A Randomized, Double-blind, Phase 3 Study to Evaluate Safety, Reactogenicity, and Immunogenicity of Co-administration of Ad26.COV2.S and Influenza Vaccines in Healthy Adults 18 Years of Age and Older
Phase: PHASE3
Conditions: COVID-19 Prevention
Sponsor: Janssen Vaccines & Prevention B.V.

CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
1
Status: Approved,Date: 15 February 2022
Janssen Vaccines & Prevention B.V.*
Clinical Protocol
A Randomized, Double-blind, Phase 3 Study to Evaluate Safety, Reactogenicity, and
Immunogenicity of Co-administration of Ad26.COV2.S and Influenza Vaccines in Healthy
Adults 18 Years of Age and Older
Protocol VAC31518COV3005; Phase 3
Version: Amendment 1
VAC31518 (JNJ-78436735)
* 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.
United States (US)sites of this study will be conducted under US Food & Drug Administration
Investigational New Drug (IND) regulations (21 CFR Part 312).
Regulatory Agency Identifier Number(s):
IND: 22657
EudraCT NUMBER: 2021-003953-43
Status: 
Approved
Date: 
15 February 2022
Prepared by: 
Janssen Vaccines & Prevention B.V.
EDMS number: 
EDMS-RIM-453567, 2.0
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.
NCT05091307

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
2
Status: Approved,Date: 15 February 2022
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document 
Date
Amendment 1 
This document
Original Protocol 
20 July 2021
Amendment 1 (This document)
Overall Rationale for the Amendment:
The study has encountered unexpected barriers and limitations in the recruitment of participants.
In view of the challenges, the non-inferiority assessment will be limited to the groups receiving
the standard dose only (Groups 1 and 2). The non-inferiority assessment of the high-dose(Groups
3 and 4) will be evaluated as a secondary endpoint due to a decrease in the sample size and a
descriptive analysis will be performed instead.
As the study considered a timeframe of 6 months since the primary COVID-19 vaccination, the
global availability of COVID-19 booster doses along with recommendations from advisory
committees to administer booster vaccinations has decreased the projected pool of participants
eligible for the study.
It has become more difficult to find eligible candidates to populate the high-dosegroups due to
early influenza campaigns prioritizing vaccination for older adults.
The overall sample size and objectives for the study have been revised to reflect the changes
described above.
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis
3 OBJECTIVES
AND ENDPOINTS
4.1 Overall Design
9.1 Statistical
Hypotheses
9.2 Sample Size
Determination
9.4.2 Inferential
Endpoints
9.4.3 Other
Secondary
Endpoints
The non-inferiority objectives for the high-dose
influenza vaccine were moved from Primary to
Secondary, with data for the high-dose vaccine to
be presented descriptively.
2-sided alpha for the non-inferiority (NI) analysis
was modified to 5%, the CIs were adjusted to 95%,
and the sample size was modified accordingly.
It is unlikely that enough
participants receiving the high-dose
influenza vaccine will be recruited
to power the assessment for the
primary analysis.
The NI assessment will be limited
to the standard-dose groups.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
3
Status: Approved,Date: 15 February 2022
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis 
3 OBJECTIVES 
AND ENDPOINTS
Text was added to the primary objectives to specify  
the assay and NI margins.
An exploratory objective was added to assess the 
correlation between the binding antibody (ELISA) 
titers and neutralizing antibody (VNA) titers to
SARS-CoV-2, in a subset of participants at
selected timepoints.
Two exploratory objectives were added: 
1. To assess humoral responses to Ad26.COV2.S
and influenza vaccine based on the previous history
of COVID-19 vaccination at entry.
2. To explore the humoral responses to
Ad26.COV2.S and influenza vaccine based on the
SARS-CoV-2 serostatus at baseline (N-serology).
Clarification
Consistency with other COVID-19
program studies
At the request of health authorities
1.1 Synopsis 
4.1 Overall Design  
9.2 Sample Size 
Determination  
The cap on 60% of participants ≤64 years of age 
was replaced with language that allows for greater 
flexibility in the enrollment of patients ≤64 years 
of age, and sample sizes were adjusted accordingly. 
Difficulty in recruitment of
participants 65 years of age and
older due to new COVID-19
booster recommendations and
influenza vaccine campaigns will
compromise the feasibility and will
not allow study endpoints to be
met.
5.1 Inclusion 
Criteria 
Inclusion criterion #5 was modified to include 
wording about the “last” COVID-19 vaccination. 
Inclusion criterion #6 was modified to reduce the 
timeframe in which medication must remain stable 
prior to study vaccination. 
Inclusion criterion #8 was modified to indicate that 
pregnancy test should occur prior to vaccination.
Most potential study participants
have now received at least one
booster vaccination.
The target population is healthy
individuals or those with stable
comorbidities. For individuals with
chronic comorbidities is not
infrequent that physicians make
dose changes to adjust the adequate
dose level regimen. Therefore, only
recent dose changes within the past
4 weeks will be exclusionary.
Clarification

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
4
Status: Approved,Date: 15 February 2022
Section Number
and Name
Description of Change 
Brief Rationale
5.2 Exclusion
Criteria
Exclusion criterion #2 was modified from a history 
of malignancy within 5 years before screening to a 
history of malignancy within 1 year before
screening.
Wording for Exclusion Criterion #5 was modified 
to indicate the definition of immunosuppressive 
dose as stated per (>20 mg prednisone or 
equivalent daily for 2 consecutive weeks). 
Intraarticular steroids have been removed from this 
sentence. 
Exclusion criterion #7 was deleted. 
Exclusion criterion #12 was modified to indicate 
that planning to receive a licensed/registered 
SARS-CoV-2 vaccine less than 6 months prior to 
first study vaccination is not exclusionary. 
Exclusion criterion #24 was modified to indicate 
that diagnostic test result should be obtained prior
to vaccination.
To align with the Phase 3 studies in
the program.
Intraarticular steroids are typically
use as a single shot indicated as
long-term pain and inflammation
reliever. The criteria defines an
immunosuppressive steroid dose is
considered to be >20 mg
prednisone or equivalent daily for 2
consecutive weeks.
That definition is not consistent
with the typical frequency of use in
clinical practice.
Eczema is a common side effect of
medication and not always an
indication of an autoimmune
disease;therefore,clinical
judgment is required to establish
the difference. These conditions are
covered under exclusion criterion
#5.
Only having actually received a
vaccine less than 6 months prior or
during the study would exclude an
individual from participating in this
study.
Clarification
2.3 Benefit-Risk
Assessment
2.3.3 Benefit-Risk
Assessment of
Study Participation
8.2 Safety
Assessments
Text regarding reporting of clinically significant 
abnormalities was modified.
Clarification
6.1 Study Vaccines
Administered
Text was modified regarding injection location and
visit windows.
Alternative injection locations are
allowed under some circumstances
however, the text was modified to
indicate that the participant should
be able to differentiate between the
2 injections in order to accurately
report local reactogenicity
symptoms. Vaccination visit
windows are critical for the study
endpoints therefore the sponsor
encourages communication from
investigators when necessary.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
5
Status: Approved,Date: 15 February 2022
Section Number
and Name
Description of Change 
Brief Rationale
6.1.1 Combination
Products
Section was added because influenza vaccines used 
in this study are considered drug/device 
combinations.
To provide guidance on
combination products
6.8Concomitant
Therapy
The sentence regarding history of SARS-CoV-2 
vaccination has been deleted, and a statement was 
added that in the event that a participant receives a 
COVID-19 vaccine outside of the study, it must be 
recorded as a concomitant medication.
The text regarding antipyretic use was modified to 
include “per the investigator’s discretion.”
The text regarding systemic corticosteroids was 
updated to include the definition of 
immunosuppressive dose, to replace “within 6 
months before planned administration of the first 
dose of study vaccine” to “treatment phase,” and to 
replace “must take priority over the study vaccine” 
with “medical judgment should prevail.”
The history of COVID-19 vaccines
is not listed as concomitant therapy
but as history of SARS-CoV-2
vaccination.
To complete the sentence
Use of an immunosuppressive dose
of steroids at study entry is
exclusionary. If it becomes
necessary due to standard of care
during the treatment phase, it is
subject to medical judgment.
7.1 Discontinuation
of Study
Vaccination
A condition was added for influenza vaccine (other 
than the one administered in the study) for the 
current influenza season in the Northern
Hemisphere.
To avoid confounding the study
endpoints
8STUDY
ASSESSMENTS
AND
PROCEDURES
Physical examination was added to the paragraph 
regarding the preferred sequence for multiple
assessments.
Investigator assessment of reactogenicity was 
added to the paragraph regarding participant diary 
completion.
To correct prior omissions
To clarify the timepoint for
reactogenicity data collection
2.3.3 Benefit-Risk
Assessment of
Study Participation
8.2.3 Clinical Safety
Laboratory
Assessments
8.3.1 Time Period
and Frequency for
Collecting Adverse
Event, Medically-
attended Adverse
Event, Adverse
Event of Special
Interest, and Serious
Adverse Event
Information
8.3.6.1 Thrombosis
with
Thrombocytopenia
Syndrome
Text was clarified regarding procedures for 
laboratory testing in the event of post-vaccination 
thrombocytopenia.
“Post vaccination” was added to
thrombocytopenia.
For consistency ofreporting
requirements of suspected AESI

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
6
Status: Approved,Date: 15 February 2022
Section Number 
and Name
Description of Change 
Brief Rationale
1.3.1 All 
Participants 
8.3.1 Time Period
and Frequency for 
Collecting Adverse 
Event, Medically- 
attended Adverse 
Event, Adverse
Event of Special
Interest, and Serious
Adverse Event
Information
A statement was added that previous SARS-CoV-2 
infection should be documented as medical history. 
A statement was added that AESIs occurring
during the study period must be reported to the
sponsor by study site personnel within 24 hours of
their knowledge of the event
To be able to capture previous
SARS-COV-2 infections
8.3.2 Method of 
Detecting Adverse 
Events, Medically- 
attended Adverse
Events, Adverse
Events of Special
Interest, and Serious
Adverse Events
11 REFERENCES
Cross-references to Appendix 6 were added for 
solicited AEs;reference to Marcy 2004 was 
removed.
To maintain consistent toxicity
grading criteria
1.3.1 All 
Participants 
1.3.2 Participants 
with a Suspected 
AESI 
8.3.6 Adverse
Events of Special
Interest
Anti-PF4 was deleted from the third paragraph of 
Section 8.3.6 and the first sentence in footnote k of 
the Schedule of Activities for All Participants, and
the first sentence of footnote d in the Schedule of
Activities for Participants with a Suspected AESI.
Anti-PF4 is not part of a complete
blood count.
1.3.1 All 
Participants 
1.3.2 Participants 
with a Suspected 
AESI 
8.3.6.1 Thrombosis
with
Thrombocytopenia
Syndrome
10.2 Appendix 2:
Clinical Laboratory
Tests
Anti-PF4 testing was changed from local to central 
laboratory testing. 
Anti-PF4 is a supportive parameter
for the investigation of a suspected
AESIs. The sponsor will test those
samples centrally,as it is not
always feasible locally.
1.1 Synopsis 
4.1 Overall Design  
6.3 Measures to
Minimize Bias:
Randomization and
Blinding
9.3 Populations for
Analysis Sets
9.4.3 Other
Secondary
Endpoints
Text was added to describe the handling of 
vaccine-naïve participants in the analysis.
At the request of health authorities
6.7Treatment of 
Overdose 
Text was added that in the event of an overdose, 
the investigator could contact the sponsor or
Medical Monitor.
Clarification

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
7
Status: Approved,Date: 15 February 2022
Section Number
and Name
Description of Change 
Brief Rationale
9.3 Populations for
Analysis Sets
PPII population: “Ad26.COV2.S” was corrected to 
“seasonal influenza vaccine” for the control group.
PPSI population: Text was added to indicate that
samples obtained from participants after natural
SARS-CoV-2 infection or after vaccination with
another COVID-19 vaccine will be excluded from
the per protocol analysis.
Corrections
9.4.2 Inferential
Endpoints
Definition of baseline was added. 
To align with SAP
9.4.6 Other
Analyses
Text was modified to indicate that site personnel 
and participants will be blinded during the 
treatment phase, rather than until the end of the 
study. 
Once participants have received
both study vaccines, they can be
unblinded. For practical reasons,
study participants need to know
whether they received
Ad26.COV2.S on Day 1 or Day 29,
first, to enable them to count a
number of months to receive a
booster vaccination and second, to
receive certification in some
countries, HCPs must complete a
form with the vaccination date and
manufacturer.
Throughout the
protocol
Minor grammatical, formatting, or spelling changes 
were made.
Minor errors were noted.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
8
Status: Approved,Date: 15 February 2022
TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................................... 2
TABLE OF CONTENTS ............................................................................................................................... 8
LIST OF IN-TEXT TABLES AND FIGURES.............................................................................................. 10
1. 
PROTOCOL SUMMARY................................................................................................................... 11
1.1. 
Synopsis......................................................................................................................................... 11
1.2. 
Schema.......................................................................................................................................... 19
1.3. 
Schedule of Activities..................................................................................................................... 20
1.3.1. 
All Participants............................................................................................................................ 20
1.3.2. 
Participants with a Suspected AESI........................................................................................... 23
2. 
INTRODUCTION................................................................................................................................ 25
2.1. 
Study Rationale.............................................................................................................................. 27
2.2. 
Background .................................................................................................................................... 28
2.3. 
Benefit-Risk Assessment............................................................................................................... 32
2.3.1 
Risks Related to Study Participation .......................................................................................... 32
2.3.2 
Benefits of Study Participation.................................................................................................... 37
2.3.3 
Benefit-Risk Assessment of Study Participation ........................................................................ 37
3. 
OBJECTIVES AND ENDPOINTS ..................................................................................................... 39
4. 
STUDY DESIGN ................................................................................................................................ 43
4.1. 
Overall Design................................................................................................................................ 43
4.2. 
Scientific Rationale for Study Design............................................................................................. 45
4.2.1. 
Study-Specific Ethical Design Considerations ........................................................................... 45
4.3. 
Justification for Dose...................................................................................................................... 46
4.4. 
End of Study Definition................................................................................................................... 46
5. 
STUDY POPULATION ...................................................................................................................... 46
5.1. 
Inclusion Criteria............................................................................................................................ 47
5.2. 
Exclusion Criteria........................................................................................................................... 49
5.3. 
Lifestyle Considerations................................................................................................................. 52
5.4. 
Screen Failures.............................................................................................................................. 52
5.5. 
Criteria for Temporarily Delaying Administration of Study Vaccine ............................................... 52
6. 
STUDY VACCINATION AND CONCOMITANT THERAPY ............................................................. 53
6.1. 
Study Vaccines Administered ........................................................................................................ 53
6.1.1. 
Combination Products ................................................................................................................ 56
6.2. 
Preparation/Handling/Storage/Accountability ................................................................................ 56
6.3. 
Measures to Minimize Bias: Randomization and Blinding............................................................. 57
6.4. 
Study Vaccination Compliance ...................................................................................................... 58
6.5. 
Dose Modification........................................................................................................................... 58
6.6. 
Access to Licensed/Authorized Study Vaccine After the End of the Study................................... 58
6.7. 
Treatment of Overdose .................................................................................................................. 59
6.8. 
Concomitant Therapy..................................................................................................................... 59
7. 
DISCONTINUATION OF STUDY VACCINATION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL............................................................................................... 61
7.1. 
Discontinuation of Study Vaccination............................................................................................. 61
7.2. 
Participant Discontinuation/Withdrawal From the Study................................................................ 61
7.2.1. 
Withdrawal From the Use of Research Samples ....................................................................... 62
7.3. 
Lost to Follow-up............................................................................................................................ 62
8. 
STUDY ASSESSMENTS AND PROCEDURES ............................................................................... 63
8.1. 
Immunogenicity Assessments ....................................................................................................... 65

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
9
Status: Approved,Date: 15 February 2022
8.2. 
Safety Assessments....................................................................................................................... 66
8.2.1. 
Physical Examinations................................................................................................................ 66
8.2.2. 
Vital Signs................................................................................................................................... 66
8.2.3. 
Clinical Safety Laboratory Assessments .................................................................................... 67
8.2.4. 
Pregnancy Testing...................................................................................................................... 67
8.3. 
Adverse Events, Serious Adverse Events, Medically-attended Adverse Events, Adverse
Events of Special Interest, and Other Safety Reporting ................................................................ 67
8.3.1. 
Time Period and Frequency for Collecting Adverse Event, Medically-attended Adverse
Event, Adverse Event of Special Interest, and Serious Adverse Event Information .................. 68
8.3.2. 
Method of Detecting Adverse Events, Medically-attended Adverse Events, Adverse
Events of Special Interest, and Serious Adverse Events ........................................................... 69
8.3.3. 
Follow-up of Adverse Events, Medically-attended Adverse Events, Adverse Events of
Special Interest, and Serious Adverse Events ........................................................................... 71
8.3.4. 
Regulatory Reporting Requirements for Serious Adverse Events ............................................. 71
8.3.5. 
Pregnancy................................................................................................................................... 71
8.3.6. 
Adverse Events of Special Interest............................................................................................. 72
8.3.6.1. 
Thrombosis with Thrombocytopenia Syndrome...................................................................... 72
9. 
STATISTICAL CONSIDERATIONS.................................................................................................. 73
9.1. 
Statistical Hypotheses.................................................................................................................... 73
9.2. 
Sample Size Determination ........................................................................................................... 74
9.3. 
Populations for Analysis Sets ........................................................................................................ 75
9.4. 
Statistical Analyses ........................................................................................................................ 76
9.4.1. 
General Considerations.............................................................................................................. 76
9.4.2. 
Inferential Endpoints................................................................................................................... 76
9.4.3. 
Other Secondary Endpoints ....................................................................................................... 77
9.4.4. 
Exploratory Endpoints................................................................................................................. 78
9.4.5. 
Safety Analyses.......................................................................................................................... 78
9.4.6. 
Other Analyses ........................................................................................................................... 79
9.5. 
Interim Analysis.............................................................................................................................. 79
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ............................ 80
10.1. 
Appendix 1: Abbreviations and Definitions .................................................................................... 80
10.2. 
Appendix 2: Clinical Laboratory Tests ........................................................................................... 82
10.3. 
Appendix 3: Regulatory, Ethical, and Study Oversight Considerations......................................... 83
10.3.1. 
Regulatory and Ethical Considerations ...................................................................................... 83
10.3.2. 
Financial Disclosure.................................................................................................................... 86
10.3.3. 
Informed Consent Process ......................................................................................................... 86
10.3.4. 
Data Protection........................................................................................................................... 87
10.3.5. 
Long-Term Retention of Samples for Additional Future Research ............................................ 88
10.3.6. 
Committees Structure................................................................................................................. 88
10.3.7. 
Publication Policy/Dissemination of Clinical Study Data............................................................ 88
10.3.8. 
Data Quality Assurance.............................................................................................................. 89
10.3.9. 
Case Report Form Completion................................................................................................... 90
10.3.10. Source Documents ..................................................................................................................... 90
10.3.11. Monitoring ................................................................................................................................... 91
10.3.12. On-Site Audits............................................................................................................................. 92
10.3.13. Record Retention........................................................................................................................ 92
10.3.14. Study and Site Start and Closure ............................................................................................... 92
10.4. 
Appendix 4: Adverse Events, Serious Adverse Events, Adverse Events of Special
Interest, Product Quality Complaints, and Other Safety Reporting: Definitions and
Procedures for Recording, Evaluating, Follow-up, and Reporting................................................. 94
10.4.1. 
Adverse Event Definitions and Classifications ........................................................................... 94
10.4.2. 
Attribution Definitions.................................................................................................................. 95
10.4.3. 
Severity Criteria.......................................................................................................................... 95
10.4.4. 
Special Reporting Situations ...................................................................................................... 96
10.4.5. 
Procedures ................................................................................................................................. 96
10.4.6. 
Product Quality Complaint Handling........................................................................................... 98

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
10
Status: Approved,Date: 15 February 2022
10.4.7. 
Contacting Sponsor Regarding Safety, Including Product Quality............................................. 98
10.5. 
Appendix 5: Contraceptive Guidance and Collection of Pregnancy Information........................... 99
10.6. 
Appendix 6: Toxicity Grading Scale............................................................................................. 100
10.7. 
Appendix 7: Summary of Guidance from CDC Website on Underlying Medical Conditions
That Lead or Might Lead to Increased Risk for Severe Illness From COVID-19......................... 104
10.8. 
Appendix 8: TTS AESI Form........................................................................................................ 105
10.9. 
Appendix 9: Thrombotic Events to be Reported as AESIs .......................................................... 109
10.10. Appendix 10: Protocol Amendment History................................................................................. 110
11. REFERENCES................................................................................................................................. 111
INVESTIGATOR AGREEMENT............................................................................................................... 115
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1: 
Adverse Drug Reactions Associated With Ad26.COV2.S ........................................................ 32
Table 2: 
Overview of the Groups and Vaccination Days ........................................................................ 43
Table 3: 
Description of Interventions ...................................................................................................... 55
Table 4: 
Summary of Humoral Immunogenicity Assays......................................................................... 65
FIGURES
Figure 1: Schematic Overview of the Study............................................................................................. 19

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
11
Status: Approved,Date: 15 February 2022
1. 
PROTOCOL SUMMARY
1.1. 
Synopsis
A Randomized, Double-blind, Phase 3 Study to Evaluate Safety, Reactogenicity, and Immunogenicity of
Co-administration of Ad26.COV2.S and Influenza Vaccines in Healthy Adults 18 Years of Age and Older.
Ad26.COV2.S (also known as VAC31518, JNJ-78436735) is a monovalent vaccine composed of a
recombinant, replication-incompetent adenovirus type 26 (Ad26) vector, constructed to encode the Spike
(S) protein derived from a SARS-CoV-2 clinical isolate (Wuhan, 2019, whole-genome sequence
NC 045512, referred to as the original strain), stabilized in its prefusion conformation.
The study aims to assess the safety, reactogenicity, and immunogenicity of the Ad26.COV2.S vaccine
co-administered with a quadrivalent standard-doseor high-doseseasonal influenza vaccine compared to
administration of each vaccine separately to explore whether Ad26.COV2.S and the influenza vaccines can
be administered concomitantly.
The primary objective (for the NI assessment) will be evaluated in approximately 610 participants aged 18
and above who have completed a primary COVID-19 vaccine series, the co-administration of the
Ad26.COV2.S and the seasonal quadrivalent standard-doseinfluenza vaccine. In a cohort of participants
aged 65 and above, the co-administration of the Ad26.COV2.S and the seasonal quadrivalent high-dose
influenza vaccine will be assessed descriptively. In another cohort of COVID-19 vaccine-naïve individuals,
immune responses will be evaluated descriptively.
OBJECTIVES AND ENDPOINTS
Objectives 
Endpoints
Primary
To demonstrate the non-inferiority (NI) of the 
humoral immune response of the 4 influenza 
vaccine strains after concomitant administration of 
the Ad26.COV2.S vaccine and a seasonal 
quadrivalent standard-dose influenza vaccine 
versus 
the 
administration 
of 
a seasonal 
quadrivalent standard-dose influenza vaccine 
administered alone.
 
Antibody hemagglutination inhibition (HI)
titers as measured by hemagglutinin inhibition
(HAI) assay titers (geometric mean titers
[GMTs]) against each of the 4 influenza
vaccine 
strains, 
28 
days 
after 
the
administration of a seasonal quadrivalent
standard-doseinfluenza vaccine
Success criteria for NI
 
the upper bound of the 2-sided 95%
confidence interval (CI) for the geometric
mean titer (GMT) ratio (Control group/co-
administration [CoAd] group) lies below 1.5
To demonstrate the NI of the binding antibody  
response after concomitant administration of 
Ad26.COV2.S vaccine and a seasonal quadrivalent 
standard-dose influenza vaccine versus the 
administration 
of 
Ad26.COV2.S 
vaccine
administered alone.
 
Antibody titers as measured by S enzyme-
linked immunosorbent assay (S-ELISA) titers
(GMC), 28 days after administration of
Ad26.COV2.S vaccine.
Success criteria for NI
 
the upper bound of the 2-sided 95% confident
interval (CI) for the GMC  ratio (Control
group/CoAd group) lies below 1.5

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
12
Status: Approved,Date: 15 February 2022
Objectives 
Endpoints
Secondary
To assess the safety and reactogenicity of a single 
dose of Ad26.COV2.S vaccine when administered 
separately or concomitantly with a seasonal 
quadrivalent high-dose influenza vaccine in
participants aged 65 years and older.
 
Solicited local (injection site) and systemic
adverse events (AEs) for 7 days after each
vaccination.
 
Unsolicited adverse events (AEs) for 28 days
after each vaccination.
 
Serious adverse events (SAEs), medically
attended adverse events (MAAEs), and
adverse events of special interest (AESIs)
throughout the study.
 
AEs leading to withdrawal from the study
throughout the study.
To assess the safety and reactogenicity of a single 
dose of Ad26.COV2.S vaccine when administered 
separately or concomitantly with a seasonal
quadrivalent standard-dose influenza vaccine in
participants aged 18 years and older.
 
Solicited local (injection site) and systemic
AEs for 7 days after each vaccination.
 
Unsolicited AEs for 28 days after each
vaccination.
 
SAEs, MAAEs, and AESIs throughout the
study.
 
AEs leading to withdrawal from the study
throughout the study.
To assess the humoral immune response against 
each of the 4 influenza vaccine strains after 
concomitant administration of the Ad26.COV2.S 
vaccine and a seasonal quadrivalent high-dose 
influenza vaccine versus the administration of a 
seasonal quadrivalent high-doseinfluenza vaccine
administered alone.
 
Antibody HI titers as measured by HAI assay
titers (GMTs) against each of the 4 influenza
vaccine 
strains, 
28 
days 
after 
the
administration of a seasonal quadrivalent
standard-doseinfluenza vaccine.
To assess the humoral immune response of
Ad26.COV2.S vaccine anda seasonal quadrivalent
high-dose standard-dose influenza vaccine versus
the administration of Ad26.COV2.S vaccine
administered alone.
 
Antibody titers as measured by S enzyme-
linked immunosorbent assay (S-ELISA) titers
(GMC), 28 days after administration of
Ad26.COV2.S vaccine.
To assess the humoral response to SARS‑CoV-2
after 
the 
concomitant 
administration 
of
Ad26.COV2.S vaccine and a seasonal quadrivalent
high-dose 
influenza 
vaccine 
versus 
the
administration of Ad26.COV2.S vaccine alone in
COVID-19 vaccine-naïve individuals.
 
Antibody titers as measured by S enzyme-
linked immunosorbent assay (S-ELISA) titers
(GMC), 28 days after administration of
Ad26.COV2.S vaccine.
To assess the humoral response to SARS‑CoV-2
after 
the 
concomitant 
administration 
of
Ad26.COV2.S vaccine and a seasonal quadrivalent
standard-dose influenza vaccine versus the
administration of Ad26.COV2.S vaccine alone in
COVID-19 vaccine-naïve individuals
 
Antibody titers as measured by S enzyme-
linked immunosorbent assay (S-ELISA) titers
(GMC), 28 days after administration of
Ad26.COV2.S vaccine.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
13
Status: Approved,Date: 15 February 2022
Objectives 
Endpoints
To compare seroconversion rates against the 
4 influenza vaccine strains after the concomitant 
administration of Ad26.COV2.S vaccine and a 
seasonal quadrivalent (high-dose and standard- 
dose) influenza vaccine versus a vaccination of a 
seasonal quadrivalent (high-dose and standard-
dose) influenza vaccine administered alone.
 
Seroconversion is defined for each of the
4 influenza vaccine strains at 28 days after the
administration of a seasonal quadrivalent
(high-dose and standard-dose) influenza
vaccine:
 
HI titer ≥1:40 in participants with a pre-
vaccination HI titer of <1:10, or
 
a ≥4-fold HI titer increase in participants
with a pre-vaccination HI titer of ≥1:10.
To assess seroprotection rates against the 
4 influenza vaccine strains after the concomitant 
administration of Ad26.COV2.S vaccine and a 
seasonal quadrivalent (high-dose and standard- 
dose) influenza vaccine versus a vaccination of a 
seasonal quadrivalent (high-dose and standard-
dose) influenza vaccine administered alone.
 
Seroprotection is defined for each of the
4 influenza vaccine strains as HI titer ≥1:40 at
28 days after the administration of a seasonal
quadrivalent (high-dose and standard-dose)
influenza vaccine.
Exploratory
To evaluate the durability of influenza-specific 
humoral immune responses after concomitant 
administration of the vaccines versus the influenza
vaccine alone.
 
GMT: Geometric mean of HI antibodies at
Day 181.
 
Percentages of participants with HI titers
≥1:40 on Day 181.
To evaluate the durability of SARS-CoV-2 specific 
humoral immune responses after concomitant 
administration  of the vaccines versus the SARS-
CoV-2 vaccine alone.
 
Antibody GMC by S-ELISA at Day 181 after
the administration of Ad26.COV2.S vaccine.
To assess the magnitude and durability of humoral
immune responses specific to influenza.
 
Serological responses to vaccination as
measured by HAI at Day 181 after the
administration of influenza vaccine.
To 
further 
assess 
humoral 
responses 
to
Ad26.COV2.
 
Serological response to vaccination, as
measured by virus neutralization assay(VNA)
(SARS-CoV-2 VNA and/or pseudovirion [ps]
VNA expressing S protein)titers.
 
Adenovirus 26 neutralization  responses
measured by VNA.
 
Functional 
and 
molecular 
antibody
characterization including Fc-mediated viral
clearance, 
avidity, 
Fc 
characteristics,
immunoglobulin (Ig) subclass, and IgG
isotype.
 
Correlation between ELISA (S-ELISA) and
VNA (wild-type virus [wt]VNA and/or
pseudovirion [ps]VNA) titers at selected
timepoints.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
14
Status: Approved,Date: 15 February 2022
Objectives 
Endpoints
To 
explore 
the 
humoral 
responses 
to 
Ad26.COV2.S and influenza vaccine based on the 
SARS-CoV-2 serostatus at baseline (N-serology). 
 
Serological response to vaccination as
measured by S-ELISA antibody concentration
28 days after 
the administration 
of
Ad26.COV2.S vaccine.
 
Antibody GMC by S-ELISA at 28 days after
the administration of Ad26.COV2.S vaccine.
 
Antibody HI titers as measured by HAI assay
titers (GMTs) against the 4 influenza strains.
To 
explore 
the 
humoral 
responses 
to 
Ad26.COV2.S and influenza vaccine based on the 
previous history of COVID-19 vaccination at entry  
(viral vector vaccine or mRNA vaccine or vaccine- 
naïve).
 
Serological response to vaccination as
measured by S-ELISA antibody concentration
28 days after 
the administration 
of
Ad26.COV2.S vaccine.
 
Antibody GMC by S-ELISA at 28 days after
the administration of Ad26.COV2.S vaccine.
 
Antibody HI titers as measured by HAI assay
titers (GMTs) against SARS-CoV-2.
Hypotheses
The primary hypotheses of this study are:
The concomitant administration of the Ad26.COV2.S vaccine and a seasonal quadrivalent influenza
vaccine (standard-dose) is non-inferior than the administration of the seasonal quadrivalent influenza
vaccine (standard-dose) alone as measured by HI titers against each of the 4 influenza vaccine strains at 28
days after the administration of a quadrivalent seasonal influenza vaccine,
AND
The concomitant administration of the Ad26.COV2.S vaccine and a seasonal quadrivalent influenza
vaccine (standard-dose) is non-inferior than  the administration of the Ad26.COV2.S vaccine alone as
measured by S-ELISA antibody titers at 28 days after the administration of the Ad26.COV2.S vaccine.
For the high-dose groups, no formal hypothesis testing is planned.
No formal statistical testing of safety data is planned. Safety data will be analyzed descriptively by vaccine
group.
OVERALL DESIGN
This is a randomized, double-blind, parallel, multicenter, interventional study in healthy (including stable
comorbidities) adults ≥18 years of age. In this study, the safety, reactogenicity, and immunogenicity of
Ad26.COV2.S co-administered with an influenza vaccine will be evaluated.
Approximately 1,100 participants will be randomized in parallel in this study. Participants aged ≥65 will be
randomized in a 1:1:1:1 ratio to 1 of 4 groups. Participants aged ≤64 will be randomized in a 1:1 ratio to
1 of 2 groups (Group 1 or Group 2). Efforts will be made to ensure good representation in terms of race,
gender,and ethnicity.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
15
Status: Approved,Date: 15 February 2022
Participants will receive Ad26.COV2.S and a seasonal quadrivalent (standard-doseor high-dose) influenza
vaccine either concomitantly on Day 1 and placebo on Day 29 (co-administration groups 1 and 3) or a
seasonal quadrivalent (standard-dose or high-dose) influenza vaccine and placebo on Day 1 and
Ad26.COV2.S on Day 29 (control groups 2 and 4).
An overview of the groups and vaccinations is given in the table below.
Table: 
Overview of the Groups and Vaccinations
Group  
Day 1 
Day 29
1 (CoAd group) 
Ad26.COV2.S + Q SD influenza vaccine 
Placebo
2 (Control group) 
Placebo + Q SD influenza vaccine 
Ad26.COV2.S
3 (CoAd group) 
Ad26.COV2.S + Q HD influenza vaccine 
Placebo
4 (Control group) 
Placebo + Q HD influenza vaccine 
Ad26.COV2.S
CoAd = co-administration; HD = high-dose; Q = quadrivalent; SD = standard-dose.
The seasonal quadrivalent standard-dose influenza vaccine (Groups 1 and 2) can be administered to all
participants. Age is included as stratification factor for Groups 1 and 2 (≥18 to ≤64 years of age and
≥65 years of age).
The seasonal quadrivalent high-dose influenza vaccine (Groups 3 and 4) will only be administered to
participants ≥65 years of age.
The previous SARS-CoV-2 vaccination history (Vaxzevria [AstraZeneca], Comirnaty [Pfizer-BioNTech],
SpikeVax [Moderna], Ad26.COV2-S [Janssen]or COVID-19 vaccine naïve) will be used as second
stratification factor. This stratification factor will aim to obtain a balanced distribution of SARS-CoV-2
vaccination history across the 4 treatment groups.
Participants can either have received a complete primary vaccination with  an authorized/licensed
COVID-19 vaccinea (completed ≥6 months prior to first study vaccination) or be COVID-19 vaccine-naïve.
The type of primary vaccination will be documented and accounted for according to interactive web
response system (IWRS) procedures.
The study duration from screening until the last follow-up visit will be approximately 7-8 months. The
study comprises screening on Day -28 to 1, vaccination visits on Days 1 and 29 with a 28-day follow-up
period after each vaccination. AEs leading to withdrawal, MAAEs, SAEs, and AESIs will be collected
throughout the study.
End of Study Definition
The end of the study is considered as the last visit for the last participant in the study.
NUMBER OF PARTICIPANTS
Overall, approximately 1,100 adult participants aged 18 years will be enrolled in the study.
a The following authorized/licensed COVID-19 vaccines are permitted in this study: Vaxzevria (AstraZeneca),
Comirnaty (Pfizer-BioNTech), SpikeVax (Moderna), and Ad26.COV2.S (Janssen).

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
16
Status: Approved,Date: 15 February 2022
DOSAGE AND ADMINISTRATION
Ad26.COV2.S will be supplied at a concentration of 1×1011 vp/mL in single-use vials, with an extractable
volume of 0.5 mL, and dosed at 5×1010 vp. Placebo (0.9% NaCl) will be supplied in single-use vials.
The seasonal influenza vaccines to be used in this study are Afluria Quadrivalent (standard-dose) and
Fluzone HD Quadrivalent (high-dose) or equivalent formulated for the 2021-2022 influenza season:
 
Afluria Quadrivalent (standard-dose) is a suspension for intramuscular (IM) injection supplied in a
0.5mL single-dose prefilled syringe. Each dose of Afluria Quadrivalent contains 60 µg of
hemagglutinin (HA): 15 µg of each of 4 influenza strains (2 influenza A strains and 2 influenza B
strains). For details, refer to the Afluria Quadrivalent package insert.
 
Fluzone HD Quadrivalent (high-dose) is a suspension for IM injection supplied in a 0.7mL single-dose
prefilled syringe. Each dose of Fluzone HD Quadrivalent contains 240 µg of HA: 60 µg of each of 4
influenza strains (2 influenza A strains and 2 influenza B strains). For details, refer to the Fluzone HD
Quadrivalent package insert.
Study vaccines will be administered by IM injection into the deltoid muscle. On Day 1, each participant
will receive 2 IM injections. Each injection should be administered in opposite arms. It is recommended to
use the right arm for the seasonal influenza vaccine on Day 1 and the left arm for the Ad26.COV2.S vaccine
or placebo on Days 1 and 29.
On Day 29, each participant will receive 1 IM injection, preferably into the deltoid muscle of the
non-dominant upper arm.
If an injection cannot be given in the deltoids due to a medical or other contraindication (for example,
tattooed upper arms rendering it difficult to assess site reactogenicity), use alternative locations such as the
hip, thigh, or buttocks (to be avoided in overweight participants). When selecting an alternative location,
the participant’s ability to assess injection site events should be considered.
In all circumstances, IM injections in other locations than the upper arm are not considered protocol
deviations.
IMMUNOGENICITY EVALUATIONS
Venous blood samples will be collected for assessment of humoral immune responses. Sample volumes
and time points are detailed in the Schedule of Activities. Humoral immunogenicity assays may include,
but are not limited to, the assays in the table below.
Table: 
Summary of Humoral Immunogenicity Assays
Assay 
Purpose
Primary endpoints
HI assaya 
Analysis of HI to influenza strains
SARS-CoV-2 binding antibodies (ELISA) 
Analysis of antibodies binding to SARS-CoV-2 or individual
SARS-CoV-2 proteins (eg, S protein)
Secondary endpoints
HI assay a 
Analysis of HI to influenza strains
SARS-CoV-2 binding antibodies (ELISA) 
Analysis of antibodies binding to SARS-CoV-2 or individual
SARS-CoV-2 proteins (eg, S protein)
Exploratory endpoints
HI assay 
Analysis of HI to influenza strains
SARS-CoV-2 binding antibodies (ELISA) 
Analysis of antibodies binding to SARS-CoV-2 or individual
SARS-CoV-2 proteins (eg, S protein)

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
17
Status: Approved,Date: 15 February 2022
Assay 
Purpose
Primary endpoints
SARS-CoV-2 neutralization (VNA) 
Analysis of neutralizing antibodies to the wild-type virus and/or
pseudovirion expressing S protein
Adenovirus neutralization 
Adenovirus 26 neutralization assay to evaluate neutralizing
antibody responses against the Ad26 vector
SARS-CoV-2 binding antibodies (ELISA 
and/or SARS-CoV-2 immunoglobulin assay)
Analysis of antibodies binding to the SARS-CoV-2 N protein
Functional and molecular antibody 
characterization  
Analysis of antibody characteristics including Fc-mediated viral
clearance, avidity, Fc characteristics, Ig subclass and IgG isotype
ELISA = enzyme-linked immunosorbent assay; Fc = Fragment crystallizable; HI assay = Hemagglutination inhibition
(HI) assay; Ig = immunoglobulin; S = Spike; SARS-CoV2 = severe acute respiratory syndrome coronavirus-2; VNA
= virus neutralization assay.
a. 
The HI antibody titers against influenza virus strains recommended by the World Health Organization (WHO)
for use in 2021-2022 in the Northern Hemisphere season will be measured using a validated HI assay platform.
SAFETY EVALUATIONS
After each vaccination, participants will remain under observation at the study site for at least 15 minutes
for presence of any acute reactions and solicited events. Participants will be asked to note in the diary
occurrences of local reactions at injection site namely pain/tenderness, erythema, swelling, and systemic
reactions namely fatigue, headache, nausea, and myalgia daily for 7 days post-vaccination  (or until
resolution).
Participants will be instructed on how to record daily temperature and local reactions using a thermometer
and a ruler provided for home use. Participants should record the temperature in the diary starting 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 one measurement is made on any given day, the highest temperature of that day should
be recorded.
Adverse events 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.
Thrombosis with thrombocytopenia syndrome is considered to be an adverse event of special interest
(AESI). Suspected AESIs (thrombotic events and thrombocytopenia [defined as platelet count below
150,000/µL]) will be monitoredfrom the moment of vaccination until the end of the study/early withdrawal.
An AESI Adjudication Committee with appropriate expertise will be established to evaluate each suspected
AESI and determine whether it is a case of thrombosis with thrombocytopenia syndrome (TTS).
All unsolicited AEs will be reported for each vaccination from the time of vaccination until 28 days
post-vaccination. All SAEs, AESIs, and AEs leading to discontinuation from the study/vaccination
(regardless of the causal relationship) are to be reported from the moment of first vaccination until the end
of the study. The investigator’s assessment of ongoing AEs at the time of each participant’s last visit should
be documented in the participant’s medical chart.
MAAEs are defined as AEs with medically-attended visits including hospital, emergency room, urgent care
clinic, or other visits to or from medical personnel for any reason. New onset of chronic diseases will be
collected as part of the MAAEs. Routine study visits will not be considered medically-attended visits.
MAAEs will be reported throughout the study.
STATISTICAL METHODS
Sample size calculations are performed under the following assumptions:

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
18
Status: Approved,Date: 15 February 2022
 
no effect of co-administration of Ad26.COV2.S vaccine and seasonal influenza vaccine on the immune
response against influenza as measured by HI antibody titers against the 4 influenza vaccine strains at
28days after the administration of seasonal influenza vaccine
 
the use of Afluria Quadrivalent for standard-dose(adults ≥18 to <64 years of age and older adults
≥65 years of age)
 
a standard deviation of 0.53 for the standard-dose at the log10 scale for HI antibody titers against the
4 influenza vaccine strains at 28 days after the administration of seasonal influenza vaccine (with or
without Ad26.COV2.S)
 
no effect of co-administration of Ad26.COV2.S vaccine and seasonal influenza vaccine on the immune
response against SARS-CoV-2 as measured by S-ELISA at 28 days after the administration of
Ad26.COV2.S vaccine
 
a standard deviation of 0.50 at the log10 scale for S-ELISA at 28 days after the administration of
Ad26.COV2.S vaccine (with or without seasonal influenza vaccine)
 
a NI margin of 1.5
 
2-sided α of 5%
A total of approximately 305 (standard-dose) participants per group are needed to have 97.45% power to
show NI in HI antibody titers for 1 influenza vaccine strain. The sample size accounts for exclusions from
the per protocol set, drop-outs and missing samples resulting in a total sample size up to approximately 610
participants who have completed a primary COVID-19 vaccine series.
The overall power to show NI in HI antibody titers against each of the 4 influenza vaccine strains at 28 days
after the administration of seasonal influenza vaccine as well as NI in S-ELISA at 28 days after the
administration of Ad26.COV2.S vaccine is at least 90%.
Planned Analyses
The primary analysis of safety and immunogenicity will be performed when all participants have completed
the 28 days after the second study vaccination visit or discontinued earlier. The primary analysis will be
performed based on sponsor’s unblinded data (sponsor, study-site personnel and participants will remain
blinded during the treatment phase up to the database lock). No interim analyses will be performed.
A final analysis will be performed when all participants have completed the 6 month follow-up period after
the second vaccination or discontinued earlier.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
22
Status: Approved,Date: 15 February 2022
d. 
For those participants who are unable to continue participation in the study, but for whom consent is not withdrawn, an early exit visit could be conducted. Participants who wish to
withdraw consent from participation in the study could be followed up for safety purposes if desired. This includes safety assessments of the early exit visit (no blood sampling for
immunogenicity)and documenting the reason.
e. 
Signing of the ICF should be done before any study relatedactivities.
f. 
History of SARS CoV 2 vaccination (name/manufacturer of the vaccine and date of administration) ≥6 months prior to the study will be collected in the SARS CoV 2 Vaccination
page in the eCRF.
g. 
A full physical examination, including height and body weight, will be carried out at screening. At other clinic visits, a symptom directed physical examination can be performed in
case of participant’s complaints.
h. 
Heart rate,systolic and diastolic blood pressure,respiratory rate,and body temperature. Heart rate and blood pressure measurements should be taken in the supine position and
preceded by at least 5 minutes of rest. Vital signs measurements should be performed before blood sampling. Body temperatures will be measured preferably via the oral route.
i. 
Investigator must check for acute illness or body temperature ≥38.0°C/100.4°F at the time of vaccination. If any of these events occur within 24 hours prior to planned vaccination,
the vaccination can be rescheduled in alignment with the protocol visit windows. If the vaccination visit cannot be rescheduled within the allowed window or the contraindications to
vaccination persist,the reason should be documented. The investigator should also check whether any other reasons for Discontinuation ofStudy Vaccination have been met.
j. 
For women of childbearing potentialonly.
k. 
Whole blood samples will be used for a complete blood count (CBC), including platelet count in a local laboratory or substitute for local laboratory, depending on local feasibility
towards turnaround time ofsample processing. Serum and plasma samples will be collected and stored for potential future coagulation related testing (including anti PF4) in a central
laboratory if the participant experiences an AESI (see Section 10.2, Appendix 2).
l. 
Participants will be observed for a minimum of 15 minutes post vaccination or according to local regulations. Any solicited local (at injection site) and systemic AEs, unsolicited
AEs, SAEs,concomitant medications,and vital signs should be documented by study site personnel. Participants will be allowed to leave the study site after the 15 minutes post
vaccination observation period iscompleted and documented.
m. 
AEs and special reporting situations that are related to study procedures or vaccine products will be reported from the time a signed and dated ICF is obtained until the end of the
study/early withdrawal. Unsolicited AEs should be reported from the from the time of vaccination until 28 days post vaccination.
n. 
All SAEs related to study procedures or vaccine products will be reported from the time a signed and dated ICF is obtained until the end of the study/early withdrawal. All other
SAEs are to be reported for all participants from the moment of the first vaccination until the end of the study.
o. 
Suspected AESIs are to be reported from the moment of vaccination until the end of the study (see Section 8.3.1).
p. 
At each visit the participant will be asked if they have had a private/off study COVID 19 test. If a participant receives a positive SARS CoV 2 result from a private/off study test
(whether through PCR or serological testing) the event should be reported as medical history, AE or SAE if the event meets the criteria for an SAE. The participant can continue in
the study in accordance with country and site level recommendations for COVID 19.
q. 
MAAEs are to be reported throughout the study. New onset of chronic diseases will be collected as part of the MAAEs.
r. 
Concomitant therapies such as analgesic/antipyretic medications and non steroidal anti inflammatory drugs,corticosteroids,antihistamines,and vaccinations must be recorded
(including dose and frequency) from the first dose of study vaccine until 28 days after administration of the last study vaccine. (See protocol Section 6.8for collection and recording
of concomitant therapies associated with SAEs, solicited and unsolicited AEs, suspected AESIs, and MAAEs. All other concomitant therapies should be recorded if administered in
conjunction with new or worsening AEs reported per protocol requirements outlined in Section8.3.1).
s. 
On Day 1, the participant’s diary, a ruler,and a thermometer will be distributed to each participant. On Day 29, the site is to conduct the last vaccination visit and confirm any
missing solicited safety data points.
t. 
The reactogenicity vaccination folder should be completed and local and systemic symptoms should be verified and entered in eDC. If a solicited event is still ongoing 7 days after
vaccination, the participant should continue reporting symptoms until resolution. If symptoms continue beyond Day 7, the diary should be reviewed again at the next visit.
AE  adverse event; AESI  adverse event of special interest; COVID 19  coronavirus disease 2019; d  day(s); eCRF  electronic case report form; ICF  informed consent form;
MAAE  medically attended adverse event; meds  medication; mo  months; N/A  not applicable; PCR  polymerase chain reaction; SAE  serious adverse event; SARS CoV 2 
severe acute respiratory syndrome coronavirus 2; vac
vaccination; vp
virus particles.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
24
Status: Approved,Date: 15 February 2022
processing. Serum and plasma samples will be collected for coagulation-related testing in a central laboratory
including anti-PF4 (see Section 10.2).
e. Medical information on local case management will be collected. Upon becoming aware of the suspected AESI,
study site personnel should provide information on an ongoing basis. See Section 8.3.6 and Section 10.8, for
further details.
f. 
Refer to Section 6.8for collection and recording of concomitant therapies associated with a suspected AESI.
AESI = adverse event of special interest; CDC = Centers for Disease Control and Prevention; PF4 = platelet
factor 4; TTS = thrombosis with thrombocytopenia syndrome.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
25
Status: Approved,Date: 15 February 2022
2. 
INTRODUCTION
Ad26.COV2.S (also known as VAC31518, JNJ-78436735) is a monovalent vaccine composed of
a recombinant, replication-incompetent human adenovirus type 26 (Ad26) vector, constructed to
encode the Spike (S) protein derived from a severe acute respiratory syndrome coronavirus-2
(SARS-CoV-2) clinical isolate (Wuhan, 2019, whole-genome sequence NC_045512, referred to as
the original strain), with 2 proline substitutions which stabilize the prefusion conformation of the
S-2P protein thereby increasing the induction of neutralizing antibodies.
The Ad26.COV2.S is designed to elicit a protective immune response to the SARS-CoV-2 S
protein, the major structural protein of the virus that has an essential role in attachment and
infection of host cells (Zhou 2004; Zumla 2016). In the absence of an established immune marker
predictive of protection against coronavirus disease-2019 (COVID-19), neutralizing antibodies,
primarily directed to the SARS-CoV-2 S protein, are thought to contribute to the protective
immune response elicited by the vaccine.
For the most comprehensive nonclinical and clinical information regarding Ad26.COV2.S, refer
to the latest version of the Investigator's Brochure (IB) (and Addenda) for Ad26.COV2.S
(IB Ad26.COV2.S 2021).
The term “study vaccine” throughout the protocol, refers to Ad26.COV2.S, placebo, and the
seasonal quadrivalent standard-doseand high-doseinfluenza vaccines as defined in Section 6.1.
Study VAC31518COV3005 is being conducted under the sponsorship of Janssen (Janssen
Vaccines & Prevention B.V.).
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. The term “participant”
throughout the protocol refers to the common term “subject.”
Adenoviral-vectored Vaccines
Recombinant, replication-incompetent adenoviral vectors are attractive candidates for expression
of foreign  genes for a number of reasons. The adenoviral genome is well characterized and
comparatively  easy to manipulate. Adenoviruses exhibit broad tropism, infecting a variety of
dividing and non-dividing cells. The adenoviral vaccine (AdVac®) vector platform, developed by
Crucell Holland B.V. (now Janssen Vaccines & Prevention B.V.)allows for high-yield production
of replication-incompetent adenovirus vectors, eg, Ad26, with desired inserts. The adenovirus E1
region is deleted to render the vector replication-incompetent and create space for transgenes,with
viral replication taking place in cells that complement for the E1 deletion in the virus genome.
Ad26 has been selected as a potential vaccine vector because there is substantial nonclinical and
clinical experience with  Ad26-based vaccines that demonstrate their capacity  to elicit strong
humoral and cellular immune responses and their acceptable safety profile, irrespective of the
antigen transgene (see also Section 2.3.1).

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
26
Status: Approved,Date: 15 February 2022
The immunogenicity profile of adenoviral vectors is illustrated by data obtained following the
immunization  of adults with  Ad26-vectored human  immunodeficiency  virus (HIV) vaccines
(Ad26.ENVA.01, Ad26.Mos.HIV and Ad26.Mos4.HIV), an Ad26-vectored Ebola virus vaccine
(Ad26.ZEBOV), Ad26-vectored respiratory syncytial virus (RSV) vaccines (Ad26.RSV.FA2 and
Ad26.RSV.preF), an Ad26-vectored Zika virus vaccine (Ad26.ZIKV.001), and an Ad26-vectored
malaria vaccine (Ad26.CS.01). Antigen-specific antibody responses are observed in almost all
participants after 1 dose, in both naïve and pre-immune individuals (RSV). These antibodies may
persist for a year or more (RSV) after a single vaccination in pre-immune participants. They have
functional properties of neutralization  (RSV, Zika), crystallizable fragment (Fc)-mediated
antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis
(HIV, malaria). Furthermore, these data support an  immunogenicity profile with  emphasis on
T-helper cell type 1 (Th)1 responses and demonstrate predominantly interferon gamma (IFN-γ)
and tumor necrosis factor alpha (TNF-α)production in cluster ofdifferentiation (CD)4+ and CD8+
T cells (Barouch 2013;Milligan 2016;Mutua 2019;Salisch 2021).
Ad26.COV2.S Candidate Vaccine
The Ad26.COV2.S vaccine has been developed in response to the global outbreak of COVID-19
caused by SARS-CoV-2. In response to the public health emergency caused by the global
SARS-CoV-2 pandemic, the Ad26.COV2.S vaccine was granted Emergency Use Authorization
(EUA) from the Food and Drug Administration (FDA) on 27February 2021 for emergency use in
the United States (FDA 2021), and Conditional Marketing Authorization approval by the European
Medicine Agency (EMA) on 11 March 2021 for emergency use within the European Union (EU).
On 12 March 2021, the Ad26.COV2.S vaccine was recommended for emergency use under the
World Health Organization (WHO) Emergency Use Listing Procedure.
COVID-19 Disease Burden
SARS-CoV-2 is a highly transmissible and pathogenic coronavirus that has spread rapidly and
globally since its emergence in late December 2019. The WHO declared that the outbreak
constituted a public health emergency of international concern on 30 January 2020 and declared
the outbreak to be a pandemic on 11 March 2020 (WHO 2020; WHO 2020a). As of 11 July 2021,
approximately 186,410,350 confirmed global cases of COVID-19 and approximately 4,024,946
COVID-19-related deaths have been reported worldwide. Within the United States alone, as of
11 July  2021 approximately 33,847,474 confirmed cases of COVID-19 and approximately
607,135 COVID-19 related deaths COVID-19 have been reported since the start of the outbreak
(Johns Hopkins CSSE 2021). Within the EU/European Economic Area (EEA) countries, as of
11 July 2021, a total of 33,270,049 cases of COVID-19 and 740,809 COVID-19-related deaths
were reported (ECDC 2021).
Influenza Disease Burden
Influenza is a worldwide public health problem, responsible for significant morbidity and
mortality, as well as a significant resource burden on countries. In a typical year, about 3 to
5 million cases of severe influenza illness and about 290,000 to 650,000 deaths are estimated to
occur worldwide (WHO 2018). In the US, more than 200,000 patients are hospitalized as a result

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
27
Status: Approved,Date: 15 February 2022
of seasonal influenza-associated illnesses each year (CDC 2021b) and influenza-related
hospitalization rate over 15 seasons was estimated to be 309 per 100,000 in individuals 65 years
and older (Zhou 2012). Notably, the incidence of pneumonia and influenza hospitalizations
increased with age during adulthood, with a dramatic increase seen above the age of 65 years. In
the US, older adults aged 85 years and older had the highest rates of influenza-associated primary
respiratory and circulatory hospitalizations, ie, 1,194.9 per 100,000 persons. (Bartozsko 2019)
Comorbidities including chronic lung disease and cardiovascular disease were found to be
important predictors of hospital admission. There was a 3-fold increase in the risk of death among
elderly people compared with non-elderly people. Elderly participants also had a higher risk of
admission to the hospital. (Mertz 2013)
Ad26.COV2.S Co-administration With Influenza Vaccines
There is currently no available data for the co-administration of the Ad26.COV2.S vaccine with
other vaccines. However, during the COVID-19 pandemic, reducing the overall burden of
respiratory illnesses is important to protect vulnerable populations at risk for severe illness, the
healthcare system, and other critical infrastructure.
According to the Centers of disease control and prevention (CDC), efforts to reduce the spread of
COVID-19, such as stay-at-home and shelter-in-place orders, have led to decreased use of routine
preventive medical services, including immunization services. Ensuring that people continue or
start getting routine vaccinations during the COVID-19 pandemic is essential for protecting people
and communities from vaccine-preventable diseases and outbreaks, including influenza
(CDC 2020). This recommendation is particularly relevant for individuals who are more
susceptible to respiratory viruses due to risk factors such as comorbidities and old age.
It is recognized that older adults and patients with comorbidities are at greater risk of COVID-19
infection and that they are also more likely to develop severe illness after infection (Perrotta 2020;
CDC 2020). Annual influenza vaccination is highly encouraged especially during the ongoing
COVID-19 pandemic. Though influenza vaccines do not protect against COVID-19, vaccination
may reduce the burden of influenza disease on the health care system, including hospitalizations,
severe outcomes, and deaths (Huang 2021). There is an urgent unmet medical need for
co-administration of prophylactic vaccines for these 2 deadliest respiratory diseases.
It was recently reported, that vaccine efficacy appeared to be preserved when co-administrating
the COVID-19 vaccine NVX-CoV2373 with an influenza vaccine in participants 18 to <65 years
of age,and no early safety concerns were observed (Toback 2021).
2.1. 
Study Rationale
The study aims to assess the safety, reactogenicity, and immunogenicity of the Ad26.COV2.S
vaccine co-administered with a quadrivalent standard-dose or high-dose seasonal influenza
vaccine compared to administration of each vaccine separately to explore whether Ad26.COV2.S
and the influenza vaccines can be administered concomitantly.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
28
Status: Approved,Date: 15 February 2022
According to the CDC, COVID-19 vaccines were previously recommended to be administered
alone, with a minimum interval of 14 days before or after administration of any other vaccines.
The initial recommendation was not due to safety or immunogenicity concerns and substantial data
have been collected on the safety of authorized COVID-19 vaccines. Guidelines have been updated
to allow COVID-19 vaccines and other vaccines to be administered without regard to timing,
including co-administration of COVID-19 vaccines and other vaccines on the same day
(CDC 2021c).
It is unknown whether the reactogenicity of Ad26.COV2.S can be influenced by co-administration
with another vaccine. In certain cases, it has been observed that vaccine co-administration can
increase systemic reactogenicity (Sadoff2020). However, extensive experience with
non-COVID-19 vaccines has demonstrated that immunogenicity and adverse event profiles are
similar when vaccines are administered simultaneously as when they are administered alone
(CDC 2021c). Vaccine’s co-administration is generally a safe and effective practice in which the
benefits outweigh the risks (Brosio 2018).
The seasonal influenza vaccines that will be used in this study are a quadrivalent high-dose
influenza vaccine approved for use in persons ≥65 years of age and a quadrivalent standard-dose
influenza vaccine approved for use in persons ≥18 years of age. These vaccines are indicated for
active immunization for prevention of disease caused by influenza A subtype viruses and type B
viruses contained in the vaccine. For more details, refer to Section 6.1.
2.2. 
Background
Nonclinical Pharmacology
Nonclinical pharmacology of Ad26.COV2.S was evaluated in murine, rabbit, Syrian hamster,
and non-human primate (NHP) animal models for immunogenicity, including assessment of
immunological parameters relevant to the theoretical risk of vaccine-associated enhanced
respiratory disease (VAERD). In addition, vaccine efficacy of Ad26.COV2.S including lung
histopathology assessment was evaluated in Syrian hamsters and NHPs. Details are provided in
the IB (IB Ad26.COV2.S 2021).
Nonclinical Safety
Biodistribution
Ad26 viral vectors (Ad26-based HIV vaccine Ad26.ENVA.01 and Ad26-based RSV vaccine
Ad26.RSV.preF) showed a similar pattern of biodistribution and clearance, despite differences in
the encoded antigen transgenes when delivered via the intramuscular (IM) route at full human dose
levels in the rabbit. Therefore, the biodistribution results are considered sufficient to inform on the
biodistribution profile of Ad26.COV2.S, for which the same (replication-incompetent) Ad26
vector backbone is used. The target organs or tissues identified in the Ad26.COV2.S toxicology
study (ie, injection site, [draining] lymph nodes, and spleen) are consistent with the tissues that
tested mostly positive for Ad26 DNA in the biodistribution studies for the Ad26 platform. Details
are provided in the IB (IB Ad26.COV2.S 2021).

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
29
Status: Approved,Date: 15 February 2022
Toxicology
In a Good Laboratory Practice (GLP)-compliant repeat-dose toxicity and local tolerance study in
rabbits, Ad26.COV2.S was well tolerated when administered on 3 occasions over 4 weeks (ie,
every 2 weeks) at 1×1011 virus particles (vp)/dose. The observed changes were related to a
normal, anticipated (local and systemic) immunologic response to vaccination. Overall, the
findings were considered non-adverse and were partially or completely reversible after a 3-week
treatment-free period. Details are provided in the IB (IB Ad26.COV2.S 2021).
Reproductive and Developmental Toxicology
There was no harmful effect of Ad26.COV2.S concerning female reproductive toxicity and
fertility as assessed in a combined embryo-fetal and pre- and postnatal development toxicity study
in the rabbit. No adverse effects were observed on reproductive performance, fertility, ovarian and
uterine examinations, or parturition. In addition, there was no adverse effect of vaccination on fetal
body weights, external, visceral and skeletal evaluations, or on postnatal development of the
offspring. The parental females as well as their fetuses and offspring exhibited SARS-CoV-2 S
protein-specific antibody titers, indicating that maternal antibodies were transferred to the fetuses
during gestation. Details are provided in  the IB (IB Ad26.COV2.S 2021).
Clinical Studies
At the time of protocol writing, Phase 1/2a (COV1001, COV1002) and Phase 2a (COV2001)
clinical studies to assess the safety, reactogenicity, and immunogenicity of Ad26.COV2.S, as well
as Phase 3 (COV3001, COV3009, COV3003) clinical studies to assess the efficacy of
Ad26.COV2.S in the prevention of molecularly confirmed moderate to severe/critical COVID-19
in adults are ongoing and data from interim analyses from these studies, except COV3009, are
available.
Efficacy
A single dose of Ad26.COV2.S at 5×1010 vp protects against COVID-19 in adults ≥18 years of
age, including adults ≥60 years of age. Based on the primary efficacy analysis of the pivotal
Phase 3 study COV3001, including 19,630 participants who received Ad26.COV2.S and
19,691 participants who received placebo, vaccine efficacy (adjusted 95% confidence interval
[CI]) for the co-primary endpoints against molecularly confirmed moderate to severe/critical
COVID-19 in participants who were seronegative at time of vaccination was 66.9% (59.03; 73.40)
when considering cases from at least 14 days after vaccination and 66.1% (55.01; 74.80) when
considering cases from at least 28 days after vaccination. Ad26.COV2.S has been shown to be
effective against all symptomatic COVID-19, highly effective in the prevention of severe/critical
COVID-19 (particularly in the prevention of hospitalization and death, across all countries and all
ages), and effective against newly emerging strains, such as the 20H/501Y.V2 strain.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
30
Status: Approved,Date: 15 February 2022
Safety
The most extensive safety information of the single-dose regimen of Ad26.COV2.S at 5×1010 vp
is available from ≥43,000 participants, 18 years of age and above, including adults 60 years of age
and above, enrolled in the ongoing pivotal Phase 3 study COV3001. A 2-dose vaccine regimen of
Ad26.COV2.S at 5×1010 vp is currently under evaluation in the ongoing Phase 3 study COV3009.
Supportive safety information (adverse events [AEs], clinical laboratory abnormalities, vital signs,
and physical examination findings) is available from the interim analysis of the Phase 1 and 2
studies COV1001, COV1002, and COV2001. In COV2001, Ad26.COV2.S is being evaluated at
a range of doses and intervals (1.25×1010 vp, 2.5×1010 vp, 5×1010 vp, and 1×1011 vp) in adolescents
12 to 17 years of age, adults 18 to 55 years of age,and 65 years of age.
Ad26.COV2.S has an acceptable safety and reactogenicity profile when administered as a
single-dose or as a 2-dose regimen in adults 18 years of age, including adults 60 years of age.
No significant safety issues were identified. In general, a lower reactogenicity profile was observed
in older adults compared to younger adults.
Overall, up to 22 January 2021, no safety concerns were identified after vaccination with
Ad26.COV2.S as a single-dose or 2-dose vaccine regimen at dose levels up to 1×1011 vp. There
was a trend towards a decrease in the frequency of solicited local and systemic adverse events
(AEs)(reactogenicity) with a decreasing dose level of Ad26.COV2.S (from 1×1011 vp to 2.5×1010
vp). Reactogenicity was demonstrated to be transient and most solicited AEs, including pyrexia,
generally resolved in 1 to 2 days post-vaccination. In the ongoing Phase 3 study COV3001, out of
over 43,000 participants, 19 deaths were reported, 3 in the Ad26.COV2.S group and 16 in the
placebo group, all of which were considered unrelated to the study vaccine by the investigator. No
AEs with a fatal outcome have been reported in the supportive Phase 1 and Phase 2 studies
COV1001, COV1002,and COV2001. In the COV3001 study, at the time of the primary analysis,
0.4% participants in the Ad26.COV2.S group and 0.6% participants in the placebo group reported
1 or more serious adverse events (SAEs). Ten (<0.1%) participants reported SAEs that were
considered to be related to the study vaccine: 7 SAEs were reported in 7 participants in the
Ad26.COV2.S group: Grade 4: Guillain-Barré syndrome and pericarditis (one of each); Grade 3:
radiculitis brachial, post-vaccination  syndrome, and Type IV hypersensitivity (one of each);
Grade 2: facial paralysis (Bell’s Palsy - 2 cases reported); 3 SAEs were reported in 2 participants
in the placebo group: Grade 4: deep vein thrombosis (DVT) (one participant); Grade 3: Epstein-
Barr virus infection and atrial flutter (both were reported in the same participant). No participants
in either vaccine group (Ad26.COV2.S or placebo) were withdrawn from the study due to AEs.
Across studies COV1001, COV1002, and COV2001, 2 participants reported SAEs which were
considered to be related to the study vaccine (both occurred in study COV1001). Early
discontinuations of vaccination or the study due to (S)AEs were infrequent in all groups.
Since then, 6 cases of severe allergic reactions were reported in study COV3012 (Sisonke
[Together]), an open-label, single-arm Phase 3b vaccine implementation study sponsored by the
South African Medical Research Council and conducted in collaboration with Janssen, which is
currently ongoing in the Republic of South Africa. One case met the Brighton Collaboration case

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
31
Status: Approved,Date: 15 February 2022
definition of anaphylaxis with level 2 of diagnosis certainty (Rüggeberg 2007). The review of the
cases of severe allergic reactions reported from this study identified a plausible causal relationship
between the administration of the Ad26.COV2.S vaccine and the occurrence of severe allergic
reactions including anaphylaxis.
Cases of thrombotic events with thrombocytopenia have very rarely been observed in individuals
who received Ad26.COV2.S. At the time of primary analysis of study COV3001 (Data lock point
22 January 2021), one case of cerebral venous sinus thrombosis (CVST) with thrombocytopenia
had been reported which triggered a temporary pause in vaccinations across Ad26.COV2.S clinical
studies. One additional case of DVT with thrombocytopenia was since reported in study
COV3001. As of 17April 2021, 6 spontaneous reports of CVST with thrombocytopenia and
1 spontaneous report of DVT with thrombocytopenia have been reported from the US in the
context of the routine vaccination programs, one of which had a fatal outcome. At that time, more
than 7.9 million people had received Ad26.COV2.S in the US.
Immunogenicity
Across studies COV1001, COV1002, and COV2001, a single dose of Ad26.COV2.S was shown
to elicit SARS-CoV-2 neutralizing antibodies in both the 18 to 55 years age group and in adults
65 years of age. In studies COV1001 and COV3001, SARS-CoV-2 S protein binding antibodies
were elicited in the vast majority of the 18 to 55 years age group and in adults 65 years of age.
In study COV1001, Ad26.COV2.S induced CD4+ T cell responses with a T-helper cell (Th)1
dominant phenotype, and CD8+ T cell responses in both 18to 55 and 65 years of age participants.
Refer to the latest IB (and Addenda) for more details on the ongoing clinical studies with
Ad26.COV2.S (IB Ad26.COV2.S 2021).
Clinical Safety Experience With Ad26-based Vaccines
Safety of Ad26-vectored vaccines has been evaluated in adults in clinical studies by the sponsor.
Replication-incompetent Ad26 is being used as a vector in the development of vaccines against
diseases such as malaria, RSV, HIV, Zika virus, filovirus, and human papillomavirus (HPV), and
has been used in the now licensed Ebola virus vaccine (Zabdeno/Ad26.ZEBOV) and for
emergency use authorized COVID-19 vaccine (Ad26.COV2.S).
As of 17 April 2021, Ad26-based vaccines developed by the sponsor have been administered to
more than 8 million participants. The majority of these participants are enrolled in an ongoing
immunization campaign in the US (COVID-19 Vaccine Program Campaign) (more than
7.9 million) and an ongoing Ebola vaccine study in the Democratic Republic of the Congo and
an ongoing immunization campaign in Rwanda (UMURINZI Ebola Vaccine Program campaign)
(more than 156,000).
Overall, the Ad26-based vaccines were well tolerated irrespective of the antigen transgene,
without significant safety issues. Recently, rare disorders including blood clots in combination

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
34
Status: Approved,Date: 15 February 2022
Committee on Immunization Practices (ACIP),which confirmed a positive benefit-risk profile for
the Janssen COVID-19 vaccine (MacNeil 2021), the US CDC and the FDA, have recommended
vaccinations with the Ad26.COV2.S vaccine for all adults aged 18 years and older. Healthcare
professionals should be mindful of signs and symptoms of thromboembolism and/or
thrombocytopenia.
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, and skin bruising and/or petechiae beyond the site of vaccination. The
medical treatment of thrombosis with thrombocytopenia is different from standard blood clot
treatments. Study site personnel and/or treating physicians should follow available guidelines for
the treatment of thrombotic thrombocytopenia (eg, from the American Society of Hematology
2021, British Society of Haematology 2021, and the CDC 2021). The use of heparin may be
harmful and alternative treatments may be needed. Consultation with a hematologist is strongly
recommended. Management of the participant should not be delayed by the decision-making of
the Janssen Adjudication Committee. Due to the possibility of the occurrence of TTS after
vaccination with Ad26.COV2.S, additional reporting, and data collection procedures have been
included in the study for thrombotic events, thrombocytopenia, and TTS (see Section 8.3.6), which
may facilitate diagnosis and clinical management of the event.
Heparin-induced Immune Thrombotic Thrombocytopenia
TTS has been found to resemble heparin-induced thrombocytopenia with thrombosis (HITT),
which is mediated by antibodies against complexes of heparin and platelet factor 4 (PF4) that
induce Fc receptor-mediated activation of platelets and hypercoagulation (Arepally 2021). Current
evidence suggests that these 2 conditions may be linked (Streiff 2021). The exact mechanisms
remain to be investigated,but anti-PF4 antibodies are suspected to be involved in the pathogenesis
of TTS associated with vaccination.
Risks Related to Adenoviral-vectored Vaccines
The sponsor’s clinical AdVac® safety database contains pooled safety data from 32 completed and
ongoing unblinded clinical studies using the following Ad26-based vaccines: Ad26.ZEBOV
(Ebola; 10 studies), Ad26.ENVA.01, Ad26.Mos.HIV, and Ad26.Mos4.HIV (HIV; 8 studies),
Ad26.CS.01 (malaria; 1 study), Ad26.RSV.FA2 and Ad26.RSV.preF (RSV; 10 studies),
Ad26.Filo (filovirus; 1 study), Ad26.ZIKV.001 (Zikavirus; 1 study), and Ad26.HPV16 and
Ad26.HPV18 (HPV; 1 study). A total of 8,152 adult participants (in 32 studies; 2,087 adults aged
18-30 years, 1,738 adults aged 31-50 years, 182 adults aged 51-59 years, and 4,145 adults aged 60
years and older) and 674 children (in 3 studies; 168 children aged 1-3 years, 252 children aged
4-11 years, and 254 children aged 12-17years) were vaccinated with an Ad26-based vaccine. The
total number of Ad26-based vaccine doses administered was 10,867 (10,169 for adults, and 698
for children) administered to 8,826 individuals. Overall, the Ad26-based vaccines were well
tolerated, without significant safety issues identified.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
35
Status: Approved,Date: 15 February 2022
Risks Related to Afluria Quadrivalent and Fluzone High-dose Quadrivalent
Afluria Quadrivalent is licensed to be used for individuals aged ≥6 months and Fluzone High-dose
Quadrivalent is licensed to be used for individuals aged ≥65 years. These seasonal quadrivalent
standard-doseand high-doseinfluenza vaccines will be administered in the study following the
approved prescribing information.
Adverse Reactions Afluria Quadrivalent
In adults 18 to 64 years of age, the most common (≥10%) solicited local AR was pain (47.9%);
the most common solicited systemic ARs were myalgia (25.5%) and headache (21.7%).
In adults 65 years of age and older, the most common (≥10%) solicited local AR was pain (24.6%);
the most common solicited systemic AR was myalgia (12.7%).
Adverse Reactions Fluzone High-doseQuadrivalent
In adults 65 years of age and older, the most common (≥10%) solicited local AR was pain (41.3%),
the most common solicited systemic ARs were myalgia (22.7%), headache (14.4%), and malaise
(13.2%).
For further details, refer to the Afluria Quadrivalent and Fluzone High-dose Quadrivalent package
inserts.
General Risks Related to Vaccination
In general, intramuscular (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. Instructions regarding the use of antipyretic medication can be found in
Section 6.8.
Syncope can occur in association with the 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 (see above risks related to Ad26.COV2.S). Severe reactions
are rare. Participants with a known 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 per the investigator’s judgment.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
36
Status: Approved,Date: 15 February 2022
After vaccination, participants will remain at the study site for at least 15 minutes and will be
closely observed by the 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.COV2.S vaccine on the fetus or a nursing baby is unknown. Active
vaccination of pregnant women is currently under evaluation  in the COV2004 clinical study.
Despite the cumulative review of pregnancy cases from completed and ongoing clinical studies as
well as a post-marketing mass vaccination campaign for Ad26 vectored vaccine products does not
reveal any safety concern related to vaccine exposure during pregnancy, pregnant women will not
take part in this study.
Participants of childbearing potential will be required to agree to practice a highly effective method
of contraception and agree to remain on such a method of contraception from providing consent
until 3 months after receiving the last study vaccine (see Section 5.1). Participants who are
pregnant at screening will be excluded from the study. Participants who become pregnant during
the study may continue study vaccination if allowed by local regulations for emergency use of
vaccines and if the investigator considers that the potential benefits outweigh any potential risks
to the mother and fetus. Participants will remain in the study and will continue to undergo all
procedures as outlined in the protocol (see also Section 8.3.5).
Participants who are breastfeeding are not allowed to participate in the study.
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.
Concomitant Vaccination
Concomitant vaccination  of the Ad26.COV2.S  vaccine with a seasonal quadrivalent influenza
vaccine might influence both the safety profile and immunogenicity ofthe Ad26.COV2.S vaccine
and/or the seasonal quadrivalent influenza vaccine.
Theoretical Risk of Enhanced Disease
Vaccine-associated enhanced disease (VAED) has been linked to a Th2-polarized immune
response and inadequate induction of neutralizing antibody responses and it was characterized by
enhanced lung histopathology in nonclinical challenge models of other coronaviruses or RSV
(Agrawal 2016;Bolles 2011;Deming 2006;Honda-okubo 2015;Houser 2017). There is, therefore,
a theoretical risk VAED, including VAERD, for SARS-CoV-2 vaccines. The potential of
Ad26.COV2.S to predispose for VAERD and VAED has been evaluated in nonclinical challenge
models established by the sponsor and partners. Ad26.COV2.S immunized Syrian hamsters and
NHP showed the absence of enhanced lung pathology and clinical signs of disease compared with
controls after SARSCoV2 inoculation, even under conditions of suboptimal immunity allowing
breakthrough infection. Together with induction of neutralizing antibodies and a Th1 dominant

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
37
Status: Approved,Date: 15 February 2022
immune response after Ad26.COV2.S dosing these data suggest that the theoretical risk of
VAERD and VAED for Ad26.COV2.S is low (He 2021;van der Lubbe 2021). In both species, no
signs of enhanced respiratory tract pathology were observed in animals dosed with Ad26.COV2.S
compared with challenge control groups.
VAERD has so far not been reported in any of the clinical studies, including interim data reported
from Phase 2/3 clinical trials of mRNA-based vaccines and an adenovector-based vaccine,
expressing SARS-CoV-2 S protein as antigen (Baden 2020; Polack 2020; Voysey 2021).
Similarly, no cases of VAERD have been reported in any of the ongoing clinical studies conducted
to date by the sponsor, including the Phase 1, Phase 2a and Phase 3 studies. The Ad26 vaccine
vector platform has been assessed in several nonclinical and clinical studies so far, and uniformly
induced potent humoral and cellular immune responses with a clear Th1 bias (Barouch 2018;
Salisch 2019; van der Fits 2020; Widjojoatmodjo 2015). The Ad26.COV2.S vaccine candidate,
which encodes the SARS-CoV-2 S protein, has been shown to induce S protein binding antibodies
and virus neutralizing antibodies in mice, rabbits, hamsters and NHP. Ad26.COV2.S was shown
to induce a Th1 skewed immune response in mice and in NHP including aged NHP.
Immunogenicity data from Study COV1001 demonstrated that a single vaccination with
Ad26.COV2.S induces robust neutralizing and binding antibody, CD4+ T cell responses with a
Th1-dominant phenotype, and CD8+ T cell responses (Anywaine 2019; Barouch 2013;
Barouch 2018;Sadoff 2021)
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 efficacy, immunogenicity, and safety data to date support a favorable benefit-risk profile for
Ad26.COV2.S in the proposed indication, ie, active immunization to prevent COVID-19 caused
by SARS-CoV-2 in adults ≥18 years of age (see Section 2.2). The overall benefit and risk balance
for individual participants is ongoing.
Vaccination with a seasonal quadrivalent influenza vaccine may provide protection against the
influenza A subtype viruses and type B viruses contained in the vaccine during the influenza
season.
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:
 A single dose of Ad26.COV2.S protects against moderate to severe/critical COVID-19 as early
as 14 days after vaccination as demonstrated in adults ≥18 years of age, including adults
≥60 years of age.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
38
Status: Approved,Date: 15 February 2022
 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 (Section 1.3).
 After each vaccination, participants will remain at the study site for at least 15 minutes and
will be closely observed by the study staff. Necessary emergency equipment and
medications must be available in the clinic to treat severe allergic reactions. Participants
will use a diary to document solicited signs and symptoms. Details are provided in
Section 8.2.
 The investigator or the designee will document unsolicited AEs, SAEs, adverse events of
special interest (AESIs), and medically attended adverse events (MAAEs), as indicated in
Section 8.2, Section 8.3, and Section 10.4.
 TTS is considered to be an AESI (Section 8.3.6). Suspected AESIs (thrombotic events and
thrombocytopenia [defined as platelet count below 150,000/μL] [Brighton Collaboration
2021] post-vaccination) must be reported to the sponsor within 24 hours of awareness.
Suspected AESIs will be followed-up as described in the Schedule of Activities in Section
1.3.2.
 Any clinically significant abnormalities will be followed by the investigator until resolution
or until clinically stable. For those abnormalities persisting at the end of the study/early
withdrawal, the outcome should be documented in the participant’s medical chart.
 Several safety measures are included in this protocol to minimize the potential risk to
participants, including the following:
 Eligibility will be reassessed pre-vaccination on Day 1.
 Studyvaccinations will be discontinued in participants for the reasons included in Section 7.
 Conditions necessitating a delay in vaccination are included in Section 5.5.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
39
Status: Approved,Date: 15 February 2022
3. 
OBJECTIVES AND ENDPOINTS
Objectives 
Endpoints
Primary
To demonstrate the non-inferiority (NI) of the 
humoral immune response of the 4 influenza 
vaccine 
strains 
after 
concomitant 
administration of the Ad26.COV2.S vaccine 
and a seasonal quadrivalent standard-dose 
influenza vaccine versus the administration of 
a 
seasonal 
quadrivalent 
standard-dose 
influenza vaccine administered alone.
 
Antibody hemagglutination inhibition
(HI) titers as measured by hemagglutinin
inhibition (HAI) assay titers (geometric
mean titers [GMTs]) against each of the 4
influenza vaccine strains, 28 days after the
administration of a seasonal quadrivalent
standard-doseinfluenza vaccine
Success criteria for NI
 
the upper bound of the 2-sided 95%
confidence interval (CI) for the geometric
mean titer(GMT)ratio (Control group/co-
administration [CoAd] group) lies below
1.5
To demonstrate the NI of the binding antibody 
response after concomitant administration of 
Ad26.COV2.S vaccine and a seasonal 
quadrivalent standard-dose influenza vaccine 
versus the administration of Ad26.COV2.S
vaccine administered alone.
 
Antibody titers as measured by S enzyme-
linked immunosorbent assay (S-ELISA)
titers (GMC), 28 days after administration
of Ad26.COV2.S vaccine.
Success criteria for NI
 
the upper bound of the 2-sided 95% CI for
the GMC  ratio (Control group/CoAd
group) lies below 1.5
Secondary
To assess the safety and reactogenicity of a 
single dose of Ad26.COV2.S vaccine when 
administered separately or concomitantly with 
a seasonal quadrivalent high-dose influenza
vaccine in participants aged 65 years and older.
 
Solicited local (injection site) and
systemic AEs for 7 days after each
vaccination.
 
Unsolicited adverse events (AEs) for 28
days after each vaccination.
 
SAEs, MAAEs, and AESIs throughout the
study.
 
AEs leading to withdrawal from the study
throughout the study.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
40
Status: Approved,Date: 15 February 2022
Objectives 
Endpoints
To assess the safety and reactogenicity of a 
single dose of Ad26.COV2.S vaccine when 
administered separately or concomitantly with 
a 
seasonal 
quadrivalent 
standard-dose
influenza vaccine in participants aged 18 years
and older.
 
Solicited local (injection site) and
systemic AEs for 7 days after each
vaccination.
 
Unsolicited AEs for 28 days after each
vaccination.
 
SAEs, MAAEs, and AESIs throughout the
study.
 
AEs leading to withdrawal from the study
throughout the study.
To assess the humoral immune response 
against each of the 4 influenza vaccine strains 
after concomitant administration of the 
Ad26.COV2.S vaccine and a seasonal 
quadrivalent high-dose influenza vaccine 
versus the administration of a seasonal
quadrivalent high-dose influenza vaccine
administered alone.
 
Antibody HI titers as measured by HAI
assay titers (GMTs) against each of the 4
influenza vaccine strains, 28 days after the
administration of a seasonal quadrivalent
standard-doseinfluenza vaccine.
To assess the humoral immune response of 
Ad26.COV2.S vaccine and a seasonal 
quadrivalent 
high-dose 
standard-dose 
influenza vaccine versus the administration of 
Ad26.COV2.S vaccine administered alone.
 
Antibody titers as measured by S enzyme-
linked immunosorbent assay (S-ELISA)
titers (GMC), 28 days after administration
of Ad26.COV2.S vaccine.
To assess the humoral response to SARS‑CoV- 
2 after the concomitant administration of 
Ad26.COV2.S vaccine and a seasonal 
quadrivalent high-dose influenza vaccine 
versus the administration of Ad26.COV2.S
vaccine alone in COVID-19 vaccine-naïve
individuals.
 
Antibody titers as measured by S enzyme-
linked immunosorbent assay (S-ELISA)
titers (GMC), 28 days after administration
of Ad26.COV2.S vaccine.
To assess the humoral response to SARS‑CoV- 
2 after the concomitant administration of 
Ad26.COV2.S vaccine and a seasonal 
quadrivalent standard-dose influenza vaccine 
versus the administration of Ad26.COV2.S
vaccine alone in COVID-19 vaccine-naïve
individuals
 
Antibody titers as measured by S enzyme-
linked immunosorbent assay (S-ELISA)
titers (GMC), 28 days after administration
of Ad26.COV2.S vaccine.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
41
Status: Approved,Date: 15 February 2022
Objectives 
Endpoints
To compare seroconversion rates against the 
4 influenza 
vaccine 
strains 
after 
the 
concomitant administration of Ad26.COV2.S 
vaccine and a seasonal quadrivalent (high-dose 
and standard-dose) influenza vaccine versus a 
vaccination of a seasonal quadrivalent (high-
dose and standard-dose) influenza vaccine
administered alone.
 
Seroconversion is defined for each of the
4 influenza vaccine strains at 28 days after
the 
administration 
of 
a 
seasonal
quadrivalent (high-dose and standard-
dose) influenza vaccine:
 
HI titer ≥1:40 in participants with a
pre-vaccination HI titer of <1:10, or
 
a ≥4-fold HI titer increase in
participants with a pre-vaccination HI
titer of ≥1:10.
To assess seroprotection rates against the 
4 influenza 
vaccine 
strains 
after 
the 
concomitant administration of Ad26.COV2.S 
vaccine and a seasonal quadrivalent (high-dose 
and standard-dose) influenza vaccine versus a 
vaccination of a seasonal quadrivalent (high-
dose and standard-dose) influenza vaccine
administered alone.
 
Seroprotection is defined for each of the
4 influenza vaccine strains as HI titer
≥1:40 at 28 days after the administration
of a seasonal quadrivalent (high-doseand
standard-dose) influenza vaccine.
Exploratory
To evaluate the durability of influenza-specific 
humoral immune responses after concomitant 
administration of the vaccines versus the
influenza vaccine alone.
 
GMT: Geometric mean of HI antibodies at
Day 181.
 
Percentages of participants with HI titers
≥1:40 on Day 181.
To evaluate the durability of SARS-CoV-2 
specific humoral immune responses after 
concomitant administration of the vaccines 
versus the SARS-CoV-2 vaccine alone.
 
Antibody GMC by S-ELISA at Day 181
after the administration of Ad26.COV2.S
vaccine.
To assess the magnitude and durability of 
humoral immune responses specific to 
influenza. 
 
Serological responses to vaccination as
measured by HAI at Day 181 after the
administration of influenza vaccine.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
42
Status: Approved,Date: 15 February 2022
Objectives 
Endpoints
To further assess humoral responses to 
Ad26.COV2. 
 
Serological response to vaccination, as
measured by virus neutralization assay
(VNA) (SARS-CoV-2 VNA and/or
pseudovirion 
[ps] 
VNA 
expressing
S protein) titers.
 
Adenovirus 26 neutralization responses
measured by VNA.
 
Functional 
and 
molecular 
antibody
characterization including Fc-mediated
viral clearance, avidity, Fc characteristics,
immunoglobulin (Ig) subclass, and IgG
isotype.
 
Correlation between ELISA (S-ELISA)
and VNA (wild-type virus [wt]VNA
and/or pseudovirion [ps]VNA) titers at
selected timepoints.
To explore the humoral responses to 
Ad26.COV2.S and influenza vaccine based on 
the SARS-CoV-2 serostatus at baseline (N- 
serology). 
 
Serological response to vaccination as
measured 
by 
S-ELISA 
antibody
concentration 
28 
days 
after 
the
administration of Ad26.COV2.S vaccine.
 
Antibody GMC by S-ELISA at 28 days
after the administration of Ad26.COV2.S
vaccine.
 
Antibody HI titers as measured by HAI
assay titers (GMTs) against the 4
influenza strains.
To explore the humoral responses to 
Ad26.COV2.S and influenza vaccine based on 
the previous history of COVID-19 vaccination 
at entry (viral vector vaccine or mRNA 
vaccine or vaccine-naïve).
 
Serological response to vaccination as
measured 
by 
S-ELISA 
antibody
concentration 
28 
days 
after 
the
administration of Ad26.COV2.S vaccine.
 
Antibody GMC by S-ELISA at 28 days
after the administration of Ad26.COV2.S
vaccine.
 
Antibody HI titers as measured by HAI
assay titers (GMTs) against SARS-CoV-
2.
Refer to Section 8, Study Assessments and Procedures for evaluations related to endpoints.
HYPOTHESES
The primary hypotheses of this study are:

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
43
Status: Approved,Date: 15 February 2022
The concomitant administration of the Ad26.COV2.S vaccine and a seasonal quadrivalent
influenza vaccine (standard-dose) is non-inferior than the administration of the seasonal
quadrivalent influenza vaccine (standard-dose) alone as measured by HI titers against each of the
4 influenza vaccine strains at 28 days after the administration of a quadrivalent seasonal influenza
vaccine,
AND
The concomitant administration of the Ad26.COV2.S vaccine and a seasonal quadrivalent
influenza vaccine (standard-dose) is non-inferior than the administration of the Ad26.COV2.S
vaccine alone as measured by S-ELISA antibody titers at 28 days after the administration of the
Ad26.COV2.S vaccine.
For the high-dose groups, no formal hypothesis testing is planned.
No formal statistical testing of safety data is planned. Safety data will be analyzed descriptively
by vaccine group.
4. 
STUDY DESIGN
4.1. 
Overall Design
This is arandomized, double-blind, parallel,multicenter,interventional studyin healthy(including
stable comorbidities) adults ≥18 years of age. In this study, the safety, reactogenicity, and
immunogenicity of Ad26.COV2.S co-administered with an influenza vaccine will be evaluated.
Approximately 1,100 participants will be randomized in parallel in this study. Participants aged
≥65 will be randomized in a 1:1:1:1 ratio to 1 of 4 groups. Participants aged ≤64 will be randomized
in a 1:1 ratio to 1 of 2 groups (Group 1 or Group 2). Efforts will be made to ensure good
representation in terms of race, gender,and ethnicity.
Participants will receive Ad26.COV2.S and a seasonal quadrivalent (standard-doseor high-dose)
influenza vaccine either concomitantly on Day 1 and placebo on Day 29 (co-administration
groups 1 and 3) or a seasonal quadrivalent (standard-dose or high-dose) influenza vaccine and
placebo on Day 1 and Ad26.COV2.S on Day 29 (control groups 2 and 4) (see Table 2).
Table 2: 
Overview of the Groups and Vaccination Days
Group  
Day 1 
Day 29
1 (CoAd group) 
Ad26.COV2.S + Q SD influenza vaccine 
Placebo
2 (Control group) 
Placebo + Q SD influenza vaccine 
Ad26.COV2.S
3 (CoAd group) 
Ad26.COV2.S + Q HD influenza vaccine 
Placebo
4 (Control group) 
Placebo + Q HD influenza vaccine 
Ad26.COV2.S
CoAd = co-administration; HD = high-dose; Q = quadrivalent; SD = standard-dose.
The seasonal quadrivalent standard-doseinfluenza vaccine (Groups 1 and 2) can be administered
to all participants. Age is included as stratification factor for Groups 1 and 2 (≥18 to ≤64 years of

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
44
Status: Approved,Date: 15 February 2022
age versus ≥65 years of age). The seasonal quadrivalent high-doseinfluenza vaccine (Groups 3
and 4) will only be administered to participants ≥65 years of age.
The previous SARS-CoV-2 vaccination history (Vaxzevria [AstraZeneca], Comirnaty
[Pfizer-BioNTech], SpikeVax [Moderna], Ad26.COV2-S [Janssen] or COVID-19 vaccine naïve)
will be used as second stratification factor. This stratification factor will aim to obtain a balanced
distribution of SARS-CoV-2 vaccination history across the 4 treatment groups.
Participants can either have received a complete primary vaccination with an authorized/licensed
COVID-19a vaccine (completed ≥6 months prior to first study vaccination) or be COVID-19
vaccine-naïve. Type of primary vaccination will be documented and accounted for according to
interactive web response system (IWRS) procedures.
A diagram of the study design is provided in Section 1.2.
Study Duration
The study duration from screening until the last follow-up visit will be approximately 7-8months.
The study comprises screening on Day -28 to 1, vaccination visits on Days 1 and 29 with a 28-day
follow-up period after each vaccination. AEs leading to withdrawal, MAAEs, SAEs, and AESIs
will be collected throughout the study.
If a participant is unable to complete the study(post-vaccination 1), but has not withdrawn consent,
an early exit visit will be conducted, or the participant can continue with other study procedures.
The end of the study is defined as the last participant’s last visit.
Unscheduled study visits may be performed based on investigator’s clinical judgment and may
include further evaluations, as needed.
Study Procedures
For each group, safety will be assessed by collection of solicited local (at injection site) and
systemic AEs, unsolicited AEs, MAAEs, AESIs, and SAEs. Other safety assessments include vital
signs measurements (heart rate, supine systolic and diastolic blood pressure, respiratory rate, and
body temperature) and physical examinations at the time points indicated in the Schedule of
Activities.
After each vaccination, participants will remain under observation at the study site for at least
15 minutes for presence of any acute reactions and solicited events. Any solicited local or systemic
AEs, unsolicited AEs, MAAEs, AESIs, SAEs, concomitant medications, and vital signs will be
documented by study-site personnel following this observation period. In addition, participants
a The following authorized/licensed COVID-19 vaccines are permitted in this study: Vaxzevria (AstraZeneca),
Comirnaty (Pfizer-BioNTech), SpikeVax (Moderna), and Ad26.COV2-S (Janssen).

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
45
Status: Approved,Date: 15 February 2022
will record solicited signs and symptoms in a diary for 7 days post-vaccination (or until resolution)
(Section 8).
The reporting periods of AEs, MAAEs, AESIs, and SAEs, and special reporting situations are
detailed in Section 8.3. Reporting periods for concomitant therapy are outlined in Section 6.8. At
each visit,the participant will be asked if they have had a private/off-study COVID-19 diagnostic
test. See Section 8.3.1 on the reporting periods of this event.
Blood samples will be collected for assessment of humoral immune responses at the time points
indicated in the Schedule of Activities.
Over the entire study, the total blood volume to be collected from each participant will be
approximately 90 mL.
4.2. 
Scientific Rationale for Study Design
For the rationale for performing this study, refer to Section 2.1.
Dose Level Selection
The rationale behind the selection of the dose level is described in Section 4.3.
Blinding, Control, Study Phase/Periods, Vaccination Groups
Randomization will be used to minimize bias in the assignment of participants to vaccination
groups, to increase the likelihood that known and unknown participant attributes (eg,demographic
and baseline characteristics) are evenly balanced across vaccination groups, and to enhance the
validity of statistical comparisons across vaccination groups. Blinded study vaccine will be used
to reduce potential bias during data collection and evaluation ofclinical endpoints.
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.
The study will be performed in adult participants who will receive vaccination against
SARS-CoV-2 and influenza and compensation for their time and any inconveniences. See
Section 2.3 for details on potential and known benefits and risks, and for the safety measures taken
to minimize risk to participants.
The total blood volume to be collected is acceptable according to the US Department of Health
and Human Services Office for Human Research Protections, and FDA guidelines (FDA 1998;
US DHHS 1998), and the European Commission guidelines (EC 1998).

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
46
Status: Approved,Date: 15 February 2022
4.3. 
Justification for Dose
The 5×1010 vp dose level used in this study is consistent with the dose level authorized for
emergency use in the United States (US) on 27 February 2021 and conditional marketing in the
EU on 11 March 2021 (see Section 2).
4.4. 
End of Study Definition
End of Study Definition
The end of the study is considered as the last visit 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.
Study Completion Definition
A participant will be considered to have completed the study if the participant has completed
assessments at 6-month follow-up visit post-vaccination 2.
Participants who prematurely discontinue the study vaccine for any reason before the second
vaccination will not be considered to have completed the study. The reasons for such cases should
be documented and available to the sponsor.
5. 
STUDY POPULATION
Screening for eligible participants could be performed within 28days before the administration of
the study vaccine. Refer to Section 5.4, Screen Failures for conditions under which the repeat of
any screening procedures are allowed.
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.
NOTE: Investigators should ensure that all study enrollment criteria have been met at screening.
If a participant’s clinical status changes (including any available laboratory results or receipt of
additional medical records) after screening but before the first dose of study vaccination and they
no longer meet all eligibility criteria, the participant should be excluded from participation in the
study (Refer to Section 5.4 for conditions for retesting).
The required source documentation to support meeting the enrollment criteria is noted in
Section 10.3.10.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
47
Status: Approved,Date: 15 February 2022
5.1. 
Inclusion Criteria
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
1. Participant must sign an informed consent form (ICF) indicating that he or she understands
the purpose, procedures, and potential risks and benefits of the study, and is willing to
participate in the study.
2. Participant is willing and able to adhere to the prohibitions and restrictions specified in this
protocol.
3. Participant is male or female aged ≥18 years of age, on the day of signing the ICF.
a. Groups 3 and 4 only: Participant is male or female aged ≥65 years of age, on the day
of signing the ICF.
4. Participant must be healthy, in the investigator’s clinical judgment, as confirmed by medical
history, physical examination, and vital signs performed at screening. Participants may have
underlying illnesses, as long as the symptoms and signs are medically controlled.
5. Criterion modified per Amendment 1
5.1 Participant either received complete primary vaccination with an authorized/licensed
COVID-19 vaccine (completed ≥6 months prior to the last vaccination  received against
COVID-19) or is COVID19 -vaccine-naïve.
Note: The following authorized/licensed COVID-19 vaccines are permitted in this study:
Vaxzevria (AstraZeneca), Comirnaty (Pfizer-BioNTech), SpikeVax (Moderna), and
Ad26.COV2-S (Janssen).
6. Criterion modified per Amendment 1
6.1 In the investigator’s clinical judgment, the participant may have a stable and well-
controlled medical condition including comorbidities associated with an increased risk of
progression to severe COVID-19 (CDC 2021a) (see Section 10.7, Appendix 7) (including
stable/well-controlled HIV infection)*. If participants are on medication for a medical
condition (including comorbidities associated with an increased risk of progression to severe
COVID-19), the medication dose cannot have been modified within 4 weeks preceding
vaccination. Participants will be included on the basis of relevant medical history  at the
investigator’s discretion.
* Stable/well-controlled HIV infection includes:
a. Documented CD4 cell count ≥300 cells/µL within 6 months prior to screening.
b. Documented HIV viral load <50 copies/mL within 6 months prior to screening.
c. Participant must be on a stable anti-retroviral treatment (ART) for 6 months (unless the
change is due to tolerability, in which case the regimen can be for only the previous
3 months; changes in the formulation are allowed; nationwide guidelines that require
transition from one ART regimen to another are allowed) and the participant must be
willing to continue his/her ART throughout the study as directed by his/her local
physician.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
48
Status: Approved,Date: 15 February 2022
Note: Participants with ongoing and progressive comorbidities associated with HIV
infection will be excluded but comorbidities associated with HIV infection that have been
clinically stable for the past 6 months are not an exclusion criterion.
Laboratory methods for confirming a diagnosis of HIV infection are: Any evidence
(historic or current) from medical records, such as ELISA with confirmation with
Western Blot or real-time reverse-transcriptase polymerase chain reaction (RT-PCR),
or of a detectable viral load (country-specific regulatory approved tests).
If a potential participant does not have HIV viral load and CD4 cell count data in his/her
medical records from the last 6 months, they will be instructed to go to their local health
care provider and obtain the necessary data for potential entry into the study. A
laboratory result within 6 months of screening does not need to be repeated.
7. Contraceptive (birth control) use by participants should be consistent with local regulations
regarding the acceptable methods of contraception for those participating in clinical studies.
Before randomization, participants who were born female must be either (as defined in
Section 10.5, Appendix 5):
a. Not of childbearing potential
b. Of childbearing potential and practicing a highly effective method of contraception
and agrees to remain on such a method of contraception from signing the informed
consent until 3 months after the administration of the last study vaccine. Use of
hormonal contraception should start at least 28 days before the first administration of
study vaccine. The investigator should evaluate the potential for contraceptive method
failure (eg, noncompliance, recently initiated) in relationship to the first vaccination.
Highly effective methods for this study include:
1. hormonal contraception;
a) combined (estrogen and progestogen containing) hormonal contraception
associated with inhibition of ovulation (oral, intravaginal, or transdermal)
b) progestogen-only hormonal contraception associated with inhibition of
ovulation (oral, injectable, or implantable)
2. intrauterine device;
3. intrauterine hormone-releasing system;
4. bilateral tubal occlusion/ligation procedure;
5. vasectomized partner (the vasectomized partner should be the sole partner for
that participant);
6. sexual abstinence*.
*Sexual abstinence is considered an effective method only if defined as refraining from
heterosexual intercourse from signing the informed consent until 3 months after the last dose of
study vaccine. 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.
8. Criterion modified per Amendment 1
8.1 All participants who were born female and are of childbearing potential must:
a. Have a negative highly sensitive urine pregnancy test at screening

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
49
Status: Approved,Date: 15 February 2022
b. Have a negative highly sensitive urine pregnancy test on the day of vaccination prior
to each study vaccine administration.
9. Participant agrees to not donate or receive bone marrow, blood, and blood products from the
administration of the study vaccine until 3 months after receiving the study vaccines.
10. Participant must be willing to provide verifiable identification to be contacted and to contact
the investigator during the study.
11. Participant must be able to read, understand, and complete questionnaires in the participant’s
diary.
12. Participant must have access to a consistent means of contact either by telephone contact or
e-mail/computer.
5.2. 
Exclusion Criteria
Any potential participant who meets any of the following criteria will be excluded from
participating in the study:
1. Participant has a clinically significant acute illness (this does not include minor illnesses such
as diarrhea or mild upper respiratory tract infection) or temperature ≥38.0ºC (100.4°F) within
24 hours prior to the planned dose of study vaccine; randomization at a later date is permitted
at the discretion of the investigator.
2. Criterion modified per Amendment 1
2.1 Participant has a history of malignancy within 1 year before screening (exceptions are
squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or
malignancies considered cured with minimal risk of recurrence per investigator’s clinical
judgment).
3. Participant has a known allergy or history of anaphylaxis or other serious adverse reactions to
vaccines or their excipients (including specifically the excipients of the study vaccine) (refer
to IB Ad26.COV2.S 2021 and its addenda for further details).
4. Participant has a history of severe allergic reactions (eg, anaphylaxis) to any component of
the seasonal quadrivalent influenza vaccines, including egg protein, or following a previous
dose of any influenza vaccine.
5. Criterion modified per Amendment 1
5.1 Participant has an abnormal function of the immune system resulting from:
a. Clinical conditions (eg, autoimmune disease or immunodeficiency) are expected to have
an impact on the immune response elicited by the study vaccine. Participants with
autoimmune diseases (eg, autoimmune thyroiditis, autoimmune inflammatory rheumatic
diseases such as rheumatoid arthritis and type 1 diabetes) that are stable and controlled
without the use of systemic immunomodulators and glucocorticoids may be enrolled at
the discretion of the investigator.
Note: Non-immunomodulatory treatment is allowed as well as steroids at a
non-immunosuppressive dose or route of administration.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
50
Status: Approved,Date: 15 February 2022
b. Chronic or recurrent use of systemic corticosteroids within 6 months before
administration of the study vaccine and during the treatment period of the study  at
immunosuppressive doses.
b.1 An immunosuppressive steroid dose is considered as >20 mg prednisone or equivalent
daily for 2 consecutive weeks.
Note: Ocular, topical, and inhaled steroids are allowed.
c. Administration of antineoplastic and immunomodulating agents or radiotherapy within
6 months before administration of the first study vaccine and during the treatment period
of the study.
6. Participant has a history of any neurological disorders or seizures including Guillain-Barré
syndrome, with the exception of febrile seizures during childhood.
7. Criterion deleted per Amendment 1
8. Participant received treatment with immunoglobulins within 3 months or exogenous blood
products (autologous blood transfusions are not exclusionary) or blood products within
4 months before the administration of the first study vaccine or plans to receive such treatment
during treatment period of the study.
Note: The use of monoclonal antibodies (MABS) before administration of study vaccine and
during the study conduct is permitted with the exception of those targeting T cells (anti-CD3,
CD4, CD33, and CD52), B cells (anti-CD45, CD19, CD20, CD22, CD27, CD38, and CD138)
and check point inhibitors (PD-1, PDL-1 and CTLA-4). Examples of not allowed MABS are:
Muromonab-CD3, Gemtuzumab ozogamicin, Alemtuzumab, Bevacizumab, Rituximab,
Ofatumumab, Ocrelizumab, Tositumomab, Veltuzumab, Obinutuzumab, Epratuzumab,
Pembrolizumab, Nivolumab, Atezolizumab, avelumab, durvalumab and CTLA-4 targeting
Ipilimumab. Participants receiving these MABS in the 2 months before the planned
administration of the first study vaccine or who plan to receive these MABS during the
treatment period of the study will be excluded from participating in the study.
9. Participant has history of TTS or heparin-induced thrombocytopenia and thrombosis (HITT).
10. Participant has history of capillary leak syndrome.
11. Participant received or plans to receive:
a. Licensed live attenuated vaccines - within 28 days before or after planned administration
of the first or subsequent study vaccines.
b. Other licensed (not live) vaccines - within 14 days before or after planned administration
of the first or subsequent study vaccines.
12. Criterion modified per Amendment 1
12.1 Participant received a licensed/registered SARS-CoV-2 vaccine less than 6 months prior
to first study vaccination or during the course of this study (other than study vaccination).
13. Participant received vaccination with a seasonal influenza vaccine for the current influenza
season in the Northern Hemisphere.
14. Participant received an investigational drug (including any investigational agent for
COVID-19 prophylaxis) or used an invasive investigational medical device within 30 days or
received an investigational vaccine within 6 months before the administration of the study

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
51
Status: Approved,Date: 15 February 2022
vaccine or is currently enrolled or plans to participate in another investigational study during
the course of this study.
Note: Participation in an observational clinical study (ie, without intervention) is allowed at
the investigator’s discretion.
15. Participant is a woman who is pregnant, or breastfeeding, or planning to become pregnant
while enrolled in this study or within 3 months after the administration of the last study
vaccine.
16. Participant has a history of an underlying clinically significant acute or chronic medical
condition or physical examination findings 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.
17. Participant had or plans to have major surgery (per the investigator’s judgment) within
4 weeks before the administration of the first study vaccine or will not have recovered from
surgery at the time of vaccination.
18. Participant has a contraindication to IM injections and blood draws (eg, bleeding disorders).
19. Participant is an 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.
20. Participant has chronic active hepatitis B or hepatitis C infection per medical history.
21. Participant has had a major psychiatric illness or drug or alcohol abuse which in the
investigator’s opinion would compromise the participant’s safety or compliance with the
study procedures.
22. Participant cannot communicate reliably with the investigator.
23. Participant 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.
24. Criterion modified per Amendment 1
24.1Participant has a positive diagnostic test result for current (viral RNA detection)
SARS-CoV-2 infection prior to vaccine administration on Day 1.
NOTE: Investigators should ensure that all study enrollment criteria have been met prior to the
first study vaccination. If a participant's clinical status changes (including any available laboratory
results or receipt of additional medical records) after screening but before the first dose of study
vaccination is given such that he or she no longer meets all eligibility criteria, then the participant
should be excluded from participation in the study. Section 5.4 describes options for retesting. The
required documentation to support meeting the enrollment criteria is described under Source
Documents in Section 10.3.10, Appendix 3.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
52
Status: Approved,Date: 15 February 2022
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 for 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 (eg, contraceptive requirements).
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 and age at initial informed consent will be used.
Individuals who do not meet the criteria for participation in this study (screen failure) may be
rescreened once. Participants who are rescreened will be assigned a new participant number,
undergo the ICF process, and then restart a new screening phase.
5.5. 
Criteria for Temporarily Delaying Administration of Study Vaccine
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.
If any of these events occur at the scheduled time for the first vaccination, randomization at a later
date within the screening window is permitted at the discretion of the investigator and the reason
should be documented. If any of these events occur at the scheduled time for one of the subsequent
vaccinations, the vaccination visit can be rescheduled, within  the allowed windows (see Visit
Windows in the Schedule of Activities).
If the vaccination visit cannot be rescheduled within the allowed window or the contraindications
to vaccination persist, the reason should be documented.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
53
Status: Approved,Date: 15 February 2022
6. 
STUDY VACCINATION AND CONCOMITANT THERAPY
6.1. 
Study Vaccines Administered
Ad26.COV2.S  will be supplied at a concentration of 1×1011 vp/mL in single-use vials, with an
extractable volume of 0.5 mL, and dosed at 5×1010 vp. Placebo (0.9% sodium chloride [NaCl])
will be supplied in single-use vials.
The seasonal influenza vaccines to be used in this study are Afluria Quadrivalent (standard-dose)
and Fluzone HD Quadrivalent (high-dose) or equivalent formulated for the 2021-2022
influenza- season:
 
Afluria Quadrivalent (standard-dose) is a suspension for IM injection supplied in a 0.5-mL
single-dose prefilled syringe. Each dose of Afluria Quadrivalent contains 60 µg of
hemagglutinin (HA): 15 µg of each of 4 influenza strains (2 influenza A strains and 2 influenza
B strains). For details, refer to the Afluria Quadrivalent package insert.
 
Fluzone HD Quadrivalent (high-dose) is a suspension for IM injection supplied in a 0.7-mL
single-dose prefilled syringe. Each dose of Fluzone HD Quadrivalent contains 240 µg of HA:
60 µg of each of 4 influenza strains (2 influenza A strains and 2 influenza B strains). For
details, refer to the Fluzone HD Quadrivalent package insert.
Participants will be vaccinated at the study site according to the schedule shown in Table 2. Study
vaccines will be administered by IM injection into the deltoid muscle. On Day 1, each participant
will receive 2 IM injections. Each injection  should be administered in opposite arms. It is
recommended to use the right arm for the seasonal influenza vaccine on Day 1 and the left arm for
the Ad26.COV2.S vaccine or placebo on Days 1 and 29.
On Day 29, each participant will receive 1 IM injection, preferably the deltoid muscle of the
non-dominant upper arm is used.
If an injection cannot be given in the deltoids due to a medical or other contraindication (for
example, tattooed upper arms rendering it difficult to assess site reactogenicity), use alternative
locations such as the hip, thigh, or buttocks (to be avoided in overweight participants). When
selecting an alternative location, the participant’s ability to assess injection site events should be
considered. In all circumstances, IM injections in other locations than the upper arm are not
considered protocol deviations.
For further information on visit windows see the Schedule of Activities in Section 1.3.1. If a
participant cannot be vaccinated within the allowed window, the decision regarding vaccination
will be assessed on a case-by-case basis upon discussion between sponsor and investigator. The
reason should be documented.
Study vaccine administration must be captured in the electronic case report form (eCRF).
Ad26.COV2.S and placebo will be manufactured and provided under the responsibility of the
sponsor. Refer to the IB for a list of excipients (IB Ad26.COV2.S 2021).

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
54
Status: Approved,Date: 15 February 2022
Refer to the study site investigational product and procedures manual (SIPPM) and the
Investigational Product Preparation Instructions (IPPI) for additional guidance on study vaccine
administration.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
55
Status: Approved,Date: 15 February 2022
Table 3: 
Description of Interventions
Intervention Name 
Ad26.COV2.S  
Placebo 
Afluria Quadrivalent 
Fluzone HD
Quadrivalent
Type 
Biologic/vaccine 
Placebo 
Biologic/vaccine 
Biologic/vaccine
Dose Formulation 
Single-use vials, with an 
extractable volume of 
0.5 mL 
Single-use vials, with an 
extractable volume of 
10 mL
0.5 mL single-dose 
prefilled syringes 
0.7mL single-dose
prefilled syringe.
Unit Dose Strength(s) 
Ad26.COV2.S at a 
concentration of 
1×1011 vp/mL
0.9% NaCl 
15 µg HA of each 
influenza strain  
60 µg HA of each
influenza strain
Dosage Level(s) 
Ad26.COV2.S 5×1010 
vp once
0.5 mL once 
60 µg HA once 
240 µg HA once
Route of Administration 
IM injection  
IM injection  
IM injection 
IM injection
Use 
Experimental 
Placebo-comparator 
Co-administration  
Co-administration
Investigational Medicinal Product (IMP) 
Yes 
Yes 
Yes 
Yes
Non-Investigational Medicinal Product/Auxiliary 
Medicinal Product (NIMP/AxMP)
No 
No 
No 
No
Sourcing 
Provided centrally by the Sponsor
Packaging and Labeling 
(Labels will contain information to meet the applicable 
regulatory requirements.) 
The study vaccines will be packaged and labeled 
according to good manufacturing practices and 
local regulations. The study vaccines will not be 
packed in individual participant kits, 1 kit will be 
used by multiple participants. Each kit will contain 
single-use vials. 
The study vaccines will be packaged and labeled
according to good manufacturing practices and
local regulations. The study vaccines will not be
packed in individual participant kits, 1 kit will be
used by multiple participants. Each kit will contain
single-use vials or prefilled syringes.
Not in child resistant packaging
HA = hemagglutinin; HD = high-dose; IM = intramuscular; vp = virus particles.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
56
Status: Approved,Date: 15 February 2022
6.1.1. 
Combination Products
For this protocol, the term “combination product” refers to the single integral drug-device
combination. The seasonal influenza vaccines administered in this study, Afluria Quadrivalent
(standard-dose) and Fluzone HD Quadrivalent (high-dose),are considered combination products.
All combination product deficiencies (including failure, malfunction, improper or inadequate
design, manufacturer error, use error, and inadequate labeling) shall be documented and reported
by the investigator throughout the study. For studies using a combination product, these
deficiencies will be reported as product quality complaints (PQC) (see Section 10.4.6; Appendix
4.6: Product Quality Complaint Handling) and appropriately managed by the sponsor.
6.2. 
Preparation/Handling/Storage/Accountability
Preparation/Handling/Storage
All study vaccine must be stored in a secured location with no access for unauthorized personnel
and at controlled temperatures as indicated on the clinical labels. If study vaccine is exposed to
temperatures outside the specified temperature range, all relevant data will be sent to the sponsor
to determine if the affected supplies can be used or will be replaced. The affected study vaccine
must be quarantined and not used until further instruction from the sponsor is received.
Refer to the SIPPM and the IPPI for additional guidance on study vaccine preparation, handling,
and storage.
An unblinded study site pharmacist, or another qualified individual, who will have no other study
function following vaccination, will prepare the appropriate vials and syringes, labeled with the
participant’s identification number, and provide the syringes for the study vaccine in a blinded
manner to the blinded vaccine administrator (a trained and qualified study nurse, medical doctor,
or otherwise qualified health care professional [HCP])who will perform the injection.
Accountability
The investigator is responsible for ensuring that all study vaccines received at the site are
inventoried and accounted for throughout the study. The study vaccines administered to the
participant must be documented on the vaccine accountability form. All study vaccines will be
stored and disposed of according to the sponsor's instructions. Study  site personnel must not
combine the contents of the study vaccine containers.
Study vaccines 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 vaccines 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 vaccines will be documented on the vaccine accountability 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 accountability form.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
57
Status: Approved,Date: 15 February 2022
Potentially hazardous materials containing hazardous liquids, such as needles and syringes should
be disposed of immediately safely and therefore will not be retained for vaccine accountability
purposes.
Study vaccines should be dispensed under the supervision of the investigator or a qualified member
of the studysite personnel, or by a hospital/clinic pharmacist. Study vaccines will be supplied only
to participants participating in the study. Returned study vaccines must not be dispensed again,
even to the same participant. Study vaccines may not be relabeled or reassigned for use by other
participants. The investigator agrees neither to dispense the study vaccines from nor store them at,
any site other than the study sites agreed upon with the sponsor. Further guidance and information
for the final disposition of unused study vaccines are provided in the SIPPM.
6.3. 
Measures to Minimize Bias: Randomization and Blinding
Vaccine Allocation
Procedures for Randomization and Stratification
Central randomization will be implemented in this study. Participants will be randomly assigned
to 1 of 2 vaccination  groups (1:1 ratio; for participants ≥18 to ≤64 years of age) or 1 of
4 vaccination groups (1:1:1:1  ratio; for participants ≥65 years of age). This will be 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 and will be stratified by
age (≥18 to ≤64 years of age versus ≥65 years of age) and previous SARS-CoV-2 vaccination
history  (Vaxzevria [AstraZeneca], Comirnaty [Pfizer-BioNTech], SpikeVax [Moderna],
Ad26.COV2-S [Janssen], or COVID-19 vaccine naïve). The type of primary vaccination will be
documented and accounted for according to IWRS procedures.
The IWRS will assign a unique intervention code, which will dictate the intervention assignment
and matching study intervention kit for the participant. The requestor must use his or her 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
Blinding will be guaranteed by the preparation of the study vaccine by an unblinded pharmacist or
other qualified study site personnel with primary responsibility for study vaccine preparation and
dispensing and by the administration of the vaccine in a masked syringe bya blinded study vaccine
administrator. Participants will be randomly assigned to 1 of the groups based on a computer-
generated randomization schedule prepared before the study by or under the supervision of the
sponsor and using the IWRS.
The investigator will not be provided with randomization codes. The codes will be maintained
within the IWRS, which has the functionality to allow the investigator to break the blind for an
individual participant.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
58
Status: Approved,Date: 15 February 2022
Data that may potentially unblind the intervention assignment (ie, immunogenicity data, study
vaccine accountability data, study vaccine allocation, or other specific laboratory data) 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.
Under normal circumstances, the blind should not be broken until all participants have completed
the treatment phase of the study and the database lock is completed. The investigator may, in an
emergency, determine the identity of the intervention  by contacting the IWRS. While the
responsibility to break the intervention code in emergency situations resides 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.
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, electronic data capture (eDC)
tool,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.
Participants who have had their intervention assignment unblinded should continue to return for
scheduled evaluations.
Participants who withdraw will not be replaced.
6.4. 
Study Vaccination Compliance
Study vaccines will be administered IM by blinded qualified study site personnel at the study site.
The date and time of study vaccine administration and the location used will be recorded in the
eCRF.
6.5. 
Dose Modification
Dose modification is not applicable in this study.
6.6. 
Access to Licensed/Authorized Study Vaccine After the End of the Study
All participants in this study will receive Ad26.COV2.S  vaccine and a seasonal quadrivalent
influenza vaccine, irrespective of the study group to which they are randomized. Participants will
not be offered another active study vaccine after the end of the study.
Participants will be instructed that a study vaccine will not be made available to them after they
have completed/discontinued the study vaccine.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
59
Status: Approved,Date: 15 February 2022
6.7. 
Treatment of Overdose
For this study, any dose of Ad26.COV2.S or of a seasonal quadrivalent influenza 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 sponsor or Medical Monitor immediately.
 
Closely monitor the participant for AEs/AESIs/SAEs/MAAEs (ie, the participant will remain
at the study site for at least 1 hour and will be closely monitored for allergic or other reactions
by the study staff. Follow-up telephone calls 12 hours and 24 hours post-dose will be made).
 
Document the quantity of the excess dose in the eCRF.
 
Report as a special reporting situation (see Appendix 10.4.4).
6.8. 
Concomitant Therapy
Prestudy specific therapies such as analgesic/antipyretic medications and non-steroidal
anti-inflammatory drugs, corticosteroids, antihistamines, and vaccinations taken  up to 30 days
before the first dose of study vaccine must be recorded at screening.
Concomitant therapies such as analgesic/antipyretic medications and non-steroidal anti-
inflammatory drugs,corticosteroids, antihistamines, and vaccinations must be recorded (including
dose and frequency) from the first dose of study vaccine until 28 days after administration of the
last study vaccine.
All other concomitant therapies should also be recorded if administered in conjunction with a
confirmed COVID-19 case or new or worsening AEs reported per protocol requirements outlined
in Section 8.3.1.
For all participants, concomitant therapies associated with an SAE or suspected AESI meeting the
criteria outlined in Sections 10.4.1 and 8.3.6, respectively, will be collected and recorded in the
eCRF from the moment of first vaccination through the end of the study. Concomitant therapies
associated with MAAEs or MAAEs leading to study discontinuation will be collected and recorded
in the eCRF throughout the study.
For all participants, concomitant therapies associated with unsolicited AEs will be collected and
recorded in the eCRF from the time of first vaccination through 28 days after the last vaccination.
Concomitant therapies associated with solicited AEs will be collected by the participants and
recorded in the eCRF from the time of each vaccination through 7 days after that vaccination (or
until resolution).
Use of any experimental medication (including experimental vaccines other than the study
vaccine) during the study is not allowed. Participants may not 1) receive an investigational drug
(including investigational drugs for prophylaxis of COVID-19); 2) use of an invasive
investigational medical device within 30 days; 3) receive an investigational immunoglobulins or

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
60
Status: Approved,Date: 15 February 2022
monoclonal antibodies within 3 months; 4) receive convalescent serum for COVID-19 treatment
within 4 months; 5) receive an investigational vaccine within 6 months before the administration
of the first study vaccine.
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, tetanus, hepatitis A, hepatitis B,
rabies) should be given at least 14 days before (or at least 14 days after) administration of the study
vaccine to avoid potential confusion of adverse reactions and potential immune interference.
The use of any SARS-CoV-2 vaccine (licensed/authorized or investigational) other than study
vaccination is disallowed less than 6 months prior to the first study vaccination and during the
course of the study. In the event that a participant does receive another COVID-19 vaccine outside
of the study, investigators are required to enter any COVID-19 vaccines (name/manufacturer of
the vaccine and date of administration) in the Concomitant Therapy eCRF.
Vaccination with a seasonal influenza vaccine for the 2021-2022 influenza season in the Northern
Hemisphere is disallowed at any time prior to vaccination and during the course of the study. If a
vaccine is indicated in a post-exposure setting (eg,rabies or tetanus), it could take priority over the
study vaccine and must be documented in the Concomitant Therapy eCRF.
Antipyretics are recommended post-vaccination for symptom relief as needed. Prophylactic
antipyretic use is not encouraged; however, in some instances, it could be considered in special
circumstances and/or comorbidities per the investigator’s discretion.
Chronic or recurrent use of systemic corticosteroidsa at immunosuppressive dose (defined as >20
mg prednisone or equivalent daily for 2 consecutive weeks) and administration of antineoplastic
and immunomodulating agents or radiotherapy is prohibited during the treatment phase (ie,
through 1 month post vaccination 2). If any of these agents are indicated in a disease setting,
medical judgment should prevail.
Treatment with immunoglobulins within 3 months or exogenous blood products (autologous blood
transfusions are not exclusionary) or blood products within 4 months before the administration of
the study vaccine or during the treatment period of the study is disallowed.
Refer to Section 5.2 for further details on time frames for prohibited therapy.
The sponsor must be notified as soon as possible of any instances in which prohibited therapies
are administered.
a Note: Ocular, topical, or inhaled steroids are allowed.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
61
Status: Approved,Date: 15 February 2022
7. 
DISCONTINUATION OF STUDY VACCINATION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL
7.1. 
Discontinuation of Study Vaccination
Study vaccinations will be withheld for the reasons listed below. These participants must not
receive any further doses of the study vaccine and could opt for an early termination visit orremain
on study for follow-up with assessments of safety and immunogenicity as indicated in the Schedule
of Activities. Additional unscheduled visits may be performed for safety/reactogenicity reasons, if
needed. In case of questions, the investigator is encouraged to contact the sponsor.
 
Any related AE, worsening of health status,or intercurrent illnesses that, in the opinion of the
investigator, requires discontinuation from study vaccine
 
Unblinding on the participant level that, in the opinion of the sponsor, would compromise the
integrity of the data
 
Anaphylactic reaction following vaccination, not attributable to causes other than vaccination
 
SAE or other potentially life-threatening (Grade 4) event that is determined to be related to
study vaccine
 
Chronic or recurrent use of systemic corticosteroids at immunosuppressive dose (see Section
6.8),and administration of antineoplastic and immunomodulating agents or radiotherapy
 
Withdrawal of consent to receive further study vaccination
 
Participant received any experimental medication (including experimental vaccines other than
the study vaccine) or receives a licensed/registered COVID-19 vaccine or treatment
 
Participant received an influenza vaccine (other than the one administered in the study) for
the current influenza season in the Northern Hemisphere
 
Participant 
previously  experienced 
TTS, including 
CVST 
or heparin-induced
thrombocytopenia (HIT)
 
Participant experiences capillary leakage syndrome after the first dose
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 from the study
 
Death
 
Repeated failure to comply with protocol requirements
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

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
62
Status: Approved,Date: 15 February 2022
is the withdrawal of consent, then no additional assessments are allowed, but an optional safety
visit could be offered.
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 consent
form apply 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 research (refer to Long-Term
Retention of Samples for Additional Future Research in Section 10.3.5, 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
To reduce the chances of a participant being deemed lost to follow-up, prior to randomization
attempts should be made to obtain contact information from each participant, eg, home, work, and
mobile telephone numbers and e-mail addresses for both the participant as well as appropriate
family members.
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 after multiple documented attempts.
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,
emails, fax, and, if necessary, a certified letter to the participant’s last known mailing address,
or local equivalent methods). Locator agencies may also be used as local regulations permit.
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.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
63
Status: Approved,Date: 15 February 2022
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.
8. 
STUDY ASSESSMENTS AND PROCEDURES
Overview
The Schedule of Activities summarizes the frequency and timing of safety, reactogenicity,
immunogenicity, and all other 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 and physical examination before blood draws.
If needed, assessments may be performed on  another day within the applicable visit window.
Actual dates and times of assessments must be recorded in the source document and the eCRF.
Participants will be provided a thermometer (to measure body temperature), ruler (to measure local
injection site reactions), and an electronic diary to record body temperature and solicited local (at
injection site) and systemic symptoms. The diary includes instructions on how to capture the data
and grading scales to assess severity of the signs and symptoms post-vaccination (reactogenicity).
The study staff is responsible for providing appropriate training to the participant to avoid missing
or incorrect data. The diary will be reviewed by the study personnel on an ongoing basis and the
investigator’s assessment of reactogenicity will be completed on the 7-day post vaccination visit
as indicated in the Schedule of Activities in Section 1.3.1). If there are ongoing symptoms, the
diary can be reviewed during the next visit. If a participant misses a vaccination, the diary covering
the period after the missed vaccination does not have to be completed.
The total blood volume to be collected from each participant throughout the study will be
approximately 90 mL. Repeat or unscheduled samples may be taken for safety reasons or for
technical issues with the samples. For participants who experience a suspected AESI, an additional
approximately 15 mL of blood will be collected for additional safety assessments, as indicated in
the Schedule of Activities in Section 1.3.2.
At each visit the participant will be asked if they have had a private/off-study COVID-19 test. If a
participant receives a positive SARS-CoV-2 result from a private/off-study test (whether through
PCR or serological testing), the event should be reported as medical history, AE or SAE if the
event meets the criteria for an SAE. The participant can continue in the study in accordance with
country and site level recommendations for COVID-19.
The study staff can recommend the participant informs their medical care provider. If there are no
local country recommendations for COVID-19, the sponsor recommends the participant self-
quarantines and does not come for a clinic visit until a negative PCR test could be obtained.
If the participant experiences signs or symptoms of COVID-19 after obtaining a positive SARS-
CoV-2 test result, they should contact the study site at the time of symptom onset for

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
64
Status: Approved,Date: 15 February 2022
recommendations on actions to follow for further care per local guidance. See section 8.3.1 on the
reporting periods of this event.
Visit Windows
Visit windows are provided in the Schedule of Activities in Section 1.3. The participant should be
encouraged to come on the day planned,but the visit window may be used.
The timings of the post-vaccination  visits will be determined relative to the actual day of the
corresponding vaccination.
If a vaccination window is missed, efforts will be made to vaccinate the participant as soon as
possible, even if out of the window. The timings of the post-vaccination visits will be determined
relative to the actual day of the corresponding vaccination, unless they overlap with other
scheduled visits, in which case the out of window visit should be documented in the source
documents. If the participant refuses to receive the second vaccination, the investigator is
encouraged to discuss it with the sponsor.
Screening
Screening may be performed within 28 days prior to the first study vaccination or on the day of
vaccination. If screening is performed on the day of vaccination, Visit 1 and Visit 2 will coincide
on Day 1. Screening must be completed and all eligibility criteria must be fulfilled prior to
randomization and vaccination.
Screening may be conducted in part via a sponsor- and Independent Ethics Committee/Institutional
Review Board (IRB/IEC)-pre-approved non-study-specific screening consent process, but only if
the relevant pre-screening tests are identical to the per protocol screening tests and are within
4 weeks prior to first vaccination. However, no study-specific procedures, other than these
pre-approved pre-screening assessments, will be performed until the participant has signed the
study-specific ICF. The -study-specific signed ICF date must be entered into the eCRF.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the eCRF or laboratory
requisition form. Refer to the Schedule of Activities in Section 1.3 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 and any Addenda for Ad26.COV2.S

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
65
Status: Approved,Date: 15 February 2022
 
Package insert for Ad26.COV2.S
 
Package inserts for Afluria Quadrivalent and Fluzone HD Quadrivalent
 
Thermometer
 
Ruler (to measure diameter of any erythema and swelling)
 
Pharmacy manual/IPPI/SIPPM
 
Laboratory manual and laboratory supplies
 
IWRS manual
 
eCRF completion guidelines
 
Sample ICF
 
Participant diary/ Site training manual
 
Contact information page(s)
8.1. 
Immunogenicity Assessments
No generally accepted immunological correlate of protection has been demonstrated for
SARS-CoV-2 to date. If a correlate or threshold for protection against COVID-19 is established in
terms of humoral immunity, then a statistical comparison to that correlate or threshold will
substitute NI testing to immune responses to vaccine at release, as outlined in the study statistical
analytical plan (SAP).
Venous blood samples will be collected for assessment of humoral immune responses. Sample
volumes and time points are detailed in the Schedule of Activities in Section 1.3.
If the participant is unable to complete the study but they did not withdraw consent,
immunogenicity samples will be taken at the early exit visit, but only if the early exit visit is at
least 10 days after the previous immunology blood draw. See the Schedule of Activities for further
details.
Humoral immunogenicity assays may include, but are not limited to, the assays summarized in
Table 4.
Table 4: 
Summary of Humoral Immunogenicity Assays
Assay 
Purpose
Humoral Immunogenicity
Primary endpoints
HI assay a 
Analysis of HI to influenza strains
SARS-CoV-2 binding antibodies (ELISA) 
Analysis of antibodies binding to SARS-CoV-2 or individual
SARS-CoV-2 proteins (eg, S protein)
Secondary endpoints
HI assay a 
Analysis of HI to influenza strains
SARS-CoV-2 binding antibodies (ELISA) 
Analysis of antibodies binding to SARS-CoV-2 or individual
SARS-CoV-2 proteins (eg, S protein)
Exploratory endpoints
HI assay 
Analysis of HI to influenza strains

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
66
Status: Approved,Date: 15 February 2022
SARS-CoV-2 binding antibodies (ELISA) 
Analysis of antibodies binding to SARS-CoV-2 or individual
SARS-CoV-2 proteins (eg, S protein)
SARS-CoV-2 neutralization (VNA) 
Analysis of neutralizing antibodies to the wild-type virus and/or
pseudovirion expressing S protein
Adenovirus neutralization 
Adenovirus 26 neutralization assay to evaluate neutralizing
antibody responses against the Ad26 vector
SARS-CoV-2 binding antibodies (ELISA 
and/or SARS-CoV-2 immunoglobulin assay)
Analysis of antibodies binding to the SARS-CoV-2 N protein
Functional and molecular antibody 
characterization  
Analysis of antibody characteristics including Fc-mediated viral
clearance, avidity, Fc characteristics, Ig subclass and IgG
isotype
ELISA = enzyme-linked immunosorbent assay; Fc = fragment crystallizable; HI assay = Hemagglutination inhibition
(HI) assay; Ig = immunoglobulin; S = Spike; SARS-CoV2 = severe acute respiratory syndrome coronavirus-2; VNA
= virus neutralization assay.
a. 
The HI antibody titers against influenza virus strains recommended by the World Health Organization (WHO)
for use in 2021-2022 in the Northern Hemisphere season will be measured using a validated HI assay platform.
8.2. 
Safety Assessments
Adverse events will be reported and followed by the investigator as specified in Section 8.3 and
Appendix 4 (Section 10.4).
Any clinically relevant changes occurring during the study period must be recorded on the AE
section of the eCRF.
Any clinically significant abnormalities will be followed by the investigator until resolution or
until a clinically stable condition is reached. For those abnormalities persisting at the end of the
study/early withdrawal, the outcome should be documented in the participant’s medical chart.
The study will include the following evaluations of safety and tolerability according to the time
points provided in the Schedule of Activities.
8.2.1. 
Physical Examinations
A full physical examination, including height and body weight, will be carried out at screening.
At all other visits, an abbreviated, symptom-directed examination might be performed by the
investigator based on any clinically relevant issues or symptoms, and medical history.
Symptom-directed physical examination may be repeated if deemed necessary by the investigator.
Physical examinations will be performed by the investigator or designated medically trained
clinician. Any clinically relevant abnormalities or changes in severity observed during the review
of body systems should be documented in the eCRF.
8.2.2. 
Vital Signs
Body temperature (oral route preferred, or in accordance with the local standard of care),
pulse/heart rate, respiratory rate, and blood pressure will be assessed.
Participants will utilize a diary to record body temperature measurements post-vaccination (see
Section 8).

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
67
Status: Approved,Date: 15 February 2022
Blood pressure and pulse/heart rate measurements will be assessed preferably supine with a
completely automated device. Manual techniques will be used only if an automated device is not
available.
Blood pressure and pulse/heart rate measurements should be preceded by at least 5 minutes of rest
in a quiet setting without distractions (eg, television, cell phones). Vital sign measurements are
recommended before blood sampling.
8.2.3. 
Clinical Safety Laboratory Assessments
Blood samples for clinical laboratory assessments (as detailed in Section 10.2, Appendix 2) will
be collected as described in the Schedule of Activities in Section 1.3.
In case ofa thrombotic event, thrombocytopenia, or TTS occurring post-vaccination, every effort
should be made to collect in a local hospital/laboratory the blood test results obtained to ensure
that the treating physician performs a rapid diagnosis and treatment.
This information should be reported through the TTS AESI form (see Section 10.8, Appendix 8)
electronically per instructions in the eCRF completion guidelines. In addition, every effort should
be made to collect blood samples from the participant for a platelet count (local laboratory or
substitute for local laboratory) and other applicable testing (central laboratory;eg, anti-PF4 see the
Schedule of Activities in Section 1.3.2 and Section 10.2, Appendix 2).
The investigator will review the laboratory test results performed locally and investigate potential
cases of thrombosis (per Appendix 9, Section 10.9) to assist the investigation of the AESI, and
document it in eDC.
See Section 8.3.6.1 for details on laboratory tests to be reported for post-vaccination
thrombocytopenia.
8.2.4. 
Pregnancy Testing
A urine pregnancy test for participants of childbearing potential will be performed at screening
and before each vaccination.
Additional pregnancy tests may be performed for participants of childbearing potential, 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. 
Adverse Events, Serious Adverse Events, Medically-attended Adverse
Events, Adverse Events of Special Interest, and Other Safety Reporting
Timely, accurate, and complete reporting and analysis of safety information, including AEs, SAEs,
MAAEs, AESIs, and PQCs, from clinical studies are crucial for the protection of participants,
investigators, and the sponsor, and are mandated by regulatory agencies worldwide.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
68
Status: Approved,Date: 15 February 2022
The sponsor has established Standard Operating Procedures in conformity with regulatory
requirements worldwide to ensure appropriate reporting of safety information; all clinical studies
conducted by the sponsor or its affiliates will be conducted in accordance with those procedures.
Adverse events 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, MAAEs, AESIs, and PQCs can be found in  Section 10.4,
Appendix 4.
8.3.1. 
Time Period and Frequency for Collecting Adverse Event, Medically-
attended Adverse Event, Adverse Event of Special Interest, and
Serious Adverse Event Information
All Adverse Events
Adverse events 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 first vaccination will be collected on the Medical History eCRF page as
pre-existing conditions.
Solicited AEs, collected through a diary, will be recorded for each vaccination from the time of
vaccination until 7 days post-vaccination (or until resolution).
All unsolicited AEs and special reporting situations, whether serious or non-serious, will be
reported for each vaccination from the time of vaccination until 28 days post-vaccination.
Unsolicited adverse events with the onset date outside the timeframe defined above (>28 days after
each study vaccination), which are ongoing on the day of the subsequent vaccination, should be
recorded as such.
At each visit the participant will be asked if they have had a private/off-study COVID-19 test. If a
participant receives a positive SARS-CoV-2 result from a private/off-study test during the study
period (whether through PCR or serological testing) the event should be reported as an AE or as
an SAE if the event meets the criteria of an SAE. The participant can continue in the study in
accordance with local country and site level recommendations for COVID-19. Any positive
SARS-CoV-2 result should be recorded in the eCRF. Previous SARS-CoV-2 infection should be
documented as medical history and does not preclude participation in the study.
All SAEs, AESIs, and AEs leading to discontinuation from the study/vaccination (regardless of
the causal relationship) are to be reported from the moment of first vaccination until the end of the
study, 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.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
69
Status: Approved,Date: 15 February 2022
MAAEs are defined as AEs with medically-attended visits including hospital, emergency room,
urgent care clinic, or other visits to or from medical personnel for any reason. Routine medical
visits for chronic comorbidities (or study visits) will not be considered medically-attended visits.
New onset of chronic diseases will be collected as part of the MAAEs. MAAEs are to be reported
for all participants throughout the study.
As long as the participant remains in the study, all AEs will be followed until resolved, until
clinically stable or the end of the study, as applicable. The investigator’s assessment of ongoing
AEs at the time of each participant’s last visit should be documented in the participant’s medical
chart.
Adverse Events of Special Interest
TTS is considered to be an AESI. Suspected AESIs (thrombotic events and thrombocytopenia
[defined as platelet count below 150,000/µL (Brighton Collaboration 2021)] post-vaccination) will
be recorded from the moment of vaccination until the end of the study/early withdrawal. An AESI
Adjudication Committee with appropriate expertise will be established to evaluate each suspected
AESI and determine whether it is a case of TTS (see Section 8.3.6).
All AESIs occurring during the study period must be reported to the sponsor by study site
personnel within 24 hours of their knowledge of the event and complete the procedures indicated
in the Schedule of Activities in Section 1.3.2.
Serious Adverse Events
All SAEs, as well as PQCs,occurring during the study must be reported to the appropriate sponsor
contact person by study site personnel within 24 hours of their knowledge of the event.
Serious adverse events, including those spontaneously reported to the investigator, must be
reported using an SAE form. The sponsor will evaluate any safety information that is
spontaneously reported by an investigator beyond the time frame specified in the protocol.
Information regarding SAEs will be transmitted to the sponsor using the SAE Form and Safety
Report Form of the CRF, which must be completed and reviewed by a physician from the study
site, and transmitted to the sponsor 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.
8.3.2. 
Method of Detecting Adverse Events, Medically-attended Adverse
Events, Adverse Events of Special Interest, and Serious Adverse
Events
Care will be taken not to introduce bias when detecting AEs, MAAEs, suspected AESIs,or SAEs.
Open-ended and nonleading verbal questioning of the participant is the preferred method to inquire
about AE occurrence.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
70
Status: Approved,Date: 15 February 2022
Solicited Adverse Events
Solicited AEs are used to assess the reactogenicity of the study vaccine and are predefined local
(at injection site) and systemic events for which the participant is specifically questioned and
which are noted by participants in their diary.
After each vaccination, participants will remain under observation at the study site for at least
15 minutes for presence of any acute reactions and solicited events.
In addition, participants will record solicited signs and symptoms in a diary for 7 days
post-vaccination  (or until resolution). All participants will be provided with a diary and
instructions on how to complete the diary (see Overview in Section 8).
Electronic diary information will be transferred from the e-diary source to the sponsor. After
review and verbal discussion of the initial electronic diary entries with the participant, the
investigator will complete his/her own assessment in the relevant sections of the CRF  (ie,
investigator’s assessment of reactogenicity). Once a solicited symptom from a diary is verified and
considered to be of severity Grade 1 or above, it will be recorded as a solicited adverse event per
FDA toxicity grading (See Appendix 6, Section 10.6).
Solicited Injection Site (Local) Adverse Events
Participants will be asked to note in the diary occurrences of local reaction at the injection site
namely pain/tenderness, erythema, swelling, and systemic reactions, namely fatigue, headache,
nausea, and myalgia daily for 7days post-vaccination (or until resolution, whatever happens first).
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 Adverse Events
Participants will be instructed on how to record daily temperature using a thermometer for home
use. Participants should record the temperature in the diary starting 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 one measurement is made on any given day, the highest temperature of that day should be
recorded.
Fever is defined as endogenous elevation of body temperature ≥38°C (100.4°F). (See Appendix 6,
Section 10.6.)
Unsolicited Adverse Events
Unsolicited AEs are all AEs for which the participant is not specifically questioned in the
participant diary.
Medically-attended Adverse Events
MAAEs are AEs with medically-attended visits including hospital, emergency room, urgent care
clinic, or other visits to or from medical personnel for any reason. New onset of chronic diseases

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
71
Status: Approved,Date: 15 February 2022
will be collected as part of the MAAEs. Routine study visits will not be considered medically-
attended visits.
Adverse Events of Special Interest
For details about AESIs, refer to Section 8.3.6.
8.3.3. 
Follow-up of Adverse Events, Medically-attended Adverse Events,
Adverse Events of Special Interest, and Serious Adverse Events
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, MAAE,
AESI, SAE, or PQC as fully as possible. This may include additional laboratory tests or
investigations, histopathological examinations, or consultation with other health care
professionals.
Adverse events, including pregnancy, will be followed by the investigator as specified in
Section 10.4, Appendix 4.
8.3.4. 
Regulatory Reporting Requirements for Serious Adverse Events
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 ofpregnancy 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.
Any participant who becomes pregnant during the study may continue study vaccination if the
investigator considers that the potential benefits outweigh any potential risks to the mother and
fetus and is allowed by local regulations.
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the
infant will be required.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
72
Status: Approved,Date: 15 February 2022
8.3.6. 
Adverse Events of Special Interest
AESIs are significant AEs that are judged to be of special interest because of clinical importance,
known or suspectedclass effects, or based on nonclinical signals. Adverse events of special interest
will be carefully monitored during the study by the sponsor.
Suspected AESIs must be reported to the sponsor within 24 hours of awareness irrespective of
seriousness (ie, serious and non-serious AEs) or causality following the procedure described above
for SAEs.
At baseline, safety blood samples will be collected. Whole blood samples will be used for a
complete blood counts (CBC), including platelet count (as part of a complete blood count), in a
local laboratory or substitute for local laboratory, depending on local feasibility towards
turnaround time of sample processing.
Serum and plasma samples will be collected and stored for potential future coagulation-related
testing in a central laboratory if the participant experiences an AESI (see Section 10.2,
Appendix 2).
Specific requirements for the AESI are described below.
8.3.6.1. 
Thrombosis with Thrombocytopenia Syndrome
As described in Section 2.3.1, TTS has been observed very rarely following vaccination with
Ad26.COV2.S 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 suspected case of TTS until further adjudication can be
performed. An AESI Adjudication Committee with appropriate expertise will be established to
evaluate each suspected AESI and determine whether it is a case of TTS. The investigator shall be
responsible for reporting any suspected AESI of TTS using the SAE form and the form detailed in
Section 10.8, Appendix 8.
A suspected TTS case is defined as:
 Thrombotic events: any thrombotic or thromboembolic event as detailed in Section 10.9,
Appendix 9
 Thrombocytopenia, defined as platelet count below 150,000/µL (Brighton Collaboration 2021)
post-vaccination
Symptoms, signs, or conditions suggestive of a thrombotic event should be recorded and reported
as a suspected 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
feasible.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
73
Status: Approved,Date: 15 February 2022
In the event of post-vaccination thrombocytopenia, study site personnel should report the absolute
value for the platelet count and the reference range for the laboratory test used in the eCRF. In the
event of thrombocytopenia post study vaccination, thrombotic events should be excluded (through
laboratory tests or imaging).
For either a thrombotic event or thrombocytopenia, testing for anti-PF4 should be performed at
the central laboratory or substitute local laboratory; repeat testing may be requested for
confirmation upon sponsor discretion.
Suspected AESIs will require enhanced data collection and evaluation (see Section 1.3.2). Every
effort should be made to report as much information as possible about the AESI to the sponsor in
a reasonable timeframe
If an event meets the criteria for an SAE (Section 10.4.1), it should be reported using the same
process as for other SAEs.
The form detailed in Section 10.8, Appendix 8is intended as a guide for assessment of the AESIs
to facilitate diagnosis and determine treatment options. 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.
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 efficacy and safety data is outlined
below. Specific details will be provided in the SAP.
9.1. 
Statistical Hypotheses
The study is successful if the below objectives are demonstrated:
 
NI of the humoral immune response as measured by the HI assay after concomitant
administration of Ad26.COV2.S vaccine and a seasonal standard-dose influenza vaccine
versus the administration of a seasonal quadrivalent standard-doseinfluenza vaccine alone,
28 days after the administration of a seasonal influenza vaccine.
AND
 
NI of the concomitant administration of Ad26.COV2.S vaccine and a seasonal quadrivalent
standard-doseinfluenza vaccine versus the administration of Ad26.COV2.S vaccine alone,
28 days after the administration of Ad26.COV2.S vaccine, in terms of humoral immune
response (ELISA)
Therefore, the following CIs will be calculated:
 
The 2-sided 95% CIs for the difference in log-transformed HI antibody titers against each of
the 4 seasonal influenza vaccine strains at 28 days after the administration of the quadrivalent
seasonal influenza vaccine between the Control and the CoAd group, and

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
74
Status: Approved,Date: 15 February 2022
 
The 2-sided 95% CIs for the difference in log-transformed ELISA titers at 28 days after the
administration of Ad26.COV2.S vaccine between the Control and the CoAd group
Only if the upper bound of the 2-sided 95% CI for the GMT ratio (Control group/CoAd group) of
the HI antibody titer for each of the 4 vaccine strains and for GMC for ELISA lies below 1.5, NI
of co-administration versus separate administration will be concluded for both vaccines (seasonal
influenza vaccine and Ad26.COV2.S vaccine). If 1 or more confidence limits for the GMT/GMC
ratio exceed 1.5, NI cannot be concluded.
The primary analysis will be performed when all participants have completed the 28 days after the
second study vaccination visit or discontinued earlier. No interim analyses will be performed.
For the high-dose groups, no formal hypothesis testing is planned.
No formal statistical testing of safety data is planned. Safety data will be analyzed descriptively
by vaccine group.
9.2. 
Sample Size Determination
Sample size calculations are performed under the following assumptions:
 
no effect of co-administration of Ad26.COV2.S vaccine and seasonal influenza vaccine on
the immune response against influenza as measured by HI antibody titers against the
4 influenza vaccine strains at 28 days after the administration of seasonal influenza vaccine
 
the use of Afluria Quadrivalent for standard-dose(adults ≥18 to <64 years of age and older
adults ≥65 years of age)
 
a standard deviation of 0.53 for the standard-dose at the log10 scale for HI antibody titers
against the 4 influenza vaccine strains at 28 days after the administration of seasonal influenza
vaccine (with or without Ad26.COV2.S)
 
no effect of co-administration of Ad26.COV2.S vaccine and seasonal influenza vaccine on
the immune response against SARS-CoV-2 as measured by S-ELISA at 28 days after the
administration of Ad26.COV2.S vaccine
 
a standard deviation of 0.50 at the log10 scale for S-ELISA at 28 days after the administration
of Ad26.COV2.S vaccine (with or without seasonal influenza vaccine)
 
a NI margin of 1.5
 
2-sided α of 5%
A total of approximately 305 (standard-dose) participants per group (total N 610) who have
completed a primary COVID-19 vaccine series are needed to have 97.45% power to show NI in
HI antibody titers for 1 influenza vaccine strain.
The sample size accounts for exclusions from the per protocol set (see Section 9.3), drop-outs and
missing samples.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
75
Status: Approved,Date: 15 February 2022
With this sample size, the overall power to show NI in HI antibody titers against each of the
4 influenza vaccine strains at 28 days after the administration of seasonal influenza vaccine as well
as NI in S-ELISA at 28 days after the administration of Ad26.COV2.S vaccine is at least 90%.
9.3. 
Populations for Analysis Sets
For purposes of analysis, the following populations are defined:
Full Analysis Set (FAS): All randomized participants with at least 1 documented study vaccine
administration, regardless of the occurrence of protocol deviations and vaccine type (seasonal
influenza, Ad26.COV2.S, or placebo). Analyses of safety and participant information will be
performed on the FAS.
Per Protocol Influenza Immunogenicity (PPII) Set: All randomized participants who received
Ad26.COV2.S vaccine in combination with a seasonal influenza vaccine for the co-administration
group and those who received a seasonal influenza vaccine alone for the control group, for whom
immunogenicity data are available for at least one of the influenza strains in the vaccine.
Samples taken after a participant experiences a major protocol deviation expected to impact the
immunogenicity outcomes will be excluded from the PPII analysis.
Per Protocol SARS-CoV-2 Immunogenicity (PPSI) Set: All randomized participants who
received Ad26.COV2.S vaccine in combination with seasonal influenza vaccine for the
co-administration group and Ad26.COV2.S vaccine alone for the control group and for whom
SARS-CoV-2 immunogenicity data are available. In addition, samples obtained at later timepoints
from participants after molecularly confirmed (viral RNA test result) natural SARS-CoV-2
infection will be excluded from the analysis.
Samples taken after a participant meets the criteria for a major protocol deviation expected to
impact the immunogenicity outcomes will be excluded from the PPSI analysis.
The list of major protocol deviations with impact in the immunogenicity analysis will be specified
in the SAP or major protocol violation criteria document. Both documents will be finalized before
database lock and unblinding.
The primary analysis set for analyses related to influenza immunogenicity is the PPII Set, the
primary analysis set for analyses related to SARS-CoV-2 immunogenicity is the PPSI Set. As a
sensitivity analysis, key tables may also be based on the FAS.
Note: Participants who have a self-confirmed history of SARS-CoV-2 infection at screening or
positive N-serology at baseline will be included in the analysis, but samples obtained after SARS-
CoV-2 (or influenza) infection during the study will be excluded.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
76
Status: Approved,Date: 15 February 2022
9.4. 
Statistical Analyses
The SAP  will be finalized prior to primary analysis database lock  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 the primary and key secondary endpoints.
9.4.1. 
General Considerations
The primary analysis will be performed when all participants have completed the 28 days after the
second study vaccination visit or discontinued earlier. No interim analyses will be performed.
9.4.2. 
Inferential Endpoints
The NI immunogenicity objectives will be assessed by calculating:
 
the 2-sided 95% CIs for the difference in log-transformed HI antibody titers against each of
the 4 influenza vaccine strains at 28 days after the administration of the seasonal influenza
vaccine between the Control and the CoAd group for the standard-dose.
 
the 2-sided 95% CIs for the difference in log-transformed S-ELISA titers at 28 days after the
administration of Ad26.COV2.S vaccine between the Control and the CoAd group for the
standard-dose.
For HI antibody titers against each of the 4 influenza vaccine strains and for S-ELISA titers, an
analysis of variance (ANOVA) model will be fitted with the respective titers as dependent variable
and group (Control or CoAd), age category (as stratified), previous SARS-CoV-2 vaccination (as
stratified),and baseline S-ELISA titers as independent variable. Based on these ANOVA models,
the CIs around the difference will be calculated and will be back transformed (by exponentiation)
to CIs around a GMC or GMT ratio (Control group/CoAd group), respectively, and compared to
the NI margin of 1.5.
Only if the upper bound of the 2-sided 95% CI for the GMT or GMC ratio (Control group/CoAd
group), respectively,of the HI antibody titer for each of the 4 vaccine strains and for S-ELISA lies
below 1.5, NI of co-administration versus separate administration will be concluded for both
vaccines (seasonal influenza vaccine and Ad26.COV2.S vaccine). If 1 or more confidence limits
for the GMT or GMC ratio exceed 1.5, non-inferiority cannot be concluded.
For immunogenicity, baseline is considered as the last assessment pre-vaccination  (ie, it
corresponds to Day 1 for CoAd groups or influenza vaccine alone, or to Day 29 for Ad26.COV2.S
vaccine). In a sensitivity analysis, different variances between the groups will be allowed.
Therefore, the CIs will be calculated via Welch’s ANOVA.
The assessment of the primary endpoints will be performed on individuals who have been
previously vaccinated with different types of COVID-19 vaccines. This factor brings a level of
variability of immune responses that is unknown.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
77
Status: Approved,Date: 15 February 2022
9.4.3. 
Other Secondary Endpoints
For either the standard-dose or high-dose, seroconversion is defined for each of the 4 influenza
vaccine strains at 28 days after the administration of a seasonal influenza vaccine:
 HI titer ≥1:40 in participants with a pre-vaccination HI titer of <1:10, or
 a ≥4-fold HI titer increase in participants with a pre-vaccination HI titer of ≥1:10
Seroprotection is defined for each of the 4 influenza vaccine strains as HI titer ≥1:40 at 28 days
after the administration of a seasonal influenza vaccine.
The difference in proportions of seroconverted and seroprotected participants between the Control
and the CoAd group will be estimated together with the 2-sided 95% CIs (calculated using
Wilson’s score method).
Serostatus at screening will be assigned according to medical records or participants' verbal
reporting. For the analysis, serostatus will be based on binding antibodies. If a participant has
detectable S-ELISA and/or N-ELISA above the limit of quantification, then the individual is
considered seropositive. The confirmation of serostatus will be performed with a sensitive S-
ELISA and N-ELISA assay. Seropositive participants are defined as previously vaccinated
individuals (ie, Vaxzevria [AstraZeneca], Comirnaty [Pfizer-BioNTech], SpikeVax [Moderna],
and Ad26.COV2-S [Janssen]), regardless of previous SARS-CoV2 infection. The following will
be presented descriptively for the secondary analyses:
 
Humoral immune response as measured by the HI assay after concomitant administration of
Ad26.COV2.S vaccine and a seasonal quadrivalent high-dose influenza vaccine versus the
administration of a seasonal quadrivalent high-doseinfluenza vaccine alone, 28 days after the
administration of a seasonal influenza vaccine.
 
Humoral immune response (ELISA) following concomitant administration of Ad26.COV2.S
vaccine and a seasonal quadrivalent high-doseinfluenza vaccine versus the administration of
Ad26.COV2.S vaccine alone, 28days after the administration of Ad26.COV2.S vaccine.
 
Humoral immune response as measured by the HI assay after concomitant administration of
Ad26.COV2.S vaccine and a seasonal quadrivalent high-dose influenza vaccine versus the
administration of a seasonal quadrivalent high-doseinfluenza vaccine alone, 28 days after the
administration of a seasonal influenza vaccine in COVID-19 vaccine-naïve individuals.
 
Humoral immune response (ELISA) following concomitant administration of Ad26.COV2.S
vaccine and a seasonal quadrivalent high-doseinfluenza vaccine versus the administration of
Ad26.COV2.S vaccine alone, 28days after the administration of Ad26.COV2.S vaccine in
COVID-19 vaccine-naïve individuals.
 
Humoral immune response as measured by the HI assay after concomitant administration of
Ad26.COV2.S vaccine and a seasonal quadrivalent standard-doseinfluenza vaccine versus
the administration of a seasonal quadrivalent standard-doseinfluenza vaccine alone, 28 days
after the administration of a seasonal influenza vaccine in COVID-19 vaccine-naïve
individuals.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
78
Status: Approved,Date: 15 February 2022
 
Humoral immune response (ELISA) following concomitant administration of Ad26.COV2.S
vaccine and a seasonal quadrivalent standard-dose influenza vaccine versus the
administration of Ad26.COV2.S vaccine alone, 28days after the administration of
Ad26.COV2.S vaccine in COVID-19 vaccine-naïve individuals.
Additionally, HI antibody titers and S-ELISA titers will be summarized with descriptive statistics.
Descriptive statistics (geometric mean and 95% CI) of the actual values will be calculated for
continuous immunogenicity parameters at all timepoints. Geometric mean fold increases from
baseline and corresponding 95% CIs might additionally be calculated. Graphical representations
of immunogenicity parameters will be created as applicable.
Additional characterization of these participants will be included in the SAP.For categorical
variables, frequency tables will be presented. Difference in proportions and corresponding CIs
may be calculated where appropriate.
9.4.4. 
Exploratory Endpoints
Exploratory endpoint analyses will be detailed in the SAP.
9.4.5. 
Safety Analyses
No formal statistical testing of safety data is planned. All safety data will be analyzed descriptively
by group. All safety analyses will be based on the FAS.
Adverse Events
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 vaccination phase (ie, AEs occurring after vaccination up to 28 days post-vaccination), and
all SAEs/MAAEs/AESIs will be included in the analysis. (S)AEs caused by molecularly confirmed
SARS-CoV-2 infection will be removed at the analysis level from the (S)AE listings and tables
and presented separately. For each AE, the percentage of participants who experience at least
1 occurrence of the given event will be summarized by vaccine group.
Summaries, listings, datasets, or participant narratives may be provided, as appropriate, for those
participants who die, who discontinue study vaccine due to an AE, or who experience a severe AE,
an AESI, or an SAE.
Solicited local (at injection site) and systemic AEs will be summarized descriptively. The number
and percentages of participants with at least one solicited local (at injection site) or systemic AE
will be presented. The frequencies by vaccine group as well as frequencies according to severity
and duration will be described for solicited AEs. Frequencies of unsolicited AEs, separately for all
and vaccination-related only, will be presented by System Organ Class and preferred term, while
those of solicited AEs will be presented only by preferred term.
Clinical Laboratory Tests
Laboratory data (abnormal or graded, when available) will be listed and/or tabulated by participant
and time point.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
79
Status: Approved,Date: 15 February 2022
Vital Signs
Vital signs including temperature, pulse/heart rate, respiratory rate, and blood pressure (systolic
and diastolic) will be summarized over time, using descriptive statistics and/or graphically. The
percentage of participants with values beyond clinically important limits will be summarized.
Physical Examinations
Physical examination findings will be summarized at baseline. Physical examination abnormal
findings will be listed.
9.4.6. 
Other Analyses
The primary analysis ofsafety and immunogenicity will be performed when all participants have
completed the 28 days after the second study vaccination visit or discontinued earlier. The primary
analysis will be performed based on sponsor’s unblinded data (sponsor, study site personnel and
participants will remain blinded during the treatment phase up to the database lock ). No interim
analyses will be performed.
A final analysis will be performed when all participants have completed the 6 month follow-up
period after the second vaccination or discontinued earlier.
9.5. 
Interim Analysis
Not applicable.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
80
Status: Approved,Date: 15 February 2022
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Abbreviations and Definitions
ACIP  
Advisory Committee on Immunization Practices
Ad26 
adenovirus type 26
ADCC  
antibody-dependent cell-mediated cytotoxicity
AdVAC® 
adenoviral vaccine (vector platform)
AE 
adverse event
AESI 
adverse event of special interest
ANOVA  
analysis of variance
aPTT  
activated partial thromboplastin time
AR  
adverse reaction
ART  
anti-retroviral treatment
BMI 
body mass index
CD  
cluster of differentiation
CDC  
Centers for Disease Control and Prevention
CI 
confidence interval
CoAd 
co-administration
COVID-19 
coronavirus disease-2019
CTLA-4 
cytotoxic T-lymphocyte-associated antigen 4
CVST  
cerebral venous sinus thrombosis
DVT  
deep vein thrombosis
eCRF  
electronic case report form
eDC  
electronic data capture
EEA  
European Economic Area
ELISA  
enzyme-linked immunosorbent assay
EMA  
European Medicines Agency
EU  
European Union
EUA  
Emergency Use Authorization
FAS  
full analysis set
Fc 
crystallizable fragment
FDA  
Food and Drug Administration
FOIA  
Freedom of Information Act
GCP  
Good Clinical Practice
GMC  
geometric mean concentration
GMT  
geometric mean titer
HA  
hemagglutinin
HAI 
hemagglutinin inhibition assay
HCP  
health care professional
HI 
hemagglutination inhibition
HIT  
heparin-induced thrombocytopenia
HITT  
heparin-induced thrombocytopenia with thrombosis
HIV  
human immunodeficiency virus
HPV  
human papillomavirus
IB  
investigator's brochure
ICF  
informed consent form
ICH  
International Conference on Harmonisation
ICMJE 
International Committee of Medical Journal Editors
ICU  
intensive care unit
IEC  
Independent Ethics Committee
IFN-γ 
interferon gamma
Ig 
immunoglobulin
IM  
intramuscular
IND  
Investigational New Drug
IPPI 
Investigational Product Preparation Instructions
IRB  
Institutional Review Board
IWRS  
interactive web response system

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
81
Status: Approved,Date: 15 February 2022
MAAE 
Medically-attended Adverse Events
MABS  
Monoclonal Antibodies
MedDRA  
Medical Dictionary for Regulatory Activities
NHP  
non-human primate
NI 
non-inferiority
PCR  
polymerase chain reaction
PCC  
protocol clarification communication
PD-1 
programmed cell death protein 1
PE 
pulmonary embolism
PF-4 
platelet factor 4
PI 
principal investigator
PPI 
per protocol immunogenicity
PPII 
per protocol influenza immunogenicity
PPSI 
per protocol SARS-CoV-2 immunogenicity
PQC  
product quality complaint
PT  
prothombin time
RNA  
ribonucleic acid
RSV  
respiratory syncytial virus
RT-PCR  
real-time reverse-transcriptase polymerase chain reaction
S 
Spike
SAE 
serious adverse event
SAP  
statistical analysis plan
SARS-CoV(-2) 
severe acute respiratory syndrome coronavirus(-2)
SIPPM  
site investigational product and procedures manual
SUSAR  
suspected unexpected serious adverse reaction
Th 
T helper
TNF-α 
tumor necrosis factor alpha
TTS  
thrombosis with thrombocytopenia syndrome
US  
United States
VAED  
vaccine-associated enhanced disease
VAERD  
vaccine-associated enhanced respiratory disease
VAERS  
Vaccine Adverse Event Reporting System
VNA  
virus neutralization assay
vp 
virus particle
VTE 
venous thromboembolism
WBC  
white blood cell
WHO  
World Health Organization
Definitions of Terms
COVID-19 
COVID-19 is the disease caused by the virus SARS-CoV-2. COVID-19 refers to
SARS-CoV-2 infection with symptoms, and can range from mild to severe disease, the latter
including pneumonia, severe acute respiratory syndrome, multi-organ failure, and death
(FDA 2020, FDA 2021a).
e-Diary  
The electronic technology used to record solicited signs and symptoms by the participants.
Study Name 
Convention  
In this document, studies are referred to using the short study name (preceding letters and
final digits of the study identifier) only (eg, COV2007).
Electronic source 
system  
Contains data traditionally maintained in a hospital or clinic record to document medical
care or data recorded in a CRF as determined by the protocol. Data in this system may be
considered source documentation.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
83
Status: Approved,Date: 15 February 2022
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 International Council for Harmonisation (ICH) guidelines on Good Clinical
Practice (GCP), and applicable regulatory and country-specific requirements.
Good Clinical Practice is 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 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.
In situations where a departure from the protocol is unavoidable during the study, 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
agree on an appropriate course of action. The data recorded in the eCRF and source documents

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
84
Status: Approved,Date: 15 February 2022
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 subinvestigators
 
Documentation of subinvestigator 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
 
Local laboratory documentation demonstrating competence and test reliability
(eg,accreditation/license), if applicable

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
85
Status: Approved,Date: 15 February 2022
Independent Ethics Committee or Institutional Review Board
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
study
 
Deviations from or changes to the protocol to eliminate immediate hazards to the participants

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
86
Status: Approved,Date: 15 February 2022
 
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.
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.
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

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
87
Status: Approved,Date: 15 February 2022
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 his or her study physician to recontact the participant for the purpose
ofobtaining 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 his or her 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 his or her personal data
and the right to request rectification of any data that are not correct or complete. Reasonable steps
will 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.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
88
Status: Approved,Date: 15 February 2022
Exploratory research is not conducted under standards appropriate for the return of data to
participants. In addition, the sponsor cannot make decisions as to the significance of any findings
resulting from exploratory research. Therefore, exploratory research data will not be returned to
participants or investigators, unless required by law or local regulations. Privacy and
confidentiality of data generated in the future on stored samples will be protected by the same
standards applicable to all other clinical data.
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.COV2.S, to understand
SARS-CoV2.S infection, to understand differential intervention  responders, and to develop
tests/assays related to Ad26-based vaccines, including Ad26.COV2.S  and SARS-CoV2.S
infection. The research may begin at any time during the study or the post study storage period.
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).
10.3.6. 
Committees Structure
AESI Adjudication Committee
An AESI Adjudication Committee with appropriate expertise will be established to evaluate each
suspected AESI and determine whether it is a case of TTS (see Section 8.3.6). A Charter will be
developed to describe the roles and responsibilities of the Committee.
10.3.7. 
Publication Policy/Dissemination of Clinical Study Data
All information, including but not limited to information regarding Ad26.COV2.S 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, including exploratory research 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 of Ad26.COV2.S, 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 exploratory

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
89
Status: Approved,Date: 15 February 2022
analyses 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 18months 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

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
90
Status: Approved,Date: 15 February 2022
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 data relating to the study must be recorded in the eCRF. 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.
All participative measurements (eg, questionnaires) will be completed by the same individual who
made the initial baseline determinations whenever possible.
If necessary, queries will be generated in the electronic data capture (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 efficacy parameters as required by the
protocol; record of all AEs and follow-up of AEs; concomitant medication; intervention
receipt/dispensing/return records; study vaccine administration information; and date of study
completion and reason for early discontinuation of study vaccine or withdrawal from the study, if
applicable.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
91
Status: Approved,Date: 15 February 2022
The author of an entry in the source documents should be identifiable.
Participant- and investigator-completed scales and assessments designated by the sponsor (ie,
diary to record solicited AEs)will be recordedand will be considered source data. The participant’s
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. These data are 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.
10.3.11. 
Monitoring
The sponsor will use a combination of monitoring techniques (central, remote, and/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 the data entered into the eCRF with the source documents
(eg,hospital/clinic/physician’s office medical records). 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.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
92
Status: Approved,Date: 15 February 2022
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
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 and available
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 he or she has
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 site open is considered the first act of recruitment and it becomes the study start date.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
93
Status: Approved,Date: 15 February 2022
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
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

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
94
Status: Approved,Date: 15 February 2022
10.4. Appendix 4: Adverse Events, Serious Adverse Events, Adverse Events of
Special Interest, Product Quality Complaints, and Other Safety Reporting:
Definitions and Procedures for Recording, Evaluating, Follow-up, and
Reporting
10.4.1. 
Adverse Event Definitions and Classifications
Adverse Event
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 intervention. 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 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.
Any respiratory tract infection that is not due to SARS-CoV-2 infection will be reported as an AE
if it occurs between the time of any vaccination through the following 28 days. Any respiratory
tract infection recorded as an AE in the eCRF will be excluded from any AE analysis if the
molecular test is subsequently found to be positive for SARS-CoV-2. Respiratory tract infections
arising from SARS-CoV-2 infection will not be reported as (S)AEs in the Clinical Study Report
but will be tabulated separately. In general, any (S)AEs caused by molecularly confirmed
SARS-CoV-2 infection will be removed at the analysis level from the (S)AE listings and tables
and presented separately. In general, (S)AEs caused by molecularly confirmed SARS-CoV-2
infection will be removed at the analysis level from the (S)AE listings and tables and presented
separately.
Note: For time period of sponsor’s AE collection, see All Adverse Events under Section 8.3.1.
Serious Adverse Event
An SAE based on ICH and EU 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

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
95
Status: Approved,Date: 15 February 2022
 
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
as a serious and unexpected suspected adverse reaction even if it is a component of the study
endpoint (eg, all-cause mortality).
Unlisted (Unexpected) Adverse Event/Reference Safety Information
An AE is considered unlisted if the nature or severity is not consistent with the applicable product
reference safety information. For Ad26.COV2.S, the expectedness of an AE will be determined
by whether or not it is listed in the IB.
10.4.2. 
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 adverse events at the injection site (local) will be considered related to
the study vaccine administration.
10.4.3. 
Severity Criteria
All AEs and laboratory data will be coded for severity using a modified version of the FDA grading
table, based on version  of September 2007 (US DHHS 2007), included in Section  10.6,
Appendix 6.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
96
Status: Approved,Date: 15 February 2022
For AEs 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 emergency room
visit or hospitalization
The severity of solicited signs and symptoms will be graded in the e-Diary by the participant based
on the severity assessment provided in the e-Diary and then verified by the investigator using the
toxicity grading scale in Section 10.6, Appendix 6. (Note: severity of the measured events will be
derived from the diameter [for erythema and swelling] and the temperature measurements [for
fever]).
10.4.4. 
Special Reporting Situations
Safety events of interest on 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
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 CRF.
10.4.5. 
Procedures
All Adverse Events
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,
runny nose, sneezing, sore throat, and head congestion should be reported as "upper respiratory

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
97
Status: Approved,Date: 15 February 2022
infection"). Investigators must record in the eCRF their opinion concerning the relationship of the
AE to study therapy. 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 24hour 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
Serious Adverse Events
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, whether or not the event is expected or associated
with the study vaccine, is considered an SAE.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
98
Status: Approved,Date: 15 February 2022
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 will be carefully monitored during the study by the sponsor. Suspected AESIs must be
reported to the sponsor within 24 hours of awareness irrespective of seriousness (ie, serious and
non-serious AEs) or causality assessment, following the procedure described above for SAEs and
will require enhanced data collection.
10.4.6. 
Product Quality Complaint 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.
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.
10.4.7. 
Contacting Sponsor Regarding Safety, Including Product Quality
The names (and corresponding telephone numbers) of the individuals who should be contacted
regarding safety issues, PQC,or questions regarding the study are listed in the Contact Information
page(s), which will be provided as a separate document.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
99
Status: Approved,Date: 15 February 2022
10.5. Appendix 5: Contraceptive Guidance and Collection of Pregnancy
Information
Participants must follow contraceptive measures as outlined in Section 5.1. Pregnancy information
will be collected and reported as noted in Section 8.3.5, Pregnancy and Section 10.4.
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 total hysterectomy, or bilateral salpingectomy, or
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.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
100
Status: Approved,Date: 15 February 2022
10.6. Appendix 6: Toxicity Grading Scale
Adapted from the FDA Guidance document “Toxicity Grading Scale for Healthy Adult and
Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials” (September 2007) (US
DHHS 2007).
A: Tables for Clinical Abnormalities
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.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
101
Status: Approved,Date: 15 February 2022
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.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
102
Status: Approved,Date: 15 February 2022
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.
B: Tables for Laboratory Abnormalities
Laboratory tests may be performed during routine medical care and assessment of AEs or other
medical events based on the investigator’s judgment.
The laboratory values provided in the tables below serve as guidelines and are dependent upon
institutional normal parameters. Institutional normal reference ranges should be provided to
demonstrate that they are appropriate.
Serum * 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life
Threatening
(Grade 4)**
Sodium –Hyponatremia mEq/L 
132 –134  
130 –131 
125 –129 
<125
Sodium –Hypernatremia mEq/L 
144 –145 
146 –147 
148 –150 
>150
Potassium –Hyperkalemia mEq/L 
5.1 –5.2 
5.3 –5.4 
5.5 –5.6 
>5.6
Potassium –Hypokalemia mEq/L 
3.5 –3.6 
3.3 –3.4 
3.1 –3.2 
<3.1
Glucose –Hypoglycemia mg/dL 
65 –69 
55 –64 
45 –54 
<45
Glucose –Hyperglycemia 
  Fasting mg/dL 
  Random –mg/dL 
100 –110 
110 –125 
111 –125 
126 –200 
>125 
>200 
Insulin
requirements or
hyperosmolar
coma
Blood Urea Nitrogen  
(BUN) mg/dL
23 –26 
27 –31 
> 31 
Requires dialysis
Creatinine –mg/dL 
1.5 –1.7 
1.8 –2.0 
2.1 –2.5 
>2.5 or requires
dialysis
Calcium –hypocalcemia mg/dL 
8.0 –8.4 
7.5 –7.9 
7.0 –7.4 
<7.0
Calcium –hypercalcemia mg/dL 
10.5 –11.0 
11.1 –11.5 
11.6 –12.0 
>12.0
Magnesium –hypomagnesemia mg/dL 
1.3 –1.5 
1.1 –1.2 
0.9 –1.0 
<0.9
Phosphorous –hypophosphatemia mg/dL 2.3 –2.5 
2.0 –2.2 
1.6 –1.9 
<1.6
Creatine phosphokinase 
(CPK) –mg/dL 
1.25 –1.5 x  
ULN***
1.6 –3.0 x ULN  3.1 –10 x ULN  
>10 x ULN
Albumin –Hypoalbuminemia g/dL 
2.8 –3.1 
2.5 –2.7 
< 2.5 
--
Total Protein –Hypoproteinemia g/dL 
5.5 –6.0 
5.0 –5.4 
< 5.0 
--
Alkaline phosphate – 
increase by factor
1.1 –2.0 x ULN  2.1 –3.0 x ULN  3.1 –10 x ULN  >10 x ULN
Liver Function Tests –ALT, AST  
increase by factor
1.1 –2.5 x ULN  2.6 –5.0 x ULN  5.1 –10 x ULN  >10 x ULN
Bilirubin –when accompanied 
by any increase in Liver Function Test 
increase by factor
1.1 –1.25 x 
ULN  
1.26 –1.5 x 
ULN  
1.51 –1.75 x 
ULN
>1.75 x ULN

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
103
Status: Approved,Date: 15 February 2022
Bilirubin –when Liver Function Test 
is normal; increase by factor
1.1 –1.5 x ULN  1.6 –2.0 x ULN  2.0 –3.0 x ULN  >3.0 x ULN
Cholesterol 
201 –210 
211 –225 
> 226 
---
Pancreatic enzymes –amylase, lipase 
1.1 –1.5 x ULN  1.6 –2.0 x ULN  2.1 –5.0 x ULN  >5.0 x ULN
* 
The laboratory values provided in the tables serve as guidelines and are dependent upon institutional normal
parameters. Institutional normal reference ranges should be provided to demonstrate that they are appropriate.
** The clinical signs or symptoms associated with laboratory abnormalities might result in characterization of the
laboratory abnormalities as potentially life-threatening (Grade 4). For example. a low sodium value that falls
within a Grade 3 parameter (125-129 mEq/L) should be recorded as a Grade 4 hyponatremia event if the
participant had a new seizure associated with the low sodium value.
*** ULN is the upper limit of the normal range.
Hematology* 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life
Threatening
(Grade 4)
Hemoglobin (Female) - gm/dL 
11.0 –12.0 
9.5 –10.9 
8.0 –9.4 
<8.0
Hemoglobin (Female) 
change from baseline value - gm/dL
Any decrease –1.5 1.6 –2.0 
2.1 –5.0 
>5.0
Hemoglobin (Male) - gm/dL 
12.5 –13.5 
10.5 –12.4 
8.5 –10.4 
<8.5
Hemoglobin (Male) 
change from baseline value –gm/dL
Any decrease –1.5 1.6 –2.0 
2.1 –5.0 
>5.0
WBC Increase - cell/mm3 
10,800 –15,000 
15,001 –20,000 20,001 –25, 000 >25,000
WBC Decrease - cell/mm3 
2,500 –3,500 
1,500 –2,499 
1,000 –1,499 
<1,000
Lymphocytes Decrease - cell/mm3 750 –1,000 
500 –749 
250 –499 
<250
Neutrophils Decrease - cell/mm3 
1,500 –2,000 
1,000 –1,499 
500 –999 
<500
Eosinophils - cell/mm3 
650 –1500 
1501 - 5000 
> 5000 
Hypereosinophilic
Platelets Decreased - cell/mm3 
125,000 –140,000 100,000 – 
124,000
25,000 –99,000 
<25,000
PT –increase by factor 
(prothrombin time) 
1.0 –1.10 x  
ULN**  
1.11 –1.20 x 
ULN
1.21 –1.25 x ULN >1.25 ULN
PTT –increase by factor 
(partial thromboplastin time) 
1.0 –1.2 x ULN  
1.21 –1.4 x 
ULN
1.41 –1.5 x ULN  > 1.5 x ULN
Fibrinogen increase - mg/dL 
400 –500 
501 –600 
> 600 
--
Fibrinogen decrease - mg/dL 
150 –200 
125 –149 
100 –124 
<100 or associated
with gross bleeding
or disseminated
intravascular
coagulation (DIC)
* The laboratory values provided in the tables serve as guidelines and are dependent upon institutional normal
parameters. Institutional normal reference ranges should be provided to demonstrate that they are appropriate.
** ULN is the upper limit of the normal range.
Urine * 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life-Threatening
(Grade 4)
Protein  
Trace 
1+  
2+ 
Hospitalization or
dialysis
Glucose 
Trace 
1+  
2+ 
Hospitalization for hyperglycemia
Blood (microscopic) – 
red blood cells per 
high power field (rbc/hpf) 
1 - 10 
11 –50 
> 50 and/or 
gross 
blood 
Hospitalization or
packed red blood cells (PRBC)
transfusion
* The laboratory values provided in the tables serve as guidelines and are dependent upon institutional normal
parameters. Institutional normal reference ranges should be provided to demonstrate that they are appropriate.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
104
Status: Approved,Date: 15 February 2022
10.7. Appendix 7: Summary of Guidance from CDC Websitea on Underlying
Medical Conditions That Lead or Might Lead to Increased Risk for Severe
Illness From COVID-19
Adults of any age with certain underlying medical conditions are at increased risk for severe
illness from COVID-19: Severe illness from COVID-19 is defined as hospitalization, admission
to the ICU, intubation or mechanical ventilation, or death.
Adults of any age with the following conditions can  be more likely to get severely ill from
COVID-19b:
 Cancer
 Chronic kidney disease
 Chronic lung diseases, including COPD (chronic obstructive pulmonary disease), asthma
(moderate to severe), interstitial lung disease, cystic fibrosis, and pulmonary hypertension
 Dementia or other neurological conditions
 Diabetes (Type 1 and Type 2)
 Down syndrome
 Heart conditions (such as heart failure, coronary artery disease, cardiomyopathies, or
hypertension)
 HIV infection
 Immunocompromised state (weakened immune system)
 Liver disease
 Overweight (BMI of >25 kg/m2 but <30 kg/m2), obesity (BMI of 30 kg/m2 but
<40 kg/m2), or severe obesity (BMI ≥40 kg/m2)
 Pregnancy
 Sickle cell disease or thalassemia
 Smoking (current and former)
 Solid organ or blood stem cell transplant
 Stroke or cerebrovascular disease, which affects blood flow to the brain
 Substance use disorders
aSource: 
https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-
conditions.html?CDC AA refVal=https%3A%2F%2Fwww.cdc.gov%2 Fcoronavirus% 2F2019-ncov%2Fneed-
extra-precautions%2Fgroups-at-higher-risk.html. Updated 13 May 2021. Accessed: 8 June 2021.
b The list of underlying medical conditions is not exhaustive and only includes conditions with sufficient evidence to
draw conclusions.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
105
Status: Approved,Date: 15 February 2022
10.8. Appendix 8: TTS AESI Form
The form below represents the type of information that may be collected in case of a suspected
AESI in order to help adjudicate whether the event is a case of TTS. Additional data may be
requested by the sponsor for investigation of the event.
Adverse Event of Special Interest Questionnaire (AESIQ) for Thromboembolism with
Thrombocytopenia Syndrome
Date of Report: 
[dd-MMM-yyyy]
1. Adverse Event Description
Participant’s clinical signs and symptoms
Leg/Calf Oedema 
Pain in Leg/Calf 
Haemoptysis
Dyspnoea 
Chest Pain/Discomfort 
Syncope
Tachypnoea 
Tachycardia 
Cough
Loss of consciousness 
Headache 
Seizure
Visual impairment 
Weakness 
Impaired speech
Confusional state 
Paresthesia 
Gait disturbance
Other symptoms:
Was patient on VTE prophylaxis? 
No 
Yes, details:
2. Medical History and Concurrent Conditions
Provide details:
Is the participant overweight or have obesity? 
No 
Yes
  If available, please provide: 
Height 
Weight 
BMI
Does the participant have a sedentary lifestylea? 
No 
Yes –details:
Has the participant been in a sitting position for long 
periods of time prior to the event?
No 
Yes –details:
Is there a current history of smoking (active or passive)? 
No 
Yes –details:
Is there a prior history of smoking (active or passive)? 
No 
Yes –details:
Does the participant have a prior history of:
Cancer 
No 
Yes –details:
Autoimmune disease (i.e., collagen-vascular disease, 
inflammatory bowel disease) or myeloproliferative
disease?
No 
Yes –details:
Clotting disorder or a hypercoagulable state 
No 
Yes –details:
Varicose veins 
No 
Yes –details:
Trauma to the involved leg or pelvis 
No 
Yes –details:
DVT/PE or other VTE  
No 
Yes –details:
Blood transfusion  
No 
Yes –details:
Cardiovascular disease 
No 
Yes –details:
a Any waking behavior characterized by an energy expenditure less than or equal to 1.5 metabolic equivalents (METs),
while in a sitting, reclining or lying posture

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
106
Status: Approved,Date: 15 February 2022
If the participant has experienced a previous thrombotic
event, address the following:
  1. Date (or estimate) 2. Provide brief description of the
nature of the event 3. Provide brief description of the
treatment of the event 4. Note any residual manifestations
of the event.
If the patient has experienced more than one previous
thrombotic event, please list other events.
Was the (female) participant pregnant at the time of 
event?
No 
Yes –details:
Does the participant has any of genetic risk factors:
Dysfibrinogenemia 
Antiphospholipid syndrome 
Factor V Leiden mutation
Protein C or S deficiency  
Elevated factor VIII levels 
Anti-thrombin deficiency
Hyperhomocysteinemia 
Prothrombin gene mutation 
Blood-clotting disorder
Thrombophilia
Does the participant have any acquired risk factors:
Reduced mobility (paralysis, paresis, travel etc.) 
Recent surgery
Indwelling central venous catheters 
Recent trauma
Recent discontinuation of anticoagulants (e.g., heparin, warfarin, DOACs)
Hormone replacement therapy (including contraceptives)
Phlebitis 
Lupus
Inflammatory bowel disease 
Myeloproliferative disorders
Diabetes mellitus 
Hyperlipidemia
Hypertension 
Dehydration
Other significant medical co-morbidities or risk factors for DVT, specify:
If yes to any of the above, provide details:
Provide Well’s score, if calculated:
3. Relevant results of diagnostic tests including laboratory tests, imaging, biopsies, etc. (Note
the levels/conclusion, date performed, normal ranges as well as any other details. Alternatively,
attach full reports of the diagnostic tests.)
Diagnostic Test 
Results at baseline or prior 
to use of product (Include 
date and value/details) 
Test results after use of
product (Include date
and value/details)
CBC with smear (microscopic
evaluation)
ESR
Platelet count
Antibodies to platelet factor 4
(PF4)
Fibrinogen levels
Clauss fibrinogen assay

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
107
Status: Approved,Date: 15 February 2022
Diagnostic Test 
Results at baseline or prior 
to use of product (Include 
date and value/details) 
Test results after use of
product (Include date
and value/details)
D-Dimer
Clotting Profile (PT, aPTT- prior
to an anticoagulation treatment)
Thrombin time (Bovine) Plasma
Prothrombin
Antithrombin activity
Factor V Leiden
Protein C activity
Protein S activity
C-reactive protein
Homocystein levels
Dilute Russells Viper Venom
Time (DRVVT), Plasma
Activated Protein C Resistance
V (APCRV), Plasma
Thrombophilia interpretation
Anticardiolipin antibodies (IgG
and IgM) or beta-2
glycoproteins antibodies
Antiphospholipid antibodies
(IgG and IgM)
Lupus anticoagulant
Heparin antibodies
ANA and ANCA
IL6 levels
ADAMTS13 Activity Assay
Ceruloplasmin
Direct Coombs test
Complement C3, C4
MethylenetetraHydrofolate
reductase gene mutation
Prothrombin gene mutation
(G20210A)
Occult blood in stool
COVID-19 test
Troponins
Brain Natriuretic Peptide

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
108
Status: Approved,Date: 15 February 2022
Diagnostic Test 
Results at baseline or prior 
to use of product (Include 
date and value/details) 
Test results after use of
product (Include date
and value/details)
Arterial Blood Gases
Chest X-Ray
Electrocardiography
Echocardiography
Duplex Ultrasonography
MRI scan
CT scan
Contrast Venography
Pulmonary Angiography
Ventilation-Perfusion Scanning
Provide details of any additional diagnostic results:

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
109
Status: Approved,Date: 15 February 2022
10.9. Appendix 9: Thrombotic Events to be Reported as AESIs
At the time of protocol writing, the list of thrombotic events to be reported to the sponsor as AESIs
is provided below. Further guidance may become available on thrombotic events of interest.
 MedDRA PTs for large vessel thrombosis and embolism:
o 
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:
o 
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

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
110
Status: Approved,Date: 15 February 2022
10.10. Appendix 10: Protocol Amendment History
This is an original protocol.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
111
Status: Approved,Date: 15 February 2022
11. 
REFERENCES
1. 
Agrawal AS (2016), Tao X, Algaissi A, et al. Immunization with inactivated Middle East Respiratory Syndrome
coronavirus vaccine leads to lung immunopathology on challenge with live virus. Hum Vaccin Immunother.
2016;12(9):2351-2356.
2. 
American Society of Hematology (2021). COVID-19 resources. Thrombosis with Thrombocytopenia
Syndrome (also termed Vaccine-induced Thrombotic Thrombocytopenia). https://www.hematology.org/covid-
19/vaccine-induced-immune-thrombotic-thrombocytopenia. Last updated: 29 April 2021. Accessed: 02 July
2021.
3. 
Anywaine Z (2019), Whitworth H, Kaleebu P, et al. Safety and immunogenicity of a 2-dose heterologous
vaccination regimen with Ad26.ZEBOV and MVA-BN-Filo Ebola vaccines: 12-month data from a Phase 1
randomized clinical trial in Uganda and Tanzania. J Infect Dis. 2019;220(1):46-56.
4. 
Arepally GM (2021), Padmanabhan, A. Heparin-induced thrombocytopenia: a focus on thrombosis. Arterioscler
Thromb Vasc Biol. 2021;41:141–152.
5. 
Baden LR (2020), El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.
N Engl J Med. 2021;384:403-416.
6. 
Barouch DH (2013), 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(2);248-256.
7. 
Barouch DH (2018), 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.
8. 
Bartoszko J (2021), Loeb M. The burden of influenza in older adults: meeting the challenge. Aging Clin Exp
Res. 2021;33(3):711-717.
9. 
Bolles M (2011), Deming D, Long K, et al. A double-inactivated severe acute respiratory syndrome coronavirus
vaccine provides incomplete protection in mice and induces increased eosinophilic proinflammatory pulmonary
response upon challenge. J Virol. 2011;85(23):12201-12215.
10. Brighton Collaboration (2021). Updated Proposed Brighton Collaboration process for developing a standard case
definition for study of new clinical syndrome X, as applied to Thrombosis with Thrombocytopenia Syndrome
(TTS). 
18 
May 
2021. 
https://brightoncollaboration.us/wp-content/uploads/2021/05/TTS-Interim-Case-
Definition-v10.16.3-May-23-2021.pdf.Accessed: 02 September 2021.
11. British Society for Haematology (2021). Guidance produced from the Expert Haematology Panel (EHP)
focussed on Covid-19 Vaccine induced Thrombosis and Thrombocytopenia (VITT). Version 1.3; 7 April 2021.
https://b-s-h.org.uk/media/19530/guidance-version-13-on-mngmt-of-thrombosis-with-thrombocytopenia-
occurring-after-c-19-vaccine 20210407.pdf. Accessed: 02 July 2021.
12. Brosio F  (2018), D'Alò GL, Baccello V, Terracciano E, Franco E, Gabutti G. Vaccine co-administration in
clinical practice. Ig Sanita Pubbl. 2018;74(5):475-494.
13. Centers for Disease Control and Prevention (2020). COVID-19 Guidance for Older Adults.
https://www.cdc.gov/aging/covid19-guidance.html. Accessed: 02 July 2021.
14. Centers for Disease Control and Prevention (2021). 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: 02 July 2021.
15. Centers for Disease Control and Prevention (2021a). Coronavirus Disease 2019 (COVID-19) Groups at Higher
Risk for Severe Illness. https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/groups-at-higher-
risk.html. Updated: 29 March 2021. Accessed: 04 June 2021.
16. Centers for Disease Control and Prevention (2021b). Seasonal influenza-associated hospitalizations in the United
States. https://www.cdc.gov/flu/about/burden/faq.htm (page last reviewed: 04 June 2021). Accessed
24 June 2021.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
112
Status: Approved,Date: 15 February 2022
17. Centers for Disease Control and Prevention (2021c). COVID-19 vaccines – Coadministration with other
vaccines. 
https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-
us.html?CDC AA refVal=https%3A%2F%2Fwww.cdc.gov%2Fvaccines%2Fcovid-19%2Finfo-by-
product%2Fclinical-considerations.html#Coadministration. Accessed: 04 June 2021.
18. Deming D (2006), Sheahan T, Heise M, et al. Vaccine efficacy in senescent mice challenged with recombinant
SARS-CoV bearing epidemic and zoonotic spike variants. PLoS Med. 2006;3(12):e525.
19. European Centre for Disease Prevention and Control (2021). COVID-19 country overviews.
https://www.ecdc.europa.eu/en/cases-2019-ncov-eueea. Accessed 11 July 2021.
20. European Commission (1998) 98/463/EC: Council Recommendation of 29 June 1998 on the suitability of blood
and plasma donors and the screening of donated blood in the European Community.
21. European Medicines Agency (2021). Vaxzevria: EMA advises against use in people with history of capillary
leak 
syndrome. 
https://www.ema.europa.eu/en/news/vaxzevria-ema-advises-against-use-people-history-
capillary-leak-syndrome. Published: 11 June 2021. Accessed: 01 July 2021.
22. Gidudu JF (2012), Walco GA, Taddio A, et al./The Brighton Immunization Site Pain Working Group.
Immunization site pain: case definition and guidelines for collection, analysis, and presentation of immunization
safety data. Vaccine. 2012:30(30);4558-4577.
23. He X (2021), Chandrashekar A, Zahn R, et al. Low-dose Ad26.COV2.S protection against SARS-CoV-2
challenge in rhesus macaques. BioRxiv 2021; doi:10.1101/2021.01.27.428380. [preprint]
24. Honda-okubo Y (2015), Barnard D, Ong CH, Peng BH, Tseng CT, Petrovsky N. Severe acute respiratory
syndrome-associated coronavirus vaccines formulated with delta inulin adjuvants provide enhanced protection
while ameliorating lung eosinophilic immunopathology. J Virol. 2015;89(6):2995-3007.
25. Houser KV (2017), Broadbent AJ, Gretebeck L, et al. Enhanced inflammation in New Zealand white rabbits
when MERS-CoV reinfection occurs in the absence of neutralizing antibody. PLoS Pathog.
2017;13(8):e1006565.
26. Huang K (2021), Lin SW, Sheng WH, Wang CC. Influenza vaccination and the risk of COVID-19 infection and
severe illness in older adults in the United States. Sci Rep 2021;11(1):11025.
27. Investigator's Brochure (2021): Ad26.COV2.S (VAC31518), Edition 5.0. Janssen Vaccines & Prevention B.V
(December 2021). Janssen Vaccines & Prevention B.V. Data on file.
28. Johns 
Hopkins 
CSSE 
(2021). 
Coronavirus 
COVID-19 
Global 
Cases.
https://www.arcgis.com/apps/dashboards/bda7594740fd40299423467b48e9ecf6. Accessed 11 July 2021.
29. Kohl KS (2007), Walop W, Gidudu J, et al./The Brighton Collaboration Local Reaction Working Group for
Swelling at or near Injection Site. Swelling at or near injection site: case definition and guidelines for collection,
analysis and presentation of immunization safety data. Vaccine 2007:25(31);5858-5874.
30. Lee GM (2021). CDC COVID-19 Vaccine Safety Technical (VaST) Work Group. Advisory Committee on
Immunization Practices (ACIP). May 12, 2021. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-
2021-05-12/08-COVID-Lee-508.pdf.
31. MacNeil JR (2021), Su JR, Broder KR, et al. Updated Recommendations from the Advisory Committee on
Immunization Practices for Use of the Janssen (Johnson & Johnson) COVID-19 Vaccine After Reports of
Thrombosis with Thrombocytopenia Syndrome Among Vaccine Recipients — United States, April 2021.
MMWR Morb Mortal Wkly Rep 2021;70:651-656.
32. Mertz D (2013), Kim TH, Johnstone J, et al. Populations at risk for severe or complicated influenza illness:
systematic review and meta-analysis. BMJ. 2013;347(aug23 1):f5061-f5061.
33. Milligan ID (2016), Gibani MM, Sewell R, et al. Safety and immunogenicity of novel adenovirus type 26- and
modified vaccinia ankara-vectored ebola vaccines: a randomized clinical trial. JAMA. 2016:315(15);1610-1623.
34. Mutua G (2019), Anzala O, Luhn K, et al. Safety and immunogenicity of a 2-dose heterologous vaccine regimen
with Ad26.ZEBOV and MVA-BN-Filo Ebola vaccines: 12-month data from a Phase 1 randomized clinical trial
in Nairobi, Kenya. J Infect Dis. 2019;220(1):57-67.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
113
Status: Approved,Date: 15 February 2022
35. Perrotta F (2020), Corbi G, Mazzeo G, et al. COVID-19 and the elderly: insights into pathogenesis and clinical
decision-making. Aging Clin Exp Res. 2020;32(8):1599-1608.
36. Polack FP (2020), Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNACOVID-19 vaccine.
N Engl J Med. 2020;383(27):2603-2615.
37. Rüggeberg JU (2007), Gold MS, Bayas J, et al. Anaphylaxis: case definition and guidelines for data collection,
analysis, and presentation of immunization safety data. Vaccine; 2007;25(31):5675-5684.
38. Sadoff J (2020), De Paepe E, Haazen W, et al. Safety and immunogenicity of the ad26. Rsv. Pref investigational
vaccine coadministered with an influenza vaccine in older adults. The Journal of Infectious Diseases.
2021;223(4):699-708.
39. Sadoff J (2021), Le Gars M, Shukarev G, et al. Interim Results of a Phase 1-2a Trial of Ad26.COV2.S Covid-19
Vaccine. N Engl J Med. Published online January 13, 2021:NEJMoa2034201.
40. Salisch NC (2019), Izquierdo Gil A, Czapska-Casey DN, et al. Adenovectors encoding RSV-F protein induce
durable and mucosal immunity in macaques after two intramuscular administrations. NPJ Vaccines. 2019;4:54.
41. Salisch NC (2021), Stephenson KE, Williams K,et al. A double-blind, randomized, placebo-controlled Phase 1
study of Ad26.ZIKV.001, an Ad26-vectored anti-zika virus vaccine. Ann Intern Med. 2021;174(5):585-594.
42. Shimabukuro T (2021). 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.
43. Streiff MB  (2021). Pathogenesis and Management of Thrombosis with Thrombocytopenia Syndrome (TTS).
Centers for Disease Control & Prevention Advisory Committee on Immunization Practices (ACIP) meeting 23
April 2021. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-04-23/02-COVID-Strieff-
508.pdf. (accessed 18 May 2021).
44. Toback S (2021), Galiza E, Cosgrove C, et al. Safety, immunogenicity, and efficacy of a COVID-19 vaccine
(NVX-CoV2373) 
co-administered 
with 
seasonal 
influenza 
vaccines. 
MedRxiv 
preprint 
doi:
https://doi.org/10.1101/2021.06.09.21258556.
45. US Department of Health and Human Services (2007), Food and Drug Administration, Center for Biologics
Evaluation and Research. September 2007. Guidance for Industry. Toxicity Grading Scale for Healthy Adult
and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.
https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidan
ces/Vaccines/ucm091977.pdf. Accessed 19 February 2020.
46. US Department of Health and Human Services (1998). Office for Human Research Protections - OHRP
Expedited Review Categories. 1998. https://www.hhs.gov/ohrp/regulations-and-policy/guidance/categoriesof-
research-expedited-review-procedure-1998/index.html. Accessed 18 September 2020.
47. US Food and Drug Administration (1998). Conditions for IRB Use of Expedited Review. Federal Register:
November 
9, 1998 
(Volume 
63, Number 
216). 
https://www.fda.gov/science-research/guidance-
documentsincluding-information-sheets-and-notices/conditions-irb-use-expedited-review. 
Accessed 
24
February 2020.
48. US Food and Drug Administration (2020). Development and Licensure of Vaccines to Prevent COVID-19.
Guidance for Industry. June 2020. https://www.fda.gov/media/139638/download. Accessed 2 April 2021.
49. US Food and Drug Administration (2021), Center for Biologics Evaluation and Research. May 2021. Guidance
for Industry. Emergency Use Authorization for Vaccines to Prevent COVID-19.
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/emergency-use-authorization-
vaccines-prevent-covid-19. Accessed 01 June 2021.
50. US Food and Drug Administration (2021a). COVID-19: Developing Drug and Biological Products for
Treatment or Prevention. Guidance for Industry. February 2021. https://www.fda.gov/media/137926/download.
Accessed 2 April 2021.
51. van der Fits L (2020), Bolder R, Heemskerk-van der Meer M, et al. Adenovector 26 encoded prefusion
conformation stabilized RSV-F protein induces long-lasting Th1-biased immunity in neonatal mice. NPJ
Vaccines. 2020;5:49.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
114
Status: Approved,Date: 15 February 2022
52. van der Lubbe JEM (2021), Rosendahl Huber SK, Vijayan A, et al. Ad26.COV2.S-elicited immunity protects
against G614 spike variant SARS2 CoV-2 infection in Syrian hamsters and does not enhance respiratory disease
in challenged animals with breakthrough infection after sub-optimal vaccine dosing. Immunology; 2021;
https://doi.org/10.1101/2021.01.08.425915.
53. Voysey M (2021), Clemens SAC, Madhi SA. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222)
against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa and the
UK. Lancet.2021;397(10269):99-111.
54. Widjojoatmodjo MN (2015), Bogaert L, Meek B, et al. Recombinant low-seroprevalent adenoviral vectors Ad26
and Ad35 expressing the respiratory syncytial virus (RSV) fusion protein induce protective immunity against
RSV infection in cotton rats. Vaccine. 2015; 33(41):5406-5414.
55. World Health Organization (2018). Influenza (Seasonal). 6 November 2018. https://www.who.int/en/news-
room/fact-sheets/detail/influenza-(seasonal). Accessed 24 June 2020.
56. World Health Organization (2020). Coronavirus disease 2019 (COVID-19) Situation Report - 51. Available at:
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports. Accessed: 02 July 2021.
57. World Health Organization (2020a). WHO Director-General's opening remarks at the media briefing on
COVID-19 - 11 March 2020. https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-
at-the-media-briefing-on-covid-19---11-march-2020. Accessed 02 July 2021.
58. Zhou H (2012), Thompson WW, Viboud CG, Ringholz CM, et al. Hospitalizations associated with influenza
and respiratory syncytial virus in the United States, 1993-2008. Clin Infect Dis. 2012;54(10):1427-1436.
59. Zhou T (2004), Wang H, Luo D, et al. An exposed domain in the severe acute respiratory syndrome coronavirus
spike protein induces neutralizing antibodies. J Virol. 2004;78(13):7217-7226.
60. Zumla A (2016), Chan JF, Azhar EI, Hui DS, Yuen KY. Coronaviruses - drug discovery and therapeutic options.
Nat Rev Drug Discov. 2016;15(5):327-347.

VAC31518 JNJ-78436735
Clinical Protocol VAC31518COV3005 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
115
Status: Approved,Date: 15 February 2022
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
 
15-Feb-2022 
17:52:23
(GMT)
Document Approval
PPD