by the sponsor in
writing, the investigator will withhold such publication for up to an additional 60 days to allow for
filing of a patent application. In the event that issues arise regarding scientific integrity or
regulatory compliance, the sponsor will review these issues with the investigator. The sponsor will
not mandate modifications to scientific content and does not have the right to suppress information.
For multicenter study designs and sub-study approaches, secondary results generally should not
be published before the primary endpoints of a study have been published. Similarly, investigators
will recognize the integrity of a multicenter study by not submitting for publication data derived
from the individual study site until the combined results from the completed study have been
submitted for publication, within 18 months after the study end date, or the sponsor confirms there
will be no multicenter study publication. Authorship of publications resulting from this study will
be based on the guidelines on authorship, such as those described in the ICMJE Recommendations
for the Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals, which
state that the named authors must have made a significant contribution to the conception or design
of the work; or the acquisition, analysis, or interpretation of the data for the work; and drafted the
work or revised it critically for important intellectual content; and given final approval of the
version to be published; and agreed to be accountable for all aspects of the work in ensuring that
questions related to the accuracy or integrity of any part of the work are appropriately investigated
and resolved.
Registration of Clinical Studies and Disclosure of Results
The sponsor will register and disclose the existence of and the results of clinical studies as required
by law. The disclosure of the final study results will be performed after the end of study in order
to ensure the statistical analyses are relevant.
10.3.8. 
Data Quality Assurance
Data Quality Assurance/Quality Control
Steps to be taken to ensure the accuracy and reliability of data include the selection of qualified
investigators and appropriate study sites, review of protocol procedures with the investigator and

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study-site personnel before the study, and periodic monitoring visits by the sponsor. Written
instructions will be provided for collection, handling, storage, and shipment of samples.
Guidelines for eCRF completion will be provided and reviewed with study-site personnel before
the start of the study. The sponsor may review the eCRF for accuracy and completeness during
on-site monitoring visits and after transmission to the sponsor; any discrepancies will be resolved
with the investigator or designee, as appropriate. After upload of the data into the study database
they will be verified for accuracy and consistency with the data sources.
10.3.9. 
Case Report Form Completion
Case report forms are prepared and provided by the sponsor for each participant in electronic
format. All eCRF entries, corrections, and alterations must be made by the investigator or
authorized study-site personnel. The investigator must verify that all data entries in the eCRF are
accurate and correct.
The study data will be transcribed by study-site personnel from the source documents onto an
eCRF, if applicable. Study-specific data will be transmitted in a secure manner to the sponsor.
Worksheets may be used for the capture of some data to facilitate completion of the eCRF. Any
such worksheets will become part of the participant’s source documents. Data must be entered into
the eCRF in English. The eCRF must be completed as soon as possible after a participant visit and
the forms should be available for review at the next scheduled monitoring visit.
If necessary, queries will be generated in the eDC tool. If corrections to an eCRF are needed after
the initial entry into the eCRF, this can be done in either of the following ways:
 Investigator and study-site personnel can make corrections in the eDC tool at their own
initiative or as a response to an auto query (generated by the eDC tool).
 Sponsor or sponsor delegate can generate a query for resolution by the investigator and study-
site personnel.
10.3.10. 
Source Documents
At a minimum, source documents consistent in the type and level of detail with that commonly
recorded at the study site as a basis for standard medical care must be available for the following:
participant identification, eligibility, and study identification; study discussion and date of signed
informed consent; dates of visits; results of safety and immunogenicity parameters as required by
the protocol; record of all AEs and follow-up of AEs; concomitant medication; vaccine
receipt/dispensing/return records; study vaccine administration information; and date of study
completion and reason for early discontinuation of study vaccination or withdrawal from the study,
if applicable.
The author of an entry in the source documents should be identifiable.

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The participant diary used to collect information regarding solicited signs and symptoms after
vaccination will be considered source data.
Specific details required as source data for the study and source data collection methods will be
reviewed with the investigator before the study and will be described in the monitoring guidelines
(or other equivalent document).
An eSource system may be utilized, which contains data traditionally maintained in a hospital or
clinic record to document medical care (eg, electronic source documents) as well as the clinical
study-specific data fields as determined by the protocol. This data is electronically extracted for
use by the sponsor. If eSource is utilized, references made to the eCRF in the protocol include the
eSource system but information collected through eSource may not be limited to that found in the
eCRF. Data in the eSource system may be considered source documentation.
10.3.11. 
Monitoring
The sponsor will use a combination of monitoring techniques (central, remote, or on-site
monitoring)to monitor this study.
The sponsor will perform on-site monitoring visits as frequently as necessary. The monitor will
record dates of the visits in a study site visit log that will be kept at the study site. The first post-
initiation visit will be made as soon as possible after enrollment has begun. At these visits, the
monitor may  compare data entered into the eCRF with the source documents
(eg, hospital/clinic/physician’s office medical records); a sample may be reviewed. The nature and
location of all source documents will be identified to ensure that all sources of original data
required to complete the eCRF are known to the sponsor and study-site personnel and are
accessible for verification by the sponsor study-site contact. If electronic records are maintained
at the study site, the method of verification must be discussed with the study-site personnel.
Direct access to source documents (medical records) must be allowed for the purpose of verifying
that the recorded data are consistent with the original source data. Findings from this review will
be discussed with the study-site personnel. The sponsor expects that, during monitoring visits, the
relevant study-site personnel will be available, the source documents will be accessible, and a
suitable environment will be provided for review of study-related documents. The monitor will
meet with the investigator on a regular basis during the study to provide feedback on the study
conduct.
In addition to on-site monitoring visits, remote contacts can occur. It is expected that during these
remote contacts, study-site personnel will be available to provide an update on the progress of the
study at the site.
Central monitoring will take place for data identified by the sponsor as requiring central review.
10.3.12. 
On-Site Audits
Representatives of the sponsor’s clinical quality assurance department may visit the study site at
any time during or after completion of the study to conduct an audit of the study in compliance

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with regulatory guidelines and company policy. These audits will require access to all study
records, including source documents, for inspection. Participant privacy must, however, be
respected. The investigator and study-site personnel are responsible for being present andavailable
for consultation during routinely scheduled study-site audit visits conducted by the sponsor or its
designees.
Similar auditing procedures may also be conducted by agents of any regulatory body, either as part
of a national GCP compliance program or to review the results of this study in support of a
regulatory submission. The investigator should immediately notify the sponsor if they have been
contacted by a regulatory agency concerning an upcoming inspection.
10.3.13. 
Record Retention
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all eCRF
and all source documents that support the data collected from each participant, as well as all study
documents as specified in ICH/GCP Section 8, Essential Documents for the Conduct of a Clinical
Trial, and all study documents as specified by the applicable regulatory requirement(s). The
investigator/institution will take measures to prevent accidental or premature destruction of these
documents.
Essential documents must be retained until at least 2 years after the last approval of a marketing
application in an ICH region and until there are no pending or contemplated marketing applications
in an ICH region or until at least 2 years have elapsed since the formal discontinuation of clinical
development of the investigational product. These documents will be retained for a longer period
if required by the applicable regulatory requirements or by an agreement with the sponsor. It is the
responsibility of the sponsor to inform the investigator/institution as to when these documents no
longer need to be retained.
If the responsible investigator retires, relocates, or for other reasons withdraws from the
responsibility of keeping the study records, custody must be transferred to a person who will accept
the responsibility. The sponsor must be notified in writing of the name and address of the new
custodian. Under no circumstance shall the investigator relocate or dispose of any study documents
before having obtained written approval from the sponsor.
If it becomes necessary for the sponsor or the appropriate regulatory authority to review any
documentation relating to this study, the investigator/institution must permit access to such reports.
10.3.14. 
Study and Site Start and Closure
First Act of Recruitment
The first participant screened is considered the first act of recruitment and it becomes the study
start date.
Study/Site Termination
The sponsor reserves the right to close the study site or terminate the study at any time for any
reason at the sole discretion of the sponsor. Study sites will be closed upon study completion. A

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study site is considered closed when all required documents and study supplies have been collected
and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable cause and
sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or investigator may include but are not
limited to:
 Failure of the investigator to comply with the protocol, the requirements of the IEC/IRB or
local health authorities, the sponsor’s procedures, or GCP guidelines
 Inadequate recruitment of participants by the investigator
 Discontinuation of further study vaccine development

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10.4. Appendix 4: Contraceptive and Barrier Guidance
Participants must follow contraceptive measures as outlined in Section 5.1, Inclusion Criteria.
Pregnancy information will be collected and reported as noted in Section 8.3.5, Pregnancy and
Appendix 2 Adverse Events, Serious Adverse Events, Product Quality Complaints, and Other
Safety reporting: Definitions and Procedures for Recording, Evaluating, Follow-up, and
Reporting.
Definition of a Person of Childbearing Potential
A Person of Childbearing Potential
A person  is considered fertile following menarche and until becoming postmenopausal unless
permanently sterile (see below).
A Person Not of Childbearing Potential
 
premenarchal
A premenarchal state is one in which menarche has not yet occurred.
 
postmenopausal
A postmenopausal state is defined as no menses for 12 months without an alternative medical
cause.
 
permanently sterile (for the purpose of this study)
Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral
oophorectomy.
Note: If the childbearing potential changes after start of the study (eg, a premenarchal person
experiences menarche) or the risk of pregnancy changes (eg, a person who is not heterosexually
active becomes active), a person must begin an acceptable effective method of contraception, as
described throughout the inclusion criteria.

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10.5. Appendix 5: New York Heart Association Classification of Cardiac Disease
The following table presents the NYHA classification of cardiac disease:
Functional Capacity 
Objective Assessment
Class I. Patients with cardiac disease but without resulting limitation of physical 
activity. Ordinary physical activity does not cause undue fatigue, palpitation, 
dyspnea, or anginal pain.
A. No objective evidence of
cardiovascular disease.
Class II. Patients with cardiac disease resulting in slight limitation of physical 
activity. They are comfortable at rest. Ordinary physical activity results in fatigue, 
palpitation, dyspnea, or anginal pain. 
B. Objective evidence of
minimal cardiovascular
disease.
Class III. Patients with cardiac disease resulting in marked limitation of physical 
activity. They are comfortable at rest. Less than ordinary activity causes fatigue, 
palpitation, dyspnea, or anginal pain. 
C. Objective evidence of
moderately severe
cardiovascular disease.
Class IV. Patients with cardiac disease resulting in inability to carry on any 
physical activity without discomfort. Symptoms of heart failure or the anginal 
syndrome may be present even at rest. If any physical activity is undertaken,
discomfort is increased.
D. Objective evidence of
severe cardiovascular disease.
*The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases
of the Heart and Great Vessels. 9th ed. Boston, Mass: Little, Brown & Co; 1994:253-256.

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10.6. Appendix 6: Toxicity Grading Scale For Use in Cohorts 1 and 2 (Adults
Aged 18 to 59 Years)
Adapted from the FDA Guidance document “Toxicity Grading Scale for Healthy Adult and
Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials” (September 2007).
Local Reaction to 
Injectable Product 
Mild (Grade 1) 
Moderate (Grade 2) Severe (Grade 3) 
Potentially Life
Threatening
(Grade 4)
Pain/Tenderness# 
Aware of symptoms 
but easily tolerated; 
Does not interfere 
with activity; 
Discomfort only to 
touch  
Notable symptoms; 
Requires modification 
in activity or use of 
medications; 
Discomfort with 
movement 
Incapacitating 
symptoms; 
Inability to do work, 
school, or usual 
activities; Use of 
narcotic pain reliever
Hospitalization;
Pain/tenderness
causing inability to
perform basic self-
care function
Erythema# 
25 –50 mm  
51 –100 mm  
> 100 mm  
Hospitalization;
Necrosis or
exfoliative dermatitis
Swelling# 
25 –50 mm  
51 –100 mm  
> 100 mm  
Hospitalization;
Necrosis
# Revised by the sponsor.
Vital Signs * 
Mild (Grade 1) 
Moderate (Grade 2) Severe (Grade 3) 
Potentially Life
Threatening
(Grade 4)
Fever (°C) ** 
           (°F)** 
38.0 - 38.4 
100.4 - 101.1 
38.5 - 38.9 
101.2 - 102.0 
39.0 - 40.0 
102.1 - 104.0 
> 40 
> 104.0
Tachycardia - beats 
per 
minute
101 –115 
116 –130 
> 130 
Hospitalization for
arrhythmia#
Bradycardia - beats 
per 
minute***
50 –54 
45 –49 
< 45 
Hospitalization for
arrhythmia#
Hypertension 
(systolic) - mm Hg 
141 –150 
151 –155 
> 155 
Hospitalization for
malignant
hypertension#
Hypertension 
(diastolic) - mm Hg 
91 –95 
96 –100 
> 100 
Hospitalization for
malignant
hypertension#
Hypotension 
(systolic) –mm Hg 
85 –89 
80 –84 
< 80 
Hospitalization for
hypotensive shock#
Respiratory Rate – 
breaths per minute
17 –20 
21 –25 
> 25 
Intubation
* Participant should be at rest for all vital sign measurements.
** For oral temperature: no recent hot or cold beverages or smoking.
*** When resting heart rate is between 60 –100 beats per minute. Use clinical judgment when characterizing
bradycardia among some healthy participant populations, for example, conditioned athletes.
# Revised by the sponsor.

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Systemic (General) Mild (Grade 1) 
Moderate (Grade 2) Severe (Grade 3) 
Potentially Life
Threatening
(Grade 4)
Vomiting# 
No interference 
with activity or 1 –2 
episodes/24 hours 
Some interference 
with activity or > 2 
episodes/24 hours 
Prevents daily  
activity, requires 
outpatient IV
hydration
Hospitalization;
Hypotensive shock
Nausea# 
Minimal symptoms; 
causes minimal or no 
interference with 
work, school, or self- 
care activities 
Notable symptoms; 
Requires modification 
in activity or use of 
medications; 
Does NOT result in 
loss of work, school, 
or cancellation of 
social activities
Incapacitating 
symptoms; 
Requires bed rest 
and/or results in loss 
of work, school, or
cancellation of social
activities
Hospitalization;
Inability to perform
basic self-care
functions
Diarrhea# 
2 –3 loose stools or 
< 400 gms/24 hours 
4 –5 stools or 
400 –800 gms/24 
hours 
6 or more watery  
stools or 
> 800 gms/24 hours 
or oral rehydration 
necessary
Hospitalization;
Hypotensive shock
OR IV fluid
replacement indicated
Headache# 
Minimal symptoms;
causes minimal or no
interference with
work, school, or self-
care activities
Notable symptoms; 
Requires modification 
in activity or use of 
medications; 
Does NOT result in 
loss of work, school, 
or cancellation of 
social activities 
Incapacitating
symptoms;
Requires bed rest
and/or results in loss
of work, school, or
cancellation of social
activities;
Use of narcotic pain
reliever
Hospitalization;
Inability to perform
basic self-care
functions
Fatigue# 
Minimal symptoms;
causes minimal or no
interference with
work, school, or self-
care activities
Notable symptoms; 
Requires modification 
in activity or use of 
medications; 
Does NOT result in 
loss of work, school, 
or cancellation of 
social activities 
Incapacitating
symptoms;
Requires bed rest
and/or results in loss
of work, school, or
cancellation of social
activities;
Use of narcotic pain
reliever
Hospitalization;
Inability to perform
basic self-care
functions
Myalgia# 
Minimal symptoms;
causes minimal or no
interference with
work, school, or self-
care activities
Notable symptoms; 
Requires modification 
in activity or use of 
medications; 
Does NOT result in 
loss ofwork, school, 
or cancellation of 
social activities 
Incapacitating
symptoms;
Requires bed rest
and/or results in loss
of work, school, or
cancellation of social
activities;
Use of narcotic pain
reliever
Hospitalization;
Inability to perform
basic self-care
functions
# Revised by the sponsor.

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Systemic Illness 
Mild (Grade 1) 
Moderate (Grade 2) Severe (Grade 3) 
Potentially Life
Threatening
(Grade 4)
Illness or clinical 
adverse 
event (as defined 
according to 
applicable
regulations)
No interference with  
activity  
Some interference 
with activity not 
requiring medical 
intervention 
Prevents daily  
activity and
requires medical
intervention
Hospitalization#
# Revised by the sponsor.

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10.7. Appendix 7: Toxicity Grading Scale For Use in Cohort 3 (Adults Aged
60Years and Older)
Adapted from the FDA Guidance document “Toxicity Grading Scale for Healthy Adult and
Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials” (September 2007).
Local Reaction to 
Injectable Product 
Mild (Grade 1) 
Moderate (Grade 2) Severe (Grade 3) 
Potentially Life
Threatening
(Grade 4)
Pain/Tenderness# 
Aware of symptoms 
but easily tolerated; 
Does not interfere 
with activity; 
Discomfort only to 
touch  
Notable symptoms; 
Requires modification 
in activity or use of 
medications; 
Discomfort with 
movement 
Incapacitating 
symptoms; 
Inability to do work, 
school, or usual 
activities; Use of 
narcotic pain reliever
Hospitalization;
Pain/tenderness
causing inability to
perform basic self-
care function
Erythema# 
25 –50 mm  
51 –100 mm  
> 100 mm  
Hospitalization;
Necrosis or
exfoliative dermatitis
Swelling# 
25 –50 mm  
51 –100 mm  
> 100 mm  
Hospitalization;
Necrosis
# Revised by the sponsor.
Vital Signs * 
Mild (Grade 1) 
Moderate (Grade 2) Severe (Grade 3) 
Potentially Life
Threatening
(Grade 4)
Fever (°C) ** 
           (°F)** 
38.0 - 38.4 
100.4 - 101.1 
38.5 - 38.9 
101.2 - 102.0 
39.0 - 40.0 
102.1 - 104.0 
> 40 
> 104.0
Tachycardia - beats 
per 
minute
101 –115 
116 –130 
> 130 
Hospitalization for
arrhythmia#
Bradycardia - beats 
per 
minute***
50 –54 
45 –49 
< 45 
Hospitalization for
arrhythmia#
Hypertension 
(systolic) - mm Hg 
141 –150 
151 –160##  
> 160##  
Hospitalization for
malignant
hypertension#
Hypertension 
(diastolic) - mm Hg 
91 –95 
96 –100 
> 100 
Hospitalization for
malignant
hypertension#
Hypotension 
(systolic) –mm Hg 
85 –89 
80 –84 
< 80 
Hospitalization for
hypotensive shock#
Respiratory Rate – 
breaths per minute
17 –20 
21 –25 
> 25 
Intubation
* Participant should be at rest for all vital sign measurements.
** For oral temperature: no recent hot or cold beverages or smoking.
*** When resting heart rate is between 60 –100 beats per minute. Use clinical judgment when characterizing
bradycardia among some healthy participant populations, for example, conditioned athletes.
# Revised by the sponsor.
## Modified upper limit regarding the participant population (participants aged 60 years and older).

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Systemic (General) Mild (Grade 1) 
Moderate (Grade 2) Severe (Grade 3) 
Potentially Life
Threatening
(Grade 4)
Vomiting# 
No interference 
with activity or 1 –2 
episodes/24 hours 
Some interference 
with activity or > 2 
episodes/24 hours 
Prevents daily  
activity, requires 
outpatient IV
hydration
Hospitalization;
Hypotensive shock
Nausea# 
Minimal symptoms; 
causes minimal or no 
interference with 
work, school, or self- 
care activities 
Notable symptoms; 
Requires modification 
in activity or use of 
medications; 
Does NOT result in 
loss of work, school, 
or cancellation of 
social activities
Incapacitating 
symptoms; 
Requires bed rest 
and/or results in loss 
of work, school, or
cancellation of social
activities
Hospitalization;
Inability to perform
basic self-care
functions
Diarrhea# 
2 –3 loose stools or 
< 400 gms/24 hours 
4 –5 stools or 
400 –800 gms/24 
hours 
6 or more watery  
stools or 
> 800 gms/24 hours 
or oral rehydration 
necessary
Hospitalization;
Hypotensive shock
OR IV fluid
replacement indicated
Headache# 
Minimal symptoms;
causes minimal or no
interference with
work, school, or self-
care activities
Notable symptoms; 
Requires modification 
in activity or use of 
medications; 
Does NOT result in 
loss of work, school, 
or cancellation of 
social activities 
Incapacitating
symptoms;
Requires bed rest
and/or results in loss
of work, school, or
cancellation of social
activities;
Use of narcotic pain
reliever
Hospitalization;
Inability to perform
basic self-care
functions
Fatigue# 
Minimal symptoms;
causes minimal or no
interference with
work, school, or self-
care activities
Notable symptoms; 
Requires modification 
in activity or use of 
medications; 
Does NOT result in 
loss of work, school, 
or cancellation of 
social activities 
Incapacitating
symptoms;
Requires bed rest
and/or results in loss
of work, school, or
cancellation of social
activities;
Use of narcotic pain
reliever
Hospitalization;
Inability to perform
basic self-care
functions
Myalgia# 
Minimal symptoms;
causes minimal or no
interference with
work, school, or self-
care activities
Notable symptoms; 
Requires modification 
in activity or use of 
medications; 
Does NOT result in 
loss of work, school, 
or cancellation of 
social activities 
Incapacitating
symptoms;
Requires bed rest
and/or results in loss
of work, school, or
cancellation of social
activities;
Use of narcotic pain
reliever
Hospitalization;
Inability to perform
basic self-care
functions
# Revised by the sponsor.

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Systemic Illness 
Mild (Grade 1) 
Moderate (Grade 2) Severe (Grade 3) 
Potentially Life
Threatening
(Grade 4)
Illness or clinical 
adverse 
event (as defined 
according to 
applicable
regulations)
No interference with  
activity  
Some interference 
with activity not 
requiring medical 
intervention 
Prevents daily  
activity and
requires medical
intervention
Hospitalization#
# Revised by the sponsor.

VAC18193 (JNJ-64400141/ JNJ-64213175)
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Status: Approved, Date: 30 November 2021
10.8. Appendix 8: Guidance on Study Conduct During a Natural Disaster
GUIDANCE ON STUDY CONDUCT DURING THE COVID-19 PANDEMIC
It is recognized that the Coronavirus Disease 2019 (COVID-19) pandemic may have an impact on
the conduct of this clinical study due to, for example, isolation or quarantine of participants and
study-site personnel; travel restrictions/limited access to public places, including hospitals; study
site personnel being reassigned to critical tasks.
The sponsor is providing options for study-related participant management in the event of
disruption to the conduct of the study. This guidance does not supersede any local or government
requirements or the clinical judgment of the investigator to protect the health and well-being of
participants and site staff. If, at any time, a participant’s travel to the study site is considered to be
dangerous, study participation may be interrupted, and study follow-up conducted. If it becomes
necessary to discontinue participation in the study, the procedures outlined in the protocol for
discontinuing study intervention will be followed.
If, as a result of the COVID-19 pandemic, scheduled visits cannot be conducted in person at the
study site, they will be performed to the extent possible remotely/virtually or delayed until such
time that on-site visits can be resumed. At each contact, participants will be interviewed to collect
safety data. Key immunogenicity endpoint assessments should be performed if required and as
feasible. Participants will also be questioned regarding general health status to fulfill any physical
examination requirement.
Every effort should be made to adhere to protocol-specified assessments for participants on study
intervention, including follow up. Modifications to protocol-required assessments may be
permitted after consultation with the participant, investigator, and the sponsor. Missed
assessments/visits will be captured in the clinical trial management system for protocol deviations.
Discontinuations of study interventions and withdrawal from the study should be documented with
the prefix “COVID-19-related” in the case report form (CRF).
If a participant has tested positive for COVID-19, the investigator should contact the sponsor’s
responsible medical officer to discuss plans for administration of study intervention, performing
study assessments, and follow-up. Modifications made to the study conduct as a result of the
COVID-19 pandemic should be summarized in the clinical study report.

VAC18193 (JNJ-64400141/ JNJ-64213175)
Clinical Protocol VAC18193RSV3006 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 30 November 2021
GUIDANCE SPECIFIC TO THIS PROTOCOL:
Screening and Randomization
 Enrollment of new participants may continue based on the investigator’s assessment of risks
versus benefits, depending on the situation at a particular site, and the ability to monitor
participant safety.
Site Visits
 
When site visits are not possible due to local/national guidelines, sites should collect the
assessments via telephone visits or home-based visits, if the participant allows. The actual
visit date and the type of visit (ie, telephone or home-based visit) should be captured in the
eCRF according to the eCRF completion guidelines. Procedures that cannot be performed
during a home-based visit (eg, blood samples, and physical examination), should be excluded. 
Vaccine Administration
 
When planning for vaccination visits, local/national or institutional guidelines will be
followed. The study vaccine must be administered by a blinded qualified individual at the
study site. If this is not possible, a solution may be considered in consultation with the sponsor
and taking into consideration participant safety.
Informed Consent Form
 
Consenting and re-consenting of participants for the measures taken (including also remote
consenting by phone or video consultation) will be performed as applicable and according to
local guidance for informed consent applicable during the COVID-19 pandemic. The process
is to be documented in the source documents.
Source Data Verification/Monitoring
 
In case on-site monitoring visits are not be possible, the site monitor may contact the
investigator to arrange monitoring visits and activities remotely (in accordance with site and
local requirements). Additional on-site monitoring visits may be needed in the future to catch
up on source data verification.
Site Audits
During the COVID-19 pandemic and at the impacted sites, study site GCP audits with direct
impact/engagement from the investigator and study site personnel would not be conducted in order
to comply with national, local, and/or organizational social distancing restrictions. Additional
quality assurance activities such as remote audits or focused review of study-related documents
may take place with limited impact/engagement if possible.

VAC18193 (JNJ-64400141/ JNJ-64213175)
Clinical Protocol VAC18193RSV3006 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 30 November 2021
10.9. Appendix 9: Thrombotic Events to be Reported as Potential AESIs
At the time of protocol writing, the list of thrombotic events to be reported to the sponsor as
potential AESIs is provided below. Further guidance may become available on thrombotic events
of interest.
 
MedDRA PTs for large vessel thrombosis and embolism
 
Aortic embolus, aortic thrombosis, aseptic cavernous sinus thrombosis, brain stem
embolism, brain stem thrombosis, carotid arterial embolus, carotid artery thrombosis,
cavernous sinus thrombosis, cerebral artery thrombosis, cerebral venous sinus
thrombosis, cerebral venous thrombosis, superior sagittal sinus thrombosis, transverse
sinus thrombosis, mesenteric artery embolism, mesenteric artery thrombosis, mesenteric
vein thrombosis, splenic artery thrombosis, splenic embolism, splenic thrombosis,
thrombosis mesenteric vessel, visceral venous thrombosis, hepatic artery embolism,
hepatic artery thrombosis, hepatic vein embolism, hepatic vein thrombosis, portal vein
embolism, portal vein thrombosis, portosplenomesenteric venous thrombosis, splenic
vein thrombosis, spontaneous heparin-induced thrombocytopenia syndrome, femoral
artery embolism, iliac artery embolism, jugular vein embolism, jugular vein thrombosis,
subclavian artery embolism, subclavian vein thrombosis, obstetrical pulmonary
embolism, pulmonary artery thrombosis, pulmonary thrombosis, pulmonary venous
thrombosis, renal artery thrombosis, renal embolism, renal vein embolism, renal vein
thrombosis, brachiocephalic vein thrombosis, vena cava embolism, vena cava
thrombosis, truncus coeliacus thrombosis
 
MedDRA PTs for more common thrombotic events
 
Axillary vein thrombosis, deep vein thrombosis, pulmonary embolism, MedDRA PTs for
acute myocardial infarction*, MedDRA PTs for stroke*
Source: Shimabukuro T. CDC COVID-19 Vaccine Task Force. Thrombosis with thrombocytopenia syndrome (TTS)
following Janssen COVID-19 vaccine. Advisory Committee on Immunization Practices (ACIP). April 23, 2021.
https://www.cdc.gov/vaccines/acip/meetings/slides-2021-04-23.html.
*Vaccine Adverse Event Reporting System (VAERS) Standard Operating Procedures for COVID-19 (as of 29 January
2021) https://www.cdc.gov/vaccinesafety/pdf/VAERS-v2-SOP.pdf

VAC18193 (JNJ-64400141/ JNJ-64213175)
Clinical Protocol VAC18193RSV3006 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 30 November 2021
10.10. Appendix 10: Guidance on Eligible Chronic Heart and Lung Conditions for
Cohort 2
The following table presents a non-exhaustive list of chronic heart and lung conditions that are
considered to either increase or not increase the risk for severe RSV infection. The list is intended
to provide guidance to investigators to assess the eligibility of participants with existing chronic
heart or lung conditions for participation in Cohort 2 of the study. Investigators must base their
conclusion on the medical history, medication and patient interview as defined in Inclusion
Criterion 10.
Conditions Considered to Increase the Risk 
for Severe RSV Infection 
Conditions Considered not to Increase the
Risk for Severe RSV Infection
Congestive heart failure 
Coronary artery disease 
 Angina pectoris 
 Ischemic cardiomyopathy  
 Coronary arterial stent insertion  
 Coronary artery bypass 
 Ischemic heart disease 
 Myocardial infarction
Congenital heart disease (eg, Tetralogy of
Fallot)
Asthma (not including exercise induced)
COPD
Interstitial lung disease
Sarcoidosis
Idiopathic pulmonary fibrosis
Stable asbestosis
Pulmonary hypertension
Hypertension
Myxoma
Deviated septum
Pacemaker implantation
Chronic cough
Aortic aneurism
Atrial fibrillation
Carotid stent placement
Pulmonary embolism
COVID-19
Post COVID-19 syndrome
Cardiac arrhythmia
Sleep apnea
Heart block
Femoral artery stent placement
Cardiac valve disease without chronic heart
failure
Carotid artery stenosis
Left carotid stent placement
Rhinosinusitis

VAC18193 (JNJ-64400141/ JNJ-64213175)
Clinical Protocol VAC18193RSV3006 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 30 November 2021
10.11. Appendix 11: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located
directly before the Table of Contents (TOC).
Amendment 1 (25 August 2021)
Overall Rationale for the Amendment: Following Health Authority feedback, the protocol is
amended to revise the primary objective of the study by adding seroresponse rates in addition to
neutralizing antibody GMTs as primary parameters to evaluate non-inferiority of immune
responses in adults (including high-risk) relative to elderly (60 years and above). The primary
immunogenicity endpoint is also modified from RSV preF IgG (by ELISA) to a functional immune
marker (anti-RSV virus neutralizing antibodies). The statistical hypotheses and success criteria
were revised accordingly, resulting also in a change in sample size and randomization ratios.
Section Number
and Name
Description of Change 
Brief Rationale
1.1 Synopsis
2.1 Study Rationale
3 OBJECTIVES AND ENDPOINTS
8.1 Immunogenicity Assessments
9.2.1 Immunogenicity
9.4.1 General Considerations
9.4.3.1 Primary Endpoints
9.4.3.2 Secondary/Exploratory
Immunogenicity Endpoints
Sections throughout were updated to
describe the revision of the immune
endpoints and modification of assay.
Following Health Authority
feedback.
1.1 Synopsis
3 OBJECTIVES AND ENDPOINTS
Secondary endpoint ‘to assess the
persistence of immune response post-
vaccination’ was changed into an
exploratory endpoint
Antibody persistence at
6 months post-vaccination
has been changed to an
exploratory objective since
this is the first study that
assesses the durability of
immune response in 18 to
59 year old individuals who
are at risk for severe RSV
disease.
1.1 Synopsis
Table 1: Overview of the Cohorts,
Groups, and Targeted Number of
Participants
4.1 Overall Design
6.3 Measures to Minimize Bias:
Randomization and Blinding
9.2 Sample Size Determination
9.2.1 Immunogenicity
9.2.2 Safety
Sections throughout were updated to
describe the change in sample size and
randomization ratios.
Following Health Authority
feedback.

VAC18193 (JNJ-64400141/ JNJ-64213175)
Clinical Protocol VAC18193RSV3006 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 30 November 2021
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis 
1.3 Schedule of Activities 
4.1 Overall Design 
6.3 Measures to Minimize Bias:
Randomization and Blinding
8 STUDY ASSESSMENTS AND
PROCEDURES
8.1 Immunogenicity Assessments
9.2 Sample Size Determination
Blood will be collected from all 
participants to assess humoral immune 
responses.
Following Health Authority
feedback.
2.2 Background 
11 REFERENCES  
Experience with Ad26-vectored 
vaccines was added. 
For alignment with the other
supportive Phase 3 study
protocols.
1.1 Synopsis 
Table 1: Overview of the Cohorts, 
Groups, and Targeted Number of 
Participants 
The following sentence was deleted: 
Recruitment will be optimized to target 
enrollment of at least 30% of 
participants in the 2 age categories, ie, 
18 to 45 years and 46 to 59 years. 
Efforts will be made to have a 
comparable number of participants per 
region between the different cohorts. 
No stratification is planned
by region or by age category
18 to 45 and 46 to 59 years
old. Monitoring of age and
region distribution of
enrolled participants per
cohort will be part of the data
surveillance during the study.
1.3 Schedule of Activities 
10.3.3 Informed Consent Process 
The following sentences were deleted: 
“Participants in the Immuno Subset and 
the Cellular Immuno Subset will need 
to consent for the additional blood 
collection in this subset.” “Informed 
consent for additional blood collection
will be requested from participants in
the Immuno Subset and the Cellular
Immuno Subset.”
The informed consent for the
additional blood collection
for the Immuno Subset will
be covered in a single overall
informed consent form.
4.2.1 Study-Specific Ethical Design 
Considerations 
The results of this study may be made 
available to all participants through a 
plain language summary at the 
conclusion of the study according to
local standards/restrictions.
For alignment with the other
supportive Phase 3 study
protocols.
2.3.1 Risks Related to Study 
Participation 
8.3.5 Pregnancy  
In case of pregnancy, postnatal 
sequelae in the infant will no longer be 
followed-up. 
According to the current
Janssen SOP ‘Receipt,
Follow-up, and Reporting of
Janssen Medicinal Product
Individual Case Safety
Reports’, follow-up of
postnatal sequelae in the
infant is not a requirement.
The sponsor protocol
template is planned to be
modified to reflect this
change.

VAC18193 (JNJ-64400141/ JNJ-64213175)
Clinical Protocol VAC18193RSV3006 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 30 November 2021
Section Number 
and Name
Description of Change 
Brief Rationale
8.3.1 Time Period and Frequency for 
Collecting AE, SAE, and AESI 
Information 
8.3.6.1 Thrombosis with
Thrombocytopenia Syndrome
The word ‘symptomatic’ was deleted
from the definition of
thrombocytopenia.
Definition of
thrombocytopenia is
broadened to include all
cases ofthrombocytopenia
the investigators observe
(including participant’s
routine blood test or blood
test performed concomitantly
to any AE/SAE/
hospitalization, or any other)
in the period of 6 months
after vaccination; these
should be reported as
potential TTS cases (please
refer to Section 8.3.6).
9.4.4 Safety Analyses 
Subsection Physical Examinations was
deleted.
For alignment with the other
supportive Phase 3 study
protocols.
Throughout the protocol 
Minor grammatical, formatting,
spelling, and administrative changes
were made.
Minor errors were noted.

VAC18193 (JNJ-64400141/ JNJ-64213175)
Clinical Protocol VAC18193RSV3006 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 30 November 2021
11. 
REFERENCES
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American Society of Hematology. COVID-19 resources. Thrombosis with Thrombocytopenia Syndrome (also
termed Vaccine-induced Thrombotic Thrombocytopenia). Updated 6 May 2021. https://www.hematology.org/covid-
19/vaccine-induced-immune-thrombotic-thrombocytopenia. Accessed: 27 April 2021.
Barouch DH, Liu J, Peter L, et al. Characterization of humoral and cellular immune responses elicited by a
recombinant adenovirus serotype 26 HIV-1 Env vaccine in healthy adults (IPCAVD 001). J Infect Dis.
2013;207:248-256.
Barouch DH, Tomaka FL, Wegmann F, et al. Evaluation of a mosaic HIV-1 vaccine in a multicentre, randomised,
double-blind, placebo-controlled, phase 1/2a clinical trial (APPROACH) and in rhesus monkeys (NHP 13-19).
Lancet. 2018;392(10143):232-243.
Brighton Collaboration. Interim Case Definition of Thrombosis with Thrombocytopenia Syndrome (TTS). 21 April
2021. https://brightoncollaboration.us/thrombosis-with-thrombocytopenia-syndrome-interim-case-definition/.
Accessed: 29 April 2021.
British Society for Haematology. Guidance produced from the Expert Haematology Panel (EHP) focused on
Covid-19 Vaccine induced Thrombosis and Thrombocytopenia (VITT). https://b-s-h.org.uk/media/19530/guidance-
version-13-on-mngmt-of-thrombosis-with-thrombocytopenia-occurring-after-c-19-vaccine 20210407.pdf. Version
1.3; 7 April 2021.  Accessed: 27 April 2021.
Centers for Disease Control and Prevention (CDC). Cases of cerebral venous sinus thrombosis with
thrombocytopenia after receipt of the Johnson & Johnson COVID-19 Vaccine. 13 April 2021.
https://emergency.cdc.gov/han/2021/han00442.asp. Accessed: 27 April 2021.
Centers for Disease Control and Prevention (CDC). Respiratory Syncytial Virus Infection (RSV). Available from:
https://www.cdc.gov/rsv/clinical/index.html#clinical. Updated 18 December 2020. Accessed 01 February 2021.
Criteria Committee of the New York Heart Association. Nomenclature and criteria for diagnosis of diseases of the
heart and great vessels, 9th  Edition. Boston: Little, Brown and Co; 1994.
de Bree GJ, Heidema J, van Leeuwen EM, et al. Respiratory syncytial virus-specific CD8+ memory T cell responses
in elderly persons. J Infect Dis. 2005;191:1710-1718.
Falsey AR, Walsh EE. Relationship of serum antibody to risk of respiratory syncytial virus infection in elderly
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Falsey AR, Hennessey PA, Formica MA, Cox C, Walsh EE. Respiratory syncytial virus infection in elderly and
high-risk adults. N Engl J Med. 2005;352(17):1749-1759.
Falsey AR, Formica MA, Hennessey PA, Criddle MM, Sullender WM, Walsh EE. Detection of respiratory syncytial
virus in adults with chronic obstructive pulmonary disease. Am J Respir CritCare Med. 2006;173:639-643.
Fleming DM, Taylor RJ, Lustig RL, et al. Modelling estimates of the burden of Respiratory Syncytial virus infection
in adults and the elderly in the United Kingdom. BMC Infect Dis. 2015;15(1):443.
Gidudu JK, Walco GA, Taddio A, et al. Immunization site pain: Case definition and guidelines for collection,
analysis, and presentation of immunization safety data. Vaccine. 2012:30;4558-4577.
Investigator’s Brochure: Ad26/protein preF RSV vaccine (JNJ-64400141/JNJ-64213175). Edition 2. Janssen
Vaccines & Prevention B.V. (April 2021).
Janssen Vaccines & Prevention B.V (data on file).
Kohl KS, Walop W, Gidudu J, et al. Swelling at or near injection site: Case definition and guidelines for collection,
analysis and presentation of immunization safety data. Vaccine. 2007:31;5858-5874.

VAC18193 (JNJ-64400141/ JNJ-64213175)
Clinical Protocol VAC18193RSV3006 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 30 November 2021
Looney RJ, Falsey AR, Walsh E, Campbell D. Effect of aging on cytokine production in response to respiratory
syncytial virus infection. J Infect Dis. 2002;185:682-685.
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VAC18193 (JNJ-64400141/ JNJ-64213175)
Clinical Protocol VAC18193RSV3006 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 30 November 2021
INVESTIGATOR AGREEMENT
I have read this protocol and agree that it contains all necessary details for carrying out this study. I will
conduct the study as outlined herein and will complete the study within the time designated.
I will provide copies of the protocol and all pertinent information to all individuals responsible to me who
assist in the conduct of this study. I will discuss this material with them to ensure that they are fully informed
regarding the study vaccine, the conduct of the study, and the obligations of confidentiality.
Coordinating Investigator (where required):
Name (typed or printed):
Institution and Address:
Signature: 
Date:
(Day Month Year)
Principal (Site) Investigator:
Name (typed or printed):
Institution and Address:
Telephone Number:
Signature: 
Date:
(Day Month Year)
Sponsor’s Responsible Medical Officer:
Name (typed or printed): 
Institution: 
Janssen Vaccines & Prevention B.V.
Signature: 
electronic signature appended at the end of the protocol 
Date:
(Day Month Year)
Note: If the address or telephone number of the investigator changes during the study, written notification will be
provided by the investigator to the sponsor, and a protocol amendment will not be required.
PPD

Signature
User 
Date 
Reason
 
30-Nov-2021 
16:29:51
(GMT)
Document Approval
PPD