An Open-label, Phase 2 Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Ad26.COV2.S in Healthy Pregnant Participants
Phase: PHASE2
Conditions: COVID-19 Prevention
Sponsor: Janssen Vaccines & Prevention B.V.

CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
1
Status: Approved, Date: 16 September 2022
Janssen Vaccines & Prevention B.V.*
Clinical Protocol
Protocol Title
An Open-label, Phase 2 Study to Evaluate the Safety, Reactogenicity, and Immunogenicity
of Ad26.COV2.S in Healthy Pregnant Participants
HORIZON 1
Protocol VAC31518COV2004; Phase 2
AMENDMENT 7
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).
IND:22657
EudraCT NUMBER:2020-005330-14
Status: 
Approved
Date: 
16 September 2022
EDMS number: 
EDMS-RIM-194495, 10.0
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.
NCT04765384

VAC31518(JNJ-78436735) 
Clinical Protocol VAC31518COV2004Amendment 7
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 16 September 2022
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document 
Date
Amendment 7 
This document
Amendment 6 
05 May 2022
Amendment 5 
18March 2022
Amendment 4 
13 December2021
Amendment 3 
02 July 2021
Amendment 2 
19 March 2021
Amendment 1 
28February 2021
Original Protocol 
07 December 2020
Amendment 7 (This Document)
Overall Rationale for the Amendment:
The purpose of the Amendment is to cease further enrollment in this study. After approximately 10 months,
recruitment continues to be challenging despite of the various Protocol Amendments intended to increase
enrollment. In addition, there is a lack of participant interest in this study, partly because ofthe widespread
use of other COVID-19 vaccines that are recommended for use in pregnant women. The participants and
their infants enrolled up to Amendment 7 will continue to be followed in this study as per protocol.
Because ofthe aforementioned enrollment challenges, the limited number of participants that are currently
included, and the availability of pregnancy registry data, some sampling time points are being removed to
reduce the burden on the participants. Changes made to the clinical protocol of study VAC31518COV2004
as part of Amendment 7 are listed below, including the rationale for each change and a list of all applicable
sections. Changes made as apart of Protocol Amendments 1 to 6 are listed in Appendix 10.14.
Section number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis 
1.3.1 Adult Participants: Group 4: (Including 
Sentinel and Safety Cohorts) 
1.3.2 Adult Participants: Groups 1-3:
Previously Vaccinated Participants: Dose 1
Schedule
4.1 Overall Design
6.3
Preparation/Handling/Storage/Accountability
9.2 Sample Size Determination
9.2.1 Immunogenicity
Clarified that further enrollment 
in this study is being ceased as of 
Amendment 7.
Due to enrollment
challenges detailed above.
1.1 Synopsis 
1.3.1 Adult Participants: Group 4: (Including 
Sentinel and Safety Cohorts) 
1.3.2 Adult Participants: Groups 1-3: 
Previously Vaccinated Participants: Dose 1 
Schedule 
9.2 Sample Size Determination
9.2.1 Immunogenicity  
Blood samples from adult 
participants for immunogenicity 
were removed from the end of
study and early exit visits and the
name of the visit was updated in
the table accordingly.
Updated wording for follow-up
safety assessments for adults at
the end of the study visit (no.12)
To reduce the burden on the
participants.
1.1 Synopsis 
1.3.3 Neonate/Infants Schedule 
3 OBJECTIVES AND ENDPOINTS  
Blood samples collection from 
neonates at 12 months for 
immunogenicity were removed
To reduce the burden on the
participants.

VAC31518(JNJ-78436735) 
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Status: Approved, Date: 16 September 2022
Section number 
and Name
Description of Change 
Brief Rationale
4.1.1 Study-Specific Ethical Design 
Considerations 
8STUDY ASSESSMENTS AND
PROCEDURES  
and the name of the visit was
updated in the table accordingly.
Updated wording for postnatal
(PN 12 months) follow-up safety
visit (no. 14).
1.1 Synopsis 
1.3.1 Adult Participants: Group 4: (Including 
Sentinel and Safety Cohorts) 
1.3.2 Adult Participants: Groups 1-3: 
Previously Vaccinated Participants: Dose 1 
Schedule 
3 OBJECTIVES AND ENDPOINTS  
4.1 Overall Design 8STUDY 
ASSESSMENTS AND PROCEDURES  
8.1.1 Immunogenicity Assessments
9.4.3 Exploratory Endpoint(s)
PBMC sampling was removed 
from the study. 
To reduce the burden on the
participants
As only 1 participant was
currently enrolled in the
peripheral blood
mononuclear cells (PBMC)
subset, this will result in
insufficient data to draw any
conclusions.
1.1 Synopsis 
9.4Statistical Analyses 
9.4.1 General Considerations 
9.5 Planned Analyses 
9.5.2 Final Analysis 
The interim analyses that were 
planned when 120 and 240 
participants reached the 28 days 
post-vaccination visit were 
removed from the study. 
Due to enrollment
challenges as described
above the anticipated target
required for interim analyses
will not be reached.
1.1 Synopsis 
9.4Statistical Analyses 
Updated wording regarding 
endpoints in alignment with  
Statistical Analysis Plan (SAP)
details.
Due to enrollment stop and
limited sample size.
General 
Textual adjustments and edits. 
Clarification and correction
of minor inconsistencies.

VAC31518(JNJ-78436735) 
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Status: Approved, Date: 16 September 2022
TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................................... 2
TABLE OF CONTENTS ............................................................................................................................... 4
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 7
1. 
PROTOCOL SUMMARY..................................................................................................................... 8
1.1. 
Synopsis........................................................................................................................................... 8
1.2. 
Schema.......................................................................................................................................... 21
1.3. 
Schedules of Activities ................................................................................................................... 22
1.3.1. 
Adult Participants: Group 4: (Including Sentinel and Safety Cohorts)........................................ 22
1.3.2. 
Adult Participants: Groups 1-3: Previously Vaccinated Participants: Dose 1 Schedule ............ 29
1.3.3. 
Neonate/Infants Schedule .......................................................................................................... 33
1.3.4. 
Procedures for Adult Participants With (Suspected) COVID-19................................................. 35
1.3.5. 
Procedures for Neonates and Infants With (Suspected) COVID-19.......................................... 38
1.3.6. 
Participants with a Suspected AESI - Pregnant Participants ..................................................... 41
2. 
INTRODUCTION................................................................................................................................ 42
2.1. 
Study Rationale.............................................................................................................................. 46
2.2. 
Background .................................................................................................................................... 46
2.3. 
Benefit-Risk Assessment............................................................................................................... 51
2.3.1. 
Risks Related to Study Participation .......................................................................................... 51
2.3.2. 
Benefits of Study Participation.................................................................................................... 56
2.3.3. 
Benefit-Risk Assessment for Study Participation ....................................................................... 56
3. 
OBJECTIVES AND ENDPOINTS ..................................................................................................... 58
4. 
STUDY DESIGN ................................................................................................................................ 65
4.1. 
Overall Design................................................................................................................................ 65
4.1.1. 
Study-Specific Ethical Design Considerations ........................................................................... 70
4.2. 
Justification for the Regimen and Dose ......................................................................................... 71
4.3. 
End of Study Definition................................................................................................................... 73
5. 
STUDY POPULATION ...................................................................................................................... 73
5.1. 
Inclusion Criteria............................................................................................................................ 73
5.2. 
Exclusion Criteria........................................................................................................................... 75
5.3. 
Lifestyle Considerations................................................................................................................. 78
5.4. 
Screen Failures.............................................................................................................................. 79
5.5. 
Criteria for Temporarily Delaying Administration of Study Vaccination ......................................... 79
6. 
STUDY VACCINATION AND CONCOMITANT THERAPY ............................................................. 80
6.1. 
Study Vaccinations Administered .................................................................................................. 80
6.2. 
Booster Vaccination ....................................................................................................................... 81
6.3. 
Preparation/Handling/Storage/Accountability ................................................................................ 81
6.4. 
Study Vaccination Compliance ...................................................................................................... 83
6.5. 
Dose Modification........................................................................................................................... 83
6.6. 
Continued Access to Study Vaccine After the End of the Study ................................................... 83
6.7. 
Treatment of Overdose .................................................................................................................. 83
6.8. 
Prestudy and Concomitant Therapy .............................................................................................. 83
6.9. 
Study Vaccination Pausing Rules.................................................................................................. 85
7. 
DISCONTINUATION OF STUDY VACCINATION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL............................................................................................... 87
7.1. 
Discontinuation of Study Vaccination............................................................................................. 87
7.2. 
Delay or Discontinuation of Vaccination due to Pregnancy-Specific Complications ..................... 87
7.3. 
Participant Discontinuation/Withdrawal From the Study................................................................ 88
7.3.1. 
Withdrawal From the Use of Research Samples ....................................................................... 88

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7.4. 
Lost to Follow-up............................................................................................................................ 88
8. 
STUDY ASSESSMENTS AND PROCEDURES ............................................................................... 89
8.1. 
Immunogenicity Assessments ....................................................................................................... 93
8.1.1. 
Immunogenicity Assessments .................................................................................................... 93
8.1.2. 
Procedures in the Event of (Suspected) COVID-19................................................................... 95
8.1.3. 
Symptomatic SARS-COV-2 Infection ....................................................................................... 109
8.1.4. 
Asymptomatic SARS-COV-2 Infection ..................................................................................... 109
8.2. 
Safety Assessments..................................................................................................................... 109
8.2.1. 
Physical Examinations.............................................................................................................. 109
8.2.2. 
Vital Signs................................................................................................................................. 111
8.2.3. 
Clinical Safety Laboratory Assessments .................................................................................. 111
8.2.4. 
Medical, Obstetric and Delivery History.................................................................................... 112
8.2.5. 
Breast Milk Production Outcomes ............................................................................................ 112
8.2.6. 
Neonatal Assessments............................................................................................................. 112
8.3. 
Adverse Events, Serious Adverse Events, Adverse Events of Special Interest, and Other
Safety Reporting .......................................................................................................................... 113
8.3.1. 
Time Period and Frequency for Collecting Information Relating to Adverse Events,
Adverse Events of Special Interest, Serious Adverse Events, Pregnancy-related
Adverse Events and Medically-attended Adverse Events........................................................ 113
8.3.2. 
Method of Detecting Adverse Events, Adverse Events of Special Interest, Serious
Adverse Events and Medically-attended Adverse Events........................................................ 115
8.3.3. 
Follow-up of Adverse Events, Serious Adverse Events, Adverse Events of Special
Interest, Pregnancy-related Adverse Events, and Medically-attended Adverse Events.......... 117
8.3.4. 
Regulatory Reporting Requirements for Serious Adverse Events ........................................... 117
8.3.5. 
Pregnancy................................................................................................................................. 117
8.3.6. 
Adverse Events of Special Interest........................................................................................... 117
8.4. 
Virology Assessments.................................................................................................................. 119
8.5. 
Genetics and Pharmacogenomics............................................................................................... 119
8.6. 
Biomarkers................................................................................................................................... 119
8.7. 
Medical Resource Utilization and Health Economics .................................................................. 119
9. 
STATISTICAL CONSIDERATIONS................................................................................................ 120
9.1. 
Statistical Hypotheses.................................................................................................................. 120
9.2. 
Sample Size Determination ......................................................................................................... 120
9.2.1. 
Immunogenicity......................................................................................................................... 121
9.2.2. 
Safety........................................................................................................................................ 122
9.3. 
Populations for Analysis Sets ...................................................................................................... 123
9.4. 
Statistical Analyses ...................................................................................................................... 124
9.4.1. 
General Considerations............................................................................................................ 124
9.4.2. 
Primary/Secondary Endpoint(s)................................................................................................ 124
9.4.3. 
Exploratory Endpoint(s)............................................................................................................ 126
9.4.4. 
Other Safety Analyses.............................................................................................................. 127
9.5. 
Planned Analyses ........................................................................................................................ 128
9.5.1. 
Primary Analysis....................................................................................................................... 128
9.5.2. 
Final Analysis............................................................................................................................ 128
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS.......................... 129
10.1. 
Appendix 1: Abbreviations ........................................................................................................... 129
10.2. 
Appendix 2: Clinical Laboratory Tests ......................................................................................... 132
10.2.1. 
Protocol Required Safety Laboratory Assessments - Adult Participants ................................. 132
10.3. 
Appendix 3: Regulatory, Ethical, and Study Oversight Considerations....................................... 134
10.3.1. 
Regulatory and Ethical Considerations .................................................................................... 134
10.3.2. 
Financial Disclosure.................................................................................................................. 137
10.3.3. 
Informed Consent Process ....................................................................................................... 137
10.3.4. 
Data Protection ......................................................................................................................... 138
10.3.5. 
Long-Term Retention of Samples for Additional Future Research .......................................... 139
10.3.6. 
Safety Monitoring Committees Structure.................................................................................. 139

VAC31518(JNJ-78436735) 
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Status: Approved, Date: 16 September 2022
10.3.7. 
Publication Policy/Dissemination of Clinical Study Data.......................................................... 140
10.3.8. 
Data Quality Assurance............................................................................................................ 141
10.3.9. 
Case Report Form Completion................................................................................................. 141
10.3.10. Source Documents ................................................................................................................... 142
10.3.11. Monitoring ................................................................................................................................. 143
10.3.12. On-Site Audits........................................................................................................................... 143
10.3.13. Record Retention...................................................................................................................... 144
10.3.14. Study and Site Start and Closure ............................................................................................. 144
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............................................... 146
10.4.1. 
Adverse Event Definitions and Classifications ......................................................................... 146
10.4.2. 
Attribution Definitions................................................................................................................ 147
10.4.3. 
Severity Criteria........................................................................................................................ 147
10.4.4. 
Special Reporting Situations .................................................................................................... 148
10.4.5. 
Procedures ............................................................................................................................... 148
10.4.6. 
Product Quality Complaint Handling......................................................................................... 150
10.4.7. 
Contacting Sponsor Regarding Safety, Including Product Quality........................................... 150
10.4.8. 
Neonate Safety Assessment: Apgar Score .............................................................................. 151
10.5. 
Appendix 5: Contraceptive Guidance .......................................................................................... 152
10.6. 
Appendix 6: Toxicity Grading Scales ........................................................................................... 153
10.7. 
Appendix 7: Multisystem Inflammatory Syndrome in Children .................................................... 158
10.8. 
Appendix 8: Case Definitions for COVID-19................................................................................ 160
10.8.1. 
Adults Case Definition for Moderate to Severe/Critical COVID-19.......................................... 160
10.8.2. 
Adult Case Definition for Mild COVID-19.................................................................................. 161
10.8.3. 
Adult US FDA Harmonized Case Definition for COVID-19...................................................... 162
10.8.4. 
Neonates and Infants Case Definition for Moderate to Severe/Critical COVID-19.................. 163
10.8.5. 
Neonates Case Definition for Mild COVID-19.......................................................................... 165
10.8.6. 
Infants Case Definition for Mild COVID-19............................................................................... 165
10.9. 
Appendix 9: Summary of Guidance from CDC Website on Underlying Medical Conditions
That Lead or Might Lead to Increased Risk for Severe Illness From COVID-19......................... 166
10.9.1. 
Appendix 9A: CDC Website Underlying Medical Conditions for Adults ................................... 166
10.9.2. 
Appendix 9B: CDC Website Underlying Medical Conditions for Children and Teens.............. 167
10.10. Appendix 10: Symptoms of Coronavirus (US Centers for Disease Control and Prevention)...... 168
10.10.1. Appendix 10A: Symptoms of Coronavirus (US Centers for Disease Control and
Prevention) in Adults................................................................................................................. 168
10.10.2. Appendix 10B: Symptoms of Coronavirus (US Centers for Disease Control and
Prevention) in Neonates ........................................................................................................... 169
10.10.3. Appendix 10C: Symptoms of Coronavirus (US Centers for Disease Control and
Prevention) in Children ............................................................................................................. 170
10.11. Appendix 11: Thrombosis with Thrombocytopenia (TTS) AESI Form......................................... 171
10.12. Appendix 12: Thrombotic Events to be Reported as Suspected AESIs...................................... 176
10.13. Appendix 13: Visit Guidance in Case of Pregnancy Termination Before the Completion of
the Applicable Study Period Visits ............................................................................................... 177
10.14. Appendix 14: Protocol Amendment History................................................................................. 178
11. REFERENCES................................................................................................................................. 207
INVESTIGATOR AGREEMENT............................................................................................................... 215

VAC31518(JNJ-78436735) 
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Status: Approved, Date: 16 September 2022
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1: 
Maximum Volume of Blood to be Collected from Each Participant.......................................... 91
Table 2: 
Summary of Humoral and Cellular Immunogenicity Assays..................................................... 94
Table 3: 
Probability of Observing at Least One Adverse Event Given a True Adverse Event
Rate......................................................................................................................................... 120
Table 4: 
Probability of Observing at Least One Th2 Event Given a True Th2 Event........................... 121
Table 5: 
Upper Limit of the 95% Two-sided Confidence Interval if no Cases are Observed for
Different Sample Sizes ........................................................................................................... 121
Table 6: 
Protocol Required Safety Laboratory Assessments to be Performed Locally........................ 132
Table 7: 
Additional Laboratory Assessments to be Performed as Required........................................ 132
FIGURES
Figure 1: Schematic Overview of the Study............................................................................................. 21
Figure 2: Decision Tree for Staggered Enrollment................................................................................... 67

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Objectives 
Endpoints
 
AEs in neonates/infants leading to
study discontinuation from birth until
discontinuation.
To assess outcomes in neonates and infants up to
approximately 12 months of age born to participants
who have received Ad26.COV2.S, during the 2nd
and/or 3rd trimester of pregnancy.
 
Outcomes in neonates and infants
(including normal neonate, term
neonate with (or without)
complications, preterm neonate with
(or without) complications, neonatal
infection, respiratory distress,
congenital anomalies, neonatal death,
low birth weight, and small for
gestational age measured from birth
until approximately 12 months of
age) (non-exhaustive).
For exploratory endpoints, please refer to Section 3.
Due to cease of enrollment and limited sample size, some endpoints might not be summarized and will only
be provided in listings. More details can be found in the SAP.
Hypothesis
No formal statistical hypothesis is to be tested. The study is designed to provide descriptive information
regarding the safety, pregnancy outcomes, and immunogenicity of Ad26.COV2.S in adult participants in
the 2nd and/or 3rd trimester of pregnancy, as well as the safety and outcomes of neonates/infants.
The study will provide descriptive information regarding the safety and immunogenicity of Ad26.COV2.S
administered as a booster dose in participants who had previously received a coronavirus disease-2019
(COVID-19) vaccine and in those that were vaccine naïve at study entry and receive a booster dose during
the study.
OVERALL DESIGN
This is an open-label multicenter, Phase 2 study in healthy pregnant (2nd and/or 3rd trimester of pregnancy)
participants ≥18 to ≤45 years of age to evaluate safety, reactogenicity, immunogenicity, and pregnancy
outcomes.
A target of 240 adult participants in the 2nd or 3rd trimester of pregnancy (Week 16 to Week 38 of gestation,
inclusive) was to be enrolled in this study. Efforts were made to ensure good representation in terms of race
and ethnicity.
As of Protocol Amendment 7 approval, participant enrollment in this study will be ceased. The enrolled
participants and their infants will continue to be followed in this study in accordance with the protocol.
The first 22 vaccine naïve participants participated in the Sentinel and Safety Cohorts to assess safety and
reactogenicity in the 1-dose regimen.
The remaining participants (who have received their last COVID-19 vaccination at least 4 months prior to
receiving the study vaccine or are vaccine naïve participants) will preferably be equally distributed between
the following groups, per their COVID-19 vaccination histories:
 
Group 1: Previous primary vaccination (2-doses) or homologous booster vaccination with Comirnaty
(Pfizer-BioNTech) or SpikeVax (Moderna)

VAC31518(JNJ-78436735) 
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Status: Approved, Date: 16 September 2022
 
Group 2: Previous primary vaccination (1-dose) or homologous booster vaccination with
Ad26.COV2.S (Janssen)
 
Group 3: Previous COVID-19 vaccination, irrespective of previous schedule and vaccine (includes
heterologous regimens) and excluding schedules for Groups 1 and 2
 
Group 4: Vaccine naïve participants, including those who are in Sentinel and Safety Cohorts
The sample size of each of the groups will be flexible, and the target will be to recruit at least 40 participants
in Groups 1-3 and at least 25 participants in Group 4. These participants will receive 1 dose of
Ad26.COV2.S at 5×1010 vp. Participants will be stratified by pregnancy stage at the time of enrollment
(Weeks ≥16 to <28 or Weeks ≥28 to ≤38), with a goal of at least approximately 25% participants per
trimester, per group.
Enrollment was staggered and started with recruitment of Sentinel participants (n=5) followed by a larger
Safety Cohort (n=17 participants, excluding sentinels) who all received 1 dose of Ad26.COV2.S vaccine at
5×1010vp.
There will be no active vaccination with Ad26.COV2.S of neonates/infants in this study.
Independent Data Monitoring Committee (IDMC) ReviewOutcome
Safety Profile Acceptable After IDMC Review
At the time of writing Amendment 5, the IDMC confirmed that the safety profile of 1 dose of Ad26.COV2.S
at 5×1010 vp was considered acceptable and no safety concerns were identified following review of the
Sentinel and Safety Cohorts safety data (see Section 10.3.6 for details).
Upon recommendation of the IDMC, the remaining participants were enrolled to receive 1 dose of
Ad26.COV2.S at 5×1010 vp.
Booster Vaccinations
Previously Vaccinated Participants
Previously vaccinated participants (Groups 1-3) will receive a single (booster) dose of Ad26.COV2.S at
5×1010 vp as part of the study. No further vaccinations will be received by these groups during the study.
Vaccine Naïve Participants
For participants that are vaccine naïve at study entry, booster vaccination with a single dose of
Ad26.COV2.S at 5×1010 vp will be offered to ongoing, consenting participants (Group 4, including Sentinel
and Safety Cohorts) who have completed the pregnancy during which they were enrolled in the study, are
not pregnant again, and have notreceived another COVID-19 vaccine (eg, national immunization program).
The booster vaccination for vaccine naïve participants at study entry should be administered not earlier than
2 months after the participant’s Ad26.COV2.S vaccination in the study.

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Decision Tree for Staggered Enrollment
Abbreviations: IDMC  Independent Data Monitoring Committee; vp  virus particles. SRP  Study Responsible Physician
A target of 240 adult participants (including 22 participants in the Sentinel and Safety Cohorts) in the 2nd or 3rd
trimester of pregnancy (Week 16 to Week 38 of gestation, inclusive) was to be enrolled. Enrollment was staggered
and started with recruitment of Sentinel participants followed by Safety Cohort (excluding Sentinels).
At the time of writing Amendment 5, the IDMC confirmed that the safety profile of 1 dose of Ad26.COV2.S at 5×1010
vp was considered acceptable and no safety concerns were identified following review of the Sentinel and Safety
Cohorts safety data.
As of Protocol Amendment 7 approval, participant enrollment in this study will be ceased. The enrolled participants
and their infants will continue to be followed in this study in accordance with the protocol.
The participants that were not enrolled in the Sentinel and Safety Cohorts will be enrolled and randomized to receive
1 dose of Ad26.COV2.S at 5×1010 vp.
Previously vaccinated participants (Group 1-3) should have received their last COVID-19 vaccination  at least 4
months prior to receiving the study vaccine.
Participants will be stratified by pregnancy stage at the time of enrollment (Weeks ≥ 16 to <28 or Weeks ≥28 to 38),
with a goal of at least approximately 25% participants per trimester per group.
* A booster vaccination with a single dose of Ad26.COV2.S at 5×1010 vp will be offered to ongoing, consenting
participants who were vaccine naïve at study entry (Group 4, including Sentinel and Safety Cohorts) and who have
completed the pregnancy during which they were enrolled in the study, are not pregnant again), and have not received
another COVID-19 vaccine (eg, national immunization program). Please refer to Section 1.3.1.1 for further details.
Safety assessments include an observation period at the study site for at least 30 minutes (60 minutes for
participants in the Sentinel and Safety Cohorts) after vaccination to monitor for the presence of any severe
acute reactions, the recording of any solicited local or systemic adverse events (AEs), unsolicited AEs,
serious AEs (SAEs), AESI, pregnancy-related AEs throughout pregnancy, and MAAEs.
Other safety assessments include clinical laboratory assessments, vital signs measurements (pulse/heart
rate, supine systolic and diastolic blood pressure, respiratory rate, and body temperature) and physical
examinations. In addition, adverse maternal/fetal outcomes, adverse neonate/infant outcomes SAEs
(including MIS-C), MAAEs and AEs leading to discontinuation will be recorded.
Immunogenicity assessments, including humoral immune responses such as neutralizing and binding
antibodies will be performed.
Active surveillance for COVID-19-like signs and symptoms in participants and neonates/infants will occur,
including a COVID-19 surveillance (symptom check) through the participant’s electronic diary (electronic
clinical outcome assessment [eCOA]).
All participants and neonates/infants with COVID-19-like signs or symptoms and all participants and
neonates/infants with a positive RT-PCR test from outside the study meeting the prespecified criteria for
suspected COVID-19 should undertake prespecified COVID-19 procedures as outlined in the body of the
protocol (see Section 8.1.2).

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If neonates were born to mothers with confirmed COVID 19 (or if a close relative from the same household
has a confirmed COVID 19 result), testing for SARS-CoV-2 should be performed for neonates/infants,
regardless of the presence of symptoms.
The occurrence of asymptomatic SARS-CoV-2 infection will also be assessed, if feasible (see
Section 8.1.4).
Enrolled participants will be counselled on SARS-CoV-2 infection prevention each time they interact with
site staff, in line with local guidelines. All necessary precautions (per local regulation) should be taken to
protect medical staff and other contacts of participants who confirmed to have COVID-19.
In the event of a confirmed SARS-CoV-2 infection, the participant will be asked to adhere to the appropriate
measures and restrictions as defined by local regulations.
Study Population
A target of 240 adult participants, who are previously vaccinated or vaccine naïve at study entry, ≥18 to
≤45 years of age, inclusive, in the 2nd and/or 3rd trimester of pregnancy(ie, Week 16 to Week 38 of gestation,
inclusive) was to be recruited for the study.
Efforts were made to ensure good representation in terms of race and ethnicity and to have at least
approximately 25% participants in each trimester of the pregnancy (Weeks ≥16 to <28 or Weeks ≥28 to
≤38) per group.
As of Protocol Amendment 7approval, participant enrollment in this study will be ceased
End of Study Definition
The end of study is considered as the last visit for the last participant in the study. For adult participants,
the last visit is at approximately 12 months postpartum. For neonates/infants the last visit is at
approximately 12 months of age.
NUMBER OF PARTICIPANTS
A target of240 adult participants, who are previously vaccinated or vaccine naïve at study entry, in the 2nd
or 3rd trimester of pregnancy, ≥18 to ≤45 years of age was planned to be enrolled in this study.
As of Protocol Amendment 7approval, participant enrollment in this study will be ceased.
DOSAGE AND ADMINISTRATION
Participants will be vaccinated at the study site according to the schedule detailed in the overall design.
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. Formulation buffer will be supplied as diluent as 15 mM citrate, 5% (w/w)
hydroxypropyl-β-cyclodextrin, 0.4% (w/w) ethanol, 0.03% (w/w) polysorbate 80, 75 mM NaCl, pH 6.2.
The vaccine will be extracted from the vial as follows: Ad26.COV2.S at 5×1010 vp dose level: 0.5 mL is
withdrawn from 1 vial containing 0.75 mL 1×1011 vp/mL.
IMMUNOGENICITY EVALUATIONS
Blood Sampling:
From all adult participants (venous blood), neonates (cord blood at birth) and infants (venous or arterial
blood) samples will be collected at selected timepoints for humoral immunogenicity assessments
(Section 8.1.1), with an emphasis on neutralizing and binding antibody responses.

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Biomarker analysis in PAXgene® tubes may be performed to explore potentially informative biomarkers
related to vaccine immunogenicity.
For adult participants who receive a booster vaccination, blood samples will be collected pre-boost and 28
days post-boost for humoral immunogenicity assessments and vaccination-related biomarkers
(Section 8.1.1).
From a subset of approximately 25 of adult participants per group, peripheral blood mononuclear cells
(PBMC)s were to be collected for analysis of cellular immunogenicity (including T helper cell subsets
[Th1/Th2] assessments). With only 1 participant in this subset at the time of writing Amendment 7, PBMC
sampling will be removed from the study as of Protocol Amendment 7approval.
A serologic test for past infection with SARS-CoV-2 will be performed per the timepoints provided in the
SoA.
Colostrum and Breast Milk Sampling
Colostrum and breast milk will be collected, if feasible, from adult participants postpartum for the
assessment of protective maternal humoral immunity, including SARS-CoV-2 binding immunoglobulins
and IgA antibodies. Colostrum and/or breast milk will also be collected, if feasible, at the time of booster
vaccination and 28 days post booster vaccination, in participants who were vaccine naïve at study entry and
receive a booster after pregnancy completion.

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Immunogenicity assessments may include, but are not limited to, the humoral and cellular immunogenicity
assays (as available and feasible) summarized in the below table.
Summary of Humoral and Cellular Immunogenicity Assays
Summary of Humoral Immunogenicity Assays
Assay 
Purpose
Primary/Secondary endpoints
SARS-CoV-2 binding antibodies
(ELISA or equivalent assay)
Analysis of antibodies binding to the SARS-CoV-2 S protein
SARS-CoV-2 neutralization
(VNA)
Analysis of neutralizing antibodies to the wild-type and/or pseudovirion
expressing S protein
Exploratory endpoints
SARS-CoV-2 binding antibodies
(ELISA and/or SARS-CoV-2
immunoglobulin assay)
Analysis of antibodies binding to the SARS-CoV-2 Spike (S) protein,
nucleocapsid (N) protein, receptor binding domain (RBD) of the SARS-
CoV-2 S protein, or other proteins, including surface proteins of other
coronaviruses
SARS-CoV-2 neutralization 
(VNA) 
Analysis of neutralizing antibodies to the wild-type virus, viral variants,
and/or pseudovirion expressing S protein
ELISA or Ig assay detecting 
coronavirus-specific antibodies 
Antibodies specific to
coronaviruses or other respiratory
viruses (MSD)
Analysis of antibodies binding to coronaviruses other than SARS-CoV-2, or
other respiratory viruses
SARS-CoV-2 binding 
immunoglobulins, including IgA 
antibodies (ELISA or equivalent
assay)
Analysis of IgA and/or other Ig subtypes against SARS-CoV-2 in colostrum
and/or breast milk
Adenovirus 26 neutralization 
(neutralization assay)
Analysis of neutralizing antibodies to Adenovirus 26
Functional and molecular antibody 
characterization  
Analysis of antibody characteristics including Fc-mediated viral clearance,
avidity, Fc characteristics, Ig subclass and IgG isotype, antibody
glycosylation, and assessment of antibody repertoire
Epitope-specificity 
characterization
Analysis of site-specificity, epitope mapping
Cytokine profiling, metabolomics 
and/or lipidomics 
Analysis of cytokines, chemokines, and other proteins, metabolites or lipid
mediators of the immune response in the serum or plasma
Passive transfer 
Analysis of immune mediators correlating with protection against
experimental SARS-CoV-2 challenge in a suitable animal model
Transcriptional analysis of 
vaccine-induced Biomarkers 
Analysis of mRNA expression levels of vaccine-induced biomarkers of
immune mediated responses, including innate and inflammatory responses
ELISA  enzyme linked immunosorbent assay; Ig  immunoglobulin; MSD  Meso Scale Discovery; SARS CoV 2  severe
acute respiratory syndrome coronavirus 2; VNA  virus neutralization assay

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Summary of Cellular Immunogenicity Assays
Assay 
Purpose
Exploratory endpoints
Flow cytometry (ICS) 
Analysis of T-cell responses to SARS-CoV-2 S protein, and/or other protein
peptides by ICS including CD4+/CD8+, IFNγ, IL2, TNFα, IL-4, IL-5, IL13, and/or
other Th1/Th2 markers,
ELISpot 
IFNγ and IL-4 responses to SARS-CoV-2 S protein peptides by PBMCs, based on
single or dual ELISpot,
Gene expression analysis 
Analysis of gene expression by RNA transcript profiling and/or analysis of protein
translates, in cells or whole blood stimulated with SARS-CoV-2 S protein peptides
or in unstimulated cells or whole blood (ex vivo),
Cytokine profiling (ELISA 
or multiplexed arrays) 
Analysis of cytokines, chemokines, and other proteins of the immune response in
cells or whole blood stimulated with SARS-CoV-2 S protein peptides, or in
unstimulated cells or whole blood, by ELISA or multiplexed arrays and
confirmation by functional in vitro assays
T and B cell phenotyping 
Analysis of the phenotype of antigen-specific T and B cells, assessed by single cell
analysis
CD  cluster of differentiation; ELISA  enzyme linked immunosorbent assay; ELISpot  enzyme linked immunospot (assay);
ICS  intracellular cytokine staining; IFNγ  interferon gamma; IL
 interleukin; PBMC  peripheral blood mononuclear cell;
RNA  ribonucleic acid; SARS CoV2  severe acute respiratory syndrome coronavirus 2; Th  T helper; Th1/Th2:T helper cell
subset(s); TNFα  tumor necrosis factor alpha; VNA  virus neutralization assay.
BIOMARKER EVALUATIONS
For all adult participants and in cord blood (if feasible), biomarker analysis in PAXgene® tubes may be
performed to explore potentially informative biomarkers related to vaccine immunogenicity.
For adult participants with a positive test result for SARS-CoV-2 infection, biomarker analysis in
PAXgene® tubes may be performed for evaluation of COVID-19 cases and to explore potentially
informative biomarkers, correlating with SARS-CoV-2 infection and COVID-19 severity, at Day 3 to 5 and
at Day 29 (±7 days) after onset of symptoms.
SAFETY EVALUATIONS
Day 1 Supplies:
Adult participants will be provided with a thermometer (to measure body temperature), ruler (to measure
local injection site reactions), and a participant reactogenicity diary in the eCOA to record body temperature
and solicited local (at injection site) and systemic signs and symptoms. Parent(s)/caregiver(s) will be
provided with a separate thermometer for the neonate/infant to record body temperature for the
neonate/infant in the eCOA in the event of confirmed or suspected COVID-19.
The site staff will be provided with ePRO and ObsRO completion guidelines that includes instructions on
capturing responses the eCOA diaries and grading scales to assess severity of the signs and symptoms after
vaccination (reactogenicity).
The study staff is responsible for providing appropriate training to the participant/parent(s)/caregiver(s) to
prevent missing or incorrect data. The reactogenicity diary will be reviewed by the study personnel at the
Day 8 visits as indicated in the Schedule of Activities (Section 1.3.1 and Section 1.3.2).
If the reactogenicity diary review is missed/unavailable at Day 8, the reactogenicity diary will be reviewed
during the following visit.
Adult participants will also be provided with a kit to collect nasal swabs in case they experience COVID-
19-like symptoms during the study.

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Safety Assessments
After vaccination, participants will remain under observation at the study site, for at least 30 minutes (60
minutes for the Sentinel and Safety Cohorts), for the presence of any severe acute reactions and solicited
events.
Vital signs, including body temperature (oral route preferred for adults, in accordance with the local
standard of care for neonates/infants), pulse/heart rate, respiratory rate, blood pressure (adults only), and
blood oxygen saturation will be assessed.
Physical examinations will be performed by the investigator or designated medically qualified healthcare
professional. Any clinically relevant abnormalities or changes in severity observed during the review of
body systems should be documented in the electronic case report form (eCRF).
General medical history will be documented in the eCRF, including previous surgery, hospitalizations, and
medication history prior to conception/pregnancy.
Obstetric medical history will be documented in the eCRF, if available, including number of live births,
stillbirths, abortions, c-sections, multiple pregnancies and complications if applicable. Any visits and results
of any routine tests obtained during pregnancy to assess pregnancy and the fetus (eg, congenital anomalies,
ultrasound, amniocentesis) should be documented. For prior pregnancies, dates of delivery or termination
of pregnancy, history of multiple pregnancies, pregnancy complications, history of caesarean section
(elective or emergency), pregnancy outcome(s) (live birth, still birth or abortion) and history of previous
early-onset neonatal infection, if feasible.
Neonatal 
medical 
history 
will 
include 
birth/termination 
outcome 
(live 
birth, 
stillbirth,
termination/miscarriage, neonatal death), demographics, physical examination, overall Apgar score,
weight, length, head circumference, key findings of fetal monitoring during labor such as fetal presentation
at delivery, gestational age, complications, fetal heart rate and uterine contractions during labor.
All AEs and special reporting situations, whether serious or non-serious, that are related to study procedures
or that are related to non-investigational sponsor products will be reported for all participants (adult
participants and neonates/infants) from the time a signed and dated informed consent form (ICF) is obtained
until the end of the study/early withdrawal.
For adult participants, solicited AEs, collected through a reactogenicity diary as part of the eCOA, will be
recorded from the time of vaccination until 7 days post-vaccination  (or until resolution). All other
unsolicited AEs and special reporting situations, whether serious or non-serious, will be reported from the
time of vaccination until 28days post-vaccination.
Subjective changes in (postpartum) breast milk production (reduction) will be collected in the eCOA diary.
All SAEs, AESI and AEs (including pregnancy-related AEs, throughout pregnancy) leading to
discontinuation from the study/vaccination (regardless of the causal relationship) are to be reported for all
adult participants from the moment of vaccination until completion of the participant’s last study-related
procedure. The investigator’s assessment of ongoing AEs at the time of each participant’s last visit should
be documented and closed in the participant’s medical record.
SAEs and AESIs in the neonates/infants will be followed up from birth until 12 months postpartum.
MAAEs are to be reported for all adult participants from the moment of vaccination until 6 months after
vaccination. MAAEs leading to study discontinuation (for both adults and neonates/infants), are to be
reported during the entire study.
Plasma and serum derived from whole blood samples will be collected from all participants for retrospective
analysis of hematological parameters, including pro- and anti-coagulation factors (see Section 8.2.3.1), in
the event of a suspected AESI of thrombosis with thrombocytopenia syndrome (TTS) post-vaccination.

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The platelet count will be performed by a local laboratory or substitute for local laboratory. In addition, the
extent to which levels of these coagulation factors fluctuate pre-and post-vaccination with Ad26.COV2.S
may be investigated for research purposes.
STATISTICAL METHODS
Sample Size Calculation
The number of adult participants that will be assessed for safety and reactogenicity of the Ad26.COV2.S
vaccine, was chosen to provide a preliminary descriptive assessment of safety and immunogenicity in this
population.
In addition, the study will provide descriptive information regarding the safety and immunogenicity of
Ad26.COV2.S administered as a booster in eligible participants.
A target of 240 adult participants in the 2nd or 3rd trimester of pregnancy, ≥18 to ≤45 years of age was
planned to be enrolled in this study. As of Protocol Amendment 7approval, participant enrollment in this
study will be ceased.
Descriptive analysis will be used to evaluate the following:
 
Safety and reactogenicity
 
Pregnancy outcomes
 
Neonate/infant outcomes
 
Immunogenicity of Ad26.COV2.S in adult participants and neonates/infants (including immunity
conferred by placental transfer of IgG antibodies).
When 40, 60, 120, and 240 participants are vaccinated, the observation of 0 AEs would be associated with
a 95% confidence (2-sided) that the true rate is less than 8.8%, 6%, 3%, and 1.5% respectively.
Populations for Analysis Set
For purpose of analysis, the following populations are defined:
Population 
Description
Enrolled Adults 
All adult participants who sign the ICF and are not screen failed
Full Analysis Set-Adults 
(FAS-A)
All enrolled adult participants with at least one vaccine administration documented
Full Analysis Set-Non- 
vaccinated 
Neonates/Infants (FAS-
NVN)
All non-vaccinated neonates/infants (NVN) born to Ad26.COV2.S vaccinated adult
participants
Per protocol 
Immunogenicity-Adults 
(PPI-A) 
All vaccinated adult participants for whom immunogenicity data are available
excluding adult participants with major protocol deviations that are expected to impact
the immunogenicity outcomes. In addition, samples obtained from participants after
SARS-CoV-2 infection occurring after baseline (if applicable) will be excluded from
the analysis
Per protocol 
Immunogenicity- Non- 
vaccinated 
Neonates/Infants (PPI- 
NVN)
All NVN born to Ad26.COV2.S vaccinated adult participants for whom
immunogenicity data are available excluding neonates/infants born to participants with
major protocol deviations that are expected to impact the immunogenicity outcomes
(for example missed vaccinations in the mothers), or neonates/infants with major
protocol deviations that are expected to impact the immunogenicity outcomes

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Population 
Description
The list of major protocol deviations to be excluded from the immunogenicity analyses will be specified in the
Major Protocol Deviation Criteria document and/or this list will be reported into the protocol deviation dataset of
the clinical database before database lock.
Primary/Secondary Endpoint(s)
Immunogenicity Endpoints
No formal statistical testing of immunogenicity data is planned. Descriptive statistics (geometric mean and
confidence intervals, or median and interquartile range Q1-Q3, as appropriate) will be calculated by group
and overall, for immunologic parameters for all available time points for adult participants receiving
Ad26.COV2.S during the 2nd and/or 3rd trimester of pregnancy.
Descriptive statistics will also be presented for neonates/infants of adult participants who have received
Ad26.COV2.S during the 2nd and/or 3rd trimester of pregnancy by group and overall.
Several definitions of serological responses will be applied (fold increases in GMC [S-ELISA] or GMT
[VNA]). Graphical representations of immunologic parameters will be prepared as applicable. Frequency
tabulations will be calculated for discrete (qualitative) immunologic parameters, as applicable.
The impact of baseline characteristics on the humoral responses may be explored graphically or with
descriptive statistics by group and overall.
For adult participants, all immunogenicity analyses will be performed on the PPI-A by group (previous
vaccination status) and overall. Immunogenicity analyses may also be performed by stage of pregnancy at
which the vaccine was administered, vaccination regimen (ie, 1-dose schedule or 1-dose schedule with a
booster dose), SARS-CoV-2 baseline serostatus and by actual vaccine history within each group.
For neonates/infants, immunogenicity analyses will be performed on the PPI-NVN setby group and overall.
Analyses may also be performed by the gestational age at the time of vaccine administration, and SARS-
CoV-2 baseline serostatus of the adult participant.
Safety Endpoints
No formal statistical testing of safety data is planned. Safety data will be analyzed descriptively for adult
participants (including pregnancy outcomes) and their neonates/infants up to approximately 12 months of
age (including neonatal outcomes) for all enrolled participants.
For adult participants, all safety analyses will be performed on the Full Analysis Set-Adults (FAS-A).
For adult participants, safety analyses may also be performed by stage of pregnancy at which the vaccine
was administered, vaccination regimen (ie, 1-dose schedule or 1-dose +booster), SARS-Cov-2 baseline
serostatus and by actual vaccine history within each group.
For neonates/infants, safety analyses will be performed on the FAS-NVN.
For neonates/infants, analyses may also be performed by vaccination regimen (1-dose schedule or 1-dose
+booster) received by the adult participant during the study.
Outcomes
Adverse maternal/fetal outcomes and adverse neonate/infant outcomes will be defined using the Case
Definitions for Pregnancy Outcomes for each endpoint.

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Planned Analyses
Primary Analysis
The primary analysis of safety and immunogenicity will be performed when all adult participants have
completed the 42-day postpartum visit in all groups (or for participants who discontinued earlier).
The analysis will include safety (AEs, SAEs, AESIs, pregnancy-related AEs throughout pregnancy and
pregnancy outcomes) and immunogenicity data (ELISA and VNA) for all adult participants and
neonates/infants and in cord blood at the time of delivery. The primary analysis will include all data up to
and the Day 42 postpartum follow-up visit (inclusive). The results of this analysis may be used for
regulatory submissions.
Final Analysis
The final analysis will be performed when all adult participants and all neonates/infants have completed
the final visit. Analysis will include safety (AEs, SAEs, and pregnancy outcomes) and immunogenicity
data. Booster dose effect will be evaluated on safety and immunogenicity.
Note: Interim analyses may be performed as required or if requested by health authorities.

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1.2. 
Schema
Figure 1: 
Schematic Overview of the Study
Monthly phone calls are intended for safety follow up and delivery planning, should start after Day 29 and continue periodically until birth.
For the main study, the aim is to recruit at least 40 participants in Groups 1 3 and at least 25 participants in Group 4. All these participants will receive a single dose of Ad26.COV2.S at
5×1010 vp.
A booster vaccination with a single dose of Ad26.COV2.S at 5×1010 vp will be offered to ongoing, consenting participants who were vaccine naïve at study entry (Group 4, including
Sentinel and Safety Cohorts), and who have completed the pregnancy during which they were enrolled in the study, are not pregnant again and have not received another COVID 19
vaccine (eg, national immunization program). If a booster is administered in these participants, the postpartum and booster visits can be combined.

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grading scale. if an event is ongoing 7 days post vaccination, the participant should be encouraged to continue filling in the diary until resolution and the rest of the diary may be
reviewed again at the next visit.
Footnotes:
a. 
Screening can be performed within 28 days prior to the study vaccination or on the day of vaccination. If screening is performed on the day ofvaccination (recommended), Visit 1
and Visit 2 will coincide on Day 1. In that case, laboratory assessments should only be done once. During the screening visit, at least, all eligibility criteria must be verified prior to
randomization and vaccination.
b. 
If allowed by local regulations: study visits may take place at the participant’s home or other location in the event of an ongoing SARS CoV 2 infection performed; visits can be
performed by a trained health care professional (HCP) via phone call or a telemedicine contact.
c. 
For those participants who are unable to continue participation in the study until the end of study visit, but for whom consent is not withdrawn, an early exit visit will be conducted as
soon as possible. Participants who wish to withdraw consent from participation in the study will be offered an optional visit for safety follow up. For these participants only the
safety assessments of the early exit visit (no blood sampling for immunogenicity) will be performed.
d. 
Postpartum (PP) 1 refers to the day of pregnancy completion/termination. Visit 9 (PP 1) should occur on the day of pregnancy completion/termination or within 3 days after
pregnancy completion/termination. Assessments collected the day before birth can be used, but are preferably collected on the date of birth. If the delivery takes place in a hospital
where the site staff does not have privileges, it is expected that medical records are obtained to collect the applicable protocol required safety information. Blood samples are not
expected in this case.
e. 
Signing of the ICF should be done before any study related procedure. The ICF can be signed remotely prior to the Screening Visit. By signing the main ICF, consent is also given to
follow up the neonates/infants after birth. Note: Logistics such as downloading of an application to the participant's eDevice, or accessing study materials for enrollment, are not
considered a study related procedure.
f. 
Check clinical status again before study vaccination.
g. 
Maternal demographic information to be collected at screening includes age, race/ethnicity, and geographical location/residence.
h. 
Information to be collected for medical and obstetric history, physical examinations and vital signs is specified in Section 8.2. Only relevant medical history (general and obstetric) is
to be collected, in particular: history ofcongenital abnormalities, history of cancer, history of immunodeficiency or conditions treated with immunomodulators, major psychiatric
illness, major cardiovascular or lung diseases, history of an allergy to vaccination, ongoing relevant comorbidities per investigator's judgement, history of any comorbidities known
to be associated with an increased risk of progression to severe COVID 19 (see Section 10.9 ) , and history of hepatitis B or hepatitis C infection.
i. 
Baseline pulse oximetry measurements will be used to estimate the amount of oxygen in the blood, low levels may indicate either SARS CoV 2 infection or an underlying medical
condition.
j. 
For laboratory assessments, including chemistry and hematology assessment of platelet counts see Appendix 2, Table 6 for details. If the data obtained from the laboratory
assessment shows abnormal results that are considered clinically significant, then additional blood samples could be taken until normalization of the readings, at the discretion of the
investigator. Urine dipstick for protein and glucose will be performed at these visits. If urinalysis results are positive additional work up for pre eclampsia or gestational diabetes
may be warranted, but do not preclude inclusion in the study.
k. 
See Section 8.2.1 for details on obstetric ultrasound. Ultrasound is not required at Visit 2 if screening (Visit 1) ultrasound has been obtained within the past 10 days and there is no
other indication for repeating the ultrasound (eg, fetal abnormalities).
l. 
Diagnostic molecular RT PCR test for SARS CoV 2 infection will be performed at a local laboratory. Test failures or tests that are indeterminate must be repeated. For exploratory
endpoint purposes, a molecular RT PCR test for SARS CoV 2 infection may be performed at a central laboratory and will not be reported to the sites. In case of a positive nasal
swab result at screening or D1, an exclusion criterion has been met, and samples will not be shipped to central laboratory.
m. 
The investigator must check for acute illness or body temperature ≥38.0°C/100.4oF at the time of vaccination. If any of these events occur within 24 hours prior to the planned
vaccination, the vaccination can be rescheduled in accordance to the protocol’s window. For further details refer to Section 5.5.
n. 
Site staff should provide training to participants to complete the reactogenicity diary using the eCOA on their own eDevice (smartphone or tablet) when feasible, provisioned devices
will be available on a limited basis. If a participant is unable to complete the eCOA, a study staff member can collect the information on the participant's behalf as detailed in
Section 8.1.2. eCOA set up should be completed before any tests, procedures, to avoid influencing participant responses.
o. 
On Day 1, all participants will be provided a pulse oximeter (to measure blood oxygen saturation and pulse rate), thermometer and a nasal swab kit to be used in case of a COVID-19
episode (see Section 8.1.2). The pulse oximeter and thermometer for the neonate/infant can also be provided.
p. 
The SIC questionnaire asks the participant if she had any of the prespecified signs or symptoms of COVID 19 (see Section 10.8Appendix 8) during the past 24 hours (including
highest temperature in the last 24 hours), and (when applicable) to rate the severity. The baseline SIC questionnaire (Visit 2) must be completed prior to vaccine administration.

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q. 
Participants will be closely observed at the site for a minimum of 30 minutes (60 minutes for Sentinels and participants in the Safety Cohort) post vaccination. Sentinels and
participants in the Safety Cohort will be vaccinated at least 1 hour apart.
r. 
Solicited AEs (reactogenicity) and unsolicited AEs will be assessed from time of vaccination until 7 days post vaccination and 28 days post vaccination, respectively.
s. 
Participants will be asked at least twice a week, through the eCOA, if they have experienced any new symptoms or health concerns that could be related to infection with
SARS CoV 2. Refer to Section 1.3.4Procedures for Participants with (Suspected) COVID 19. In addition, participants will be asked daily within the 30 day time period post
vaccination if they have experienced any health concerns related to suspected AESI’s, and if so, participants will be advised to contact the study center. Refer to Section 8.3.6
Adverse Events of Special Interest.
t. 
All SAEs related to study procedures or 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. MAAE are to be reported for all participants from the moment of the vaccination until 6 months after vaccination. MAAEs leading to study discontinuation which are to
be reported until completion of the participant’s last study related procedure. New onset of chronic diseases will be collected as part of the MAAEs. See Section 8.3.1 for more
details.
u. 
Refer to Section 6.8for collection and recording of concomitant therapies.
v. 
Information to be collected for delivery history.
w. 
Blood volume will be divided into plasma and serum as described in the laboratory manual and stored for potential coagulation and/or hematology related testing in a central
laboratory (see Section 10.2, Appendix 2, Table 7). Unused samples may be used for immunogenicity testing.
x. 
Approximately 0.5 mL of colostrum should be collected within 1 week postpartum and approximately ≥5 mL of breast milk around PP43. Collection of breast milk and colostrum is
optional. Whether the adult participant is breastfeeding, and until when, will be recorded.
y. 
A booster vaccination with a single dose of Ad26.COV2.S at 5×1010 vp will be offered to ongoing, consenting participants who were vaccine naïve at study entry (Group 4,
including Sentinel and Safety Cohorts) and who have completed the pregnancy during which they were enrolled in the study, are not pregnant again (as specified in Section 1.3.1.1)
under the conditions delineated in Section 6.2. The booster vaccination will be administered not earlier than 2 months after the participant’s Ad26.COV2.S vaccination in the study.
The Booster Vaccination Visit should preferably coincide with a scheduled visit. If not operationally feasible to coincide with an existing visit, an unscheduled visit may be planned.
After the booster vaccination and 28day post booster visit, participants will continue procedures and visits as in the original SoA.
z. 
In the situation of a completion/ termination of the pregnancy before the completion of the applicable Study Period visits, PP1 (Visit 9) is to be completed. The participant should
then follow the visits scheduled in the ‘Study Period’ up to Visit 5 (meaning all scheduled visits in this period except for the monthly phone calls  Visits 6 8) AND the ‘Follow up’
section of the schedule of activities (Visits 10 12). Additional guidance if the pregnancy is completed/ terminated before the pre partum visits are completed is provided in Appendix
10.13.
aa. 
Body temperature will be measured preferably via the oral route, or in accordance with the local standard of care.
bb. History of COVID 19 vaccination (name/manufacturer of the vaccine and date of administration) ≥4months prior to the study vaccine will be reported in the eCRF.
cc. 
Laboratory assessments performed at Visits 4 and 5 are optional. If the outcome from the laboratory assessment at Visit 3 show abnormal results that are considered clinically
significant, then an on site visit should be performed. In this case, an additional sample should be taken for further assessment 7 days later and until normalization of the readings, at
the discretion of the investigator and targeted physical examinations and vital signs should be collected. If the outcome from the laboratory assessment at Visit 3 show normal results,
only a safety phone call is required (no physical examinations and vital signs needed).
dd. With only 1 participant in this subset at the time of writing this Protocol Amendment 7, PBMC sampling will be removed from the study as of Protocol Amendment 7 approval.
ee. 
The Follow up safety assessments for adults at the end of the study visit (no.12) may be performed simultaneously with postnatal (PN 12 months) follow up safety visit (no. 14) as
feasible.
AE  adverse event; AESI  adverse event of special interest; COVID 19  coronavirus disease 2019; d  day(s); eCOA  electronic clinical outcome assessment; eDC  electronic data
capture; FU  follow up; ICF  informed consent form; MAAE  medically attended adverse event; m  months; PBMC  peripheral blood mononuclear cell; PP  postpartum; SAE
serious adverse event; SIC  Symptoms of Infection with Coronavirus 19; SARS CoV 2  severe acute respiratory syndrome coronavirus2.

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1.3.1.1. 
Vaccine Naïve Adult Participants (Group 4, Including Sentinel and
Safety Cohorts): Booster Vaccination Visits
Participants who are vaccine naïve at study entry will be offered an (optional) booster vaccination
with a single dose of Ad26.COV2.S at 5×1010 vp.
The booster will be offered (as outlined in Section 6.2) to:
1. Group 4participants, including Sentinel and Safety Cohorts,
2. Participants who are ongoing and consenting,
3. Participants who have completed the pregnancy during which they were enrolled in the study,
are not pregnant again,
4. Participants have not received another COVID-19 vaccine (eg, national immunization
program), and
5. Participant does not meet any criterion per section 7.1 (Discontinuation of Study Vaccination)
Previously vaccinated participants (Groups 1-3) will receive a single dose of Ad26.COV2.S at
5×1010 vp as part of the study, but are not eligible for a second booster during the study.

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1.3.1.2. 
Vaccine Naïve Adult Participants (Group 4, Including Sentinel and,
Safety Cohorts): Booster Vaccination Schedule
Visit # 
Booster Vaccination Visit PB 1a 
PB 1 + 28db
Visit Timing and Window 
No earlier than Vac1 + 2 months 
PB 29 (±7d)
Informed consentc
#
Vital signs including body temperatured
#
Pulse oximetry  
#
Pre-vaccination symptomse 
#
Targeted physical examinationf 
# 

Urine pregnancy test 
#
Blood sample for humoral immunogenicity  
(serum), mLg 
#10 mL 
10 mL
N-serologyg 
#2.5 mL 
2.5 mL
Vaccination-related biomarker blood sample 
(PAXgene® tubes, 2.5 mL)
#2.5 mL 
2.5 mL
Colostrum (≥0.5 mL)/ Breast milk sample
(≥5mL) (optional)n 


Clinical laboratory blood sample (whole
blood)g,h
#15 mL 
15 mL
Vaccination  

30 minutes post-vaccination observation  

Solicited AE recordingi 

Investigator’s assessment of reactogenicity 
(participant’s diary)
 
 j
Breast milk production changesp 
 

Unsolicited AE recordingi 

(Suspected) COVID-19 surveillance
(symptom check)k
-----------------------Continuous----------------
AE/SAE/MAAE/AESI recordingl 
-----------------------Continuous----------------
Concomitant therapiesm 
o

# Procedure to be completed pre-vaccination
a. 
The booster vaccination will be administered not earlier than 2 months after completion of the participant’s Ad26.COV2.S
vaccination in the study and should be administered latest at birth +11 months. The study duration will not be extended.
(See Section 6.2).
b. 
After the Booster Vaccination Visit, participants will resume procedures and visits depicted in Schedule of Activities,
Section 1.3.1.
c. 
Signing of the ICF should be done before any visit related procedures are performed.
d. 
Body temperature will be measured preferably via the oral route, or in accordance with the local standard of care.
e. 
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 24hours prior to the planned vaccination, the vaccination can be rescheduled as long as this is within
the allowed window.
f. 
Information to be collected for targeted physical examinations and vital signs is specified in Section 8.2
g. 
For the booster vaccination visit, blood samples should be taken except when the previous sample for assessment of
humoral immunogenicity occurred within 5 days of the visit. If a scheduled visit falls within the PB 1 + D28 visit window
(±7d), the PB 1 + D28 visit may be combined with the scheduled visit, and any blood samples that are listed in both visits
should only be collected once.
h. 
Whole blood samples (~2mL) will be used for immediate measurement of a platelet count (as part of a complete blood
count, if applicable) in a local laboratory or substitute for local laboratory, depending on local feasibility towards
turnaround time of sample processing. Serum (4 mL) and plasma (2.5 mL) samples will be derived from the whole blood
samples (8 mL and 5 mL, respectively) for retrospective coagulation related testing in a central laboratory in case of a
suspected AESI (see Section 10.2, Appendix 2). Unused samples may be used for immunogenicity testing. If a whole blood
sample has been taken within 5 days before vaccination, sample collection does not need to be performed before
vaccination.
i. 
Solicited AEs (reactogenicity) and unsolicited AEs will be assessed from time of vaccination until 7 days post vaccination
and 28 post vaccination, respectively.

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j. 
If an event is ongoing 7 days post vaccination, the participant should keep filling in the diary until resolution and the diary
may be reviewed again at the next visit.
k. 
Each participant will be asked at least twice a week, through the eCOA, if they have experienced any new symptoms or
health concerns that could be related to infection with SARS CoV 2. Refer to Section 1.3.4Procedures for Participants
with (Suspected) COVID 19. In addition, participants will be asked daily within the 30 day time period post vaccination if
they have experienced any health concerns related to suspected AESI’s, and if so, participants will be advised to contact the
study center. Refer to Section 1.3.4 Adverse Events of Special Interest
l. 
All SAEs related to study procedures or 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. MAAE are to be reported for all participants from the
moment of the vaccination until 6 months after vaccination or end of study duration, whatever comes first, except for
MAAEs leading to study discontinuation which are to be reported until completion of the participant’s last study related
procedure. New onset of chronic diseases will be collected as part of the MAAEs. See Section 8.3.1 for more details.
m. 
Refer to Section 6.8for collection and recording of concomitant therapies.
n. 
Approximately 0.5 mL of colostrum or approximately ≥5 mL of breast milk will be collected if participant is breastfeeding.
Collection of breast milk and colostrum is optional.
o. 
Investigator must check if the participant has received another COVID 19 vaccine outside the study (eg, national
immunization program). If so, the participant is not allowed to receive the booster dose
p. 
Participants will be asked to confirm whether subjective changes in (postpartum) breast milk production (reduction) have
been noticed (yes/no) and report changes daily in the eCOA diaries.
AE
adverse event; AESI
adverse event of special interest; D day(s); ICF informed consent form; MAAE
medically
attended adverse event; PB  post booster; SAE
serious adverse event; SARS CoV 2
severe acute respiratory syndrome
coronavirus 2.

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d. 
Postpartum (PP) 1 refers to the day of pregnancy completion/termination. Visit 9 (PP 1) should occur on the day of pregnancy completion/termination or within 3 days after
pregnancy completion/termination. Assessments collected the day before birth can be used but are preferably collected on the date of birth (for example in case of pre planned
ceasarian). If the delivery takes place in a hospital where the site staff does not have privileges, it is expected that medical records are collected to collect the applicable protocol
required information. Blood samples are not expected in this case.
e. 
Signing of the ICF should be done before any study related procedure. The ICF can be signed remotely prior to the Screening Visit. Downloading of an application to the
participant's eDevice, to access materials for enrollment and study information, is not considered a study related procedure. By signing the main ICF, consent is also given to follow
up the neonates/infants after birth.
f. 
Check clinical status again before study vaccination.
g. 
Maternal demographic information to be collected at screening includes age, race/ethnicity, and geographical location/residence.
h. 
Information to be collected for medical and obstetric history, physical examinations and vital signs is specified in Section 8.2. Only relevant medical history (general and obstetric) is
to be collected, in particular: history of congenital abnormalities, history of cancer, history of immunodeficiency or conditions treated with immunomodulators, major psychiatric
illness, major cardiovascular or lung diseases, history of an allergy to vaccination, ongoing relevant comorbidities per investigator's judgement, history of any comorbidities known
to be associated with an increased risk of progression to severe COVID 19 (see Section 10.9) , and history of hepatitis B or hepatitis C infection.
i. 
Baseline pulse oximetry measurements will be used to estimate the amount of oxygen in the blood, low levels may indicate either SARS CoV 2 infection or an underlying medical
condition.
j. 
For laboratory assessments, including chemistry and hematology assessment of platelet counts (to be done locally within 72 hours of blood collection) see Appendix 2, Table 6 for
details. If the outcome from the laboratory assessment shows abnormal results that are considered clinically significant, then additional blood samples could be taken until
normalization of the readings, at the discretion of the investigator. Urine dipstick for protein and glucose will be performed at these visits. If urinalysis results are positive additional
work up for pre eclampsia or gestational diabetes may be warranted, but do not preclude inclusion in the study.
k. 
See Section 8.2.1 for details on obstetric ultrasound. Ultrasound is not required at Visit 2 if screening (Visit 1) ultrasound has been obtained within the past 10 days and there is no
other indication for repeating the ultrasound (eg, fetal abnormalities).
l. 
Diagnostic molecular RT PCR test for SARS CoV 2 infection will be performed at a local laboratory. For exploratory endpoint purposes, a molecular RT PCR test for SARS CoV 2
infection may be performed at a central laboratory and will not be reported to the sites. Test failures or tests that are indeterminate must be repeated. In case of a positive nasal swab
result at screening or D1, an exclusion criterion has been met, and samples will not be shipped to central laboratory.
m. 
The investigator must check for acute illness or body temperature ≥38.0°C/100.4oF at the time of vaccination. If any of these events occur within 24 hours prior to the planned
vaccination, the vaccination can be rescheduled in accordance to the protocol’s window. For further details refer to Section 5.5.
n. 
Participants will complete the reactogenicity diary using the eCOA on their own eDevice (smartphone or tablet) when feasible, also provisioned devices will be available on a limited
basis. If a participant is unable to complete the eCOA, a study staff member can collect the information on the participant's behalf as detailed in Section 8.1.2. All eCOA assessment
should be conducted/completed before any tests, procedures, or other consultations, in order to avoid influencing participant responses.
o. 
At Baseline, all participants will be provided a pulse oximeter (to measure blood oxygen saturation and pulse rate), thermometer and a nasal swab kit to be used in case of a COVID
19 episode (see Section 8.1.2). The pulse oximeter and thermometer for the neonate/infant can also be provided.
p. 
The SIC questionnaire asks the participant if she had any of the prespecified signs or symptoms of COVID 19 (see Section 10.8Appendix 8) during the past 24 hours (including
highest temperature in the last 24 hours), and (when applicable) to rate the severity. The baseline SIC questionnaire (Visit 2) must be completed prior to vaccine administration.
q. 
Participants will be closely observed at the site for a minimum of 30 minutes post vaccination.
r. 
Solicited AEs (reactogenicity) and unsolicited AEs will be assessed from time of vaccination until 7 days post vaccination and 28 post vaccination, respectively.
s. 
Participant will be asked at least twice a week, through the eCOA, if they have experienced any new symptoms or health concerns that could be related to infection with
SARS CoV 2. Refer to Section 1.3.4Procedures for Participants with (Suspected) COVID 19. In addition, participants will be asked daily within the 30 day time period post
vaccination if they have experienced any health concerns related to suspected AESI’s, and if so, participants will be advised to contact the study center. Refer to Section 8.3.6
Adverse Events of Special Interest.
t. 
All SAEs related to study procedures or 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. MAAE are to be reported for all participants from the moment of the vaccination until 6 months after vaccination. MAAEs leading to study discontinuation which are to
be reported until completion of the participant’s last study related procedure. New onset of chronic diseases will be collected as part of the MAAEs. See Section 8.3.1 for more
details.
u. 
Refer to Section 6.8for collection and recording of concomitant therapies
v. 
Information to be collected for delivery history.

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w. 
Blood volume will be divided into plasma and serum as described in the laboratory manual and stored for potential coagulation and/or hematology related testing in a central
laboratory (see Section 10.2, Appendix 2, Table 7). Unused samples may be used for immunogenicity testing.
x. 
Approximately 0.5 mL of colostrum should be collected within 1 week postpartum and approximately ≥5 mL of breast milk around PP43. Collection of breast milk and colostrum is
optional. Whether the adult participant is breastfeeding, and until when, will be recorded.
y. 
In the situation of a completion/ termination of the pregnancy before the completion of the applicable Study Period visits, PP1 (Visit 9) is to be completed. The participant should
then follow the visits scheduled in the ‘Study Period’ up to visit 5 (meaning all scheduled visits in this period except for the monthly phone calls  Visits 6 8) AND the ‘Follow up’
section of the schedule of activities (Visits 10 12). Additional guidance if the pregnancy is completed/ terminated before the pre partum visits are completed is provided in Appendix
10.13.
z. 
Body temperature will be measured preferably via the oral route, or in accordance with the local standard of care.
aa. 
Any history of COVID 19 vaccination (name/manufacturer of the vaccine and date of administration) ≥4months prior to the study will be reported in the eCRF.
bb. Laboratory assessments performed at Visits 4 and 5 are optional. If the outcome from the laboratory assessment at Visit 3 show abnormal results that are considered clinically
significant, then an on site visit should be performed. In this case, an additional sample should be taken for further assessment 7 days later and until normalization of the readings, at
the discretion of the investigator and targeted physical examinations and vital signs should be collected. If the outcome from the laboratory assessment at Visit 3 show normal results,
only a safety phone call is required (no physical examinations and vital signs needed).
cc. 
With only 1 participant in this subset at the time of writing this Protocol Amendment 7, PBMC sampling will be removed from the study as of Protocol Amendment 7 approval.
dd. The Follow up safety assessments for adults at the end of the study visit (no.12) may be performed simultaneously with postnatal (PN 12 months) follow up safety visit (no. 14) as
feasible.
AE  adverse event; AESI  adverse event of special interest; COVID 19  coronavirus disease 2019; d  day(s); eCOA  electronic clinical outcome assessment; FU  follow up; ICF 
informed consent form; MAAE  medically attended adverse event; m  months; PBMC  peripheral blood mononuclear cell; PP  postpartum; SAE
 serious adverse event; SIC 
Symptoms of Infection with Coronavirus 19; SARS CoV 2  severe acute respiratory syndrome coronavirus.

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b. 
If allowed by local regulations: study visits may take place at the participant’s home or other location in the event of ongoing SARS CoV 2 transmission in the area of the
participant. ; visits can be performed by a phone call or a telemedicine contact. Scheduled assessments may also be performed by a trained HCP.
c. 
At approximately 6 months of age or 28 days after the last routine primary vaccination (dependent on the local primary vaccinations schedule)
d. 
For those participants who are unable to continue participation in the study up to Visit 14, but for whom consent is not withdrawn, an early exit visit will be conducted as soon as
possible. Parent(s)/caregiver(s) who wish to withdraw consent from participation of the participant in the study will be offered an optional visit for safety follow up for the
participant. This includes the safety assessments of the early exit visit. For these participants only the safety assessments of the early exit visit (no blood sampling for
immunogenicity) will be performed.
e. 
Refer to Section 8.2.6 for assessments to be performed as part of neonatal medical history.
f. 
All SAEs related to study procedures or non investigational sponsor products will be reported from birth until the end of the study/early withdrawal. All other SAEs are to be
reported from the moment of birth until completion of the participant’s last study related procedure.
g. 
MAAE are to be reported for all participants from the moment of birth until 6 months of age, except for MAAEs leading to study discontinuation, are to be reported from birth until
the participant’s last study related procedure. New onset of chronic diseases will be collected as part of the MAAEs
h. 
Refer to Section 6.8for collection and recording of concomitant therapies associated with SAEs and MAAEs.
i. 
Refer to Section 8.2.1 for assessments to be performed.
j. 
Heart rate, respiratory rate, and body temperature. Vital signs measurements are recommended before blood sampling. Body temperatures will be measured according to the local
standard of care (actual routes to be recorded in the eCRF).
k. 
The overall Apgar score is required to be documented in the eDC. The Apgar score comprises of the parameters: color, heart rate, reflexes, muscle tone, and respiration that could be
entered in the eDC if available (See Section 8.2.1).
l. 
Blood sample for humoral immunity also includes sample for previous sero confirmation of SARS CoV 2 infection (antibody).
m. 
Baseline pulse oximetry measurements will be used to estimate the amount of oxygen in the blood, with low levels indicative either of SARS CoV 2 infection or an underlying
medical condition.
n. 
If not given on Day 1, parent(s)/caregiver(s) will be provided with a pulse oximeter (to measure blood oxygen saturation and pulse rate) and thermometer no later than Visit PN 1 (to
be used during a COVID 19 episode in the neonate/infant [see Section 1.3.5]).
o. 
If a participant develops (suspected) COVID 19, refer to Section 1.3.5. Each parent/caregiver will be asked at least twice a week, through the eCOA, if the participant has
experienced any new symptoms or health concerns that could be related to infection with SARS CoV 2. Sites should reach out to a parent/caregiver if the parent/caregiver fails to
complete the surveillance question upon any of these reminders. The questionnaire will be accessible on the eCOA platform in between scheduled reminders and
parent(s)/caregiver(s) will be encouraged to answer the surveillance question in the eCOA as soon as possible after the onset of COVID 19 like symptoms. Every effort will be made
to document the status of all participants that are lost to follow up due to the parent/caregiver not completing the eCOA and for whom hospitalization has not been recorded.
p. 
eCOA set up should be done by site staffaccording to PN1 visit window. Actual training can be completed remotely by the parent(s)/caregiver(s); sites should ensure that parents
perform this training no later than on PN14. Parent(s)/caregiver(s) will complete the eCOA using an application on their own eDevice (smartphone or tablet) if their device is
compatible with the application. All eCOA assessments should be conducted/completed before any tests, procedures, or other consultations to prevent influencing participant
responses. If a parent/caregiver is unable to complete the eCOA, a study staff member can collect information on the participant’s behalf as detailed in Section 8.1.2.
q. 
The PedSIC questionnaire asks the parent(s)/caregiver(s) if their neonate/infant had any of the prespecified signs or symptoms of COVID 19 during the past 24 hours (including
highest temperature in the last 24 hours), and (when applicable) to rate the severity.
r. 
Neurodevelopmental status will be measured using the Ages & Stages Questionnaire, 3rd edition (ASQ 3) as outlined in Section 8.2.6.
s. 
If Early Exit occurs when the infant is 2, 6 or 12 months old.
t. 
The PN 6 mo and PN 12 mo visit may coincide with the PP 6 m and PP 12 m, if feasible to respect the visit windows.
u. 
The Follow up safety assessments for adults at the end of the study visit (no.12) may be performed simultaneously with postnatal (PN 12 months) follow up safety visit (no. 14) as
feasible.
d  days; eCOA  electronic clinical outcome assessment; eDC  electronic data capture; mo  months of age; ObsRO  observer reported outcomes; PedSIC  Pediatric Symptoms of
Infection with Coronavirus 19; PN  postnatal; SAE  serious adverse event.

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f. 
Participants should undertake the COVID 19 procedures until 14 days after symptom onset (COVID 19 Day 15) or until resolution of the COVID 19 episode, whichever comes last.
Resolution of a COVID 19 episode is defined as having 2 consecutive SARS CoV 2 negative nasal swabs and 2 consecutive days with no COVID 19 related signs or symptoms.
Once past COVID 19 Day 15, participants should stop the collection of nasal swabs samples as soon as 2 consecutive nasal samples are SARS CoV 2 negative, but (if still
symptomatic at that time) should continue completing the ePROs (including SIC, body temperature, and pulse oximetry) in the eCOA until 2 consecutive days with no COVID 19
related signs or symptoms.
g. 
Only applicable for participants that have at least 1 SARS CoV 2 positive nasal swab collected on COVID 19 Day 1 2 or Day 3 5. COVID 19 Day 29 should still be performed even
if the nasal swab results are still pending.
h. 
The visit on COVID 19 Day 29 can be combined with a regular study visit if within the applicable visit windows.
i. 
The COVID 19 Day 1 2 nasal swab can be collected at the study site (or hospital or other location, if needed), if preferred by the participant.
j. 
All COVID 19 Day 3 5 and Day 29 assessments may be performed by a trained HCP at the participant’s home, if allowed per local regulations.
k. 
If a participant has a positive test result for SARS CoV 2 infection and/or depending on the medical status of the participant. If necessary, study site personnel or a trained HCP may
visit the participant at home (or at the hospital or other location, if needed), if allowed by local regulations. Under these circumstances, the participant will be contacted by the site at
least once per week.
l. 
In case of COVID 19 like symptoms, based on the information collected through the SIC, the site will reach out to the participant at the latest on COVID 19 Day 2 (the day after the
day of symptom onset) to assess whether the reported signs and symptoms qualify as a suspected COVID 19 episode using prespecified criteria (Section 8.1.2.4). As several of the
prespecified criteria for suspected COVID 19 overlap with vaccine related reactogenicity, investigators' clinical judgement is required to exclude vaccine related events when
assessing suspected COVID 19. In case the participant would actively reach out to the site already on COVID 19 Day 1, the site should already make a first assessment on COVID
19 Day 1 to check whether the reported signs and symptoms qualify as a suspected COVID 19 episode using prespecified criteria (Section 8.1.2.4).
m. 
In case of COVID 19 like symptoms, the site will interview the participant to assess whether the reported signs and symptoms still qualify as a suspected COVID 19 episode using
prespecified criteria (Section 8.1.2.4).
n. 
A nasal swab should be collected from the participant at home (using available material for home swabs provided by the study staff) as soon as the prespecified criteria for suspected
COVID 19 are met and preferably on the day of symptom onset or the day thereafter (COVID 19 Day 1 2). The sample collected on COVID 19 Day 1 2 should be transferred to the
study site, as arranged by the study site, as soon as possible after collection, preferably within 3 days. Nasal swabs should also be collected once every 7 days until 14 days after
symptoms onset (COVID 19 Day 15) or until resolution of the COVID 19 episode, whichever comes last. These samples should be transferred to the study site, as arranged by the
study site, within 3 days after collection. Details are provided in the laboratory manual. If the participant requires assistance, a trained HCP can help the participant to collect the
nasal swabs. If 2 consecutive nasal swabs negative for SARS CoV 2 are not available due to operational reasons (eg, delays in results availability), participants may cease collection
of nasal swabs at the COVID 19 Day 29 visit, provided they have 2 consecutive days with no COVID 19 related signs and symptoms. In these cases, participants may be asked to
resume sample collection if nasal sample results
once available
do not present with 2 consecutive negative swabs for SARS CoV 2. All nasal swabs will be tested by a local
laboratory for case management.
o. 
The nasal swab should be collected and pulse oximetry (3 times a day), should be started as soon as possible after it has been confirmed that the prespecified criteria for suspected
COVID 19 (Section 8.1.2.4) are met. On the first day the participant experiences signs/symptoms, the participant should record at least 1 of the 3 pulse oximetry readings in the last
24 hours in the eCOA.
p. 
Nasal swabs will be tested by a local laboratory for case management. For participants with suspected COVID 19, confirmation of SARS CoV 2 infection by RT PCR or other
molecular diagnostic test at a central laboratory may be used for the analysis of the case definition.
q. 
Blood sample for humoral immunity may include a sample for sero confirmation of previous SARS CoV 2 infection (antibody).
r. 
Participants should complete the (suspected) COVID 19 surveillance (symptom check) in the eCOA. In case of COVID 19 like signs and symptoms, participants should be
encouraged by the site to complete the SIC daily, preferably in the evening around the same time each day, starting on the first day they experience symptoms. Sites should remind
the participant to complete the SIC, unless special circumstances occur such as hospitalization or ventilation, in which case the reason for not completing the SIC should be recorded
by site staff in the clinical database. If signs and symptoms are still ongoing on COVID 19 Day 3 5, collection of SIC will be continued until at least 14 days after symptoms onset
unless both COVID 19 Day 1 2 and COVID 19 Day 3 5 nasal swabs are negative. If either of the swabs are positive or the result is unknown AND the participant is beyond 14 days
after onset of symptoms, the SIC can be stopped after 2 days without signs and symptoms.
If a participant is unable to complete the eCOA, a study staff member or a caregiver can collect information on the participant’s behalf as detailed in Section 8.1.2.1.
Participant should measure body temperature daily (oral route preferred, or in accordance with the local standard of care) and record the highest temperature in the last 24 hours.
s. 
If the participant does not have symptoms at that time, he/she will only need to complete the (suspected) COVID 19 surveillance (symptom check) in the eCOA.

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t. 
Includes measurement of vital signs (preferably supine systolic and diastolic blood pressure, heart rate, and respiratory rate [after at least 5 minutes rest] and body temperature). It is
recommended that vital signs are measured before collection of nasal swabs and blood draws.
u. 
In case of COVID 19 like symptoms, the participant will be asked to measure blood oxygen saturation and pulse rate at home 3 times a day (preferably in the morning, at lunch time,
and in the evening). The results will be recorded by the participant in the eCOA.
Upon closure of the COVID 19 episode and procedures, all participants will fall back to the default Schedule of Activities. Closure of a COVID 19 episode should occur at the last study
visit. If the episode is ongoing, it should be marked as such in the eCRF. The episode will be followed by the investigator until resolution or until a clinically stable condition is reached,
and the outcome recorded in the participant’s medical chart.
COVID 19  coronavirus disease 2019; eCOA  electronic clinical outcome assessment; RNA  ribonucleic acid; SARS CoV 2  severe acute respiratory syndrome coronavirus 2; SIC 
Symptoms of Infection with Coronavirus 19.

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d. 
Parent(s)/caregiver(s) should be encouraged by the site to have nasal swabs collected from participants (by qualified study staff/HCP) as indicated in the Schedule of Activities. If the
parent/caregiver or participant is unable or unwilling to have all samples collected as requested, the participant should still complete the other COVID 19 assessments, including the
visit at COVID 19 Day 29.
e. 
If the nasal swab collected on COVID 19 Day 1 to 3 is negative for SARS CoV 2, the participant will not undertake any further COVID 19 procedures and will fall back to the
default Schedule of Activities in Section 1.3.3.
f. 
Participants should undertake the COVID 19 procedures until 14 days after signs or symptom onset/positive molecular test from outside the study (COVID 19 Day 15) or until
resolution of the COVID 19 episode, whichever comes last. Resolution of a COVID 19 episode is defined as having 1 SARS CoV 2 negative nasal swab and 2 consecutive days
with no COVID 19 related signs or symptoms. Once past COVID 19 Day 15, collection of nasal swab samples from participants should be stopped as soon as 1 nasal swab is
SARS CoV 2 negative, but (if still symptomatic at that time) the participant or parent(s)/caregiver(s) should continue completing the ObsROs (including SIC, body temperature, and
pulse oximetry) in the eCOA until 2 consecutive days with no COVID 19 related signs or symptoms.
g. 
The visit on COVID 19 Day 29 can be combined with a regular study visit if within the applicable visit windows.
h. 
If allowed by local or institutional regulations, if a participant has a positive test result for SARS CoV.2 infection and/or depending on the medical status of the participant, the
participant may be requested not to visit the study site but to stay at home; if necessary, study site personnel may visit the participant at home. Under these circumstances, the
participant will be contacted by the site staff at least once per week to follow up on the participant’s condition. The site staff or HCP visiting the participant at home will use personal
protective equipment. A nasal swab should be collected from the participant by qualified study staff as soon as the prespecified criteria for suspected COVID 19 are met and, in case
of COVID 19 like symptoms, preferably on the day of symptom onset or in the 2 days thereafter (COVID 19 Day 1 3). In case of a positive RT PCR sample, nasal swabs should
also be collected once every 7 days until 14 days after signs and symptoms onset/positive RT PCR test from outside the study (COVID 19 Day 15, if applicable) or until resolution
of the COVID 19 episode, whichever comes last. Participants that have a nasal swab taken at Day 1 3 do not need to repeat the swab at Day 4 7, but go straight into the 7 day cycle.
If the nasal swab (Day 1 3, Day 4 7, 7 day cycle) is collected at the participant’s home, study staff should arrange transfer of the sample to the study site as soon as possible after
collection (and within the timelines specified in Section 8.1.2.2). Details are provided in the laboratory manual.
i. 
The nasal swab should be collected and pulse oximetry (3 times a day), should be started (if not started already) as soon as possible after it has been confirmed that the prespecified
criteria for suspected COVID 19 (Section 8.1.2.5 and 8.1.2.6) are met. On the first day the participant experiences signs/symptoms, the participant should record at least 1 of the 3
pulse oximetry readings in the last 24 hours in the eCOA.
j. 
All nasal swabs will be tested by a local laboratory for case management and remaining aliquots will be sent to the central laboratory. For participants with suspected COVID 19
after a positive local test, confirmation of SARS CoV 2 infection by a central laboratory will be used for the analysis of the case definition. Nasal swabs may also be tested for the
presence of other respiratory pathogens using a broad respiratory pathogens panel.
k. 
Blood sample for humoral immunity may include sero confirmation of previous SARS CoV 2 infection (antibody).
l. 
Parent(s)/caregiver(s) should complete the (suspected) COVID 19 surveillance (symptom check). In case of COVID 19 like signs and symptoms, parent(s)/caregiver(s) should be
encouraged by the site to complete the PedSIC daily, preferably in the evening around the same time each day, starting on the first day the participant experiences signs or
symptoms. Sites should remind the parent/caregiver to complete the PedSIC, unless special circumstances occur such as hospitalization or ventilation, in which case the reason for
not completing the PedSIC should be recorded by site staff in the clinical database. If a parent/caregiver is unable to complete the eCOA, a study staff member can collect
information on the parent’s/caregiver’s behalf as detailed in Section 8.1.2.2.
Parent(s)/caregiver(s) should measure body temperature daily (in accordance with the local standard of care) and record the highest temperature in the last 24 hours.
m. 
If the participant does not have symptoms at that time, the parent(s)/caregiver(s) will only need to complete the (suspected) COVID 19 surveillance (symptom check).
n. 
Includes measurement heart rate, respiratory rate [after at least 5 minutes rest, if feasible] and body temperature. It is recommended that vital signs are measured before collection of
nasal swabs and blood draws.
o. 
In case of COVID 19 like signs or symptoms, the parent(s)/caregiver(s) will be asked to measure blood oxygen saturation and pulse rate at home 3 times a day (preferably in the
morning, at lunch time, and in the evening). The results will be recorded by the parent(s)/caregiver(s) in the eCOA. On the first day the participant experiences signs/symptoms, the
participant should record at least 1 of the 3 pulse oximetry readings in the last 24 hours in the eCOA.

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Upon closure of the COVID 19 episode and procedures, all participants will fall back to the default Schedule of Activities. Closure of a COVID 19 episode should occur at the last study
visit. If the episode is ongoing, it should be marked as such in the eCRF. The episode will be followed by the investigator until resolution or until a clinically stable condition is reached,
and the outcome recorded in the participant’s medical chart.
COVID 19  coronavirus disease 2019; eCOA  electronic clinical outcome assessment; ObsRO  observer reported outcomes; RNA  ribonucleic acid; SARS CoV 2  severe acute
respiratory syndrome coronavirus 2; PedSIC Pediatric Symptoms of Infection with Coronavirus 19.
Note: Testing is recommended for all neonates born to mothers with confirmed COVID 19 at the time of birth, regardless of whether there are signs of infection in the neonate (see
Section 8.1.2).

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2. 
INTRODUCTION
Ad26.COV2.S (also known as Ad26COVS1) is a monovalent vaccine composed of a recombinant,
replication-incompetent Ad26 vector, constructed to encode the S protein derived from a SARS-
CoV-2 clinical isolate (Wuhan, 2019, whole genome sequence NC_045512), stabilized in its
prefusion conformation.
On 27 February 2021, the US Food and Drug Administration (FDA) issued emergency use
authorization (EUA) for Ad26.COV2.S for the prevention of COVID-19. On 11 March 2021, the
EuropeanCommission granted conditional marketing authorization for the Ad26.COV2.S vaccine.
Other regulatory agencies have subsequently authorized or (conditionally) approved the vaccine.
A single dose of Ad26.COV2.S (5×1010 vp) has been granted EUA for active immunization to
prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) in individuals 18 years of age and older. The purpose of the current
study is to evaluate safety and immunogenicity of 1 dose of Ad26.COV2.S in pregnant women.
For the most comprehensive nonclinical and clinical information regarding Ad26.COV2.S, refer
to the latest version of the Investigator’s Brochure (IB) for Ad26.COV2.S  (IB 2021) and its
addenda.
The term “study vaccine” throughout the protocol, refers to Ad26.COV2.S  as defined in
Section 6.1. The term “sponsor” used throughout this document refers to the entities listed in the
Contact Information page(s), which will be provided as a separate document. The term
“participant” throughout the protocol refers to the common term “subject.”
COVID-19 Vaccine and Considerations
Currently, there is only limited data about the safety of vaccines for the prevention of COVID-19
in pregnant women. The development of a safe and effective COVID-19 vaccine is considered
critical to contain the current outbreak and help prevent future outbreaks. COVID-19 vaccination
is recommended for people who are trying to get pregnant now or might become pregnant in the
future, as well as their partners (CDC 2021).
The quantitative correlate of protection against SARS-CoV-2 infection has not yet been identified
in humans. Based on experience with severe acute respiratory syndrome coronavirus (SARS-CoV)
and, more recently, in SARS-CoV-2 vaccine efficacy studies and mechanism of protection studies
in nonhuman primates (NHP), binding and neutralizing antibody responses have been identified
as the predominant correlates of protection (MacMahan 2020, Tostanoski 2020, Yu J 2020), and
the correlation has been confirmed for Ad26.COV2.S in NHP and Syrian hamster challenge studies
(Roozendaal 2021, Van der Lubbe 2021).
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

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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).
Before the development of Ad26.COV2.S, the immunogenicity profile of Ad26-vectored vaccine
candidates has been 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 of differentiation (CD) 4+ and CD8+ T cells. (Barouch 2013,
Milligan 2016, Mutua 2019, Salisch & Stephenson 2021).
Ad26.COV2.S Candidate Vaccine
The aim of the COVID-19 vaccine clinical development program is to develop a safe and effective
vaccine for the prevention of COVID-19. The candidate vaccine to be assessed in this study is
Ad26.COV2.S, which is a recombinant, replication-incompetent Ad26 encoding a prefusion
stabilized variant of the SARS-CoV-2 S protein. The parental S protein sequence was derived from
a SARS-CoV-2 clinical isolate (Wuhan, 2019, whole genome Sequence NC_045512). The
selection of antigen was based on previous work on the SARS-CoV and MERS-CoV candidate
vaccines (Chen 2005, Faber 2005, Modjarrad 2019). The S protein is the major surface protein on
coronaviruses and is responsible for binding to the host cell receptor and mediating the fusion of
host and viral membranes, thereby facilitating virus entry into the cell (Zumla 2016). In this study,
the Ad26.COV2.S vaccine is administered and was assessed in 22 healthy adult participants in
their 2nd and/or 3rd trimester of pregnancy  at a single dose of 5×1010 vp (Sentinel and Safety
Cohorts).
SARS-CoV-2 Virology and COVID-19 Disease Burden
SARS-CoV-2 is an enveloped, positive-sense, single-stranded ribonucleic acid (RNA)
Betacoronavirus (CSG 2020, Wu 2020). It was first identified following reports of a cluster of
acute respiratory illness cases in Wuhan, Hubei Province, China in December 2019 (Chen 2020,

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Li 2020). Genomic sequencing performed on bronchoalveolar lavage fluid samples collected from
patients with viral pneumonia, which identified a novel RNA virus from the family Coronaviridae
(Lu 2020, WHO 2005). Phylogenetic analysis of the complete viral genome revealed that the virus,
SARS-CoV-2, is part of the subgenus Sarbecovirus of the genus Betacoronavirus, and is most
closely related (approximately 88% identity) to a group of SARS-CoV-like coronaviruses
previously sampled from bats in China (Lu 2020, Zhou 2020).
SARS-CoV-2 has spread rapidly and globally since its emergence. The World Health Organization
(WHO) declared that the outbreak constituted a public health emergency of international concern
on January 30, 2020, and declared the outbreak to be a pandemic on March 11, 2020 (WHO 2005,
WHO 2020b, WHO 2004). As of 18March 2021, approximately 121,382,067 cases and
approximately 2,683,209 COVID-19-related deaths have been reported worldwide. In the US,
approximately 29,609,194 cases and 538,124deaths have been reported (J Hopkins 2020). As of
18 March 2021, approximately 24,175,984 cases and 577,310 deaths have been reported in the
European Union/European Economic Area (EU/EEA: ECDC 2020a) and the United Kingdom
(ECDC 2020b).
Respiratory symptoms of COVID-19 typically appear 5 to 6 days following exposure to the virus,
but may appear from 2 to 14 days following exposure, with the clinical manifestations ranging
from mild symptoms to severe illness or death  (CDC 2020a,c; Guan 2020; Linton 2020;
UC San Diego; WHO 2020a). Descriptions of COVID-19 clinical case definitions compiled by
the US Centers for Disease Control and Prevention (CDC) and Janssen-sponsored interviews with
COVID-19-experienced clinicians include the following: signs and symptoms of respiratory
distress such as blue lips, extreme shortness of breath and dyspnea, persistent cough, deep vein
thrombosis (DVT), Kawasaki-like disease, discoloration of feet and toes, chills, shaking chills,
loss of sense of taste and smell, signs of stroke, disorientation, inability to respond or understand
verbal communication, among others. Other less common gastrointestinal symptoms have been
reported by CDC (nausea, vomiting, diarrhea) (CDC 2020c).
Pregnant women may also be at increased risk for severe COVID-19 due to changes in their
immune system and respiratory physiology. Furthermore, adverse birth outcomes, such as preterm
delivery and stillbirth, may be more common among women infected with SARS-CoV-2 during
pregnancy. Currently, information relating to the impact of SARS-CoV-2 infection on pregnancy,
is limited. The US Centers for Disease Control (CDC)Immunization Safety Office, Vaccine Safety
Datalink (VSD) found that over a period of 3 months (March 01-May 30, 2020), out of a total of
4,408 persons hospitalized with a COVID-19 diagnosis, 105 (2.4%) pregnant women with SARS-
CoV-2 infection were hospitalized, including 62 (59%) women admitted for obstetric reasons (ie,
labor and delivery or another pregnancy-related indication) of which 12 (19.4%) had COVID-19
comparable symptoms and 50 (80.6%) were asymptomatic; and 43 (41%) women were
hospitalized for COVID-19 related symptoms without an obstetric reason. Of those 43 pregnant
women that were hospitalized due to COVID-19 related symptoms, 13 (30%) required intensive
care unit (ICU) admission, 6 (14%) required mechanical ventilation, and one patient admitted at
15 weeks gestation died from COVID-19. Furthermore, there was an increased prevalence of
pre-pregnancy obesity (a body mass index ≥30 kg/m2) and gestational diabetes in pregnant women

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hospitalized for COVID-19 related symptoms as compared to pregnant women hospitalized for
obstetric reasons. In pregnant women hospitalized with COVID-19, preterm delivery prevalence
was 15.1% overall and 12.2% among live births, almost 70% higher than VSD baseline rates
recorded (8.9% overall out of 43,571 live births and still births) during the study period. The
presence of stillbirth (3.2%) was almost 4times higher among women with SARS-CoV-2 than the
VSD baseline rate during the study period of 0.6% (Panagiotakopoulos 2020).
A separate analysis of 11 case studies on perinatal outcomes of neonates born to women infected
with SARS-CoV-2 during pregnancy, that was conducted in a cohort of 65 women and
67neonates, found that the most common outcome of infection during pregnancy included fetal
distress, reported in 30% of pregnancies, with 37% of women delivering preterm. Neonatal
complications included respiratory distress pneumonia (18%), disseminated intravascular
coagulation (3%), and asphyxia (2%) (Zimmermann 2020).
Clinical manifestations of disease are less severe in children than adults, with the majority of cases
reported as being asymptomatic, mild or moderate (CDC 2020e, Deming 2006, Dong 2020). A
study of 149,082 COVID-19 cases reported in the US found that only 1.7% of these cases occurred
in persons aged <18years, with relatively few pediatric COVID-19 cases hospitalized, indicating
that COVID-19 might have a mild course among younger patients. Hospitalization was most
common among pediatric patients aged <1 year and those with underlying conditions, with the
highest proportion of severe and critical cases, by age group, reported for children aged <1 year of
age (10.6% of cases in this age group), indicating that younger children, particularly infants, are
more susceptible than older children to severe disease (CDC 2020 d,i).
Although the understanding of the epidemiology and clinical spectrum of COVID-19 is still
evolving, the disease burden is rapidly mounting, highlighting the urgent medical need for a
prophylactic vaccine.
It is not known if SARS-CoV-2 will remain as a worldwide pandemic. It is also not known if
immunity is acquired after symptomatic or asymptomatic SARS-CoV-2 infection and how long it
might last. Currently, the only preventive measures that have been employed with some success
have been social distancing and quarantine after contact tracing and testing. Test and treat
approaches await an effective proven safe therapy that can be implemented on a mass scale. It is
generally believed that an effective vaccine will be one of the most important tools to help control
this highly contagious respiratory virus.
The sponsor has developed a COVID-19 vaccine based on a human replication-incompetent Ad26
vector encoding the SARS-CoV-2 S protein. The S protein is the major surface protein of
coronaviruses. Different animal models have been used for the evaluation of candidate coronavirus
vaccines against SARS-CoV (2002-2003 outbreak), and the common conclusion that has emerged
from the evaluation of several different vaccines is that the viral S protein is the only significant
target for neutralizing antibodies (Buchholz 2004, Sui 2005, Zhang 2004, Zhou 2004)and the only
viral protein that can elicit protective immunity in animal models (Berry 2004, Bisht 2004,
Bukreyen 2004, Subbarao 2004, Yang 2004). Based on these findings, the S protein was selected
as the sponsor’s candidate vaccine antigen.

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2.1. 
Study Rationale
Although data are still being accrued on the risks associated with developing COVID-19 during
pregnancy, increased rates of complications, Caesarean sections, preterm delivery and of stillbirth
have been observed during pregnancy with SARS-CoV-2 infection. In addition, it appears from
current reviews that pre-pregnancy obesity and pregnancy diabetes are risk factors for severe
COVID-19 in this population (Panagiotakopoulos 2020). Therefore, access to vaccination against
COVID-19 is warranted during pregnancy. Furthermore, health care workers, who may be among
the first groups targeted for vaccination, include people of reproductive age who may be pregnant,
and therefore there is a need to understand the safety and reactogenicity of the Ad26.COV2.S
vaccine in this population.
There is an increased risk of severe COVID-19 during pregnancy, as well as an increased risk of
adverse birth outcomes (Villar 2021). Therefore, the aim of this study is to assess the safety,
reactogenicity and immunogenicity of Ad26.COV2.S in adult participants in the 2nd and/or 3rd
trimester of pregnancy. Due to the inherently higher rates of spontaneous abortions during the 1st
trimester of pregnancy, participants will be vaccinated in the 2nd and/or 3rd trimester of pregnancy.
A potential benefit of this approach is the higher levels of protective maternal antibodies that are
expected to be transferred to the infant at birth in participants vaccinated during the 2nd and 3rd
trimester (Munoz 2014). Phase 1 and 2 clinical studies VAC31518COV1001, COV1002, and
COV2001 and the Phase 3 efficacy studies VAC31518COV3001 and COV3009 have
demonstrated post-dose 1 safety of the vaccine in adults. The preclinical embryofetal and pre-and
postnatal development toxicity (EFPPND) study (Study TOX14389) confirmed the absence of
developmental and reproductive toxicity in animals. Please refer to the IB  (IB 2021) and its
addenda for VAC31518 (JNJ-78436735) for the most current information.
2.2. 
Background
Nonclinical Pharmacology
Nonclinical studies were performed to test the immunogenicity of different vaccine candidates,
leading to the selection of the current vaccine for this development program.
Nonclinical pharmacology was evaluated in murine, rabbit, Syrian hamster and nonhuman NHP
animal models for immunogenicity and included assessment of immunological parameters
relevant to the theoretical risk of vaccine-associated enhanced respiratory disease (VAERD). A
single immunization with Ad26.COV2.S (5×1010 vp) was shown to be immunogenic, induce S
protein binding antibodies, SARS-CoV-2 neutralizing antibodies and a Th1 mediated immune
response. Efficacy was demonstrated in the Syrian hamster model, in which immunization with
Ad26.COV2.S resulted in a significantly lower infectious viral load in the lungs, as compared with
the Ad26 control vector. Histological analysis of lung tissue at the end of the SARS-CoV-2
challenge study showed minimal pulmonary pathology in the lungs ofAd26.COV2.S immunized
animals. There was no signs of VAERD after SARS-CoV2 inoculation of Ad26.COV2.S
immunized NHP, even under conditions of suboptimal immunity. More details are provided in the
IB (IB 2021) and its addenda.

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Nonclinical Safety
Biodistribution
To assess distribution, persistence, and clearance of the Ad26 viral vector platform, intramuscular
(IM) biodistribution studies have been conducted in rabbits using an Ad26-based HIV vaccine,
Ad26.ENVA.01, and an Ad26-based RSV vaccine, Ad26.RSV.preF. In the available
biodistribution studies, the Ad26 vector did not widely distribute following IM administration in
rabbits. Ad26 vector deoxyribonucleic acid (DNA) was primarily detected at the site of injection,
draining lymph nodes and (to a lesser extent) the spleen. Clearance of the Ad26 vector from the
tissues was observed. Both Ad26 vectors showed a comparable biodistribution despite carrying
different antigen transgenes. These data further indicate that the Ad26 vector does not replicate
and/or persist in the tissues following IM injection. These platform data are considered sufficient
to inform on the biodistribution profile of Ad26.COV2.S for which the same Ad26 vector
backbone is used.
Toxicology
A combined GLP repeated dose toxicity and local tolerance study with Ad26.COV2.S was
conducted in male and female New Zealand White (NZW) rabbits. In this study, Ad26.COV2.S
was well tolerated when administered on 3 occasions over 4 weeks (ie, every 2 weeks) at
1 x 1011 vp/dose. The observed changes were related to a normal, anticipated (local and systemic)
immunologic response to vaccination, and consisted clinically of(rare) transient local injection
site dermal reactions, with transient minimal hyperthermia and minimal body weight loss or
lower body weight gain after injection. This was associated with a transient (acute
phase/immune) response in clinical pathology parameters, characterized by increases in plasma
proteins (C-reactive protein, fibrinogen and globulins), and white blood cell counts (monocytes
and lymphocytes). Microscopic pathology findings of minimal to slight inflammation and
hemorrhage were observed at the injection sites, along with increased lymphoid cellularity of
germinal centers in popliteal and iliac lymph nodes and the spleen, which is consistent with an
immune response to the vaccine administration. Overall, the findings were considered non-
adverse and were partially or completely reversible after a 3-week treatment-free period. All
vaccinated animals developed an antibody response against SARS-CoV-2 S protein, confirming
responsiveness of the rabbits to the vaccine.
Reproductive and Developmental Toxicology
A GLP compliant combined embryofetal and pre- and postnatal development study was conducted
with Ad26.COV2.S in female NZW rabbits. In this study, female NZW rabbits were injected IM
with a control solution (0.9% sodium chloride) or 1×1011 vp Ad26.COV2.S on Day 1 (ie, 7 days
prior to mating), Gestation Day (GD) 6 and GD 20. The study included 2 subgroups, 1 group
consisting of animals that were necropsied on GD 29 and had a uterine and fetal examination
(external, visceral, and skeletal exams), and 1 group consisting of animals that were allowed to
give birth and in which the survival and development of the kits were evaluated through Lactation
Day 28. There was no evidence of impaired female fertility, and the vaccine did not show any
harmful effect with regard to embryofetal or postnatal development. The parental females as well

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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.
Clinical Studies
The safety and immunogenicity (post-dose 1) of Ad26.COV2.S, administered at several dose
levels, has been demonstrated in healthy adults in the first-in-human study VAC31518COV1001
(IB 2021 and its addenda, Sadoff2020).
At the time of protocol Amendment 4 writing, a robust clinical safety database is available
consisting of all adult participants who received at least 1 dose of Ad26.COV2.S in the clinical
studies 
VAC31518COV1001, 
VAC31518COV1002, 
VAC31518COV1003,
VAC31518COV2001, VAC31518COV3001, and VAC31518COV3009.
The Phase 1/2a and Phase 2a clinical studies VAC31518COV1001, VAC31518COV1002 and
VAC31518COV2001 have shown that a single dose of Ad26.COV2.S elicited a SARS-CoV-2
neutralizing antibody (wtVNA) and SARS-CoV-2 Spike-binding antibody (S-ELISA) response by
Day 15 (14days post-dose 1) and Day 29 (28 days post-dose 1) in adult participants ≥18 to ≤55
years and ≥65 years of age.
Consistent with data from ongoing Phase 1 and Phase 2 studies, the results of both Study
VAC31518COV3001 and VAC31518COV3009 indicate that a single dose of Ad26.COV2.S at a
dose level of 5×1010 vp was well tolerated and no vaccine-related safety signals were observed. In
VAC31518COV3009, data from the primary/final analysis (end of double-blind phase) show that
the reactogenicity and tolerability profile after a second dose of Ad26.COV2 was comparable to
receiving the 1st dose. In addition, the data show that after administration of a second dose vaccine
efficacy was increased. The available data indicate that an increase in immunogenicity after a
second dose of Ad26.COV2.S correlates with increased vaccine efficacy. This was also shown for
COVID-19 caused by variants of concern (eg, Alpha [B.1.1.7] and Mu [B.1.621]) for which
enough cases were accrued to draw conclusions.
Overall, all safety data show that Ad26.COV2.S administered at a 1-dose or 2-dose level of
5×1010 vp has an acceptable safety and reactogenicity profile in participants ≥18years of age.
Refer to the IB (IB 2021) and its addenda for a high level description of all ongoing studies with
Ad26.COV2.S.
Clinical Safety Experience With Ad26-based Vaccines
As described above, replication-incompetent Ad26 is being used as a vector in the development of
vaccine candidates against diseases such as malaria, RSV, HIV, Zika virus and filovirus, and has
been used in the now licensed Ebola virus vaccine (Zabdeno / Ad26.ZEBOV).
As of 21 December 2020, Ad26-based vaccines developed by the sponsor have been administered
to approximately 193,000 participants. The majority of these participants (more than 153,000) are
enrolled in an ongoing Ebola vaccine study in the Democratic Republic of the Congo and an
ongoing immunization campaign in Rwanda (UMURINZI Ebola Vaccine Program campaign) and

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approximately 35,000 participants are enrolled in other ongoing studies. The remainder of
participants were included in studies that have been completed.
The sponsor’s clinical adenoviral vaccine (vector platform) (AdVac®) safety database report
(V5.0, dated 10 April 2020, cut-off date 20 December 2019) describes integrated safety data from
26 completed clinical studies using Ad26-based vaccines for which the database was locked for
final analysis. In these 26 studies, 4,224 adult participants were vaccinated with an Ad26-based
vaccine and 938adult participants received a placebo. A total of 6,004 Ad26-based vaccine doses
were administered to adults. Most adult participants (3,557 of 4,224; 84.2%) received Ad26-based
vaccine at a dose level of 5×1010 vp, while 284 adult participants (6.7%) received Ad26-based
vaccine at the 1×1011 vp dose level (the highest dose level tested).
Overall, the Ad26-based vaccines were well tolerated, irrespective of the antigen transgene,
without significant safety issues identified to date. See Section 2.3.1 for a summary of data from
the AdVac® safety database report.
Ad26-based Vaccines in Pregnant Women
A review of individual case safety reports of pregnancy exposures performed by the Sponsor for
all ongoing and completed Ad26-based vaccine clinical studies (covering a range of dose levels
from 1×109 vp to 1.6×1011 vp), identified 22 studies in which pregnancies were reported up to a
cut-off date of 31 December 2020. These included clinical trials for severe acute respiratory
syndrome coronavirus 2  (COVID-19) vaccine, Ebola vaccine, HIV vaccine, Human Papilloma
Virus (HPV) vaccine, RSV vaccine and Zika vaccine.
The reports included a total of 1,618 pregnancies, of which 1,615 female study participants
reported exposure to an Ad26 vectored vaccine product or control. Of these 1,615 cases, 1,421
reported potential exposure to the vaccine product during pregnancy whereas the remaining 194
cases were excluded as these cases reported either vaccine exposure outside pregnancy window or
no exposure during pregnancy. The 1,421 cases corresponded to 1,408 individual pregnancies
(1,395 mother cases, 2 mother/father linked pairs, and 11 mother/child pairs). Of these 1,408
pregnancies, 1,406 pregnancies were reported in female study participants whereas the remaining
2 pregnancies were reported in female partners of the male study participants, both of which
reported exposure to Ad26.ZEBOV vaccine. The majority of these pregnancy cases (1,061
pregnancy cases reported out of a total of 20,432 participants enrolled)originated from the ongoing
immunization campaign in the Democratic Republic of the Congo from the Ebola vaccine
program, where pregnancy is not an exclusion criterion.
Overall, review of the available data obtained from over 1,600 reported pregnancies, with over
900 reported pregnancy outcomes in clinical trials with Ad26-based vaccines, is not suggestive of
a pregnancy-related safety concern. There is no evidence of an increased risk of adverse outcomes
either in the mother or the infant when administered within 3 months prior to onset of pregnancy
or during pregnancy.

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Th1/Th2 Profile of Ad26-based Vaccines in Clinical Studies
In the 1960s, a formalin-inactivated (FI) RSV vaccine was associated with enhanced respiratory
disease (ERD) in young children, characterized by an increased rate of RSV-mediated, severe
lower respiratory tract infection in the vaccinated individuals compared with the control group
(Chin 1969, Fulginiti 1969, Kapikian 1969, Kim 1969). Although the mechanisms for ERD are
not fully understood, it is thought that the FIRSV -vaccine may have: 1) failed to induce adequate
neutralizing antibody titers; 2) led to an overproduction of binding antibodies promoting immune
complex deposition and hypersensitivity reactions; 3) failed to induce adequate numbers of
memory cluster of differentiation (CD)8+ T cells important for viral clearance; and 4) induced a T
helper cell (Th) type 2-skewed type T-cell response (Moghaddam 2006). Vaccine-induced ERD
has also been described for SARS-CoV and MERS-CoV in some animal models in which
candidate vaccines induced a Th2 -biased immune response (Agrawal 2016, Bolles 2011,
Deming 2006, Honda-Okubo 2015, Houser 2017, Smatti 2018), but proof of human SARS-CoV
or MERS-CoV vaccine-associated enhanced disease does not exist as these candidate vaccines
were never tested for efficacy nor used in outbreak situations. For SARS and MERS, the
mechanism of enhanced disease observed in mice has been associated with a Th2-mediated
eosinophilic infiltration in the lung, which is reminiscent of ERD effects observed after RSV
infection of mice immunized with FI-RSV. Similar to RSV vaccines, enhanced disease has been
shown for whole-inactivated SARS-CoV vaccines, as well as subunit vaccines inducing a Th2-type
immune response, which can be rescued by formulating vaccines in Th1-skewing adjuvants. In
addition to a Th1-biased immune response, also induction of a high proportion of neutralizing
antibodies compared with virus binding antibodies is desirable to prevent predisposition to
enhanced disease as observed for RSV vaccines. While vaccine--associated enhanced disease was
observed in nonclinical studies with experimental SARS and MERS vaccines, it is not a given that
the same risk applies to COVID-19 vaccines. To the sponsor’s knowledge, antibody-related
COVID-19 disease enhancement has not been observed in nonclinical models yet. Antibodies
against the receptor binding domain of SARS-CoV-2 were shown not to enhance in vitro
infectivity. Repeated SARS-CoV-2 challenge of NHP or NHP studies with Th2-biasing
COVID-19 vaccines that would be expected to predispose to enhanced disease did not show any
signs of enhanced disease. In addition, disease enhancement was not observed in NHP immunized
with ChAdOx1 encoding SARS-CoV-2 S protein prior to challenge with SARS-CoV-2 (IB 2021
and its addenda). The Ad26 vector was chosen due to its ability to induce humoral and strong
cellular responses with a Th1 immune phenotype (Anywaine 2019, Barouch 2018, Colby 2020,
Milligan 2016, Salisch 2019, Stephenson 2020, van der Fits 2020, Widjojoatmodjo 2015,
Zahn 2012). This type 1 polarity of the immune response minimizes the risk of enhanced disease
after SARS-CoV-2 infection.
The immunogenicity profile of adenoviral vectors, with particular emphasis on Th1 responses, is
illustrated by data obtained from immunization of adults with Ad26-vectored HIV vaccines
(Ad26.ENVA.01 and Ad26.Mos.HIV) and Ad26-vectored Ebola vaccine (Ad26.ZEBOV). These
data show predominantly IFNγ and TNFα production in CD4+ and CD8+ T cells (Anywaine 2019,
Barouch 2013, Barouch 2018).

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The initial clinical immunogenicity data from Study VAC31518COV1001 shows that the
Ad26.COV2.S vaccine induces robust neutralizing and binding antibody responses, a Th1-skewed
phenotype, and robust CD4+ and CD8+ T-cell responses. Furthermore, results from the safety and
reactogenicity analyses showed that the 5×1010 vp and 1×1011 vp Ad26.COV2.S dose levels had
an acceptable tolerability in participants aged ≥18 to ≤55 years and in participants aged ≥65 years
of age, with no significant safety issues in either age group during the observation period. The
induction of a Th1-skewed response in all participants in both Ad26.COV2.S vaccine dose groups,
indicates that the theoretical risk for predisposition of VAERD  is minimal (IB 2021 and its
addenda).
2.3. 
Benefit-Risk Assessment
More detailed information about the known and expected benefits and risks of Ad26.COV2.S may
be found in the IB (IB 2021) and its addenda.
2.3.1. 
Risks Related to Study Participation
The following potential risks for Ad26.COV2.S  will be monitored during the study and are
specified in the protocol:
Risks Related to Ad26.COV2.S
Overall, all safety data (including reactogenicity) to date, show that Ad26.COV2.S at a dose level
of 5×1010 vp as a 1-dose or 2-dose schedule, has an acceptable safety and reactogenicity profile in
participants ≥18 years of age. Reactogenicity to Ad26.COV2.S in adults ≥18 years of age was
demonstrated to be transient and most solicited AEs generally resolved in 1 to 2 days
post-vaccination.
The most frequently reported solicited (local and systemic) AEs (collected up to 7 days after
vaccination in the safety subset population) were vaccination site pain, fatigue, headache, and
myalgia. Most AEs were of mild or moderate severity, were transient in nature and generally
resolved within 1 to 2 days post-vaccination. Pyrexia was reported in 9.0% of participants
receiving a single dose of Ad26.COV2.S at the 5×1010 dose level, as compared to 0.6% of
participants in the placebo group. Grade 3 pyrexia was reported in 0.2% of participants in the
Ad26.COV2.S group, of which the majority occurred in the younger age group. No Grade 3
pyrexia was reported in the placebo group. All fevers started on the day of vaccination or the day
after and had a median duration of 1 day after vaccination with Ad26.COV2.S. Antipyretics were
recommended post-vaccination for symptom relief as needed and were used more frequently in
the Ad26.COV2.S group compared to placebo. Otherwise, the reactogenicity profile of
Ad26.COV2.S was generally similar across sex, race/ethnicities, geographies, comorbidities,
SARS-CoV-2 or HIV serostatus at baseline. The most frequently reported unsolicited AEs
(collected up to 28 days after vaccination in the safety subset population) were fatigue, myalgia,
and headache. Most were of mild or moderate severity, and most were considered not related to
the study vaccine by the investigator.

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For the most comprehensive nonclinical and clinical information regarding Ad26.COV2.S, refer
to the latest version of the IB (IB 2021) and its addenda.
Sites should advise participants that side effects include fever as well as injection site pain,
headache, fatigue, myalgia, and nausea per the current ICF. Anaphylaxis has been identified as a
risk for Ad26.COV2.S. Individuals should be observed by a healthcare provider after vaccination
per protocol requirements and in accordance with local regulations. Refer to the latest version of
the IB (IB 2021) and its addenda (if applicable) for further details.
Thrombosis in combination with thrombocytopenia (TTS), in some cases accompanied by
bleeding, has been observed very rarely following vaccination with Ad26.COV2.S. These cases
occurred approximately 3 weeks following vaccination, mostly in women under 60 years of age.
Thrombosis in combination with thrombocytopenia can be fatal. The exact physiology of TTS is
unclear. Post-vaccination TTS is considered an identified risk for Ad26.COV2.S.
Participants should be instructed to seek immediate medical attention if they develop symptoms
such as shortness of breath, chest pain, leg swelling, persistent abdominal pain, severe or persistent
headaches, blurred vision, skin bruising and/or petechiae beyond the site of vaccination. The
medical management of thrombosis with thrombocytopenia is different from the management of
isolated thromboembolic diseases. Study site personnel and/or treating physicians should follow
available guidelines for treatment of thrombotic thrombocytopenia (eg, from the American Society
of Hematology 2021, British Society of Haematology - Expert Haematology Panel 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 decision making of the AESI 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 8.3.6.1), which may facilitate diagnosis and clinical
management of the event.
Guillain-Barré syndrome (GBS) has been reported very rarely following vaccination with
Ad26.COV2.S. As a result, it is considered an identified risk. Investigators should be alert to GBS
signs and symptoms to facilitate diagnosis, and to initiate adequate supportive care and treatment.
For the most comprehensive nonclinical and clinical information regarding Ad26.COV2.S, refer
to the most recent version of the IB (IB 2021) and its addenda.
Risks Related to Ad26.COV2.S Administration after Previous Vaccination Ad26.COV2.S
Preliminary safety data of an Ad26.COV2.S booster (5×1010 vp, 2.5×1010 vp, or 1×1010 vp)
administered ≥6 months post-primary single dose Ad26.COV2.S (5×1010 vp) vaccination are
available from 244 participants (dose level blinded data). The data indicate that the safety and
reactogenicity of a second Ad26.COV2.S dose is acceptable and in line with the safety and
reactogenicity observed after the Ad26.COV2.S dose. There is no indication of increased

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reactogenicity upon administration of a second dose of Ad26.COV2.S and no safety concerns have
been observed.
In addition, the primary analysis of the study COV3009 indicated that the safety profile of the
Ad26.COV2.S vaccine remained consistent and was generally well tolerated when administered
as a second dose according to the study schedule (vaccinations at Day 1 and Day 57) (Johnson &
Johnson 2021)
Risks Related to Adenoviral-vectored Vaccines
The clinical AdVac® safety database (report version 5.0, dated 10 April 2020, cut-off date
20 December 2019) contains pooled safety data from 26 Janssen-sponsored clinical studies with
Ad26 vaccine candidates: 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; 6 studies), and Ad26.Filo (filovirus; 1 study). In these studies, 4,224 adult
participants and 650 children received at least 1 vaccination with an Ad26-based vaccine. The
AdVac® safety database report includes data only from studies for which the database has been
locked for the final analysis; therefore, of the studies including an Ad26.RSV.preF-based regimen
mentioned in Section 2.2, only data for approximately 230 participants aged ≥60 years from
studies VAC18193RSV1003, VAC18193RSV1005, and VAC18193RSV2003 were included.
Overall, the Ad26-based vaccines were well tolerated, without significant safety issues identified.
The majority of solicited local and systemic AEs were of mild or moderate severity and usually
started within 1 to 2 days after vaccination. Most of the events resolved within 1 to 3 days.
In adults, the most frequently reported solicited local AE was injection site pain (56.9% of Ad26
participants, compared with 22.5% of placebo participants). All other solicited local AEs were
experienced by less than 25% of adult participants. The most frequently experienced solicited local
AE in children was injection site pain, reported in 13.9% of children aged 1-3 years, 29.8% of
children aged 4-11 years, and 24.8% of children aged 12-17 years after vaccination with an
Ad26-based vaccine. For placebo, these percentages were 29.2% in children aged 4-11 years and
14.3% in children aged 12-17 years. No children aged 1-3 years have received placebo.
Severe injection site pain was experienced by 1.0% of adult Ad26 participants and 0.8% of children
aged 4-11 years. No children in the other 2 age groups and no placebo participants experienced
severe injection site pain.
There was a trend toward an increase in the frequency of some local AEs with an increase in Ad26
dose, ie, injection site pain (18.7% of participants at the 0.8×1010 vp dose level, 38.7% of
participants at the 2×1010 vp dose level, 52.0% of participants at the 5×1010 vp dose level, and
77.1% of participants at the 1×1011 vp dose level), and to a lesser extent injection site swelling
(6.7%, 2.7%, 9.3%, and 17.6%, respectively). Injection site warmth was not collected at the
0.8×1010 vp and the 2×1010 vp dose level. The frequency of injection site warmth at the 5×1010 vp
and the 1×1011  vp dose level was 19.5%, and 26.7%, respectively. This trend needs to be
interpreted with caution since the participants in the lower dose groups (0.8×1010 vp and 2×1010 vp

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dose level) were all from a single study (VAC52150EBL3002), and the majority of the participants
in the highest dose group (1×1011 vp dose level) were also from a single study
(VAC18193RSV2003).
The most frequently reported solicited systemic AEs (ie, reported in more than 30% of
participants) for adult Ad26 participants were malaise (53.8%), fatigue (48.3%), headache
(45.7%), and myalgia (38.3%), all of which were more frequent for Ad26 participants compared
with placebo (36.4%, 30.7%, 30.0%, and 17.7% of placebo participants, respectively). Most of
these events were considered related to the study vaccine. Pyrexia (9.9%) and vaccine-related
pyrexia (9.0%) were also reported more frequently after administration of an Ad26-based vaccine
compared with placebo (3.5% and 2.9%, respectively).
Solicited systemic AEs reported in ≥10% of children aged 1-3 years were decreased appetite
(13.9%), decreased activity (13.2%), pyrexia (11.1%), and irritability (10.4%). The most
frequently reported solicited systemic AEs in children aged 4-11 years (reported in ≥15% of Ad26
participants) were headache (23.6%; no data are available for the placebo arm in this age group),
and decreased activity (18.5%) and irritability (17.6%), which were both reported in 4.2% (N 1)
of placebo participants. The most frequently reported solicited systemic AEs in children aged
12-17 years (reported in ≥15% of Ad26 participants) were headache (34.6%) and fatigue (24.0%),
compared to 33.3% and 19.0% of placebo participants, respectively. Most of the frequently
experienced solicited systemic AEs in children were considered related to the study vaccine.
The majority of solicited systemic AEs were of mild or moderate severity. For adults, 6.5% of
Ad26 participants and 2.0% of placebo participants reported severe solicited systemic AEs, mostly
malaise and fatigue. Other severe solicited systemic AEs were reported in less than 3% of adult
Ad26 participants.
There was a trend toward an increase in the frequency of solicited systemic AEs with an increase
in Ad26 dose (35.3% at the 0.8×1010 vp dose level, 49.3% at the 2×1010 vp dose level, 64.5% at
the 5×1010 vp dose level, and 70.4% at the 1×1011 vp dose level). The frequency of severe solicited
systemic AEs also tended to increase with higher Ad26 dose, ie, 1.3% of participants at the
0.8×1010 vp and the 2×1010 vp dose level, 5.3% of participants at the 5×1010 vp dose level, and
14.4% of participants at the 1×1011 vp dose level. This trend needs to be interpreted with caution
since the participants in the lower dose groups (0.8×1010 vp and 2×1010 vp dose level) were all
from a single study (VAC52150EBL3002), and the majority of the participants in the highest dose
group (1×1011 vp dose level) were also from a single study (VAC18193RSV2003).
The most frequently reported unsolicited AE in adult Ad26 participants was upper respiratory tract
infection (5.3% vs 7.0% in adult placebo participants). The most frequently reported unsolicited
AEs considered related to the vaccine were neutropenia (1.0% of adult Ad26 participants vs 0.5%
of adult placebo participants) and dizziness (0.7% vs 0.2%, respectively).
General Risks Related to Vaccination
In general, IM injection may cause local itching, warmth, pain, tenderness, erythema/redness,
induration, swelling, arm discomfort, or bruising of the skin. Participants may exhibit general signs

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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. Instructions regarding use of antipyretic
medication can be found in Section 6.8.
Syncope can occur in association with administration of injectable vaccines. Syncope can be
accompanied by falls. Procedures should be in place to avoid falling injury. If syncope develops,
participants should be observed until the symptoms resolve. Fear of injection might lead to fainting
and fast breathing.
Participants may have an allergic reaction to the vaccination. An allergic reaction may cause a
rash, urticaria, or even anaphylaxis (see above risks related to Ad26.COV2.S). Severe reactions
are rare. Participants with a known or suspected allergy, or history of anaphylaxis, or other serious
adverse reactions to vaccines or their excipients (including specifically the excipients of the study
vaccine) will be excluded from the study.
After vaccination, participants will remain at the study site for at least 1 hour (Sentinel and Safety
Cohorts) and 30 minutes (the remaining participants) to be observed by the study staff. Necessary
emergency  equipment and medications must be available in the clinic to treat severe allergic
reactions.
Pregnancy
The effect of the study vaccine on a fetus or on a nursing baby is unknown and will be evaluated
in this study. See also Section 2.2.
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.
Risks from Collection of Nasal Swabs
Collection of a nasal swab may cause a nosebleed.
Risks from Genomic Research
Generally genomic research have little physical risk. Diagnostic testing will not be performed. The
results of the study are intended for exploratory research purposes only (eg, RNAseq) and will not
be provided to the participant.
Theoretical Risk of Enhanced Disease
Vaccine-associated enhanced disease has been described for SARS-CoV and MERS-CoV in some
animal models (Agrawal 2016, Bolles 2011, Deming 2006, Honda-Okubo 2015, Houser 2017),
and is associated with non-neutralizing antibodies and a Th2-skewed immune response, but proof
of human SARS-CoV or MERS-CoV VAERD does not exist as these candidate vaccines were
never tested for efficacy nor used in outbreak situations. In contrast, the Ad26-based vaccines have
been shown to induce a clear Th1-skewed immune response and generate potent neutralizing

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antibody responses in both humans and animal models (see Section 2.2). The initial clinical
immunogenicity data from Study VAC31518COV1001 have also demonstrated the induction of a
Th1-skewed response in all participants in both Ad26.COV2.S vaccine dose groups, indicating
that the theoretical risk for predisposition of VAERD is minimal, also in case antibodies are
transferred to the infant via the placenta(IB 2021 and its addenda).Participants in the present study
will be informed of the theoretical risk of disease enhancement in the ICF. Furthermore, as a risk
mitigation strategy, all participants in the study will be passively and actively monitored for
acquisition of molecularly confirmed COVID-19 (see Section 4.1 and Section 8.1.2).
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.
Currently, there is only limited data about the safety of vaccines for the prevention of COVID-19
in pregnant women (refer to Section 2 for more details on pregnancy). The overall benefit and risk
balance for individual participants thus, cannot be ascertained. Animal studies with COVID-19
Vaccine Janssen do not indicate direct or indirect harmful effects with respect to pregnancy,
embryo/fetal development, parturition, or postnatal development.
The decision on whether to use the vaccine in pregnant women should be made in close
consultation with a healthcare professional after considering the benefits and risks.
Cumulative review of pregnancies in clinical studies conducted by the Sponsor using Ad26 based
vaccine constructs (based on data obtained from over 1,600 reported pregnancies, with over 900
reported pregnancy outcomes) did not reveal any safety concern related to Ad26-based vaccine
exposure during pregnancy. Therefore, administration of Ad26.COV2.S in pregnancy may be
considered when the potential benefits outweigh any potential risks to the mother and fetus.
Preliminary immunogenicity and safety data for an Ad26.COV2.S booster dose (5×1010 vp) at
≥6 months post-primary single dose Ad26.COV2.S administration, and efficacy data for a second
dose of Ad26.COV2.S 2-3 months post-primary single dose Ad26.COV2.S administration support
a favorable benefit-risk profile of booster administration in participants who received a single dose
of Ad26.COV2.S.
2.3.3. 
Benefit-Risk Assessment for 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:
 
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.

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 
Safety will be closely monitored throughout the study:
 
In general, safety evaluations will be performed at scheduled visits during the study, as
indicated in the Schedule of Activities.
 
After vaccination, participants will remain at the study site for at least 30 minutes (with
participants in the Sentinel and Safety Cohorts under observation for at least 60 minutes)
and will be monitored by study staff. Necessary emergency equipment and medications
must be available in the clinic to treat severe allergic reactions. Adult participants will
use a reactogenicity diaryin the eCOA to document solicited signs and symptoms. Details
are provided in Section 8.2 and Section 8.3.
 
Participants will be asked to confirm whether subjective changes in (postpartum) breast
milk production (reduction) have been noticed and report changes in the eCOA diaries.
 
The investigator or the designee will document unsolicited AEs, serious adverse events
(SAEs), AESI, pregnancy-related AEs throughout pregnancy, and MAAEs, as indicated
in Section 8.2, Section 8.3, and Section 10.4.
 
From the time of local approval of protocol Amendment 3 onwards, 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 post-vaccination, see American Society of
Hematology (ASH) 2021]) 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 1.3.6.
 
Any clinically significant abnormalities (including those persisting at the end of the
study/early withdrawal) 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 record.
 
Several safety measures are included in this protocol to minimize the potential risk to
participants, including the following:
 
Eligibility criteria will be reassessed pre-vaccination on Day 1.
 
There are prespecified rules for all participants, that if met would result in pausing of
further vaccinations, preventing exposure of new participants to study vaccine until the
IDMC reviews all safety data (see Section 6.9).
 
All participants will be monitored in this study to diagnose COVID-19 infection, if
applicable.
 
Study vaccinations will be discontinued in participants for the reasons included in
Section 7.
 
Criteria to delay administration of the study vaccine are included in Section 5.5.

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3. 
OBJECTIVES AND ENDPOINTS
Objectives 
Endpoints
Primary
To assess the safety and reactogenicity of 
Ad26.COV2.S administered intramuscularly 
(IM) as a 1-dose (5×1010 vp) schedule in adult 
participants, during the 2nd and/or 3rd trimester of 
pregnancy, and (potentially) postpartum. 
 Solicited local and systemic AEs for 7
days after vaccination, or until
resolution.
 Unsolicited AEs for 28days after
vaccination.
 SAEs and AESI throughout the study
(from vaccination until end of the
study, ie, at least 12 months after
delivery).
 MAAEs until 6 months after
vaccination.
 AEs leading to study discontinuation
(during the entire study).
To assess the humoral immune response in 
peripheral blood of adult participants to 
Ad26.COV2.S administered IM as a 1-dose 
(5×1010 vp) schedule, during the 2nd and/or 3rd
trimester of pregnancy, 28 days after
vaccination.
 Serological response to vaccination as
measured by ELISA; [S-ELISA,
EU/mL]), 28 days after vaccination.
Secondary
Adults
To assess safety of the booster dose of
Ad26.COV2.S at 5×1010 vp on participants who
were vaccine naïve at study entry.
 Solicited local and systemic AEs for 7
days after booster vaccination, or until
resolution.
 Unsolicited AEs for 28days after
vaccination.
 SAEs and AESI throughout the study
(from vaccination until end of the
study, ie, at least 12 months after
delivery).
 MAAEs until 6 months after
vaccination.
 AEs leading to study discontinuation
(during the entire study).
To assess pregnancy outcomes in adult
participants who have received Ad26.COV2.S
during the 2nd and/or 3rd trimester of pregnancy.
 Pregnancy outcomes (including, live
term birth, live preterm birth,
stillbirth, and abortion) (non-
exhaustive).
To assess pregnancy-related AEs in adult
participants who have received Ad26.COV2.S
during the 2nd and/or 3rd trimester of pregnancy.
 Pregnancy-related AEs throughout
pregnancy (including gestational
diabetes, gestational hypertension,
premature rupture of membranes,
premature labor, premature uterine

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contractions, poor or restricted fetal
growth, pre-eclampsia, eclampsia,
vaginal or intrauterine hemorrhage)
(non-exhaustive).
To assess the humoral immune response in
peripheral blood of adult participants induced by
Ad26.COV2.S administered IM as a 1-dose
(5×1010 vp) schedule during the 2nd and/or 3rd
trimester of pregnancy, at all blood collection
timepoints.
 Serological response to vaccination as
measured by ELISA (S-ELISA;
EU/mL) and/or equivalent assay, at all
blood collection timepoints.
To assess the humoral immune response in
peripheral blood of adult participants to
Ad26.COV2.S administered IM as a 1-dose
(5×1010 vp) schedule during the 2nd and/or 3rd
trimester of pregnancy, 28days after
vaccination.
 Serological response to vaccination as
measured by VNA titers, 28days after
vaccination.
To evaluate the humoral immune response in
adult participants who are vaccine naïve at study
entry and receive a booster dose during the
study, pre-boost and at selected time points post
booster vaccination.
 Serological response to vaccination
measured by binding (S-ELISA and/or
equivalent assay) and/or neutralizing
(VNA) antibody titers.
Neonates and Infants
To assess antibody levels against SARS-CoV-2
in neonates and infants, born to adult participants
who have received Ad26.COV2.S during the 2nd
and/or 3rd trimester of pregnancy, at birth (ie, in
cord blood) and at approximately 2 months and
6 months of age.
 Serological response to vaccination as
measured by ELISA (S-ELISA,
EU/mL) and/or equivalent assay, at
birth (ie, in cord blood) and at
approximately 2 months and 6 months
of age.
To assess antibody levels against SARS-CoV-2
in neonates/infants, born to adult participants
who have received Ad26.COV2.S during the 2nd
and/or 3rd trimester of pregnancy, at birth (ie, in
cord blood).
 Serological response to vaccination as
measured by VNA titers at birth (ie, in
cord blood).
To assess safety in neonates and infants born to
adult participants who have received
Ad26.COV2.S, during the 2nd and/or 3rd
trimester of pregnancy.
 SAEs (including Multisystem
Inflammatory Syndrome in Children
[MIS-C]) and AESIs in neonates and
infants from birth approximately 12
months of age.
 MAAEs in neonates and infants from
birth until 6 months of age.
 AEs in neonates/infants leading to
study discontinuation from birth until
discontinuation.

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SARS-CoV-2 at baseline on Ad26.COV2.S 
vaccine immunogenicity. 
other respiratory viruses by ELISA or
equivalent assay.
To assess the presence of immunoglobulins 
against SARS-CoV-2 in colostrum and breast 
milk 
in 
adult 
participants 
in 
response 
Ad26.COV2.S administered IM as a 1-dose 
(5×1010 
vp) schedule and after booster
vaccination.
IgA and/or other Ig types against SARS-CoV-
2 and/or emerging variants in colostrum and
breast milk measured by ELISA or equivalent
assay.
To further explore humoral immune responses in 
peripheral blood and cord blood of adult 
participants 
induced 
by 
Ad26.COV2.S
administered IM as a 1-dose (5×1010 vp) schedule
before and after booster vaccination, at all or
selected blood collection timepoints.
Exploratory  analyses may include the
following:
 
SARS-CoV-2 neutralization as assessed
by SARS-CoV-2 neutralization assays
(VNA).
 
Adenovirus neutralization as measured by
VNA.
 
Functional 
and 
molecular 
antibody
characterization including Fc-mediated
viral clearance, avidity, Fc characteristics,
immunoglobulin (Ig) subclass and IgG
isotype, antibody glycosylation, and
assessment of antibody repertoire.
 
Analysis of antibodies to the spike (S),
nucleocapsid (N), and RBD of the SARS-
CoV-2 S protein, and surface proteins of
other coronaviruses.
 
Epitope-specificity characterization of
antibodies.
 
Cytokine profiling: Analysis of cytokines,
chemokines, and other proteins of the
immune response in the serum or plasma.
 
Passive transfer: Analysis of immune
mediators correlating with protection
against 
experimental 
SARS-CoV-2
challenge in a suitable animal model.
 
Analysis of binding and/or neutralizing
antibodies against emerging SARS-CoV-
2 variants.
To further explore cellular immune responses in 
peripheral blood of adult participants to 
Ad26.COV2.S administered IM as a 1-dose 
(5×1010 vp) schedule at selected blood collection
Exploratory analyses may include the
following for a subset of participants, if
feasible:
 
Analysis of gene expression in cells
stimulated with SARS-CoV-2 S protein

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timepoints, including after booster vaccination, if
feasible.
peptides, or in unstimulated cells (ex
vivo).
 
Analysis of messenger ribonucleic acid
(mRNA) expression levels of vaccine-
induced biomarkers of immune mediated
responses.
 
Cytokine profiling: Analysis of cytokines,
chemokines, and other proteins of the
immune response in cells stimulated with
SARS-CoV-2 S protein peptides, or in
unstimulated cells (ex vivo).
 
Epitope-specificity characterization for B
and T-cells.
 
Analysis of the phenotype of antigen-
specific T and B cells, assessed by single
cell analysis.
To assess the occurrence of symptomatic
molecularly confirmed COVID-19 and severity
of COVID-19 signs and symptoms in adult
participants who have received Ad26.COV2.S
during the 2nd and/or 3rd trimester of pregnancy.
 
The 
number 
of participants 
with
molecularly confirmed COVID-19.
 
Presence and severity of COVID-19 signs
and symptoms as measured by the
Symptoms 
of 
Infection 
with
Coronavirus-19 (SIC).
To assess the occurrence of asymptomatic SARS-
CoV-2 infection in adult participants who have
received Ad26.COV2.S during the 2nd and/or 3rd
trimester of pregnancy.
 
The number of adult participants with
positive non-S ELISA and/or SARS-
CoV-2 immunoglobulin assay that is
dependent 
on 
the 
SARS-CoV-2
nucleocapsid (N) protein.
 
Asymptomatic infection detected by RT-
PCR.
To assess the impact of the Ad26.COV2.S
vaccine on the incidence of co-infections with
SARS-CoV-2 and other respiratory pathogens in
participants who have received Ad26.COV2.S
during the study period, up to delivery.
 
Analysis of broad respiratory pathogens
panel in the nasal swabs collected during
a confirmed COVID-19 episode and in a
subset of nasal swab samples from adult
participants with a symptomatic infection,
up to delivery.
To examine the immune response in vaccinated
adult participants after SARS-CoV-2 infection
and to explore other potentially informative
biomarkers (eg, those associated with more severe
disease).
 
Confirmation of SARS-CoV-2 infection
by molecular testing.
 
SARS-CoV-2 neutralizing titers in serum
measured by a VNA.
 
SARS-CoV-2-binding 
antibodies
measured by ELISA: Analysis of

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To assess SARS-CoV-2 viral load during a
confirmed COVID-19 episode in neonates/infants
born to adult participants who have received
Ad26.COV2.S during the 2nd and/or 3rd trimester
of pregnancy.
 
Analysis of SARS-CoV-2 viral load (via
qRT-PCR) in nasal swabs collected
during a confirmed COVID-19 episode.
To assess the impact of the Ad26.COV2.S
vaccine on the incidence of co-infections with
SARS-CoV-2 and other respiratory pathogens in
neonates/infants born to participants who have
received Ad26.COV2.S during the study period.
 
Analysis of broad respiratory pathogens
panel in the nasal swabs collected during
a confirmed COVID-19 episode and in a
subset of nasal swab samples from
neonates/infants with a symptomatic
infection.
To 
examine 
the 
immune 
response 
in
neonates/infants born to participants who have
received Ad26.COV2.S during the 2nd and/or 3rd
trimester of pregnancy, after SARS-CoV-2
infection.
 
Confirmation of SARS-CoV-2 infection
by molecular testing.
 
SARS-CoV-2 neutralizing titers in serum
measured by VNA.
 
SARS-CoV-2-binding 
antibodies
measured by ELISA: Analysis of
antibodies binding to the SARS-CoV-2 S
and/or N-protein.
To assess antibody levels against SARS-CoV-2 in
neonates/infants, born to adult participants who
have received Ad26.COV2.S during the 2nd
and/or 3rd trimester of pregnancy, at all or selected
blood collection timepoints.
 
Serological response to vaccination as
measured by SARS-CoV-2 VNA titers at
birth (ie, in cord blood) and at
approximately 2 months and 6 months of
age.
To further explore humoral immune responses in
neonates/infants born to participants who have
received Ad26.COV2.S during the 2nd and/or 3rd
trimester of pregnancy, at all or selected blood
collection timepoints.
Exploratory analyses may include the
following:
 
SARS-CoV-2 neutralization as assessed
by SARS-CoV-2 neutralization assays
VNA.
 
Adenovirus neutralization as measured by
VNA.
 
Functional and 
molecular 
antibody
characterization including Fc-mediated
viral clearance, avidity, Fc characteristics,
immunoglobulin (Ig) subclass and IgG
isotype, antibody glycosylation, and
assessment of antibody repertoire.
 
Analysis of antibodies to the spike (S),
nucleocapsid (N), and RBD of the SARS-
CoV-2 S protein, and surface proteins of
other coronaviruses.

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 
Epitope-specificity characterization of
antibodies.
 
Cytokine profiling: Analysis of cytokines,
chemokines, and other proteins of the
immune response in the serum or plasma.
 
Passive transfer: Analysis of immune
mediators correlating with protection
against 
experimental 
SARS-CoV-2
challenge in a suitable animal model.
 
Analysis of binding and/or neutralizing
antibodies against emerging SARS-CoV-
2 variants.
To evaluate neurodevelopmental status in
neonates and infants.
 Summary of developmental outcomes
using the Ages & Stages Questionnaire, 3rd
edition (ASQ3) at 2, 6 and 12 months of
age.
To explore changes in the SARS-CoV-2 genome  Identification of SARS-CoV-2 variants by
sequencing of nasal swabs samples (as
available)
Refer to Section 8for evaluations related to endpoints.
HYPOTHESIS
No formal statistical hypothesis is to be tested. The study is designed to provide descriptive
information regarding the safety, pregnancy outcomes, and immunogenicity of Ad26.COV2.S in
adult participants in the 2nd and/or 3rd trimester of pregnancy, as well as the safety and outcomes
of neonates/infants.
The study will provide descriptive information regarding the safety and immunogenicity of
Ad26.COV2.S administered as a booster dose in participants who had previously received a
COVID-19 vaccine and in those that were vaccine naïve at study entry and receive a booster dose
during the study.
4. 
STUDY DESIGN
4.1. 
Overall Design
This is an open-label multicenter, Phase 2 study in healthy pregnant (2nd and/or 3rd trimester of
pregnancy) participants ≥18 to ≤45 years of age to evaluate safety, reactogenicity,
immunogenicity, and pregnancy outcomes. In this study, Ad26.COV2.S will be assessed as a
single dose of 5×1010 vp  in pregnant women who were previously vaccinated with another
COVID-19 vaccine regimen or who were vaccine naïve at study entry.
A diagram of the study design is provided in Section 1.2.

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A target of 240 adult participants in the 2nd or 3rd trimester of pregnancy (Week 16 to Week 38 of
gestation, inclusive) was to be enrolled in this study. Efforts were made to ensure good
representation in terms of race and ethnicity. The sample size of each of the groups were preferably
equally distributed but flexible, and the target was to recruit at least 40 participants in Groups 1 to
3 and at least 25 participants in Group 4. As of Protocol Amendment 7 approval, participant
enrollment in this study will be ceased. These participants will continue to be followed in this
study in accordance with the protocol.
The first 22 vaccine naïve participants participated in the Sentinel and Safety Cohorts to assess
safety and reactogenicity in the 1-dose regimen.
The remaining participants (who have received their last COVID-19 vaccination at least 4 months
prior to receiving the study vaccine or are vaccine naïve participants) will preferably be equally
distributed between the following groups, per their COVID-19 vaccination histories:
 
Group 1: Previous primary vaccination (2-doses) or homologous booster vaccination with
Comirnaty (Pfizer-BioNTech) or SpikeVax (Moderna)
 
Group 2: Previous primary vaccination (1-dose) or homologous booster vaccination with
Ad26.COV2.S (Janssen)
 
Group 3: Previous COVID-19 vaccination, irrespective of previous schedule and vaccine
(includes heterologous regimens) and excluding schedules for Groups 1 and 2
 
Group 4: Vaccine naïve participants, including those who are in Sentinel and Safety Cohorts
These participants will receive 1 dose of Ad26.COV2.S at 5×1010 vp. Participants will be stratified
by pregnancy stage at the time of enrollment (Weeks ≥16 to <28 or Weeks ≥28 to ≤38), with a
goal of at least approximately 25% participants per trimester, per group.
Enrollment was staggered and started with recruitment of vaccine naïve Sentinel participants
followed by a larger Safety Cohort (n 17 participant, excluding sentinels) who all received 1 dose
of Ad26.COV2.S vaccine at 5×1010 vp.
There will be no active vaccination with Ad26.COV2.S of neonates/infants in this study.
IDMC ReviewOutcome
Safety Profile Acceptable After IDMC Review
At the time of writing Amendment 5, the IDMC confirmed that the safety profile of 1 dose of
Ad26.COV2.S at 5×1010 vp was considered acceptable and no safety concerns were identified
following review of the Sentinel and Safety Cohorts safety data. The remaining participants will
receive 1 dose of Ad26.COV2.S at 5×1010 vp. The vaccination schedule is presented in Figure 2.

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Booster Vaccinations
Previously Vaccinated Participants
Previously vaccinated participants (Groups 1-3) will receive a single (booster) dose of
Ad26.COV2.S at 5×1010 vp as part of the study. No further vaccinations by these groups will be
received during the study.
Vaccine Naïve Participants
For participants that are vaccine naïve at study entry, a booster vaccination with a single dose of
Ad26.COV2.S at 5×1010 vp will be offered to ongoing, consenting participants (Group 4, including
Sentinel and Safety Cohorts) who have completed the pregnancy during which they were enrolled
in the study, are not pregnant again, and have notreceived another COVID-19 vaccine (eg, national
immunization program).
The booster vaccination will be administered not earlier than 2 months after completion of the
participant’s Ad26COV2.S vaccination in the study.
Figure 2: 
Decision Tree for Staggered Enrollment
A target of 240 adult participants (including 22 participants in the Sentinel and Safety Cohorts) in the 2nd or 3rd trimester of
pregnancy (Week 16 to Week 38 of gestation, inclusive) was to be enrolled. As of Protocol Amendment 7approval, participant
enrollment in this study will be ceased.
Enrollment was staggered and started with recruitment of Sentinel participants followed by Safety Cohort (excluding Sentinels).
At the time of writing Amendment 5, the IDMC confirmed that the safety profile of 1 dose of Ad26.COV2.S at 5×1010 vp was
considered acceptable and no safety concerns were identified following review of the Sentinel and Safety Cohorts safety data.
The remaining participants were enrolled and randomized to receive 1 dose of Ad26.COV2.S at 5×1010 vp.
Previously vaccinated participants (Groups 1 to 3) should have received their last COVID 19 vaccination at least 4 months prior
to receiving the study vaccine.
Participants will be stratified by pregnancy stage at the time of enrollment (Weeks ≥ 16 to <28 or Weeks ≥28 to 38), with a goal
of at least approximately 25% participants per trimester per group.
* A booster vaccination with a single dose of Ad26.COV2.S at 5×1010 vp will be offered to ongoing, consenting participants
(Group 4, including Sentinel and Safety Cohorts) who were vaccine naïve at study entry and who have completed the pregnancy
during which they were enrolled in the study, are not pregnant again, and have not received another COVID 19 vaccine (eg,
national immunization program). Please refer to Section 6.2 for further details.
IDMC  Independent Data Monitoring Committee; vp  virus particles
Study Duration
For each adult participant, the total study duration from screening until the last follow-up visit will
be approximately 16 months. The study will consist of a 28-day screening phase, a study period

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from vaccination to pregnancy completion/termination, and a follow-up period of 12 months post
pregnancy completion/termination.
Neonates/infants born to the participants in the study will be followed forapproximately12 months
postpartum (see Section 1.3.3).
The booster vaccination will be administered not earlier than 2 months after completion of the
participant’s Ad26.COV2.S vaccination in the study. The study duration will not be extended to
accommodate a booster visit.
Study Procedures
Safety will be assessed by collection of solicited local (at injection site) and systemic AEs,
unsolicited AEs, and SAEs. Other safety assessments include vital signs measurements (heart rate,
supine systolic and diastolic blood pressure [adults only], respiratory rate, body temperature, etc.)
and physical examinations at the time points indicated in the Schedules of Activities inSection 1.3.
After vaccination, adult participants will remain under observation at the study site, for at least
30 minutes (60 minutes for participants in the Sentinel and Safety Cohorts), for the presence of
any severe acute reactions and solicited events.
Any solicited local or systemic AEs, unsolicited AEs, SAEs, AESI, pregnancy-related AEs
throughout pregnancy, MAAEs, concomitant medications, and vital signs will be documented by
study site personnel following this observation period. In addition, adult participants will record
solicited signs and symptoms in a reactogenicity diary for 7 days post-vaccination.
The reporting periods of unsolicited AEs, SAEs, AESI, pregnancy-related AEs throughout
pregnancy, MAAEs, and special reporting situations are detailed in Section 8.3. Reporting periods
for concomitant therapy are outlined in Section 6.8.
In addition, participants will be asked daily if they have experienced any health concerns
(including new onset of symptoms such as shortness of breath, chest pain, leg swelling, persistent
abdominal pain, severe or persistent headaches or blurred vision, easy bruising, or tiny blood spots
under the skin beyond the site of the injection) within the 30-day time period post-vaccination, and
if so, participants will be advised to contact the study center. For Group 4 booster participants
only, subjective changes in (postpartum) breast milk production (reduction) will be collected in
the eCOA diary.
Adverse maternal/fetal outcomes and adverse neonate/infant outcomes SAEs (including MIS-C),
MAAEs and AEs leading to discontinuation will be recorded. A final safety follow-up visit is
scheduled 12 months postpartum for adult participants and approximately 12 months after birth
for the neonates/infants.
From all adult participants and neonates/infants, blood samples will be collected at selected
timepoints indicated in the Schedules of Activities in Section 1.3, for humoral immunogenicity
assessments, with an emphasis on neutralizing and binding antibody responses. In addition, blood

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samples will be collected at selected timepoints indicated in the Schedules of Activities in
Section 1.3; analysis of vaccination-related biomarkers in PAXgene® tubes may be performed.
From a subset of approximately 25 adult participants per group, PBMCs were to be collected for
analysis of cellular immunogenicity (including Th1/Th2 assessments). With only 1 participant in
this subset at the time of writing this Protocol Amendment 7, PBMC sampling will be removed
from the study as of Protocol Amendment 7approval.
For vaccine naïve participants at study entrywho receive a booster vaccination, blood samples will
be collected from adults pre-boost and 28 days post-boost for humoral immunogenicity
assessments and whole blood will be collected for the analysis of vaccination-related biomarkers.
Further details about the immunogenicity assessments are provided in Section 8.1.1.
Active surveillance for COVID-19-like signs and symptoms in participants and neonates/infants
will occur, including a COVID-19 surveillance (symptom check) through the participant’s
electronic diary eCOA.
For the duration of the study, each participant or parent(s)/caregiver(s) for the neonate/infant will
be asked at least twice a week, through the eCOA, if the participant or their neonate/infant have
experienced any new symptoms or health concerns that could be related to infection with SARS-
CoV-2 ([suspected] COVID-19 surveillance [symptom check]).
All participants and neonates/infants with COVID-19-like signs or symptoms and all participants
and neonates/infants with a positive RT-PCR test from outside the study meeting the prespecified
criteria for suspected COVID-19 should undertake prespecified COVID-19 procedures as outlined
in the Schedule of Activities in Section 1.3.4and Section 1.3.5, respectively.
If neonates were born to mothers with confirmed COVID-19, or if a close relative from the same
household as the neonate/infant has confirmed COVID-19, testing for SARS-CoV-2 should be
performed for the neonate/infant, regardless of whether there are signs of infection in the
neonate/infant. Details are provided in Section 8.1.2. The occurrence of asymptomatic SARS-
CoV-2 infection will also be assessed, if feasible (see Section 8.1.4).
Site staff and participants will not be blinded as to the outcome of the molecular test results from
the local (hospital) laboratory. Their routine HCP can obtain external diagnostics, including RT-
PCR or other molecularly confirmed viral tests, as medically needed.
All necessary precautions (per local regulations) should be taken to protect site staff and other
contacts of participants and neonates/infants who are confirmed to have COVID-19 until proven
negative by molecular techniques or until resolution.
In the event of a confirmed SARS-CoV-2 infection, the participant or parent/caregiver (for
neonate/infant) will be notified, and the participant or parent/caregiver (for neonate/infant) will be
asked to adhere to the appropriate measures and restrictions as defined by local regulations.

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Enrolled participants will be counselled on SARS-CoV-2 infection prevention each time that they
have a contact with site staff, in line with local guidelines.
If a participant should have COVID-19 and their symptoms deteriorate, they will be instructed
seek medical care.
An IDMC has been commissioned for this study. Refer to Committees Structure in Section 10.3.6
The planned primary and final analyses are detailed in Section 9.5 Planned Analyses.
Dose Level Selection
The rationale behind the selection of the dose level of Ad26.COV2.S is described in Section 4.2.
Study Population
Adult participants in the 2nd and/or 3rd trimester of pregnancy(ie, Week 16 to Week 38 of gestation,
inclusive) will be recruited for the study.
Participants should either have completed a primary vaccine regimen of Comirnaty (Pfizer-
BioNTech, Group 1), SpikeVax (Moderna, Group 1), Ad26.COV2-S (Janssen, Group 2) or from
another manufacturer (Group 3) who have received their last COVID-19 vaccination at least 4
months prior to receiving the study vaccine; or be vaccine naïve (Group 4).
Participants with severe medical complications, obstetric risks or risk factors that put them at
higher risk for complications will be excluded to avoid confounding of vaccine safety endpoints.
See also Sections 5.1 and 5.2.
Blinding, Control, Study Phase/Periods, Vaccine Groups
This is a non-randomized open-label study. There is no placebo group.
Biomarker Collection
For PAXgene® tubes collected in  adult participants and in cord blood (if feasible), biomarker
analysis may  be performed to explore potentially informative biomarkers related to vaccine
immunogenicity.
For adult participants with a positive test result for SARS-CoV-2 infection, biomarker analysis
may  be performed on in PAXgene® tubes for evaluation of COVID-19 cases and to explore
potentially informative biomarkers, correlating with SARS-CoV-2 infection and COVID-19
severity, at Day 3 to 5 and at Day 29 (±7 days) after onset of symptoms.
4.1.1. 
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

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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.
Adult participants in the 2nd and/or 3rd trimester of pregnancy  and subsequently in  their
neonates/infants may  not receive a tangible benefit from participation in the study, except for
compensation for the time and inconveniences that may arise from participation in the study. See
Section 2.3 for details on potential and known benefits and risks, and for the safety measures taken
to minimize risk to participants.
The study-specific ethical considerations will be described in the ICF, where the terms legal
guardian and legally acceptable representative refer to the legally appointed guardian of the
neonate/infant with authority to authorize participation in research. For each neonate/infant, his or
her parent(s) (both parents, if available) or legally acceptable representative(s), as required by local
regulations, must give written consent (permission) according to local requirements after the nature
of the study has been fully explained and before the performance of any study-related assessments.
For the purposes of this study, all references to neonate/infant participants who have provided
consent refers to the neonate/infant participants and his or her parent(s) or the neonate/infant
participant’s legal guardian(s) or legally acceptable representative(s) who have provided consent
according to this process.
The total blood volume to be collected from adults is considered to be an acceptable amount of blood
to be collected over this time period from the population in this study based upon the US Department
of Health and Human Services Office for Human Research Protections, and US (FDA) guidelines
of 550 mL in any 8-week period (US HHS 1998, US HHS 2019), as well as the European
Commission guidelines of 500 mL per donation and 3 L per consecutive 12 month period
(98/463/EC).
The total blood volume to be collected from infants is considered to be acceptable according to
guidelines (EU 2008, Howie 2011, Peplow 2019, US HHS 2019) and will not exceed 3.5 mL per
blood draw for infants ≤6 months of age. Except cord blood, no blood will be collected from
newborns.
4.2. 
Justification for the Regimen and Dose
The regimen and dose selection in this study are aimed primarily at providing information on
safety, reactogenicity, and immunogenicity of Ad26.COV2.S at a dose level of 5×1010 vp in adult
participants in the 2nd and/or 3rd trimester of pregnancy. All participants are planned to receive a
single dose of Ad26COV2.S at 5×1010 vp.
The 5×1010 vp dose level is currently being evaluated in ongoing clinical studies
VAC31518COV1001, VAC31518COV1002, VAC31518COV2001, VAC31518COV3001, and
VAC31518COV3009. Interim analysis results from study VAC31518COV1001 have
demonstrated safety and immunogenicity for the 5×1010 vp dose level, which has been confirmed
in the other studies.

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Overall, the reactogenicity data from the current study is consistent with the reactogenicity data
observed in the Phase 1 study VAC31518COV1001 post-dose 1 and the Phase 2 study
VAC31518COV2001 post-dose 1 for the groups with the same dose level (ie, 5×1010 vp dose level
of Ad26.COV2.S).
Based on the VAC31518COV3001 primary analysis results, EUA for active immunization to
prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) in individuals 18 years of age and older was granted.
The most extensive clinical safety information is available from the Phase 3 study
VAC31518COV3001 that has been conducted with 43,000 participants 18years of age to date,
and includes exposure to a single dose or 2-dose vaccination regimen with Ad26.COV2.S at the
selected dose level (5×1010 vp) with at least a 56-day interval between doses for the 2-dose
regimen. A total of27,181 received at least 1 dose of Ad26.COV2.S at the selected dose level of
5×1010 vp. Overall, the results from the safety and reactogenicity analyses showed that the 5×1010
vp dose level of Ad26.COV2.S administered as a 1-dose regimen had an acceptable safety and
reactogenicity profile with no significant safety issues identified. In general, a lowerreactogenicity
was observed for the older adults compared to the younger adults.
Based on the primary analysis data (cut-off date 22 January 2021), the results of this study indicate
that a single dose of Ad26.COV2.S at a dose level of 5×1010 vp was well tolerated.
The safety of 2 doses of Ad26.COV2.S administered with a 56-day interval was evaluatedin Study
VAC31518COV3009. 16,751 participants received 2 doses of vaccine - 8,655 received
Ad26.COV2.S and 8,096 received placebo. The data indicate that the safety and reactogenicity of
a second Ad26.COV2.S dose is acceptable and in line with the safety and reactogenicity observed
after the first Ad26.COV2.S dose. There is no indication of increased reactogenicity upon
administration of a second dose of Ad26.COV2.S and based on the initial clinical assessment no
safety concerns have been observed.
A single dose of Ad26.COV2.S vaccine is immunogenic and highly efficacious against severe
COVID-19 disease and COVID-19 related hospitalization and death. Furthermore, while
protection against variants of concern (such as the Beta and Mu variants in study COV3001 and
the Delta variant in the Sisonke study  [Gray 2021]) remains high against serious disease,
hospitalization, and death, this protection is lower against, eg, the Gamma variant compared to the
reference Wuhan strain.
Giving a second dose of Ad26.COV2.S results in marked increases of immune responses and those
higher immune responses correlate with better protection against COVID-19, as shown in the
primary analysis of study COV3009 (Johnson & Johnson 2021). The CDC (CDC 2021a) recently
advised to give a booster vaccination, therefore, boosting will be offered to all eligible participants
in this study who receive only a single vaccination with Ad26.COV2.S in the study. As the Janssen
vaccine is approved as a single dose vaccine, participants who received 2 doses ofAd26COV2.S,
if applicable, are considered to already have received the booster dose.

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There will be no active vaccination with Ad26.COV2.S of neonates/infants in this study.
4.3. 
End of Study Definition
End of Study Definition
The end of study is considered as the last visit shown in the Schedule of Activities for the last
participant in the study.
 
For adult participants, the last visit is at approximately 12 months postpartum.
 
For neonates/infants, the last visit is at approximately 12 months of age.
Study Completion Definition
An adult participant will be considered to have completed the study if she has completed
assessments at the 12 months postpartum visit, or has experienced a clinical endpoint that
precludes further continuation in the study.
An infant will be considered to have completed the study if he or she has completed assessments
at the visit 12 months after birth or has experienced a clinical endpoint that precludes further
continuation in the study.
All participants who prematurely discontinue study participation for any reason before completion
of the 12 months postpartum visit will not be considered to have completed the study.
5. 
STUDY POPULATION
Screening for eligible participants will be performed within 28 days before study vaccination.
Refer to Section 5.4for 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.
Eligibility criteria to receive the booster vaccination are described in Section 6.2.
If there is a question about these criteria, the investigator must consult with the sponsor to try to
resolve any issues before enrolling a participant in the study. Waivers are not allowed.
5.1. 
Inclusion Criteria
Each potential adult participant must satisfy all of the following criteria to be enrolled in the study:
1. Participant must sign an ICF  indicating that she understands the purpose, procedures and
potential risks and benefits of the study, is willing to participate in the study. Within the ICF,
the participant must also give consent to follow-up the neonate/infant after birth.
2. Criterion modified per Amendment 1
2.1 Participant is 18 (or the legal age of consent in the jurisdiction in which the study is taking
place) to 45 years of age, inclusive, on the day of signing the ICF.
3. Criterion modified per Amendment 3

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3.1 Participant must be healthy as confirmed by medical history, physical examination, vital signs,
and obstetric history performed at Screening, and must not have medical history of comorbidities
related to an increased risk of severe COVID-19 (refer to Exclusion Criterion 24) or high-risk
pregnancy (refer to Exclusion Criterion 2). Participant may have underlying illnesses (eg,
stable/well-controlled HIV infection*), as long as the symptoms and signs are medically controlled
and not considered to be comorbidities related to an increased risk of severe COVID-19 or high-
risk pregnancy.
* 
Stable/well-controlled HIV infection includes:
Criterion modified per Amendment 6
a. CD4 cell count ≥300 cells/µL
b. HIV viral load <50 copies/mL.
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 formulation are allowed) and the participant must be willing to
continue his/her ART throughout the study as directed by his/her local physician.
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 by Western
Blot or PCR, or of a detectable viral load (country-specific regulatory approved tests). A
laboratory result within 6 months of screening does not need to be repeated.
Criterion modified per Amendment 6
If a potential participant does not have HIV viral load and CD4 cell count data in their
medical records from the last 6 months, efforts will be made to obtain the necessary data
for potential entry into the study. A laboratory result within 6 months of screening does not
need to be repeated.
4. Criterion modified per Amendment 4.
a. If on medication for a condition, the medication dose must have been stable for at least
4weeks preceding vaccination.
5. Participant will be included on the basis of physical examination, medical history, and vital
signsa.
6. Criterion modified per Amendment 1.
a. Criterion modified per Amendment 4
a 
Participants may be enrolled with Grade 1 or Grade 2 toxicity gradings for vital signs measurements per the
Investigator’s discretion.

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b. Participant will be at 2nd or 3rd trimester of pregnancy, ie, Week 16 to Week 38 of
gestation  (inclusive), at the time of vaccination, based on ultrasound at the time of
screening (or not longer than 10 days prior to vaccination if performed elsewhere).
7. Participant agrees to not donate bone marrow, blood, and blood products from the first study
vaccine administration until 3 months after receiving the last dose of study vaccine.
8. Participant must be willing to provide verifiable identification, has means to be contacted and
to contact the investigator during the study.
9. Participant must have access to a consistent means of contact either by telephone contact or
e-mail/computer.
10. Must be able to read, understand and complete questionnaires in a digital application (ie, The
“COVID 19 signs and symptoms surveillance question,” the “SIC” for adults and the
“PedSIC” for children); and the reactogenicity diary (adults only).a
11. Criterion modified per Amendment 4.
11.1 Criterion modified per Amendment 6
a. Participant either received their last COVID-19 vaccination with an authorized/licensed
COVID-19 vaccine (at least 4 months prior to first study vaccination) or is COVID-19
vaccine naïve.
5.2. 
Exclusion Criteria
Any potential participant who meets any of the following criteria will be excluded from
participating in the study:
1. Criterion modified per Amendment 4
1.1 Participants with medical or obstetric histories that put them at higher risk for maternal or
fetal complications (eg, chronic pregnancy-related disorders, birth defects or genetic
conditions during previous pregnancy).
2. Criterion modified per Amendment 4
2.1 Participants with risk factors for the current pregnancy (eg, multiple pregnancies [twins or
higher order multiples], unstable diabetes, high blood pressure, morbid obesity [before
pregnancy], epilepsy, ongoing thyroid disease, heart or blood disorders, autoimmune
disorders) or complications (eg, abnormal placenta position, fetal growth less than the 10th
percentile for gestational age [fetal growth restriction]) for the current pregnancy.
3. Participants with close relatives with known congenital disorders or anomalies.
4. Participant with abnormal pregnancy screening testb (eg, ultrasound fetal abnormalities,
maternal blood screen).
5. Criterion modified per Amendment 1.
a 
Participants with visual impairment are eligible for study participation and may have assistance in completing the
eCOA questionnaires
b 
https://www.cdc.gov/ncbddd/birthdefects/diagnosis.html, last reviewed on 05 Dec 2019.

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5.1 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 24hours prior to the planned first dose of study vaccine; vaccination at a later date
(refer to Section 5.5) is permitted at the discretion of the investigator and after consultation
with the sponsor.
6. Criterion modified per Amendment 4:
6.1 Participant has a history of malignancy within 2 years before screening (exceptions are
squamous, basal cell carcinomas of the skin, carcinoma in situ of the cervix, or a malignancy
considered cured with minimal risk of recurrence).
7. Participant has a known or suspected allergy or history of anaphylaxis or other serious adverse
reactions to vaccines or their excipients (including specifically the excipients of the study
vaccine) (refer to the IB 2021 and its addenda).
8. Criterion modified per Amendment 4.
8.1 Participant has abnormal function of the immune system resulting from:
a. Clinical conditions (eg, potential immune mediated disease or known or suspected
immunodeficiency, chronic kidney disease [with dialysis]) expected to have an impact on
the immune response elicited by the study vaccine.
Participants with clinical conditions stable under non-immunomodulator treatment (eg,
autoimmune thyroiditis, autoimmune inflammatory rheumatic disease such as
rheumatoid arthritis) 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.
Criterion modified per Amendment 6
b.1 Chronic or recurrent use of systemic corticosteroids within 6 months before
administration of study vaccine and during the study. A substantial immunosuppressive
steroid dose is considered to be (>20 mg prednisone or equivalent daily for 2 consecutive
weeks).
Note: Ocular, topical or inhaled steroids are allowed.
c. Administration of antineoplastic and immunomodulating agents or radiotherapy within
6 months before administration of study vaccine and during the study.
9. Criterion modified per Amendment 1
9.1 Participant has a history of any serious, chronic, or progressive neurological disorders or
seizures including GBS, with the exception of febrile seizures during childhood.
10. Participant has a history of chronic urticaria (recurrent hives), eczema or adult atopic
dermatitis.
11. Criterion modified per Amendment 4.
11.1 Participant received treatment with immunoglobulins in the 3 months or blood products
in the 4 months before the planned administration of the study vaccine or has any plans to
receive such treatment during the study.
RHo (D) immunoglobulin injection can be given at any time.

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12. Criterion modified per Amendment 1
12.1 Participant received or plans to receive:
a. Licensed live attenuated vaccines - within 28 days before or after planned administration
of the 1st and booster study vaccinations
b. Other licensed (not live) vaccines - within 14 days before or after planned administration
of the 1st and booster study vaccinations.
13. Criterion modified per Amendment 4
Criterion modified per Amendment 6
13.2 Participant received an investigational drug or used an invasive investigational medical
device within 30 days, or received investigational immunoglobulin or monoclonal antibodies
within 3 months, or received convalescent serum for COVID-19 treatment within 4 months
or received an investigational vaccine (including investigational Adenoviral-vectored
vaccines and vaccines against COVID-19) within 4months, before the planned administration
of the first dose of study vaccine or is currently enrolled in another investigational study during
the course of this study.
Note: Participation in an observational clinical study is allowed at the investigator’s discretion. Please notify
the sponsor (or medical monitor) of this decision.
14. 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.
15. Participant had major surgery per the investigator’s judgement within 12 weeks before
vaccination, or will not have fully recovered from surgery, or has a major surgery planned
(except for Caesarean Section) within 6 months after the last dose of the study vaccine.
16. Participant has a contraindication to IM injections and blood draws eg, bleeding disorders.
17. Criterion modified per Amendment 1.
17.1 Criterion deleted per Amendment 2.
17.2 Criterion reinstated per Amendment 3
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.
18. Participant has chronic active hepatitis B or hepatitis C infection per medical history.
19. Participant has had 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.
20. Participant cannot communicate reliably with the investigator.
21. 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.
22. Criterion deleted per Amendment 4.

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23. Criterion modified per Amendment 2.
23.1 Participant has a positive diagnostic test result (PCR-based viral RNA detection)
SARS-CoV-2 infection at screening or Day 1 (if more than 4 days in between).
24. Participants with medical history of comorbidities that are or might be associated with an
increased risk of progression to severe COVID-19. Examples of such conditions are severe
asthma; chronic lung diseases (eg, chronic obstructive pulmonary disease [COPD], idiopathic
pulmonary fibrosis and cystic fibrosis); diabetes (including type 1, type 2, or gestational);
serious heart conditions, including heart failure, coronary artery disease, congenital heart
disease, cardiomyopathies, and (pulmonary) hypertension or high blood pressure; pre-
pregnancy obesity; severe obesity (BMI ≥ 40 kg/m2); chronic liver disease, including
cirrhosis; sickle cell disease; thalassemia; cerebrovascular disease; neurologic conditions; and
(unstable/uncontrolled) HIV infection.
A list of underlying medical conditions that increase the risk of progression to severe COVID-
19 for non-pregnant adults is available at the CDC website (at the time of writing this protocol)
(CDC 2020b, d) and in Section 10.9.
25. Criterion deleted per Amendment 1
26. Criterion deleted per Amendment 2
27. History of confirmed SARS or MERS
28. Criterion added per Amendment 1
28.1 Criterion modified per Amendment 4
28.2 At the time of consenting, participants should agree to practicing an acceptable effective
method of contraception postpartum and agree to remain on such a method of contraception
following the birth of the infant until 3 months after administration of the last study vaccine.
Participants should follow contraceptive (birth control) measures consistent with local
regulations regarding the acceptable methods of contraception (see Section 10.5).
29. Criterion added per Amendment 3
Participant has a history of TTS, including cerebral venous sinus thrombosis (CVST), or
heparin-induced thrombocytopenia (HIT).
30. Criterion added per Amendment 3
Participant has a history of Capillary leak syndrome (CLS).
NOTE: Investigators should ensure that all study enrollment criteria have been met prior to the
first dose. If a participant’s clinical status changes (including any available laboratory results or
receipt of additional medical records) after screening but before the dose of study vaccination and
they no longer meet all eligibility criteria, the participant should be excluded from participation in
the study. Section 5.4describes options for rescreening.
The required documentation to support meeting the enrollment criteria is described under Source
Documents in Section 10.3.10.
5.3. 
Lifestyle Considerations
Potential adult participants must be willing and able to adhere to the following lifestyle restrictions
during the course of the study to be eligible for participation:

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1. Refer to Section 6.8for 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 for adult participants (Section 5.1 and Section 5.2).
3. Adult participants should agree to follow requirements for the electronic completion of the
COVID-19 signs and symptoms surveillance questions in the eCOA, as applies to both
themselves and to their neonate/infants.
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 enrolled into
the study, the date seen 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 on 1 occasion only. Participants who are rescreened will be assigned a new participant
number, undergo the informed consent process, and then restart a new screening phase.
5.5. 
Criteria for Temporarily Delaying Administration of Study Vaccination
The following events constitute a temporary contraindication to study vaccination:
 
Clinically significant pregnancy-related conditions according to medical judgement (see
Section 7.2).
 
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 either of these events occur at the scheduled time for vaccination, then vaccination at a later date
within the screening window is permitted at the discretion of the investigator and after consultation
with the sponsor. If the vaccination  cannot occur within the screening window, rescreening is
required. All participants may be rescreened once (see Section 5.4).
The events listed above also apply to the booster vaccination visit for eligible participants. In
addition, a urine pregnancy test (for participants of childbearing potential, according to the local
guidelines) will be required for the Booster Visit for all participants in Group 4. Participants from
Group 4who are pregnant are not eligible to receive the booster vaccination (see Section 6.2).

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If the vaccination visit cannot be rescheduled within the allowed window or the contraindications
to vaccination persist, the rationale should be documented.
6. 
STUDY VACCINATION AND CONCOMITANT THERAPY
6.1. 
Study Vaccinations Administered
Study Vaccine Information
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. Formulation buffer will be supplied as diluent as 15 mM citrate,
5% (w/w) hydroxypropyl-β-cyclodextrin, 0.4% (w/w) ethanol, 0.03% (w/w) polysorbate 80,
75 mM NaCl, pH 6.2,
The vaccine will be extracted from the vial as outlined below:
 
Ad26.COV2.S:
 
5×1010 vp dose level: 0.5 mL is withdrawn from one vial containing 0.75 mL
1×1011 vp/mL.
There will be no active vaccination with Ad26.COV2.S of neonates/infants in this study.
Participants will receive a single dose of Ad26.COV2.S at the 5×1010 vp dose level, irrespective
of gestational age.
The study vaccine will be administered by IM injection into the deltoid muscle, preferably of the
non-dominant arm. Subsequent booster vaccination (for Group 4 participants) are preferably
administered in the opposite arm. If an injection cannot be given in the deltoid muscle due to a
medical or other contraindication (for example, tattooed upper arms rendering it difficult to assess
site reactogenicity), alternative locations such as the hip, thigh or buttocks can be used. If
alternative locations are used for vaccine administration, the participant’s ability to assess injection
site events should be considered.
For information on vaccination windows, see Section 8: Study Assessments and Procedures. If a
participant cannot be vaccinated within the allowed window (eg, if the window is missed due to a
study pause, see Section 6.9), the decision regarding vaccination will be assessed on a case-by-
case basis.
Study vaccine administration must be captured in the source documents and eCRF.
Ad26.COV2.S will be manufactured and provided under the responsibility of the sponsor. Refer
to the IB (IB 2021)and its addenda for a list of excipients.
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.

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6.2. 
Booster Vaccination
Vaccine Naïve Participants
Vaccine naïve participants at study entry (Group 4, including Sentinel and Safety Cohorts) who
have completed the pregnancy during which they were enrolled in the study, are not pregnant again
will be offered an (optional) booster vaccination with a single dose of Ad26.COV2.S at 5×1010 vp.
They must not meet any study discontinuation criteria as specified in Section 7.1 and have not
received another COVID-19 vaccine (eg, national immunization program) outside the study as
indicated in the SoA in Section 1.3.1.1.
The booster vaccination will be administered not earlier than 2 months after completion of the
participant’s Ad26.COV2.S vaccination in the study. The booster vaccination and the booster
follow-up visit should not extend the study duration.
The Booster Vaccination Visit for vaccine naïve participants at study entry  should preferably
coincide with a scheduled visit from the original SoA in Section 1.3.1. If not operationally feasible
to coincide with an existing visit, an unscheduled visit may be planned.
Participants will continue to follow the Schedule of Activities in Section 1.3.1. All participants
(whether they consent to the booster vaccination or not) will be encouraged to remain in the study.
Previously Vaccinated Participants (Group 1-3)
Previously vaccinated participants (Groups 1-3) will receive a single (booster) dose of
Ad26.COV2.S at 5×1010 vp as part of the study, but are not eligible for a second booster during
the study.
6.3. 
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.
A pharmacist or other qualified individual will prepare the appropriate vial and syringe, labeled
with the participant’s identification number, and provide the syringe to the vaccine administrator
(a trained and qualified study nurse, medical doctor, otherwise qualified HCP) who will perform
the injection.

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Accountability
The investigator is responsible for ensuring that all study vaccine received at the site is inventoried
and accounted for throughout the study. The study vaccine administered to the participant must be
documented on the vaccine accountability form. All study vaccine will be stored and disposed of
according to the sponsor’s instructions. Study site personnel must not combine contents of the
study vaccine containers.
Study vaccine must be handled in strict accordance with the protocol and the container label and
must be stored at the study site in a limited-access area or in a locked cabinet under appropriate
environmental conditions. Unused study vaccine must be available for verification by the
sponsor’s study site monitor during on-site monitoring visits. The return to the sponsor of unused
study vaccine will be documented on the vaccine accountability form. When the study site has an
authorized destruction unit and study vaccine supplies are destroyed on-site, this must also be
documented on the vaccine accountability form.
Potentially hazardous materials containing hazardous liquids, should be disposed of immediately
in a safe manner and therefore will not be retained for vaccine accountability purposes.
Study vaccine should be dispensed under the supervision of the investigator or a qualified member
of the study site personnel, or by a hospital/clinic pharmacist. Study vaccine will be administered
only to participants participating in the study. Returned study vaccine must not be dispensed again,
even to the same participant. Study vaccine may not be relabeled or reassigned for use by other
participants. The investigator agrees neither to dispense the study vaccine from, nor store it at, any
site other than the study sites agreed upon with the sponsor. Further guidance and information for
the final disposition of unused study vaccine are provided in the SIPPM.
Measures to Minimize Bias: Vaccine Allocation
Sentinel and Safety Cohorts participants received 1 dose of Ad26.COV2.S at 5×1010 vp. At the
time of writing Amendment 5, the IDMC confirmed that the safety profile of 1 dose of
Ad26.COV2.S at 5×1010 vp was considered acceptable and no safety concerns were identified
following review of the Sentinel and Safety Cohorts safety data. The remaining participants will
receive 1 dose of Ad26.COV2.S at 5×1010 vp.
Participants will be stratified by pregnancy stage (Weeks ≥16 to <28 or Weeks ≥28 to ≤38). Efforts
will be made to enroll at least approximately 25% per trimester, per group. The assignment will
utilize a computer-generated schedule prepared before the study under the sponsor’s oversight.
Participants who were vaccine naïve at study entry will be offered a booster dose of Ad26.COV2.S
at 5×1010 vp during the study.
Blinding
This is an open-label study, therefore, blinding procedures are not applicable.

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6.4. 
Study Vaccination Compliance
Study vaccines will be administered IM by qualified study site personnel at the study site per local
regulations. Details of each administration will be recorded in the eCRF (including date and time
of injection, and the location used for injection [deltoid or alternative location]).
6.5. 
Dose Modification
The safety and tolerability of a single dose of the Ad26.COV2.S vaccine at 5 ×1010 vp in adult
participants was assessed in Sentinel and Safety Cohorts.
At the time of writing Amendment 5, the IDMC confirmed that the safety profile of 1 dose of
Ad26.COV2.S at 5×1010 vp was considered acceptable and no safety concerns were identified
following review of the Sentinel and Safety Cohorts safety data.
The remaining participants will receive 1 dose of Ad26.COV2.S at 5×1010 vp dose level.
6.6. 
Continued Access to Study Vaccine After the End of the Study
Not applicable.
6.7. 
Treatment of Overdose
For this study, any dose of Ad26.COV2.S greater than the assigned dose will be considered an
overdose. The sponsor does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator should:
 
Contact the relevant sponsor or delegate immediately.
 
Closely monitor the participant for AEs/SAEs/pregnancy-related AEs/MAAEs (ie, the
participant will remain at the study site for at least 1 hour and will be closely monitored for
allergic or other reaction by study staff. Follow-up telephone calls 12 hours and 24 hours post-
vaccination can be made).
 
Document the quantity of the excess dose in the eCRF.
 
Report as a special reporting situation.
6.8. 
Prestudy and Concomitant Therapy
Prestudy therapies such as analgesic/antipyretic medications and non-steroidal anti-inflammatory
drugs, corticosteroids, and antihistamines used 30 days before administering the study vaccine
must be recorded.
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 study vaccination until 28 days after administration of study
vaccine. All other concomitant therapies should also be recorded if administered in conjunction
with a confirmed COVID-19 case or with new or worsening AEs or suspected AESI reported per
protocol requirements outlined in Section 8.3.1.

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Concomitant therapies associated with an SAE meeting the criteria outlined in Section 10.4.1 will
be collected and recorded in the eCRF from study vaccination through the end of the study for
adult participants and from birth until the end of the study for neonates/infants. Concomitant
therapies associated with MAAEs will be collected and recorded in the eCRF from study
vaccination until 6 months after vaccination for adults and from birth until 6 months of age for
neonates/infants. Concomitant therapies associated with AEs leading to study discontinuation will
be recorded in the eCRF during the entire study for both adult and neonates/infants.
Use of any investigational medication (including experimental vaccines other than the study
vaccine) during the study, other than the study vaccine, will lead to discontinuation of
administration of any subsequent study vaccination. Participants may not receive:
 
an investigational drug or use an invasive investigational medical device within 30 days, or
 
investigational immunoglobulin or monoclonal antibodies within 3 months, or
 
convalescent serum for COVID-19 treatment within 4 months, or
 
an investigational vaccine (including investigational Adenoviral-vectored vaccines) within
4months before the planned administration of study vaccine.
During the study, the use of investigational COVID-19 vaccines other than the study vaccine is
not allowed, and the use of investigational drugs is only allowed if medically indicated. In the
event that a participant receives 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.
Treatment with investigational COVID-19 drugs after diagnosis of a COVID-19 case is allowed
during the postpartum follow-up period and needs to be recorded in the COVID-19 episode
description.
Licensed live attenuated vaccines are generally contraindicated during pregnancy. Licensed (not
live) vaccines (eg, the DtaP [reduced Diphtheria toxoid, Tetanus toxoid, and acellular Pertussis],
influenza, tetanus, hepatitis A, hepatitis B, rabies vaccines) should be given at least 14days before
or at least 14 days after administration of study vaccine in order to avoid potential confusion of
adverse reactions and potential immune interference, and must be recorded. The use of any
coronavirus vaccine (licensed or investigational) is disallowed at any time prior to vaccination
except for those licensed vaccines indicated in inclusion criteria. The use of any coronavirus
vaccine (licensed or investigational) is disallowed during the study, and must be reported in EDC.
If a vaccine is indicated in a post-exposure setting (eg, rabies or tetanus), it should take priority
over the study vaccine, and any vaccinations must be recorded.
All vaccines administered to the babies during the study should be captured.
Treatment with immunoglobulins and blood products is disallowed in the 3 months and 4 months
before the planned administration of study vaccine, respectively, and during the study.
Immunoglobulin Rho (D) can be given at any time.

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Antipyretics (eg, acetaminophen/paracetamol) after vaccination, and additional doses spaced 6
hours apart may be administered thereafter for symptom relief as needed. Prophylactic antipyretic
use is not encouraged; however, it could be considered per investigator’s discretion.
Chronic (daily for 2 consecutive weeks) or recurrent use of systemic corticosteroids (>20 mg/day
of prednisone or equivalent)a at immunosuppressive doses and administration of antineoplastic and
immunomodulating agents or radiotherapy are prohibited during the study and within 6 months
before the planned administration of study vaccine. If any of these agents are indicated in a disease
setting, treatment takes priority over the study vaccine.
Refer to Section 5.2 for further details of prohibited therapy.
The sponsor must be notified as soon as possible of any instances in which prohibited therapies
are administered. Depending on the time of the occurrence, any participant who receives a
prohibited concomitant medication will not be included in the immunogenicity analyses.
6.9. 
Study Vaccination Pausing Rules
The Sponsor (including designated sponsor teams) and/or Sponsor Committee as well as the
Investigator(s) will monitor safety, including the study vaccination pausing rules.
If a study vaccination is considered to raise significant safety concerns (and a specific pause rule
has been met), further vaccination of participants will be paused.
The IDMC will review all available safety data and make recommendations regarding the
continuation of the study to the sponsor study team. The formal recommendation from IDMC will
be provided by the sponsor to applicable health authorities.
The occurrence of any of the following events will lead to a pause in further study vaccination:
1. Death of an adult participant, considered related to study vaccine or if the causal relationship
to the study vaccine cannot be excluded; OR
2. One or more adult participants experience an SAE, a suspected AESI or a Grade 4 (solicited
or unsolicited) AE or a persistent (upon repeat testing) Grade 4 laboratory abnormality that is
determined to be related to study vaccine; OR
3. Three or more adult participants experience a Grade 3 unsolicited AE of the same type (per
medical judgement of the sponsor), that is determined to be related to study vaccine; OR
4. Three or more adult participants experience a persistent (upon repeat testing) Grade 3
laboratory abnormality related to the same laboratory parameter and considered related to
study vaccine; OR
a 
Note: Ocular, topical or inhaled steroids are allowed.

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5. Three or more adult participants experience a Grade 3 solicited AE of the same type,
determined to be related to study vaccine, and persisting as Grade 3 for
longer than 3 consecutive days (ie, the day of occurrence of the AE is counted as Day 1). a
For number 2 and number 4: to assess abnormal laboratory values, the test must be repeated at
least once, within 48 hours of the site becoming aware of the abnormal value.
For number 2, number 3, and number 5: after each IDMC review of similar AEs, the Committee
will indicate the conditions under which it requires further notification and review of any
subsequent similar AEs.
Note: the occurrence of a study pause in any other ongoing study with Ad26.COV2.S may trigger
a pause in further vaccination in the current study, if considered to be medically relevant. Any
subsequent study visits as a result of a delayed vaccination following a study pause are not
considered to be protocol violations, however, the data at these timepoints may be eliminated from
certain statistical analyses.
Based on the pausing criteria, the sponsor will notify other sites in case of a study pause. To enable
prompt response to a situation that could trigger pausing rules, the investigator should notify the
sponsor, immediately and no later than 24 hours after becoming aware of any related AE of Grade
3 or above and update the eCRF with relevant information on the same day the AE information is
collected.
A thorough analysis of all Grade 3 (or above) cases will be carried out by the sponsor, irrespective
of whether the criteria for pausing the study are met. Based on the pausing criteria, the sponsor
will notify other sites in case of a study pause. The sponsor’s medical monitor or designee is
responsible for notification of IDMC members in case a study pause is declared.
Vaccinations for an individual participant may be suspended for safety concerns other than those
described in the pausing criteria, at the discretion of the investigator if he/she feels the participant’s
safety may be threatened. The sponsor may initiate IDMC review for any single event or
combination of multiple events which, in their professional opinion, could jeopardize the safety of
the participants or the reliability of the data.
Resumption of vaccinations will start upon receipt of written recommendations by the IDMC. If
any pausing rule is met (refer to Section 10.3.6 Safety Monitoring Committee Structure) and, if
following appropriate safety review it is deemed appropriate to restart dosing, the sponsor will
comply with regulatory requirements per competent authority(ies).
The clinical site(s) will be allowed to resume activities upon receipt of a written notification from
the sponsor. These communications from the IDMC will be forwarded to relevant parties
according to local regulations.
a 
The day of occurrence of the AE is counted as Day 1.

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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 could remain
on the study for safety and immunogenicity follow-up. Additional unscheduled visits may be
performed for safety reasons, if needed. In case of questions, the investigator is encouraged to
contact the sponsor.
A participant’s study vaccination must be discontinued if:
 
Any serious related AE, worsening of health status or intercurrent illnesses that, in the opinion
of the investigator, requires discontinuation from study vaccine.
 
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 (daily for 2 consecutive weeks) or recurrent use of systemic corticosteroids
(>20 mg/day of prednisone or equivalent)a and administration of antineoplastic and
immunomodulating agents or radiotherapy.
 
Withdrawal of consent to receive further study vaccination.
 
Participant receives a experimental medication (including vaccines during the study) or
receives a COVID-19 vaccine outside the study.
 
Participant who had previously experienced TTS or HIT.
 
Participant who has previously experienced CLS or GBS.
7.2. 
Delay or Discontinuation of Vaccination due to Pregnancy-Specific
Complications
The booster vaccination (Group 4 only) (see Section 6.2) may be withheld or delayed if the
participant experiences any of the following pregnancy-specific complications prior to the
scheduled booster vaccination:
 
severe vaginal bleeding;
 
preterm premature rupture of membranes;
 
severe pre-eclampsia, eclampsia;
 
hemolysis elevated liver enzymes and low platelets (HELLP) syndrome;
 
stillbirth;
 
fetal loss;
a 
Note: Ocular, topical or inhaled steroids are allowed.

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 
preterm birth;
 
participant has a positive diagnostic molecular test result for SARS-CoV-2 infection on the
day of the booster vaccination.
In the event that any of the above occurs, the participant (and infant, if applicable) will continue
to be followed until the end of the study in accordance with the Schedules of Activities.
7.3. 
Participant Discontinuation/Withdrawal From the Study
A participant will be withdrawn from the study for any of the following reasons:
 
Lost to follow-up
 
Withdrawal of consent
 
Death
 
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
is withdrawal of consent, then no additional assessments are allowed.
For those participants who are unable to continue participation in the study up to the last planned
study visit, but for whom consent is not withdrawn, an early exit visit will be conducted as soon
as possible. Participants who wish to withdraw consent from participation in the study will be
offered an optional visit for safety follow-up. This includes the safety assessments of the early exit
visit (no blood sampling for immunogenicity).
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.
7.3.1. 
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). 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.
7.4. 
Lost to Follow-up
To reduce the chances of a participant being deemed lost to follow-up, 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 (adult, neonate, and infant) will be considered lost to follow-up if they repeatedly fails

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to return for scheduled visits and is unable to be contacted by the study site after multiple
documented attempts.
A participant (adult, neonate, and infant) cannot be deemed lost to follow-up until all reasonable
efforts made by the study site personnel to contact the participant are deemed futile. The following
actions must be taken if a participant fails to return to the study site for a required study visit:
 
The study site personnel must attempt to contact the participant to reschedule the missed visit
as soon as possible, to counsel the participant on the importance of maintaining the assigned
visit schedule, to ascertain whether the participant wishes to or should continue in the study.
 
Before a participant is deemed lost to follow-up, the investigator or designee must make every
reasonable effort to regain contact with the participant (where possible, 3 telephone calls,
e-mails, fax, and, if necessary, a certified letter to the participant’s last known mailing address,
or local equivalent methods). 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.
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 may be transferred to another study
site.
8. 
STUDY ASSESSMENTS AND PROCEDURES
Overview
The Schedules of Activities (Section  1.3) summarize the frequency and timing of safety,
reactogenicity, immunogenicity, and other measurements applicable to this study. All participants
or parent(s)/caregiver(s) (in case of neonates/infants) in the study will be counselled on COVID-
19 infection at any interaction with study site staff in line with local guidelines.
All adult participants will be provided access to an eCOA. The eCOA device will be used to collect
(suspected) COVID-19 signs and symptoms surveillance information(Symptoms of Infection with
Coronavirus-19 [SIC], including body temperature, and pulse oximetry results) at baseline and in
case of COVID-19-like signs and symptoms.
All eCOA assessments should be conducted/completed before any tests, procedures, or other
consultations to prevent influencing participant responses. Parents/caregivers should also perform
(suspected) COVID-19 surveillance (symptom check) and record any signs or symptoms that are
suggestive of possible COVID-19 for the neonate/infant and complete the ObsRO for the Pediatric
Symptoms of Infection with Coronavirus-19 [PedSIC], including the highest body temperature
recorded within 24hours, blood oxygen saturation levels, and pulse rate, in the eCOA. Procedures
for adult participants and neonates/infants with (suspected) COVID-19 are outlined in
Section 1.3.4and Section 1.3.5, respectively.

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Adult participants will be provided with a thermometer (to measure body temperature), ruler (to
measure local injection site reactions) to record body temperature and solicited local (at injection
site) and systemic signs and symptoms in the eCOA device. Parent(s)/caregiver(s) will be provided
with a separate thermometer for the neonate/infant to record body temperature for the
neonate/infant in the eCOA, in the event of confirmed or suspected COVID-19.
The site staff will be provided with  ePRO and ObsRO completion guidelines that includes
instructions on capturing responses in the eCOA and grading scales to assess severity of the signs
and symptoms after vaccination (reactogenicity). The study staff is responsible for providing
appropriate training to the participant/parent(s)/caregiver(s) to prevent missing or incorrect data.
The reactogenicity diary will be reviewed by the study personnel at the Day 8visits indicated in
the Schedule of Activities (Section 1.3.2 and Section 1.3.3, respectively). If the reactogenicity
diary review is missed/unavailable at Day 8, the reactogenicity diary will be reviewed during the
following visit.
Sites should reach out to a participant if the participant fails to complete any of the questions
displayed in the eCOA. The questionnaire will be accessible on the eCOA platform in between
scheduled reminders and participants will be encouraged to answer the surveillance question in the
eCOA as soon as possible after the onset of COVID-19-like symptoms, or any other symptoms
with new onset, including those listed above. Every effort will be made to document the status of
all participants that are lost to follow-up due to not completing the eCOA and for whom
hospitalization has not been recorded.
If multiple assessments are scheduled for the same timepoint, it is recommended that procedures
be performed in the following sequence: (a) for adult participant: physical/obstetric examination
and vital signs, ultrasound blood draws, and vaccination; (b) for neonate/infant: physical
examination and vital signs, blood draws. If needed, assessments may be performed at another day
within the applicable visit window. Actual dates and times of assessments will be recorded in the
source documentation and eCRF.
Adult participants will also be provided with a kit to collect nasal swabs at Day 1 to be used in
case they experience COVID-19-like symptoms during the study (see Section 8.1.2). In the event
of the neonate/infants developing COVID-19 like symptoms, the parent(s)/caregiver(s) should
contact the site, who will provide a trained HCP to collect nasal swabs from the neonate/infant.
If allowed by local regulations, study visits other than screening and vaccination visit may take
place at other locations if there are travel restrictions in case of exceptional situations (eg,
pandemic).
Blood Collection -Adult Participants
The maximum total blood volume (without blood samples for PBMCs) to be collected over the
course of the study is approximately 166 mL from adult participants receiving 1 dose of
Ad26.COV2.S at 5×1010 vp.

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Visit Windows
Visit windows that will be allowed are provided in Section 1.3 and summarized below. The
participant should be encouraged to come on the day planned but using the visit windowis allowed.
The timings of the post-vaccination visits will be determined relative to the actual day of the
corresponding vaccination. If a participant misses a vaccination or has a delayed vaccination, the
post-vaccination visits will be calculated from the imputative vaccination date according to
protocol.
If a vaccination window is missed, efforts will be made to vaccinate and collect samples from the
participant, even if out of window. The timings of the post-vaccination visits will be determined
relative to the actual day of the vaccination, unless they overlap with other scheduled visits. If so,
it would be evaluated in a case-by-case basis in which case the sponsor should be contacted, and
a case-by-case assessment agreed.
Screening
Screening will be performed within 28 days prior to study vaccination or on the day of vaccination.
If screening is performed on the day of vaccination, study visits will be combined (ie, for adult
participants, Visits 1 and 2 will occur on Day 1). Screening must be completed, and all eligibility
criteria must be fulfilled prior to vaccination. Participants may be rescreened only once (see
Section 5.4).
The nasal swab for the RT-PCR test for the presence of SARS-CoV-2 infection must be done
within 4days before vaccination and repeated pre-vaccination if necessary. The study-specific ICF
date will 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 Section 1.3 for the timing and frequency of all sample collections.
Instructions for the collection, handling, storage, and shipment of samples can be 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:
 
Latest version of the Ad26.COV2.S Investigator Brochure and Addenda
 
Thermometer (for adults and neonates/infants)
 
Ruler (to measure diameter of any erythema and swelling)
 
An approved pulse oximeter (for adults and neonates/infants)
 
Pharmacy manual/SIPPM

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 
Laboratory manual
 
IWRS Manual
 
eCRF completion guidelines
 
Sample ICF
 
Nasal swab kit, and participants instructions
 
eCOA platform access and participant instructions (participants may use their own eDevice
using an application if their device [smartphone or tablet] is compatible, or a web portal).
Provisioned devices will be available on a limited basis. Adult participant reactogenicity
diaries and the latest Independent Ethics Committee/Institutional Review Board (IEC/IRB)-
approved versions of the PedSIC/SIC are part of the eCOA
 
Contact information page(s)
 
Tablet for eConsent, if applicable
8.1. 
Immunogenicity Assessments
8.1.1. 
Immunogenicity Assessments
Blood Sampling
From all adult participants (venous blood), neonates (cord blood at birth), and infants (venous or
arterial blood), blood samples will be collected at selected timepoints for humoral immunogenicity
assessments, with an emphasis on neutralizing and binding antibody responses. In addition, blood
samples will be collected at selected timepoints, analysis of vaccination-related biomarkers in
PAXgene® tubes may be performed. From a subset of approximately 25 adult participants per
group, PBMCs was planned to be collected for analysis of cellular immunogenicity (including
Th1/Th2 assessments). With only 1 participant in this subset at the time of writing this Protocol
Amendment 7, PBMC sampling will be removed from the study as of Protocol Amendment 7
approval.
For participants who receive a booster vaccination, blood samples will be collected from adults
pre-boost and 28 days post-boost for humoral immunogenicity assessments and vaccination-
related biomarkers.
Sample volumes and time points for adult participants and neonates/infants are detailed in the
Schedules of Activities in Section 1.3, and outlined below.
Humoral and cellular immunogenicity assays may include, but are not limited to, the assays
summarized in Table 2.

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Table 2: 
Summary of Humoral and Cellular Immunogenicity Assays
Summary of Humoral Immunogenicity Assays
Assay 
Purpose
Primary/Secondary endpoints
SARS-CoV-2 binding antibodies 
(ELISA or equivalent assay)
Analysis of antibodies binding to the SARS-CoV-2 S protein
SARS-CoV-2 neutralization 
(VNA) 
Analysis of neutralizing antibodies to the wild-type and/or pseudovirion
expressing S protein
Exploratory endpoints
SARS-CoV-2 binding antibodies 
(ELISA and/or SARS-CoV-2 
immunoglobulin assay) 
Analysis of antibodies binding to the SARS-CoV-2 Spike (S) protein,
nucleocapsid (N) protein, RBD of the SARS-CoV-2 S protein, or other
proteins, including surface proteins of other coronaviruses
SARS-CoV-2 neutralization 
(VNA) 
Analysis of neutralizing antibodies to the wild-type virus, viral variants,
and/or pseudovirion expressing S protein
ELISA or Ig assay detecting 
coronavirus-specific antibodies 
Antibodies specific to
coronaviruses or other respiratory
viruses (MSD)
Analysis of antibodies binding to coronaviruses other than SARS-CoV-2, or
other respiratory viruses
SARS-CoV-2 binding 
immunoglobulins, including IgA 
antibodies (ELISA or equivalent
assay)
Analysis of IgA and/or other Ig subtypes against SARS-CoV-2 in colostrum
and/or breast milk
Adenovirus 26 neutralization 
(neutralization assay)
Analysis of neutralizing antibodies to Adenovirus 26
Functional and molecular antibody 
characterization  
Analysis of antibody characteristics including Fc-mediated viral clearance,
avidity, Fc characteristics, Ig subclass and IgG isotype, antibody
glycosylation, and assessment of antibody repertoire
Epitope-specificity 
characterization
Analysis of site-specificity, epitope mapping
Cytokine profiling, metabolomics 
and/or lipidomics 
Analysis of cytokines, chemokines, and other proteins, metabolites or lipid
mediators of the immune response in the serum or plasma
Passive transfer 
Analysis of immune mediators correlating with protection against
experimental SARS-CoV-2 challenge in a suitable animal model
Transcriptional analysis of 
vaccine-induced Biomarkers 
Analysis of mRNA expression levels of vaccine-induced biomarkers of
immune mediated responses
ELISA  enzyme linked immunosorbent assay; Ig  immunoglobulin; MSD  Meso Scale Discovery; SARS CoV 2  severe
acute respiratory syndrome coronavirus 2; VNA  virus neutralization assay.

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Summary of Cellular Immunogenicity Assays
Assay 
Purpose
Exploratory endpoints
Flow cytometry (ICS) 
Analysis of T-cell responses to SARS-CoV-2 S protein, and/or other protein
peptides by ICS including CD4+/CD8+, IFNγ, IL-2, TNFα, IL-4, IL-5, IL-13,
and/or other Th1/Th2 markers
ELISpot 
IFNγ and IL-4 responses to SARS-CoV-2 S protein peptides by PBMCs, based on
single or dual ELISpot
Gene expression analysis 
Analysis of gene expression by RNA transcript profiling and/or analysis of protein
translates, in cells or whole blood stimulated with SARS-CoV-2 S protein peptides
or in unstimulated cells or whole blood (ex vivo)
Cytokine profiling (ELISA 
or multiplexed arrays) 
Analysis of cytokines, chemokines, and other proteins of the immune response in
cells or whole blood stimulated with SARS-CoV-2 S protein peptides, or in
unstimulated cells or whole blood, by ELISA or multiplexed arrays and
confirmation by functional in vitro assays
T and B cell phenotyping 
Analysis of the phenotype of antigen-specific T and B cells, assessed by single cell
analysis
CD  cluster of differentiation; ELISA  enzyme linked immunosorbent assay; ELISpot  enzyme linked immunospot (assay);
ICS  intracellular cytokine staining; IFNγ  interferon gamma; IL
 interleukin; PBMC  peripheral blood mononuclear cell;
RNA  ribonucleic acid; SARS CoV 2  severe acute respiratory syndrome coronavirus 2; Th  T helper; Th1/Th2:T helper cell
subset(s); TNFα  tumor necrosis factor alpha; VNA  virus neutralization assay.
Colostrum and Breast Milk Sampling
Colostrum (approximately 0.5 mL) should be collected within 1 week postpartum and breast milk
(≥5 mL)at Day 43 (±14days) during the postpartum follow-up phase, if feasible, from participants
who have received Ad26.COV2.S to assess the presence of immunoglobulins, including IgA
against SARS-CoV-2 (see Schedules of Activities in Section 1.3.2 and Section 1.3.3). Colostrum
and/or breast milk will also be collected, if feasible, at the time of booster vaccination and 28 days
post booster vaccination, in participants who were vaccine naïve at study entry and receive a
booster after pregnancy completion.
8.1.2. 
Procedures in the Event of (Suspected) COVID-19
Procedures to be performed in the event a participant (adult or neonate/infant) experiences signs
or symptoms suggesting possible COVID-19, or a participant became aware of a RT-PCR test
result for SARS-CoV-2 outside the study context, whether symptomatic or asymptomatic, are
detailed in the Schedule of Activities in Section 1.3.4(adults)and Section 1.3.5 (neonates/infants).
Note: if a clinic visit is not feasible a home may be allowed ifallowed per local regulations.
If site staff are unable to perform home visits, a trained and delegated HCP may perform the visits
and assessments described below if allowed by local regulations. If a home visit is not feasible,
procedures and activities may be done by other methods where possible (such as telephone or
video conferencing). The principal investigator (PI) continues to be responsible for reviewing all
protocol-related assessments. Site staff/HCP visiting participants at home will use personal
protective equipment according to local regulation.
In case the participant experiences any signs or symptoms suggesting possible COVID-19, medical
management of the case should follow local recommendations/guidelines.

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8.1.2.1. 
Procedures for Adult Participants in Case of Signs and Symptoms of
COVID-19
Day 1-2 Procedures in Case of Signs and Symptoms
If an adult participant (or their designated caregiver) records in the eCOA or informs the site that
she experienced any signs or symptoms suggesting possible COVID-19, this will be considered
COVID-19 Day 1 (day of onset of signs and symptoms). The adult participant will be asked to
complete the ePROs (ie, the SIC, including body temperature) in the eCOA.
Notes:
 
The SIC questionnaire asks the adult participant if she had any of the prespecified signs
or symptoms during the past 24 hours, and (when applicable) to rate the severity. The SIC
questionnaire takes approximately 5 minutes to complete.
 
The adult participant should record the highest temperature in the last 24 hours in the SIC.
 
The adult participant should record 1 of the 3 pulse oximetry readings in the last 24hours
in the eCOA.
 
If an adult participant is unable to complete the SIC in the eCOA, the site can collect
information on the participant’s symptoms and body temperature, by contacting the
participant by telephone (or visit the participant at home), reading the questions aloud to
the participant and entering the participant’s responses on the participant’s behalf. More
details are provided in the eCOA Study Manual.
 
If a participant is unable to complete the SIC in eCOA, the reason for missing the SIC
completion should be recorded in the eCRF.
Based on the information collected through the SIC, the site will reach out to the adult participant
at the latest on COVID-19 Day 2 (the day after the day of symptom onset) to assess whether the
reported signs and symptoms qualify as a suspected COVID-19 episode using prespecified criteria
(Section 8.1.2.4). As several of the prespecified criteria for suspected COVID-19 overlap with
vaccine-related reactogenicity, investigators' clinical judgement is required to exclude vaccine-
related events when assessing suspected COVID-19. If the adult participant would actively reach
out to the site already on COVID-19 Day 1, the site should already make a first assessment on
COVID-19 Day 1 to check whether the reported signs and symptoms qualify as a suspected
COVID-19 episode using prespecified criteria (Section 8.1.2.4). As soon as the prespecified
criteria for suspected COVID-19 are met (COVID-19 Day 1-2), the adult participant will be asked
to undertake the COVID-19 procedures. In particular:
 
The adult participant will be asked to continue to complete the ePROs in the eCOA as
specified above for COVID-19 Day 1:
o 
SIC (including body temperature): every day, preferably in the evening around the
same time each day. If more than one measurement is made on any given day, the
highest temperature of that day will be recorded.

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o 
Blood oxygen saturation and pulse rate using a pulse oximeter 3 times a day,
preferably in the morning, at lunch time, and in the evening.
Note: the ePROs do not have to be completed if special circumstances occur, such as
hospitalization or ventilation, in which case the reason for not completing the ePROs
should be recorded by site staff in the eCRF.
 
The adult participant will be asked to collect a nasal swab at home on COVID-19
Day 1-2, as soon as possible after it has been confirmed that the prespecified criteria for
suspected COVID-19 are met. If the adult participant requires assistance, a trained HCP
can help the participant to collect the nasal swab. The study site should arrange transfer
of the nasal swab to the study site as soon as possible after collection, preferably within
3 days. The COVID-19 Day 1-2 nasal swab can also be collected at the study site (or
hospital or other location, if needed), if preferred by the adult participant.
Day 1-2 Procedures in Case of a Positive RT-PCR Test Outside the Study Site Context
If an adult participant becomes aware of a positive RT-PCR test for SARS-CoV-2 she should
contact the site as soon as possible. The day the adult participant became aware of the positive
PCR test will be considered COVID-19 Day 1. Regardless of whether the adult participant is
symptomatic or asymptomatic, they will be asked to:
 
Complete the (suspected) COVID-19 surveillance (symptom check) in the eCOA. In case
of COVID-19-like signs and symptoms they will need to complete the SIC (including
body temperature) in the eCOA.
 
The adult participant will be asked to collect a nasal swab at home on COVID-19
Day 1-2, as described for the participants with signs and symptoms (see above).
If a participant has a positive test result for SARS-CoV-2 infection, if necessary, study-site
personnel may visit the participant at homea. The participant will be contacted by the site at least
once per week. The SIC will be reviewed by study staff during these contacts (phone call or visit).
Day 3-5 Procedures for all Adult Participants Who Have met the Prespecified Criteria for
(Suspected) COVID-19
The adult participant will be asked to come to the site on COVID-19 Day 3-5 (between 2 and 4
days after symptom onset/becoming aware of a positive RT-PCR test).
 
If a site visit is not feasible, a member of the study staff could visit the participant at home
(or at the hospital or other location, if needed), if allowed by local regulations. The study
staff visiting participants at home will use personal protective equipment according to
local regulations. The COVID-19 Day 3-5 assessments may also be performed by a
trained HCP, if allowed per local regulations.
 
During Part 1 of the COVID-19 Day 3-5 visit, if the adult participant has experienced
COVID-19 like signs and symptoms, the site will interview the participant to assess
whether the reported signs and symptoms still qualify as a suspected COVID-19 episode
a 
The study staff visiting participants at home will use personal protective equipment according to local regulations.

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using prespecified criteria (Section 8.1.2.4). In addition, for all participants with
(suspected) COVID-19, a qualified member of the study site will measure vital signs
(body temperature, blood pressure, heart rate, and respiratory rate) and pulse oximetry. A
targeted physical examination will be performed based on the judgement of the
investigator or designated medically qualified healthcare professional. A nasal swab will
be collected for detection of SARS-CoV-2 by a qualified member of the study site.
 
If the prespecified criteria for suspected COVID-19 are still met on COVID-19 Day 3-5
or if at least one nasal swab from COVID-19 Day 1-2 or Day 3-5 visits is positive for
SARS-CoV-2 (tested by RT-PCR), the following assessments and procedures are to be
performed during Part 2 of the COVID-19 Day 3-5 visit: blood samples for exploration
of biomarkers that correlate with SARS-CoV-2 infection and COVID-19 severity and for
exploration of antibody responses to infection with SARS-CoV-2 will be collected by a
qualified member of the study site and the procedures for the 7-day cycles should be
started (see below).
 
The medical history (general and obstetric) and description of COVID-19 episode will be
collected by interview with the participant.
 
If signs and symptoms are still ongoing on COVID-19 Day 3-5, collection of SIC will
continue as specified in the next section (Closure of the COVID-19 episode).
 
If the prespecified criteria for suspected COVID-19 are no longer met on COVID-19
Day 3-5, the participant will not undertake any further COVID-19 procedures. She will
fall back to the default Schedule of Activities.
Procedures During the 7-day Cycles
If an adult participant meets the prespecified criteria at Day 3-5 (even if nasal swab results from
Day 1-2 and Day 3-5 are pending) and/or has at least one positive nasal sample for SARS-CoV-2
at COVID-19 Day 1-2 or COVID-19 Day 3-5, she will be asked to undertake the COVID-19
procedures, in particular:
 
In case of signs and symptoms: The participant will be reminded to further complete the
ePROs in the eCOA as described for COVID-19 Day 1-2:
In case the nasal swabs collected at Day 1-2 or Day 3-5 visits are tested positive for
SARS-CoV-2 and the participant is asymptomatic: The participant will be reminded to
further complete (suspected) COVID-19 surveillance (symptom check, at least twice a
week).
 
All participants will be asked to collect a nasal swab at home once every 7 days. If the
participant requires assistance, a trained HCP can help the participant to collect the nasal
swabs. The study site should arrange transfer of the nasal swabs to the study site within
3 days after collection. Details are provided in the laboratory manual.
 
If, due to lack of signs and symptoms and unavailability of results from nasal swabs
collected on Day 1-2 and/or Day 3-5 visits, the participant stopped the COVID-19
procedures and returned to default Schedule of Activities on COVID-19 Day 3-5, the

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participantwill be contacted as soon as at least one of these samples is found to be positive
for SARS-CoV-2 The participant will be asked to resume COVID-19 procedures until 14
days after symptom onset (COVID-19 Day 15) or until resolution of the COVID-19
episode, whichever comes last.
Note: If results of both Day 1-2 and Day 3-5 nasal swabs once available are negative, the
participant will stop the 7-day cycle and fall back to the default Schedule of Activities.
Note: Participants should be encouraged by the site to collect nasal swabs as indicated in
Section 1.3.4. If the participant is unable or unwilling to collect all samples as requested,
the participant should still complete the other COVID-19 assessments, including the visit
at COVID-19 Day 29.
COVID-19 Day 29 Procedures
If an adult participant has at least 1 SARS-CoV-2 positive nasal swab collected on COVID-19
Day 1-2 or Day 3-5, then she will be asked to return to the site on COVID-19 Day 29 (±7 days)
where a blood sample will be drawn for sero-confirmation and exploration of biomarkers that
correlate with SARS-CoV-2 infection and COVID-19 severity. A qualified member of the study
site will measure vital signs (body temperature, blood pressure, heart rate, and respiratory rate)
and pulse oximetry. A targeted physical examination will be performed based on the judgement of
the investigator or designated medically qualified healthcare professional. The medical history
(general and obstetric)and description of COVID-19 episode will be collected by interview with
the participant. If the participant is still symptomatic, she will complete the SIC in the eCOA.
Asymptomatic participants will complete the (suspected) COVID-19 surveillance (symptom
check).
Notes: COVID-19 Day 29 procedures should still be performed even if the nasal swabs results are
still pending. The COVID-19 Day 29 assessments may also be performed by a trained HCP
at the participant’s home, if allowed per local regulations.
This visit can be combined with a regular study visit if within the applicable visit windows.
Closure of the COVID-19 Episode
The adult participant should continue the COVID-19 procedures until any of the following occurs,
based on molecular test results:
 
If both nasal swabs (collected on COVID-19 Day 1-2 and COVID-19 Day 3-5) are
negative for SARS-CoV-2, the participant will not undertake any further COVID-19
procedures and will fall back to the default Schedule of Activities.
 
If the participant has at least 1 SARS-CoV-2 positive nasal swab collected on COVID-19
Day 1-2 or Day 3-5, then the participant will be asked to undertake the COVID-19
procedures until 14 days after symptom onset (COVID-19 Day 15, if applicable) or until

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resolution of the COVID-19 episode, whichever comes lasta. Resolution of the
COVID-19 episode is defined as having 2 consecutive SARS-CoV-2 negative nasal
swabs and 2 consecutive days with no COVID-19-related signs or symptoms. Once past
COVID-19 Day 15, participants should stop the collection of nasal swabs as soon as
2 consecutive nasal swabs are SARS-CoV-2 negative, but (if still symptomatic at that
time) should continue completing the ePROs (including SIC, body temperature, and pulse
oximetry) in the eCOA until 2 consecutive days with no COVID-19-related signs or
symptoms.
 
If signs and symptoms are still ongoing on COVID-19 Day 3-5, collection of SIC will be
continued until at least 14 days after onset unless both COVID-19 Day 1-2 and COVID-
19 Day 3-5 nasal swabs are negative. If either of the swabs is positive or the result is
unknown AND the participant is beyond 14 days after onset of symptoms, the SIC can
be stopped after 2 days without signs and symptoms.
 
For participants with a positive test result for SARS-CoV-2 infection, a study visit will
be conducted 28 days after symptom onset (ie, at the COVID-19 Day 29 visit) to assess
the clinical course of the infection.
 
If 2 consecutive nasal swabs negative for SARS-CoV-2 are not available due to
operational reasons (eg, delays in results availability), participants may cease collection
ofnasal swabs samples at the COVID-19 Day 29 visit, provided they have 2 consecutive
days with no COVID-19-related signs and symptoms. In these cases, participants may be
asked to resume sample collection if nasal sample results
once available
do not
present with 2 consecutive negative swabs for SARS-CoV-2.
Upon closure of the COVID-19 episode and procedures, all adult participants will fall back to the
default Schedule of Activitiesb (Section 1.3.2).
If the adult participant experiences new signs or symptoms suggesting possible COVID-19 at a
later point in time, the participant would restart the COVID-19 procedures from COVID-19 Day 1
onwards.
8.1.2.2. 
Procedures for Neonate and Infant Participants in Case of Signs and
Symptoms of COVID-19
The following procedures are specific for the study:
Day 1-3 Procedures in Case of Signs and Symptoms
If a parent/caregiver records in the eCOA or informs the site that the neonate/infant experienced
any signs or symptoms suggesting possible COVID-19, this will be considered COVID-19 Day 1
(day of onset of signs and symptoms). The parent(s)/caregiver(s) will be asked to complete the
electronic ObsRO (ie, the PedSIC, including body temperature) in the eCOA.
a 
long-term sequelae of COVID-19 will not be followed until their resolution
b 
Closure of a COVID-19 episode should occur at the last study visit. If the episode is ongoing, it should be marked
as such in the eCRF. The episode will be followed by the investigator until resolution or until a clinically stable
condition is reached, and the outcome recorded in the participant’s medical chart.

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Notes:
 
The PedSIC questionnaire asks the parent(s)/caregiver(s) if the neonate/infant had any of
the prespecified signs or symptoms during the past 24 hours, and (when applicable) to
rate the severity. The PedSIC questionnaire takes approximately 5 minutes to complete.
 
The parent(s)/caregiver(s) should measure body temperature of the neonate/infant (in
accordance with the local standard of care) in the evening. If more than one measurement
is made, the highest temperature of that day will be recorded in the PedSIC.
 
The parent(s)/caregiver(s) should record at least 1 of the 3 pulse oximetry readings in the
last 24hours in the eCOA.
 
If a parent/caregiver is unable to complete the PedSIC in the eCOA, a study staff member
can collect information on the neonate/infant’s symptoms, body temperature and pulse
oximetry, by contacting the caregiver by telephone (or visit the neonate/infant at home,
if allowed by local regulations), reading the questions aloud to the caregiver and entering
the caregiver’s responses on the caregiver’s behalf. More details are provided in the
eCOA Study Manual.
 
If a participant is unable to complete the PedSIC in eCOA, the reason for missing the
PedSIC completion should be recorded in the eCRF.
Based on the information collected through the PedSIC, the site will reach out to the
parent(s)/caregiver(s) at the latest on COVID-19 Day 2 (the day after the day of symptom onset)
to assess whether the reported signs and symptoms qualify as a suspected COVID-19 episode using
prespecified criteria (Section 8.1.2.5 and 8.1.2.6). If the caregiver would actively reach out to the
site already on COVID-19 Day 1, the site should already make a first assessment on COVID-19
Day 1 to check whether the reported signs and symptoms qualify as a suspected COVID-19
episode using prespecified criteria (Sections 8.1.2.5 and 8.1.2.6). As soon as the prespecified
criteria for suspected COVID-19 are met (COVID-19 Day 1-3), the parent(s)/caregiver(s) of the
neonate/infant will be asked to undertake the COVID-19 procedures. In particular:
 
The parent(s)/caregiver(s)will be asked to continue to complete the ObsROs in the eCOA
on behalf of the neonate/infant, as specified above for COVID-19 Day 1:
o 
PedSIC (including body temperature): every day, preferably in the evening around
the same time each day. If more than one measurement is made on any given day,
the highest temperature of that day will be recorded.
o 
Blood oxygen saturation and pulse rate using a pulse oximeter 3 times a day,
preferably in the morning, at lunch time, and in the evening.
Note: the ObsROs do not have to be completed if special circumstances occur, such
as hospitalization, in which case the reason for not completing the ObsROs should
be recorded by site staff in the eCRF.
 
A trained HCP will collect a nasal swab from the neonate/infant on COVID-19 Day 1-3,
as soon as possible after it has been confirmed that the prespecified criteria for suspected
COVID-19 are met. In case if the nasal swab is collected at the participant’s home, the

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study site should arrange transfer of the nasal swab to the study site within 3 days after
collection. The COVID-19 Day 1-3 nasal swab can also be collected at the study site by
the trained HCP  (or hospital or other location, if needed), if preferred by the
parent(s)/caregiver(s).
Day 1-3 Procedures in Case of a Positive RT-PCR Test Outside the Study Site Context
(Including a Positive RT-PCR Test of a Close Relative from the Same Household)
If a parent/caregiver becomes aware of a positive RT-PCR test for SARS-CoV-2 for the
neonate/infant or from a close relative from the neonate/infant, the parent/caregiver should contact
the site as soon as possible. The day the parent/caregiver became aware of the positive PCR test
will be considered COVID-19 Day 1. Regardless of whether the neonate/infant is symptomatic or
asymptomatic, the parent/caregiver will be asked to:
 
Complete the (suspected) COVID-19 surveillance (pediatric symptom check) in the
eCOA. In case of COVID-19-like signs and symptoms they will need to complete the
PedSIC, including body temperature and pulse oximetry, resultsin the eCOA.
 
In case of positive RT-PCR test from mother or close relative from the same household:
site staff will collect, regardless of whether there are signs of infection in the infant, a
nasal swab from the neonate/infant on COVID-19 Day 1-3, as described for the
neonate/infant with signs and symptoms (see above). The day the parent/caregiver
became aware of the positive PCR test will be considered COVID-19 Day 1.
 
In case of a positive RT-PCR test for the neonate/infant from outside the study: the
COVID-19 Day 4-7 procedures will be initiated, as described below. COVID-19 Day 1-
3 is not expected.
If a neonate/infant has a positive test result for SARS-CoV-2 infection, the parent(s)/caregiver(s)
will be notified and may be requested to keep the neonate/infant at home and not visit the study
site. If necessary, study-site personnel may visit the neonate/infant at homea (if allowed by local
regulations). The parent(s)/caregiver(s) will be contacted by the site at least once per week  to
follow-up on the neonate/infant’s condition. The PedSIC will be reviewed by study staff during
these contacts (phone call or visit).
If a neonate/infant has a negative test result for SARS-CoV-2 infection, the parent(s)/caregiver(s)
and neonate/infant will not undertake any further COVID-19 procedures and will fall back to the
default Schedule of Activities.
a 
The study staff visiting participants at home will use personal protective equipment according to local regulations.

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Day 4-7 Procedures for all Neonates/Infants Who Have met the Prespecified Criteria for
(Suspected) COVID-19
The parent(s)/caregiver(s) will be asked to come to the site with the neonate/infant on COVID-19
Day 4-7 (between 1 and 6 days after symptom onset and becoming aware of a positive RT-PCR
test on COVID-19 Day 1-3 or a positive RT-PCR test from outside the study).
 
If a site visit is not feasible, a member of the study staff could visit the neonate/infant at
home (or at the hospital or other location, if needed), if allowed by local regulations. The
study staff visiting participants at home will use personal protective equipment according
to local regulations. The COVID-19 Day 4-7 assessments may also be performed by a
trained HCP, if allowed per local regulations.
 
For all neonates/infants with confirmed COVID-19 (by molecular diagnostic RT-PCR),
study staff will measure vital signs (body temperature, heart rate, and respiratory rate)
and oxygen saturation (via pulse oximetry). A targeted physical examination will be
performed based on the judgement of the investigator or designated medically qualified
healthcare professional.
 
A nasal swab (only for participants who had a positive RT-PCR test from outside the
study) will be collected from the participant by a trained member of the study site staff.
In case the nasal swab is taken at home, the study site should arrange transfer of the nasal
swab to the study site as soon as possible after collection (within 3 day maximum).
 
A blood sample will be collected by a study staffand the procedures for the 7-day cycles
should be started (see below). The medical history and description of COVID-19 episode
will be collected by interview with the parent(s)/caregiver(s).
Procedures During the 7-day Cycles
If a neonate/infant has a positive nasal sample for SARS-CoV-2 at COVID-19 Day 1-3 or has a
positive nasal sample for SARS-CoV-2 from outside the study, the parent(s)/caregiver(s) will be
asked to undertake the COVID-19 procedures, in particular:
 
In case of signs and symptoms: The parent(s)/caregiver(s) will be reminded to further
complete the ObsROs in the eCOA as described for COVID-19 Day 1-3:
In case of positive PCR and asymptomatic: The parent(s)/caregiver(s) will be reminded
to further complete (suspected) COVID-19 surveillance (pediatric symptom checkat least
twice a week).
In case if the nasal swab is collected at the participant’s home, the study site should
arrange transfer of the nasal swabs to the study site within 3 days after collection.
Note: Parent(s)/caregivers should be encouraged by the site to allow the collection of
nasal swabs from the neonate/infant as indicated in Section 1.3.5. If the parent/caregiver
is unable or unwilling to collect all samples as requested, the neonate/infant should still
complete the other COVID-19 assessments, including the visit at COVID-19 Day 29.

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COVID-19 Day 29 Procedures
If a neonate/infant has a SARS-CoV-2 positive nasal swab collected on COVID-19 Day 1-3 or
from outside the study, then the parent(s)/caregiver(s) will be asked to return to the site with the
neonate/infant on COVID-19 Day 29 (±7 days) where a blood sample will be drawn from the
neonate/infant. Study staffwill measure vital signs (body temperature, heart rate, and respiratory
rate) and oxygen saturation (via pulse oximetry). A targeted physical examination will be
performed based on the judgement of the investigator or designated medically qualified healthcare
professional. The medical history and description of COVID-19 episode will be collected by
interview with the parent(s)/caregiver(s). If the neonate/infant is still symptomatic, the
parent(s)/caregiver(s) will complete the PedSIC in the eCOA. For asymptomatic neonates/infants,
the (suspected) COVID-19 surveillance (pediatric symptom check) will be completed by the
parent(s)/caregiver(s).
Notes: COVID-19 Day 29 procedures should still be performed even if the nasal swabs results are
still pending. The COVID-19 Day 29 assessments may also be performed by a trained HCP
at the participant’s home, if allowed per local regulations.
This visit can be combined with a regular study visit if within the applicable visit windows.
Closure of the COVID-19 Episode
The parent(s)/caregiver(s) and neonate/infant should continue the COVID-19 procedures until any
of the following occurs, based on molecular test results:
 
If the nasal swab collected from the neonate/infant on COVID-19 Day 1-3 is negative for
SARS-CoV-2, the parent(s)/caregiver(s) and neonate/infant will not undertake any
further COVID-19 procedures and will fall back to the default Schedule of Activities.
 
For participants with a positive test result for SARS-CoV-2 infection, a study visit will
be conducted 28 days after symptom onset (ie, at the COVID-19 Day 29 visit) to assess
the clinical course of the infection.
 
If the neonate/infant has a SARS-CoV-2 positive nasal swab collected on COVID-19 Day
1-3 or from outside the study, then the parent(s)/caregiver(s) will be asked to undertake
the COVID-19 procedures with the neonate/infant until 14 days after symptom onset
(COVID-19 Day 15, if applicable) or until resolution of the COVID-19 episode,
whichever comes lasta. Resolution of the COVID-19 episode is defined as having 1
SARS-CoV-2 negative nasal swab and 2 consecutive days with no COVID-19-related
signs or symptoms. Once past COVID-19 Day 15, nasal swabs will no longer be collected
from the neonate/infant as soon as 1 nasal swab is SARS-CoV-2 negative, but (if the
neonate/infant is still symptomatic at that time) the parent(s)/caregiver(s) should continue
completing the ObsROs (including PedSIC, body temperature, and pulse oximetry) in the
eCOA until 2 consecutive days with no COVID-19-related signs or symptoms.
a 
long-term sequelae of COVID-19 will not be followed until their resolution

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Note: for neonates/infants who have signs and symptoms present at baseline (assessed
pre-vaccination), only signs and symptoms that are associated with COVID-19 and that
developed during the COVID-19 episode are to be taken into account.
Upon closure of the COVID-19 episode and procedures, all neonates/infants will fall back to the
default Schedule of Activities (Section 1.3.3).
All confirmed COVID-19 episodes will be communicated to the respective parent(s)/caregiver(s)
if required per local regulations.
If the neonate/infant experiences new signs or symptoms suggesting possible COVID-19 at a later
point in time, the neonate/infant would restart the COVID-19 procedures from COVID-19 Day 1
onwards.
8.1.2.3. 
Procedures for Neonates Born to Mothers With Confirmed COVID-19
Testing for SARS-CoV-2 should be performed for all neonates, regardless of whether there are
signs of infection in the neonate, if they were born to mothers with confirmed COVID-19 at the
time of birth, or if a close relative from the same household has confirmed COVID-19 at the time
of birth.
Testing for diagnosis of SARS-CoV-2 infection will be performed on nasal swab samples by the
local laboratory.
Testing of asymptomatic and symptomatic neonates should be performed as soon as feasible. If
initial test results are negative, or not available, testing should be repeated for confirmation.
For asymptomatic neonates expected to be discharged at <48 hours of age, a single test can be
performed prior to discharge, between 24-48 hours of age (recommendation).
It is recommended, for neonates presenting with signs of infection suggestive of COVID-19
(including fever, lethargy, rhinorrhea, cough, tachypnea, difficulty breathing, vomiting, diarrhea,
bluish lips or face, red or bruised looking feet or toes, or poor feeding), or with a positive SARS-
CoV-2 test, refer to a hospital as outlined in the procedures in Section 8.1.2.2.
8.1.2.4. 
Prespecified Criteria for Suspected COVID-19 in Adults
For adults, the criteria for suspected COVID-19 (ie, the triggers to proceed with contacting the
study site and home-collection of the nasal swab) are prespecified as follows:

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A positive RT-PCR result for SARS-CoV-2, through a private or public laboratory
independent of the study, whether symptomatic or asymptomatic
OR
New onset or worsening of any 1 of these symptoms, which lasts for at least 24 hours, not
otherwise explained:
 
Headache
 
Malaise (appetite loss, generally unwell, fatigue, physical weakness)
 
Myalgia (muscle pain)
 
Chest congestion
 
Cough
 
Runny nose
 
Shortness of breath or difficulty breathing (resting or on exertion)
 
Sore throat
 
Wheezing
 
Eye irritation or discharge
 
Chills
 
Fever (≥38.0°C or ≥100.4°F)
 
Pulse oximetry value ≤95%, which is a decrease from baseline
 
Heart rate ≥90 beats/minute at rest, which is an increase from baseline
 
Gastrointestinal symptoms (diarrhea, vomiting, nausea, abdominal pain)
 
Neurologic symptoms (numbness, difficulty forming or understanding speech)
 
Red or bruised looking toes
 
Skin rash
 
New or changing olfactory or taste disorders
 
Symptoms of blood clots: pain/cramping, swelling or redness in your legs/calves
 
Confusion
 
Bluish lips or face
 
Clinical suspicion/judgement by investigator of symptoms suggestive of COVID-19
As several of the prespecified criteria for suspected COVID-19 overlap with vaccine-related
reactogenicity, investigators' clinical judgement is required to exclude vaccine-related events when
assessing suspected COVID-19.

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8.1.2.5. 
Prespecified Criteria for Suspected COVID-19 for Neonates
For neonates, the criteria for suspected COVID-19 (ie, the triggers to proceed with contacting the
study site and collection of the nasal swab by the HCP) are prespecified as follows:
A positive RT-PCR result for SARS-CoV-2 for the neonate, through a private or public
laboratory independent of the study, whether symptomatic or asymptomatic
OR
A positive RT-PCR result for SARS-CoV-2 for a parent/caregiver, or any other close relative
of the neonate, through a private or public laboratory independent of the study, whether
symptomatic or asymptomatic
OR
New onset or worsening of any 1 of these symptomsa, which lasts for at least 24 hours, not
otherwise explained:
 
Fever (≥38.0°C or ≥100.4°F)
 
Lethargy (decreased activity)
 
Nasal congestion of runny nose (rhinorrhea)
 
Cough
 
Tachypnea (according to age)
 
Difficulty breathing
 
Vomiting
 
Diarrhea
 
Poor feeding
 
Bluish lips or face
 
Bloodshot eyes
 
Red or bruised looking feet or toes
 
Clinical suspicion/judgement by investigator of symptoms suggestive of COVID-19,
including MIS-C
a 
Adapted from Section 10.10.2

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8.1.2.6. 
Prespecified Criteria for Suspected COVID-19 for Infants
For infants, the criteria for suspected COVID-19 (ie, the triggers to proceed with contacting the
study site and collection of the nasal swab by the HCP) are prespecified as follows:
A positive RT-PCR result for SARS-CoV-2 for the infant, through a private or public
laboratory independent of the study, whether symptomatic or asymptomatic
OR
A positive RT-PCR result for SARS-CoV-2 for a parent/caregiver, or any other close relative
of the infant, through a private or public laboratory independent of the study, whether
symptomatic or asymptomatic
OR
New onset or worsening of any 1 of these symptomsa, which lasts for at least 24 hours, not
otherwise explained:
 
Fever (≥38.0°C or ≥100.4°F) or chills
 
Cough
 
Wheezing
 
Nasal congestion or runny nose (rhinorrhea)
 
Shortness of breath or difficulty breathing
 
Diarrhea
 
Vomiting
 
Lethargy/Tiredness/Decreased activity
 
Poor appetite or poor feeding
 
Mood behaviors (frequent crying, irritability)
 
Tachypnea (according to age)
 
Rash
 
Bloodshot eyes
 
Bluish lips or face
 
Red or bruised looking feet or toes
 
Clinical suspicion/judgement by investigator of symptoms suggestive of COVID-19,
including MIS-C
a 
Adapted from Section 10.10.3

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8.1.3. 
Symptomatic SARS-COV-2 Infection
Identification and molecular confirmation of SARS-CoV-2 infection and symptomatic COVID-19
will be performed throughout the study as described in Section 8.1.2. The ePRO/eObsRO  to
evaluate exploratory vaccine parameters will be the SIC/PedSIC.
Molecular confirmation of SARS-CoV-2 infection by a central laboratory will be used for the
exploratory analysis of the case definition only. The severity of all COVID-19 cases will be
assessed using the case definitions in Section 10.8.
8.1.4. 
Asymptomatic SARS-COV-2 Infection
An immunologic test for SARS-CoV-2 seroconversion (non-S ELISA and/or SARS-CoV-2
immunoglobulin assay) based on SARS-CoV-2 N-protein, will be performed in adult participants
to identify cases of asymptomatic infection.
Asymptomatic infections also include those detected by confirmed molecular tests (either in this
study or outside study), in the absence of the relevant symptoms.
8.2. 
Safety Assessments
Details regarding the IDMC are provided in Section 10.3.6.
AEs will be reported and followed by the investigator as specified in Section 8.3 and Section 10.4.
Any clinically relevant changes occurring during the study must be recorded in the eCRF, as
specified in Section 8.3.1.
Any clinically significant abnormalities persisting at the end of the study/early withdrawal will be
followed by the investigator until resolution or until a clinically stable condition is reached.
The study will include the following evaluations of safety and reactogenicity according to the time
points provided in the Schedules of Activities (Section 1.3).
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 qualified
healthcare professional Any clinically relevant abnormalities or changes in severity observed
during the review  of body systems should be documented in the eCRF, in accordance with
Section 8.3.1.

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The following physical examinations will be performed:
Full physical examination includes height, body weighta, examination of skin, respiratory,
cardiovascular, abdominal, limited neurological, musculoskeletal, external ano-genital systems (if
clinically necessary), general appearance, head/ear/nose/throat, neck and extremities. This will be
carried out at screening, on the day of vaccination (Study Day 1 and the Booster Visit, if
applicable). A full physical examination will be performed at the Early Exit visit, if applicable.
Obstetric examination will include measurement of fundal height, fetal heart tones, determination
of position of the fetus, and internal manual pelvic examination (if clinically necessary). This will
be carried out at screening, on the day of vaccination (Study Day 1 [-14 days and +14days]). If
pregnant at the time of the Early Exit visit, an obstetric examination will be performed.
Obstetric ultrasound  is performed by a qualified provider to confirm normal intrauterine
pregnancy, estimate gestational age, and identify any fetal abnormalities as appropriate to stage of
pregnancy (intrauterine growth retardation, congenital malformations).
Targeted physical examination includes an assessment of any systems that are indicated by
history or observation. This will be carried out on Study Day 8 (7 days after vaccine) ± 3 days,
Study Day 29 (28 days after the vaccine) ± 7days, PP1, 6 months, and 12 months postpartum. If
applicable, participants who receive the booster vaccination will have a targeted examination at
the Day 29 PB visit.
Neonatal physical examination includes gestational age, sex (male, female or indeterminate),
(birth) weight, length and head circumference, general appearance (syndromic or normal),
generalized dermatological signs, cardiovascular signs, respiratory signs, hematological signs,
gastrointestinal signs, urogenital signs, musculoskeletal signs, neurological signs (including
audiological test results), neurodevelopmental signs, ocular/visual signs, endocrine/metabolic
signs; presence of congenital malformations or birth injuries; presence of signs of congenital or
acute infection in the neonate, and the overall Apgar score (Apgar 2015).
The overall Apgar score is required to be documented in the eDC. The Apgar score comprises of
the parameters: include color, heart rate, reflexes, muscle tone, and respiration that could be
entered in the eDC if available. The assessment is performed at 1 minute and 5 minutes after birth,
and may be checked at 10 minutes and 20 minutes after birth, if required (see Neonate/Infants
Schedule in Section 1.3.3). Further details of the Apgar score can be found in Section 10.4.8.
Infant physical examination includes weight, length, head circumference, general appearance,
skin, head and neck, cardiovascular, neurologic, respiratory, abdominal and musculoskeletal
examination.
a 
To obtain the actual body weight, participants must be weighed lightly clothed. The height should be measured
without footwear.

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8.2.2. 
Vital Signs
Body temperature (oral route preferred for adults, in accordance with the local standard of care for
neonates/infants), pulse/heart rate, respiratory rate, blood pressure (adults only), and blood oxygen
saturation will be assessed.
Adult participants will utilize a reactogenicity diary to record body temperature measurements
from the time of vaccination until 7 days after vaccination in the eCOA (see Section 8).
All participants with COVID-19 signs and symptoms should measure body temperature daily (in
accordance with the local standard of care) and record the highest temperature in the last 24 hours
each day in the ePRO in the eCOA, for the duration of follow-up of COVID-19 episodes (as
defined in Section 8.1.2.1).
All parent(s)/caregiver(s) of neonates/infants with (suspected) COVID-19 should measure blood
oxygen saturation 3 times a day and body temperature daily (the highest temperature in the last
24hours each day) and record it in the eCOA for the duration of follow-up of COVID-19 episodes
(as defined in Section 8.1.2.2).
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 signs are recommended
before blood sampling.
8.2.3. 
Clinical Safety Laboratory Assessments
Blood samples for hematology and a random urine sample for pregnancy testing and urine dipstick
for urinalysis will be collected as noted in Section 10.2. The investigator must review the
laboratory results, document this review, and record any clinically relevant changes occurring
during the study in the AE section of the eCRF, in accordance with Section 8.3.1.
8.2.3.1. 
Hematology Clinical Laboratory Assessments
Blood samples for hematology (as detailed in Section  10.2) will be collected for adults at the
timepoints indicated in the Schedules of Activities (see Section 1.3).
Serum samples originally drawn or yet to be drawn for the humoral immunogenicity assessments
could be used for the testing of relevant coagulation biomarkers
The investigator must review the laboratory results, document this review, and record any
clinically relevant changes occurring during the study in the AE or medical history (general and
obstetric)section of the CRF, as applicable.
Plasma and serum derived from whole blood samples will be collected from all participants at
selected time points for retrospective analysis of hematological parameters, including pro- and
anti-coagulation factors, in the event of a suspected AESI of TTS post-vaccination.

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Coagulation factors, platelet counts and cell blood count (CBC) will be determined locally. The
extent to which levels of these coagulation factors fluctuate pre-and post-vaccination with
Ad26.COV2.S may be investigated for research purposes.
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) (see
the Schedule of Activities in Section 1.3.6 and Section 10.2, Appendix 2).
In case of a post-vaccination thrombotic event or TTS, every effort should be made to collect local
hospital/laboratory test results obtained by the treating physician to allow rapid diagnosis and
treatment. This information should be reported through the TTS AESI form (see Section 10.11,
Appendix 11) electronically per instructions in the eCRF completion guidelines.
See Section 8.3.6.1 for details on laboratory test details to be reported for an AE of
thrombocytopenia.
8.2.4. 
Medical, Obstetric and Delivery History
Medical history includes general medical history including preexisting non-obstetric conditions,
previous surgery, medication history up to one month prior to conception/pregnancy, and
hospitalizations.
Obstetric medical history includes order of the current pregnancy, gravidity, parity, attendance
at antenatal visits and results of any routine tests obtained during pregnancy to assess pregnancy
and the fetus (eg, congenital anomalies, ultrasound, amniocentesis). For prior pregnancies, dates
of delivery or termination of pregnancy, history of multiple pregnancies, pregnancy complications,
history of caesarean section (elective or emergency), pregnancy outcome(s) (live birth, still birth
or abortions, c-sections, multiple pregnancies and complications if applicable) and history of
previous early-onset neonatal infection, if feasible.
Delivery history includes place of delivery (District Hospital or other); mode of delivery (normal
spontaneous vaginal delivery, elective versus emergency caesarean section); length of first stage
of labor, length of second stage of labor; date and time of rupture of membranes; date and time of
birth; presence and type of health care assistant at delivery (physician, midwife, other); delivery
complications (including blood loss and intrapartum infection); singleton vs multiple birth.
8.2.5. 
Breast Milk Production Outcomes
Subjective changes in (postpartum) breast milk production (reduction) will be collected in the
eCOA diary.
8.2.6. 
Neonatal Assessments
Neonatal medical history  includes birth/termination outcome (live birth, stillbirth,
termination/miscarriage, neonatal death) demographics, physical examination, overall Apgar
score, weight, length, head circumference, and key findings of fetal monitoring during labor such

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as fetal presentation at delivery, gestational age (ultrasound), complications, fetal heart rate and
uterine contractions during labor.
Neurodevelopmental status will be measured using the Ages & Stages Questionnaire, 3rd edition
(ASQ-3; Schonhaut 2013). The ASQ-3 includes a series of questions designed to assess 5 areas of
development (communication, gross motor, fine motor, problem solving and personal-social). If
any infant scores in the “gray” or “black” zones, the participant will be advised to discuss with the
infant’s pediatrician.
8.3. 
Adverse Events, Serious Adverse Events, Adverse Events of Special
Interest, and Other Safety Reporting
Timely, accurate, and complete reporting and analysis of safety information, including AEs,
suspected, SAEs, AESIs, pregnancy-related AEs throughout pregnancy, MAAEs, and product
quality complaint (PQC), from clinical studies are crucial for the protection of participants,
investigators, and the sponsor, and are mandated by regulatory agencies worldwide. The sponsor
has established Standard Operating Procedures in conformity with regulatory requirements
worldwide to ensure appropriate reporting of safety information; all clinical studies conducted by
the sponsor, or its affiliates will be conducted in accordance with those procedures.
AEs will be reported by the participant (or, when appropriate, by a parent/caregiver, surrogate, or
the participant's legally acceptable representative) for the duration of the study.
Further details on AEs, suspected SAEs, AESI, pregnancy-related AEs throughout pregnancy,
MAAEs, and PQC can be found in Section 10.4.
8.3.1. 
Time Period and Frequency for Collecting Information Relating to
Adverse Events, Adverse Events of Special Interest, Serious Adverse
Events, Pregnancy-related Adverse Events and Medically-attended
Adverse Events
All Adverse Events
All AEs and special reporting situations, whether serious or non-serious, that are related to study
procedures or that are related to non-investigational sponsor products will be reported for all
participants (adult participants and neonates/infants) 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 the ICF and moment of first vaccination will be collected on the Medical History eCRF page as
pre-existing conditions.
For adult participants, solicited AEs, collected through a reactogenicity diary as part of the eCOA,
will be recorded for vaccination from the time of vaccination until 7days post-vaccination (or until
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All other unsolicited AEs and special reporting situations, whether serious or non-serious, will be
reported from the time of vaccination until 28days post-vaccination. Unsolicited AEs with the
onset date outside the timeframe defined above (>28 days after previous study vaccination), which
are ongoing on the day of the subsequent vaccination, should be recorded as such.
All SAEs, AESI, AEs and pregnancy-related AEs throughout pregnancyleading to discontinuation
from the study/vaccination (regardless of the causal relationship) are to be reported for all adult
participants from the moment of first vaccination until completion of the participant’s last study-
related procedure, which may include contact for safety follow-up. The investigator’s assessment
of ongoing AEs at the time of each participant’s last visit should be documented and closed in the
participant’s medical record. The sponsor will evaluate any safety information that is
spontaneously reported by an investigator beyond the time frame specified in the protocol.
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 study visits
will not be considered medically-attended visits. New onset of chronic diseases will be collected
as part of the MAAEs. MAAE are to be reported for all participants from the moment of the
vaccination until 6 months after vaccination. MAAEs leading to study discontinuation which are
to be reported until completion of the participant’s last study-related procedure. New onset of
chronic diseases will be collected as part of the MAAEs.
AEs leading to discontinuation will be reported throughout the study.
All AEs will be followed until resolution or until clinically stable.
Adverse Events of Special Interest
From the time of local approval of protocol Amendment 3 onwards, post-vaccination TTS is
considered to be an AESI. Suspected AESIs (thrombotic events and thrombocytopenia [defined as
platelet count below 150,000/µL post-vaccination, see Brighton Collaboration Interim Case
Definition, 2021]) 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).
Serious Adverse Events
All SAEs, as well as PQC, occurring during the study must be reported to the appropriate sponsor
contact person by study site personnel within 24hours of their knowledge of the event.
Serious adverse events, including those spontaneously reported to the investigator within 30 days
after the last dose of study vaccine, 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.
SAEs in adult participants will be assessed and reported throughout the study, from the date of
vaccination until end of study or at least 12 months postpartum. SAEs in the neonates/infants will
be followed up until end ofstudy (up to approximately 12 months of age).

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Information regarding SAEs will be transmitted to the sponsor using the Serious Adverse Event
Form and Safety Report Form of the eCRF, which must be completed and reviewed by a physician
from the study site andtransmitted 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.
Signs and symptoms of Multisystem Inflammatory Syndrome in Children (MIS-C) will be
monitored and reported as SAE from birth until study end in neonates/infants with (suspected)
COVID-19 as confirmed by a positive RT-PCR result for SARS-CoV-2, and in neonates/infants
of mothers or a close relative with prior (within 4-weeks) or current suspected or confirmed
COVID-19. Further details on case definition and reporting ofMIS-C in infants can be found in
Section 10.7.
8.3.2. 
Method of Detecting Adverse Events, Adverse Events of Special
Interest, Serious Adverse Events and Medically-attended Adverse
Events
Care will be taken not to introduce bias when detecting AEs, suspected AESI, or SAEs. Open-
ended and nonleading verbal questioning of the adult participant is the preferred method to inquire
about AE occurrence.
Study site personnel, as well as parent(s)/caregiver(s), should be instructed how to interpret signs
and symptoms (eg, crying and pain) in their individual neonate/infant. They will be instructed to
report both specific and non-specific symptoms (including vomiting, diarrhea, sleepiness,
variation in the intensity and pattern of crying, etc.). These non-specific symptoms may be the
only manifestations of some adverse reaction observed in neonates/infants. Care should be taken
that the clinical presentation of adverse reactions is not misinterpreted as the manifestation of a
preexisting or unrelated condition.
Moreover, symptoms that are dependent on participant communication ability (eg, nausea, pain,
mood alterations) in neonates/infants could potentially be at risk for under- or misreporting.
Solicited Adverse Events
Solicited AEs are used to assess the reactogenicity of the study vaccine and are predefined local
(at the injection site) and systemic events for which the adult participant is specifically questioned,
and which are noted by participants in their reactogenicity diary.
After vaccination, adult participants will remain under observation at the study site for at least
30 minutes (1 hour for Sentinel and Safety Cohorts) for the presence of any severe acute reactions
and solicited events.
In addition, adult participants will record solicited signs and symptoms in a reactogenicity diary
for 7 days after vaccination. All adult participants will be provided with a reactogenicity diary and
instructions on how to complete the reactogenicity diary  (see Overview in Section 8). The
reactogenicity diary  information will be transferred to the sponsor. After review and verbal
discussion of the initial reactogenicity diary  entries with the participant, the investigator will

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complete his/her own assessment in the relevant sections of the eCRF/eCOA. Once a solicited sign
or symptom from the reactogenicity diary is considered to be of severity Grade 1 or above, it will
be recorded as a solicited AE.
Solicited Injection Site (Local) Adverse Events
Adult participants will be asked to note in the reactogenicity diary, occurrences of injection site
pain/tenderness, erythema and swelling at the study vaccine injection site daily for 7 days post-
vaccination (day of vaccination and the subsequent 7 days). The extent (largest diameter) of any
erythema and swelling should be measured (using the ruler supplied) and recorded daily. The case
definitions for solicited injection site events can be found in the references (Gidudu 2012,
Kohl 2007).
Solicited Systemic Adverse Events
Adult participants will be instructed on how to record daily temperature using a thermometer
provided for home use. Adult participants should record the temperature in the reactogenicity diary
in the evening of the day of vaccination, and then daily for the next 7 days approximately at the
same time each day. If more than one measurement is made on any given day, the highest
temperature of that day will be recorded in the reactogenicity diaryandused in the relevant sections
of the eCRF/eCOA.
Fever is defined as endogenous elevation of body temperature ≥38.0°C or ≥100.4°F, as recorded
in at least 1 measurement (Marcy 2004).
Adult participants will also be instructed on how to note signs and symptoms in the reactogenicity
diary on a daily basis for 7 days post-vaccination (day of vaccination and the subsequent 7 days),
for the following events: fatigue, headache, nausea, and myalgia.
For Group 4 booster participants changes (reduction) in postpartum breast milk production will be
recorded in the breat milk diary daily for 7 days post-vaccination and will be evaluated by the PI.
Unsolicited Adverse Events
Unsolicited AEs are all AEs for which the participant is not specifically questioned in the
participant's reactogenicity diary.
Adult participants will record unsolicited signs and symptoms of AEs in a reactogenicity diary for
28days after vaccination.
For details about AESIs, refer to Section 8.3.6.
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
will be collected as part of the MAAEs. Routine study visits will not be considered
medically-attended visits.

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8.3.3. 
Follow-up of Adverse Events, Serious Adverse Events, Adverse
Events of Special Interest, Pregnancy-related Adverse Events, and
Medically-attended 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, SAE,
suspected AESI, pregnancy-related AEs throughout pregnancy, MAAE, or PQC as fully as
possible. This may include additional laboratory tests or investigations, histopathological
examinations, or consultation with other health care professionals.
AEs, including pregnancy, will be followed by the investigator as specified in Section 10.4.
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. Participating investigators and IEC/IRB will receive a SUSAR summary.
8.3.5. 
Pregnancy
All initial reports of pregnancy in participants, with onset after the PP1 visit, 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 after the
PP1 visit will not be eligible to receive the booster vaccination. These participants will remain in
the study and will continue to undergo all procedures for surveillance and follow-up of COVID-
19, immunogenicity and safety as outlined in the protocol for all participants.
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 class effects, or based on nonclinical signals. AESIs will be carefully monitored during the
study by the sponsor. Participants will be reminded daily within the 30 day time period post-
vaccination via eCOA diaries if they have experienced any health concerns (including new onset
of symptoms such as shortness of breath, chest pain, leg swelling, persistent abdominal pain,
severe or persistent headaches or blurred vision, easy bruising, or tiny blood spots under the skin
beyond the site of the injection) related to suspected AESI’s post-vaccination, and if so,
participants will be advised to contact the study center.
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.
Specific requirements for the AESI are described below.

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8.3.6.1. 
Thrombosis with Thrombocytopenia Syndrome (TTS)
As described in Section 2.3.1, Risks Related to Study Participation, 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.
Because this syndrome is rare and not completely understood, all cases of thrombosis and/or
thrombocytopenia will be considered a suspected case of post-vaccination 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 post-
vaccination TTS. The investigator shall be responsible for reporting any suspected AESI of post-
vaccination TTS using the SAE form and the form detailed in Section  10.11, Appendix 11: A
suspected TTS case is defined as:
 
Thrombotic events: suspected deep vessel venous or arterial thrombotic events as detailed in
Section 10.12, Appendix 12 OR,
 
Thrombocytopenia, defined as platelet count below 150,000/μL (Brighton Collaboration,
Interim Case Definition 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 they
become available.
In the event of thrombocytopenia post-vaccination, study site personnel should report the absolute
value for the platelet count and the reference range for the laboratory test used.
In the event of a thromboembolic event or suspected TTS  post-vaccination, serum samples
obtained both pre- and pos-vaccination should be retrospectively analyzed by the central
laboratoryfor the presence of coagulation factors; repeat testing may be requested for confirmation
upon sponsor discretion.
Suspected AESIs will require enhanced data collection and evaluation (see Section 1.3.6). 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 10.11, Appendix 11 is 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. The sponsor will also attempt

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to collect information from any thrombotic event, thrombocytopenia, or TTS reported prior to the
current protocol Amendment 3.
8.4. 
Virology Assessments
Nasal swabs will be used to detect and/or quantify SARS-CoV-2. The presence of SARS-CoV-2
infection in nasal swabs will be assessed by the local laboratory (if feasible) and confirmed by the
central laboratory using a PCR-based or other molecular diagnostic test.
Gene sequencing may be performed to detect changes in the S gene and potentially also other parts
of the viral genome, if a sample is available.
Nasal swabs collected from adult participant or from neonates and infants (to be collected by
qualified HCP only) with COVID-19-like symptoms will also be tested at the central laboratory
for the presence of other respiratory pathogens using a broad respiratory pathogens panel (results
may be shared with the site).
Adult participants, with stable/well-controlled HIV infection, will be encouraged to have HIV
RNA viral load and CD4 cell count assessed at least twice a year and to provide these data for
inclusion in the eCRF.
8.5. 
Genetics and Pharmacogenomics
Blood will be drawn at selected timepoints during the study for additional exploratory
immunogenicity assessments, which may include limited genomic research (eg, RNAseq) .
8.6. 
Biomarkers
Blood will be drawn (PAXgene®) at selected timepoints during the study, as indicated in the
Schedule of Activities.
For PAXgene® tubes collected in  adult participants and in cord blood (if feasible), biomarker
analysis may  be performed to explore potentially informative biomarkers related to vaccine
immunogenicity.
For adult participants with a positive test result for SARS-CoV-2 infection, biomarker analysis
may  be performed on PAXgene® tubes for evaluation of COVID-19 cases, and to explore
potentially informative biomarkers correlated to SARS-CoV-2 infection and COVID-19 severity
at Days 3 to 5, and at Day 29 (±7 days) after onset of symptoms.
8.7. 
Medical Resource Utilization and Health Economics
Health Economics/Medical Resource Utilization and Health Economics parameters are not
evaluated in this study.

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1-dose (5×1010 vp) schedule during the 2nd and/or 3rd trimester of pregnancy, with antibody levels
and serological responses measured at 28days after vaccination by ELISA (S-ELISA, EU/mL).
A secondary objective of this study is to assess the humoral immune response in peripheral blood
of adult participants induced by Ad26.COV2.S administered IM as a 1-dose (5×1010 vp) schedule,
during the 2nd and/or 3rd trimester of pregnancy, with serological responses (including antibody
levels) measured at all blood collection timepoints by group and overall (including at the time of
delivery [both peripheral blood and cord blood]), by ELISA (S-ELISA, EU/mL).
A further secondary objective is to assess the humoral immune response in peripheral blood of
adult participants induced by Ad26.COV2.S administered IM as a 1-dose (5×1010 vp) schedule,
during the 2nd and/or 3rd trimester of pregnancy, at all blood collection timepoints by group and
overall, as measured by VNA titers (antibody GMTs), 28days after vaccination (ie, on Day 29).
Serological response to vaccination as measured by binding (S-ELISA and/or equivalent assay)
and neutralizing (VNA) antibody titers will be assessed to evaluate the humoral immune response
in adult participants who receive a booster dose, pre-boost and at selected time points post booster
vaccination by group and overall.
Neonates and Infants
No formal statistical hypothesis for immunogenicity will be tested. Immunogenicity analyses will
be performed on the PPI-NVN set. Analyses may also be performed by vaccination regimen
received by the infant’s mother during pregnancy and the gestational age at the time of vaccine
administration and/or by SARS-CoV-2 baseline serostatus of the infant’s mother. The effect of
homologous and heterologous boosters on binding antibodies and neutralizing antibody titers in
neonates born to previously vaccinated mothers will be evaluated descriptively  by group and
overall.
A secondary objective of the study is to assess antibody levels against SARS-CoV-2 in
neonates/infants born to adult participants who have received Ad26.COV2.S during the 2nd and/or
3rd trimester of pregnancy, at birth (ie, in cord blood) and at approximately 2 months and 6 months,
of age by group and overall, using ELISA (S-ELISA, EU/mL and GMCs).
A further secondary objective of the study is to assess antibody levels against SARS-CoV-2 in
neonates/infants born to adult participants who have received Ad26.COV2.S during the 2nd and/or
3rd trimester of pregnancy, at birth (ie, in cord blood), as measured by VNA titers (antibody GMTs)
by group and overall.
9.2.2. 
Safety
The primary and secondary objectives of the study are to explore the safety and reactogenicity of
Ad26.COV2.S administered IM as a 1-dose (5×1010 vp) schedule, during the 2nd and/or 3rd
trimester of pregnancy by group and overall. In addition, safety and reactogenicity of a booster
vaccination of Ad26.COV2.S at 5×1010 vp, in eligible, consenting vaccine naïve participants at
study  entry  (Group 4), administered IM not earlier than 2 months after completion of the

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participant’s Ad26.COV2.S vaccination in the study. Safety will be evaluated by group and overall
by monitoring:
 
For adult participants, AEs including solicited local and systemic AEs for up to 7 days after
vaccination, or until resolution, and unsolicited AEs for 28 days after vaccination, SAEs, and
AESIs observed following vaccination will be collected for the whole study duration and up
to 12 months postpartum, and MAAEs (including new onset of chronic diseases) up to
6 months post-vaccination or up to 12 months if resulting in study discontinuation; AEs
leading to discontinuation (entire study); pregnancy outcomes (including, live term birth, live
preterm birth, stillbirth, and abortion).
 
Pregnancy-related AEs throughout pregnancy in adult participants (including gestational
diabetes, gestational hypertension, premature rupture of membranes, premature labor,
premature uterine contractions, poor or restricted fetal growth, pre-eclampsia, eclampsia,
vaginal or intrauterine hemorrhage [non-exhaustive]).
 
Outcomes in neonates and infants (normal neonate, term neonate with (or without)
complications, preterm neonate with (or without) complications, neonatal infection,
respiratory distress, congenital anomalies, neonatal death, low birth weight, and small for
gestational age from birth until approximately 12 months of age [non-exhaustive]), SAEs
(including MIS-C), and AESIs in neonates and infants from birth until end of study
(approximately 12 months of age), and MAAEs in neonates/infants from birth until 6 months
of age or from birth until discontinuation, if the MAAE is resulting in study discontinuation;
AEs leading to discontinuation (entire study).
9.3. 
Populations for Analysis Sets
For purposes of analysis, the following populations are defined:
Population 
Description
Enrolled Adults 
All adult participants who sign the ICF
Full Analysis Set-Adults 
(FAS-A)
All enrolled adult participants with at least one vaccine administration documented
Full Analysis Set-Non- 
vaccinated 
Neonates/Infants (FAS-
NVN)
All non-vaccinated neonates/infants (NVN) born to Ad26.COV2.S vaccinated adult
participants
Per protocol 
Immunogenicity-Adults 
(PPI-A) 
All vaccinated adult participants for whom immunogenicity data are available
excluding adult participants with major protocol deviations that are expected to impact
the immunogenicity outcomes. In addition, samples obtained from participants after
SARS-CoV-2 infection occurring after baseline (if applicable) will be excluded from
the analysis
Per protocol 
Immunogenicity- Non- 
vaccinated 
Neonates/Infants (PPI- 
NVN)
All non-vaccinated neonates/infants (NVN) born to Ad26.COV2.S vaccinated adult
participants for whom immunogenicity data are available excluding neonates/infants
born to participants with major protocol deviations that are expected to impact the
immunogenicity outcomes (for example missed vaccinations in the mothers), or
neonates/infants with major protocol deviations that are expected to impact the
immunogenicity outcomes
The list of major protocol deviations to be excluded from the immunogenicity analyses will be specified in the
Major Protocol Deviation Criteria document and/or this list will be reported into the protocol deviation dataset of
the clinical database before database lock.

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9.4. 
Statistical Analyses
The SAP will be finalized prior to the data base lock (DBL) of the primary analysis, and it will
include a more technical and detailed description of the statistical analyses described in this
section. This section is a summary of the planned statistical analyses of the most important
endpoints including primary and key secondary endpoints. Due to cease of enrollment and limited
sample size, some endpoints might not be summarized and will only be provided in listings. More
details can be found in the SAP.
9.4.1. 
General Considerations
Analysis populations are defined in Section 9.3.
Primary and final analyses are defined in Sections 9.5.1 and 9.5.2.
No formal statistical testing of safety or immunogenicity data is planned. Safety and
immunogenicity will be summarized with descriptive statistics by group and overall. Safety and
immunogenicity analyses may also be performed by stage of pregnancy  (16-27 weeks, 28-38
weeks), administration of booster (Yes, No), SARS-CoV-2 baseline serostatus (Positive, Negative)
at which the vaccine was administered and by actual vaccine history within each group.
For adult participants, all safety analyses will be performed on the FAS-A and immunogenicity
analyses will be performed on the PPI-A by group and overall.
For neonates/infants, safety analyses will be performed on the FAS-NVN and immunogenicity
analyses will be performed on the PPI-NVN set by group and overall.
The number and percentage of participants screened, enrolled, vaccinated, received a booster
vaccine and completed follow-up will be summarized by group and overall.
Baseline is considered as the last available assessment before vaccination. For neonates baseline
is value at birth.
9.4.2. 
Primary/Secondary Endpoint(s)
Immunogenicity Endpoints
Descriptive statistics (geometric mean and confidence intervals, or median and interquartile range
Q1-Q3, as appropriate) will be calculated by group and overall for immunologic parameters for all
available time points for adult participants receiving Ad26.COV2.S during the 2nd and/or 3rd
trimester of pregnancy. Descriptive statistics will also be presented for neonates/infants of adult
participants who have received Ad26.COV2.S during the 2nd and/or 3rd trimester of pregnancy by
group and overall. Several definitions of serological response will be applied (fold increases in
GMC [S-ELISA] or GMT [VNA]). Graphical representations of immunologic parameters will be
prepared as applicable. Frequency tabulations will be calculated for discrete (qualitative)
immunologic parameters, as applicable.

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The impact of baseline characteristics on the humoral responses may be explored graphically or
with descriptive statistics by group and overall.
For adult participants, immunogenicity analyses may also be performed by stage of pregnancy at
which the vaccine was administered, SARS-CoV-2 baseline serostatus and by actual vaccine
history within each group.
For neonates/infants, analyses may also be performed by the gestational age at the time of vaccine
administration, and SARS-CoV-2 baseline serostatus of the adult participant.
Safety Endpoints
No formal statistical testing of safety data is planned. Safety data will be analyzed descriptively
by group and overall for adult participants (including pregnancy outcomes: live term birth, live
preterm birth, stillbirth, and abortion) and their neonates/infants up to approximately 12 months of
age (including normal neonate, term neonate with (and without) complications, preterm neonate
with (and without) complications, neonatal infection, respiratory distress, congenital anomalies,
neonatal death, low birth weight, and small for gestational age) for all adult participants receiving
the Ad26.COV2.S vaccine. Safety data from participants vaccine naïve at study entry who receive
a booster may be provided as a separate descriptive analysis by group and overall (further details
are available in the SAP).
For adult participants, safety analyses may also be performed by stage of pregnancy at which the
vaccine was administered and by SARS-CoV-2 baseline serostatus.
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 and events-related
reactogenicity diary information will be included in the analysis: solicited local at injection site
and systemic AEs with onset after vaccination, and unsolicited AEs with onset after vaccination.
For each AE, the percentage of participants who experience at least one occurrence of the given
event will be summarized by group and overall separately for adult participants (up to at least 12
months postpartum) and their neonates/infants (up to approximately 12 months of age).
Pregnancy-related AEs throughout pregnancy (including gestational diabetes, gestational
hypertension, premature rupture of membranes, premature labor, premature uterine contractions,
poor or restricted fetal growth, pre-eclampsia, eclampsia, vaginal or intrauterine hemorrhage [non-
exhaustive]) will be assessed and analyzed for adult participants by group and overall. The
complete list of preferred terms to be included as pregnancy-related AEs will be provided in the
SAP.
For SAEs, suspected AESIs and AEs leading to discontinuation throughout the study (from first
vaccination until end of the study [at least 12 postpartum]), the percentage of adult participants
who experience at least 1 occurrence of the given event will be summarized by group, overall and
by phase including post booster (if applicable). For MAAEs (from vaccination until 6 months after

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vaccination or until end of study when leading to study discontinuation), the percentage of adult
participants who experience at least 1 occurrence of the given event will be summarized by group
and overall. SAEs in the neonates/infants from birth until end of study (approximately 12 months
of age) will be assessed by group and overall. MAAEs in the neonates/infants (from birth until 6
months of age or from birth until discontinuation [if MAAE is leading to study discontinuation])
will be assessed by group and overall.
Summaries, listings, datasets, or participant narratives may be provided, as appropriate, for those
participants who die, who discontinue vaccine due to an AE, or who experience a severe AE, an
SAE, or a suspected AESI by group and overall.
Solicited local (at injection site) and systemic AEs will be summarized descriptively by group and
overall. The number and percentages of participants with at least one solicited local (at injection
site) or systemic AE will be presented by group and overall. The frequencies by group and overall
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.
Outcomes
Adverse maternal/fetal outcomes and adverse neonatal/infant outcomes will be defined using the
Case Definitions for Pregnancy Outcomes for each endpoint.
The frequency and percentage of participants for whom at least one of the indicated adverse
outcomes was reported will be summarized by group and overall. For each separate adverse
maternal/fetal and adverse neonatal/infant outcome, the number and percentage of participants
who experience at least 1 occurrence of the given event will also be tabulated by group and overall.
9.4.3. 
Exploratory Endpoint(s)
Transfer of maternal humoral immunity to the infant will be assessed, including:
 
levels of maternal IgA and/or other Ig subtypes against SARS-CoV-2 in colostrum and breast
milk within 1 week  postpartum and at 6 weeks postpartum (Day 43 PP  follow-up visit),
respectively, if feasible, in a subset of participants who had received Ad26.COV2.S vaccine
during the 2nd and/or 3rd trimester of pregnancy. Levels of maternal IgA and/or other Ig
subtypes against SARS-CoV-2 will also be assessed in colostrum and/or breast milk, if
feasible, at the time of booster vaccination and 28 days post booster vaccination, in
participants who were vaccine naïve at study entry and receive a booster after pregnancy
completion.
 
levels of antibodies in peripheral blood from adult participants and cord blood at the time of
delivery. Serological response as measured ELISA will be assessed using GMCs. The GMR
(ratio of immunologic parameters between blood and cord blood at time of delivery) will be
calculated together with confidence intervals. Additional characterizations will be described
in the SAP.

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Cellular immune responses induced in participants during the 2nd and/or 3rd trimester of pregnancy
after vaccination with Ad26.COV2.S may be further explored using PBMCs obtained on Day 1
(pre-dose), 28 days after vaccination, and at the time of delivery (if feasible), for a subset of
participants. With only 1 participant in this subset at the time of writing this Protocol Amendment
7, PBMC sampling may  be removed from the study as of Protocol Amendment 7 approval.
Analysis will be described in more detail in the SAP.
The correlation between the binding antibody (ELISA) titers and neutralizing antibody (VNA)
titers to SARS-CoV-2 will be assessed at selected timepoints using Spearman's rank correlation.
Additional details will be provided in the SAP.
The occurrence and severity of COVID-19 infection (asymptomatic and symptomatic) in adult
participants or in neonates/infants of participants who have received Ad26.COV2.S during the 2nd
and/or 3rd trimester of pregnancy, will be assessed using the case definitions in outlined in
Section 10.8.
Plasma and serum derived from whole blood samples will be collected from all participants for
retrospective analysis of hematological parameters, including pro- and anti-coagulation factors in
the event of a suspected AESI of post-vaccination TTS. The extent to which these coagulation
factors correlate with platelet counts assessed at the time, as part of the routine CBC assessment
will be determined, and the extent to which levels of these coagulation factors fluctuate pre-and
post-vaccination with Ad26.COV2.S may be investigatedfor research purposes. The platelet count
will be performed by a local laboratory or substitute for local laboratory. Blood samples will be
collected as detailed in Section 1.3 Schedules of Activities.
Developmental outcomes on the ASQ-3 at 2, 6 and 12 months will be summarized.
9.4.4. Other Safety Analyses
Clinical Laboratory Tests
Laboratory data (adult only) will be summarized by group and overall by type of laboratory test.
Reference ranges and markedly abnormal results (specified in the SAP) will be used in the
summary of laboratory data. Descriptive statistics will be calculated for all laboratory analyte at
each time point. A listing of participants with any laboratory results outside the reference ranges
will be provided. A listing of participants with any markedly abnormal laboratory results will also
be provided.
Vital Signs
Vital signs including body temperature, pulse/heart rate, respiratory rate, and blood pressure
(adults only: systolic and diastolic) and blood oxygen saturation will be summarized over time by
group and overall, using descriptive statistics and/or graphically. The percentage of participants
with values beyond clinically important limits (specified in the SAP) will be summarized by group
and overall.

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Physical Examinations
Physical examination findings will be summarized at baseline (adults) and at each timepoint for
neonates/infants by group and overall. A listing of abnormalities will be made for each scheduled
time point.
9.5. 
Planned Analyses
The SAP will describe the planned primary analysis and final analysis, in greater detail. The results
of any analysis may be used for regulatory submissions.
Unplanned interim analyses may be as required or if requested by health authorities.
The IDMC will review safety and reactogenicity data as described in Section 10.3.6.
9.5.1. 
Primary Analysis
The primary analysis of safety and immunogenicity will be performed when all adult participants
have completed the visit that takes place approximately 42 days postpartum in all groups or if adult
participants are discontinued earlier. The analysis will include safety (AEs, SAEs, and pregnancy
outcomes) and immunogenicity data (S-ELISA and VNA) for all adult participants and
neonates/infants and in cord blood at the time of delivery. The primary analysis will include all
data up to and including the Day 42 postpartum follow-up visit. The results of this analysis may
be used for regulatory submissions.
9.5.2. 
Final Analysis
The final analysis will be performed when all adult participants and all neonates/infants have
completed the final visit per the Schedules of Activities in Section 1.3. Analysis will include safety
(AEs, SAEs, and pregnancy outcomes) and immunogenicity data. Booster dose effect will be
evaluated on safety and immunogenicity.
The SAP will describe the planned analyses in greater detail.
Note: Interim analyses may be performed as required or if requested by health authorities.

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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Abbreviations
Ad26 
adenovirus type 26
AdVAC® 
adenoviral vaccine (vector platform)
AE 
adverse event
AESI 
adverse event of special interest
ALT  
alanine aminotransferase
Anti-PF4 
anti-platelet factor 4
AST  
aspartate aminotransferase
BMI 
body mass index
BUN  
Blood Urea Nitrogen
CD  
cluster of differentiation
CDC  
Centers for Disease Control and Prevention
CLS  
Capillary leak syndrome
COPD  
chronic obstructive pulmonary disease
COVID-19 
coronavirus disease-2019
CPK  
creatine phosphokinase
eCRF  
Electronic case report form(s)
DBL 
data base lock
DNA  
deoxyribonucleic acid
DTaP  
Diphtheria toxoid, Tetanus toxoid, and acellular Pertussis
DVT  
deep vein thrombosis
eCOA  
electronic clinical outcome assessment
eDC  
electronic data capture
ePRO  
electronic patient-reported outcomes
EF-PPND  
embryofetal and pre-and postnatal development toxicity
ELISA  
enzyme-linked immunosorbent assay
ELISpot 
enzyme-linked immunospot
ERD  
enhanced respiratory disease
FAS  
Full Analysis Set
Fc 
crystallizable fragment
FDA  
Food and Drug Administration
FI 
formalin-inactivated
GCP  
good clinical practice
GD  
gestation day
GLP  
good laboratory practice
GMC  
Geometric mean concentration
GMT  
Geometric mean titer
HCP  
health care professional
HELLP  
hemolysis elevated liver enzymes and low platelets
HIT  
heparin-induced thrombocytopenia
HIV  
human immunodeficiency virus
IB  
investigator's brochure
ICF  
informed consent form
ICS  
intracellular cytokine staining
ICH  
International Conference on Harmonization
ICU  
intensive care unit
IDMC  
Independent Data Monitoring Committee
IEC  
Independent Ethics Committee
IFN-γ 
interferon gamma
Ig 
immunoglobulin
IL 
interleukin
IM  
intramuscular
IPPI 
Investigational Product Preparation Instructions
IRB  
Institutional Review Board
IWRS  
interactive web response system

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MAAE 
Medically-attended adverse event
MedDRA  
Medical Dictionary for Regulatory Activities
MERS (-CoV) 
Middle East respiratory syndrome (coronavirus)
MIS-C 
Multisystem Inflammatory Syndrome in Children
N 
nucleocapsid
ObsRO  
Observer-reported outcomes
PBMC  
peripheral blood mononuclear cell
PedSIC  
Pediatric Symptoms of Infection with Coronavirus-19
PI 
principal investigator
PPI 
per protocol immunogenicity
PQC  
product quality complaint
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  
severe acute respiratory syndrome
SARS-CoV(-2) 
severe acute respiratory syndrome coronavirus(-2)
SIC  
Symptoms of Infection with Coronavirus-19
SIPPM  
site investigational product and procedures manual
SpO2 
oxygen saturation
SRP/S  
study responsible physician/scientist
SUSAR  
suspected unexpected serious adverse reaction
TTS  
Thrombosis with thrombocytopenia syndrome
Th 
T helper
Th1/Th2 
T helper cell subset(s)
TNF-α 
tumor necrosis factor alpha
ULN  
upper limit ofthe normal range
US  
United States
VAERD  
vaccine-associated enhanced respiratory disease
VSD  
Vaccine Safety Datalink
VNA  
virus neutralization assay
vp 
virus particle
WBC  
white blood cell
WHO  
World Health Organization
Definition 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, multiorgan  failure, and death
(US FDA May 2020, US FDA June 2020).
eCOA  
Electronic Clinical Outcome Assessment. An umbrella term encompassing different types of
outcomes assessments, which may include the COVID-19 signs and symptoms surveillance
question, SIC (as an ePRO for adults), PedSIC (as an ObsRO for neonates/infants) and the
reactogenicity diary (to record vaccine reactogenicity) in adults.
Note: should the eCOA not be available, paper format will be used to collect the data.
ePRO  
The electronic technology used to collect the patient-reported outcome data. PROs are reports
that come directly from the participant without interpretation by clinician or anyone else. This
includes the SIC questionnaire and the recording of pulse oximetry results.
reactogenicity diary  
Used to record solicited signs and symptoms by the participants.

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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.
ObsROs 
Observer-reported Outcomes. Used to collect the observer-reported outcome data. ObsROs are
reports that come directly from the legal guardian/caregiver without interpretation by a
clinician or anyone else. This includes the PedSIC questionnaire and the recording of pulse
oximetry results.

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10.3. Appendix 3: Regulatory, Ethical, and Study Oversight Considerations
10.3.1. 
Regulatory and Ethical Considerations
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the
protocol, current International Conference on Harmonization (ICH) guidelines on Good Clinical
Practice (GCP), and applicable regulatory and country-specific requirements.
GCPis an international ethical and scientific quality standard for designing, conducting, recording,
and reporting studies that involve the participation of human participants. Compliance with this
standard provides public assurance that the rights, safety, and well-being of study participants are
protected, consistent with the principles that originated in the Declaration of Helsinki, and that the
study data are credible.
Protocol Amendments
Neither the investigator nor the sponsor will modify this protocol without a formal amendment by
the sponsor. All protocol amendments must be issued by the sponsor, and signed and dated by the
investigator. Protocol amendments must not be implemented without prior IEC/IRB approval, or
when the relevant competent authority has raised any grounds for non-acceptance, except when
necessary to eliminate immediate hazards to the participants, in which case the amendment must
be promptly submitted to the IEC/IRB and relevant competent authority. Documentation of
amendment approval by the investigator and IEC/IRB must be provided to the sponsor. When the
change(s) involve only logistic or administrative aspects of the study, the IEC/IRB (where
required) only needs to be notified.
During the course of the study, in situations where a deviation from the protocol is unavoidable,
the investigator or other physician in attendance will contact the appropriate sponsor representative
listed in the Contact Information page(s), which will be provided as a separate document. Except
in emergency situations, this contact should be made before implementing any deviation 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 will reflect any deviation from the protocol, and the source documents will describe
this deviation 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:

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 
Protocol and amendment(s), if any, signed and dated by the PI
 
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 PI, 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
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

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 
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
 
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.

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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 4.1.1.
Other Ethical Considerations
For study-specific ethical design considerations, refer to Section 4.1.1.
10.3.2. 
Financial Disclosure
Investigators and subinvestigators 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 course of
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
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
of obtaining consent for additional safety evaluations, if needed.
The participant will be given sufficient time to read the ICF and the opportunity to ask questions.
After this explanation and before entry into the study, consent should be appropriately recorded

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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.
Informed consent for follow-up of the neonates/infants up to approximately 12 months will be
obtained from the parent(s), of which the mother is also an adult participant in this study, at the
time of screening of adult participants.
Participants who are rescreened are required to sign a new ICF.
Eligible participants that want to receive the booster vaccination will need to reconsent before any
procedure of the Booster Vaccination Visit is performed.
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.
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.

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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 vaccination with Ad26 based
vaccines including Ad26.COV2.S, to understand SARS-CoV-2 infection, to understand
differential vaccine responders, and to develop tests/assays related to Ad26-based vaccines and to
Ad26.COV2.S and SARS-CoV-2 infection. If any trends are observed in thromboembolic events,
plasma samples may be tested for markers of thromboembolic events. 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 7.3.1).
10.3.6. 
Safety Monitoring Committees Structure
Independent Data Monitoring Committee
The IDMC will be established to monitor safety data on an ongoing basis to ensure the continuing
safety of the participants enrolled in this study. The IDMC consists of members that are not directly
involved in the study conduct, data management, or statistical analysis, will be established and will
monitor data to ensure the continuing safety of the participants enrolled in this study. The IDMC
will consist of at least 1 medical expert in the relevant therapeutic area of pediatrics and at least 1
external statistician independent of the sponsor and not involved in the final analysis of the study
who will prepare the data and perform all IDMC safety analyses and interim analyses for review
by the IDMC. Committee membership responsibilities, authorities, and procedures will be
documented in its charter.
The IDMC will review data as indicated in Section 4.1. IDMC safety reviews will be based on
descriptive safety tables and listings from all accumulated safety data at that point in time. After
each review, the IDMC will make recommendations regarding the continuation of the study. When
appropriate, the conclusions of the IDMC will be communicated to the investigators, the IEC/IRB,
and the national regulatory authorities.
The IDMC responsibilities, authorities, and procedures will be provided in its charter.
An ad hoc review may be performed further to the occurrence of any AE/SAE leading to a study
pausing situation as outlined in Section 6.9 or at request of the sponsor’s medical monitor or
designee. The PI and sponsor's SRP will inform the IDMC of any AE of concern.
It will also be possible for the IDMC to review immunogenicity data during the course of the study
if this is deemed necessary for future vaccine development-related decisions. If this is the case, a
biomarker representative (not involved in the conduct of the study) will be part of the IDMC.
If any pausing rule is met (refer to Section 6.9) and, if following appropriate safety review it is
deemed appropriate to restart dosing, the sponsor must submit a request to restart dosing with
pertinent data to competent authority as a request for a substantial amendment, as required by local

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regulations or authority request (eg, MHRA). If needed, this will be followed by a substantial
amendment of the IB and/or protocol.
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 biomarker 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 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
biomarker 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

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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
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 will review 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 eCRF  or eCOA. 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.

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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
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 (including relevant medical, obstetric and delivery history,
and including anything related to the footnotes related to relevant medical and obstetric history,
pre-pregnancy and prestudy therapies to the Schedule of Activities [Section 1.3.1 footnote h and
Section 1.3.2, footnote h]), and study identification; study discussion and date of signed informed
consent; dates of visits; results of safety parameters as required by the protocol; record of all AEs
and follow-up of AEs; concomitant medication; vaccine receipt/dispensing/return records; study
vaccine administration information; and date of study completion and reason for early
discontinuation of study vaccination or withdrawal from the study, if applicable.
The author of an entry in the source documents should be identifiable. Given that ObsROs are
reports of an infant participant's health that come directly from the parent(s)/caregiver(s) without
interpretation by a clinician or anyone else, the responses to ObsRO measures entered by the
parent(s)/caregiver(s) into source records cannot be overridden by site staff or investigators.
Participant/parent(s)/caregiver(s)- and investigator-completed scales and assessments designated
by the sponsor (ie, reactogenicity diaryto record solicited AEs, a signs and symptoms surveillance
question, and SIC/PedSIC) will be recorded and will be considered source data. The participant’s
reactogenicity 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).

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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, 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 will 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.
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. Remote auditing techniques may also be utilized,
if necessary. 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.

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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.
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.

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Reasons for the early closure of a study site by the sponsor or investigator may include but are not
limited to:
 Failure of the investigator to comply with the protocol, the requirements of the IEC/IRB or
local health authorities, the sponsor's procedures, or GCP guidelines
 Inadequate recruitment of participants by the investigator
 Discontinuation of further study vaccine development

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10.4. Appendix 4: 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 vaccine. An AE can therefore be any unfavorable and unintended
sign (including an abnormal finding), symptom, or disease temporally associated with the use of a
medicinal (investigational or non-investigational) product, whether or not related to that medicinal
(investigational or non-investigational) product. (Definition per 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, (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
 
Is a suspected transmission of any infectious agent via a medicinal product
 
Is Medically Important*

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*Medical and scientific judgement 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).
If a participant receives a positive SARS-CoV-2 result from a private/off-study test during the
study, and the positive result occurs within 28 days after vaccination, the event will be reported as
an AE. If it occurs after 28 days, the event will be recorded as an SAE only if the event qualifies
as serious. The participant can continue in the study if they choose to; however, this must be in
accordance with local country and site level recommendations for COVID-19.
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 AEs 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 the version of September 2007(US HHS 2007), included in Section 10.5.

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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 ER visit or hospitalization
The severity of solicited signs and symptoms will be graded in the reactogenicity diary by the
participant based on the severity assessment provided in the reactogenicity diary and then verified
by the investigator using the toxicity grading scale in Section 10.5. (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)
Special reporting situations should be recorded in the eCRF. Any special reporting situation that
meets the criteria of an SAE should be recorded on the SAE page of the eCRF.
10.4.5. 
Procedures
All Adverse Events
All AEs (including pregnancy-related AEs throughout pregnancy), regardless of seriousness,
severity, or presumed relationship to study vaccination, 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 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.

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For all studies with an outpatient phase, including open-label studies, the participant must be
provided with a "wallet (study) card" and instructed to carry this card with them for the duration
of the study indicating the following:
 
Study number
 
Statement, in the local language(s), that the participant is participating in a clinical study
 
Investigator's name and 24-hour contact telephone number
 
Local sponsor's name and 24-hour contact telephone number (for medical personnel only)
 
Site number
 
Participant number
Serious Adverse Events
All SAEs (including pregnancy-related AEs throughout pregnancy), 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)
Suspected transmission of an infectious agent by a medicinal product will be reported as an SAE.
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.
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

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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 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.

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10.4.8. 
Neonate Safety Assessment: Apgar Score
Definition: The Apgar score provides an accepted method for reporting the status of the neonate
immediately after birth and the response to resuscitation, if needed.
The Apgar score is used to obtain information on the condition of the neonate at birth (including,
when available, Apgar scores at 1 minutes and 5 minutes). It is listed in the nonbinding
recommendations for pregnancy safety studies, as laid out in the Guidance for Industry by the US
Department of Health and Human Services, FDA Center for Drug Evaluation and Research, Draft
Guidelines published May 2019 (FDA Guidance 2019).
The Apgar Scoring System: This provides a standardized assessment for infants after delivery.
The Apgar score comprises 5 components (1) color; (2) heart rate; (3) reflexes; (4) muscle tone;
and (5) respiration. Each of these components is given a score of 0, 1, or 2. The Apgar score is the
total of these numbers. The lowest score is 0 and the highest score is 10. A neonate with an Apgar
score of 7 or more is considered healthy. The Apgar score can be used to quantify signs of neonatal
depression, such as cyanosis or pallor, bradycardia, depressed reflex  response to stimulation,
hypotonia, and apnea or gasping respiration. The assessment is performed at 1 minute and 5
minutes, in case the infant scores less than 7, other time points would be checked (eg, 10 and 20
minutes) after birth. A copy of the expanded Apgar score reporting form is provided below:

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10.5. Appendix 5: Contraceptive Guidance
At the time of consenting, participants should agree to practicing an acceptable effective method
of contraception postpartum and agree to remain on such a method of contraception following the
birth of the infant until 3 months after administration of the study vaccine.:
Contraceptive (birth control) use by a participant of childbearing potential should be consistent
with local regulations regarding the acceptable methods of contraception for those participating in
clinical studies.
Participant who will receive a booster of study vaccine postpartum, should be using a highly
effective method of contraception and agree to remain on such a method of contraceptionfollowing
the birth of the infant until 3 months after the booster of study vaccine. Use of hormonal
contraception should start at least 28 days before the administration of study vaccine. 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 (IUD)
3. intrauterine hormone-releasing system (IUS)
4. bilateral tubal occlusion/ligation procedure
5. vasectomized partner (the vasectomized partner should be the sole partner for that participant)
6. sexual abstinence**
* or per physician preference/local standard of care in a woman who is breastfeeding
**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.

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10.6. Appendix 6: Toxicity Grading Scales
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 FDA CBER 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 judgement when characterizing bradycardia
among some healthy participant populations, for example, conditioned athletes.
# Revised by the sponsor.

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

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Systemic Illness 
Mild (Grade 1) 
Moderate (Grade 2) Severe (Grade 3) 
Potentially Life
Threatening
(Grade 4)
Illness or clinical 
adverse 
event (as defined 
according to 
applicable
regulations).
No interference with  
activity  
Some interference 
with activity not 
requiring medical 
intervention 
Prevents daily  
activity and
requires medical
intervention
Hospitalization#
# Revised by the sponsor.
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 judgement.
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: alanine 
aminotransferase (ALT), aspartate
aminotransferase (AST) -
increase by factor
1.1 –2.5 x ULN  2.6 –5.0 x ULN  5.1 –10 x ULN  
> 10 x ULN

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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
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 ifthe
participant had a new seizure associated with the low sodium value.
***ULN is the upper limit ofthe 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
Prothrombin time (PT) –increase by 
factor 
1.0 –1.10 x  
ULN** 
1.11 –1.20 x 
ULN
1.21 –1.25 x ULN  
> 1.25 ULN
Partial thromboplastin time (PTT) – 
increase by factor 
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 ofthe normal range.

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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.

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10.7. Appendix 7: Multisystem Inflammatory Syndrome in Children
Multisystem Inflammatory Syndrome in Children (MIS-C)
MIS-C is a serious and potentially fatal condition that can arise in infants and children infected
with SARS-CoV-2, and which can result in inflammation of a range of organs. Patients with
MIS-C usually present with persistent fever, fatigue and a variety of signs and symptoms including
multiorgan (eg, cardiac, gastrointestinal, renal, hematologic, dermatologic, neurologic)
involvement, elevated inflammatory markers and, in severe cases, hypotension and shock.
MIS-C may present weeks after an infant is infected with SARS-CoV-2. The infant may have been
infected from an asymptomatic contact and, in some cases, the infant and their
parent(s)/caregiver(s) may not even know that they have been infected.
Although different presentations have been described, common symptoms include:
 
Kawasaki disease-like features: conjunctivitis, red eyes; red or swollen hands and feet; rash;
red cracked lips, swollen glands. Coronary artery enlargement and/or aneurysms have been
described. Other symptoms include gastrointestinal (abdominal pain or diarrhea) and
neurologic (headaches/meningitis) manifestations.
 
Toxic shock syndrome-like features with hemodynamic instability.
 
Cytokine storm/macrophage activation or hyperinflammatory features.
 
Thrombosis, poor heart function, diarrhea and gastrointestinal symptoms, acute kidney injury.
 
Shortness of breath suggestive of congestive heart failure.
The Centerfor Disease Control and Prevention (CDC 2020h) issued a Health Advisory on May 14,
2020, that outlines the following case definition for MIS-C (https://www.cdc.gov/mis-
c/hcp/index.html):
Case definition for MIS-C
 
An individual aged <21 years presenting with fevera, laboratory evidence of inflammationb,
and evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ
involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or
neurological); AND
 
No alternative plausible diagnoses; AND
 
Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or
exposure to a suspected or confirmed COVID-19 case within the 4 weeks prior to the onset of
symptoms.
a * Fever >38.0°C for ≥24 hours, or report of subjective fever lasting ≥24 hours
b 
Including, but not limited to, one or more of the following: an elevated C-reactive protein (CRP), erythrocyte
sedimentation rate (ESR), fibrinogen, procalcitonin, d-dimer levels, ferritin, lactic acid dehydrogenase (LDH), or
interleukin 6 (IL-6), elevated neutrophils, reduced lymphocytes and low albumin

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Common Signs and Symptoms associated with MIS-C include the following (adapted for infants
<1 year of age):
 
Fever (fever ≥38.0oC for ≥24 hours, or report of subjective fever lasting ≥24 hours)
 
Vomiting
 
Diarrhea
 
Rash
 
Bloodshot eyes
 
Feeling extra tired
Note: not all infants will have the same signs and symptoms, and some infants may have symptoms
that are not listed here.
Immediate emergency care is required in the event of the infant showing any of the following
signs of MIS-C (adapted for infants <1 year of age):
 
Trouble breathing
 
Inability to wake or stay awake
 
Bluish lips or face
Common laboratory findings include:
 
An abnormal level of inflammatory markers in the blood, including elevated erythrocyte
sediment rate (ESR)/C-reactive protein (CRP) and ferritin, lactate dehydrogenase (LDH).
 
Lymphopenia <1000, thrombocytopenia <150,000, neutrophilia.
 
Elevated B-type natriuretic peptide (BNP) or NT-proBNP (pro-BNP), hyponatremia, elevated
D-dimer levels.

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10.8. Appendix 8: Case Definitions for COVID-19
10.8.1. 
Adults Case Definition for Moderate to Severe/Critical COVID-19
Case Definition for Moderate COVID-19
 
A SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract
sample (eg, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other
sample.
AND at any time during the course of observationa:
Any 1 of the following new or worsening signs
or symptoms:
OR
Any 2 of the following new or worsening signs or
symptoms:
 
Respiratory rate ≥20 breaths/minute
 
Abnormal saturation of oxygen (SpO2)
but still >93% on room air at sea level*
 
Clinical or radiologic evidence of
pneumonia
 
Radiologic evidence of DVT
 
Shortness of breath or difficulty
breathing
 
Fever (≥38.0°C or ≥100.4°F)
 
Heart rate ≥90 beats/minute
 
Shaking chills or rigors
 
Sore throat
 
Cough
 
Malaise as evidenced by 1 or more of the
following**:
- Loss of appetite
- Generally unwell
- Fatigue
- Physical weakness
 
Headache
 
Muscle pain (myalgia)
 
Gastrointestinal symptoms (diarrhea,
vomiting, nausea, abdominal pain)
 
New or changing olfactory or taste
disorders
 
Red or bruised looking feet or toes
SpO2 criteria will be adjusted according to altitude.
** Having 2 or more elements of a symptom (eg, vomiting and diarrhea or fatigue and loss of appetite) is counted only as 1
symptom for the case definition. To meet the case definition, a participant would need to have at least 2 different symptoms.
a 
Participants will be asked to undertake the COVID-19 procedures until 14 days after symptom onset (COVID-19
Day 15) or until resolution of the COVID-19 episode, whichever comes last (see Section 8.1.2).

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Case Definition for Severe/Critical COVID-19
 
A SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract
sample (eg, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other
sample
AND any 1 of the following at any time during the course of observationa:
 
Clinical signs at rest indicative of severe systemic illness (respiratory rate ≥30 breaths/minute,
heart rate ≥125 beats/minute, oxygen saturation [SpO2] ≤93% on room air at sea level*, or
partial pressure of oxygen/fraction of inspired oxygen [PaO2/FiO2] <300 mm Hg)
* SpO2 criteria will be adjusted according to altitude.
 
Respiratory failure (defined as needing high-flow oxygen, non-invasive ventilation,
mechanical ventilation, or extracorporeal membrane oxygenation [ECMO])
 
Evidence of shock (defined as systolic blood pressure <90 mm Hg, diastolic blood pressure
<60 mm Hg, or requiring vasopressors)
 
Significant acute renal, hepatic, or neurologic dysfunction
 
Admission to the ICU
 
Death
10.8.2. 
Adult Case Definition for Mild COVID-19
 
A SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract
sample (eg, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other
sample;
AND at any time during the course of observationa:
 
One of the following symptoms: fever (≥38.0°C or ≥100.4°F), sore throat, malaise (loss of
appetite, generally unwell, fatigue, physical weakness), headache, muscle pain (myalgia),
gastrointestinal symptoms, cough, chest congestion, runny nose, wheezing, skin rash, eye
irritation or discharge, chills, new or changing olfactory or taste disorders, red or bruised
looking feet or toes, or shaking chills or rigors.
A case is considered clinically mild when it meets the above case definition but not the moderate
to severe/critical definition in Section 10.8.1.
a 
Participants will be asked to undertake the COVID-19 procedures until 14 days after symptom onset (COVID-19
Day 15) or until resolution of the COVID-19 episode, whichever comes last (see Section 8.1.2).

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10.8.3. 
Adult US FDA Harmonized Case Definition for COVID-19
If a participant presents with symptoms as those listed by the US FDA harmonized case definition
(CDC 2020c), the investigator (or designated medically trained clinician) should assess if these
are suggestive of COVID-19:
 
A SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract
sample (eg, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other
sample; AND
 
COVID-19 symptoms consistent with those defined by the US FDA harmonized case
definition  (CDC 2020c) at the time of finalization of this protocol: fever or chills, cough,
shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss
of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, diarrhea.

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10.8.4. 
Neonates and Infants Case Definition for Moderate to Severe/Critical
COVID-19
Case Definition for Moderate COVID-19
 
A SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract
sample (eg, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other
sample.
AND at any time during the course of observationa:
Any 1 of the following new or worsening signs
or symptoms:
OR
Any 2 of the following new or worsening signs or
symptoms:
 
Abnormal respiratory rateb
o 
but still ≤70 breaths/minute for
neonates and infants <6 months
of age
o 
but still ≤60 breaths/minute for
infants ≥6 months of age
 
Abnormal saturation of oxygen (SpO2)
but still >90% on room air at sea level*
 
Clinical or radiologic evidence of
pneumonia
 
Intercostal retractions (in-drawing)
 
Heart rate ≥160 beats/minute for
neonates (≤28 days of age) and ≥140
beats/minute for infants >28 days to ≤12
months of age)
 
Rash
 
Bloodshot eyes
 
Fever (≥38.0°C or ≥100.4°F)
 
Shaking chills or rigors
 
Wheezing
 
Cough
 
Malaise as evidenced by 1 or more of the
following**:
- Poor feeding
- Moodiness (frequent crying,
irritability)
- Lethargy/tiredness
 
Gastrointestinal symptoms** (diarrhea,
vomiting)
 
Red or bruised looking feet or toes
* SpO2 criteria will be adjusted according to altitude.
** Having 2 or more elements of a symptom (eg, vomiting and diarrhea or lethargy and loss of appetite/poor feeding) is counted
only as 1 symptom for the case definition. To meet the case definition, a participant would need to have at least 2 different
symptoms.
a 
Participants will be asked to undertake the COVID-19 procedures until 14 days after symptom onset (COVID-19
Day 15) or until resolution of the COVID-19 episode, whichever comes last (see Section 8.1.2).
b 
Per Golan-Tripto I et al 2018.

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Case Definition for Severe/Critical COVID-19
 
A SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract
sample (eg, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other
sample
AND any 1 of the following at any time during the course of observationa:
 
Clinical signs at rest indicative of severe systemic illness (respiratory rate ≥71 breaths/minute
for neonates and infants <6 months of age and ≥61 breaths/minute for infants ≥6 months of
ageb, heart rate ≥180 beats/minutec, SpO2 ≤89% on room air at sea level*, or PaO2/FiO2 <300
mm Hg)
*SpO2 criteria will be adjusted according to altitude
 
Respiratory failure (defined as needing high-flow oxygen, non-invasive ventilation,
mechanical ventilation, or ECMO)
 
Evidence of shock (defined as systolic blood pressure <65mmHg to 75mmHg for neonates
and <100 mm Hg for infants, or requiring vasopressors)
 
Significant acute renal, hepatic, or neurologic dysfunction
 
Multisystem inflammatory syndrome (MIS-C)d
 
symptoms: fever, vomiting, diarrhea, rash, bloodshot eyes, feeling extra tired
 
trouble breathing, inability to stay awake, bluish lips or face
 
Admission to the Pediatric ICU
 
Death
a 
Participants will be asked to undertake the COVID-19 procedures until 14 days after symptom onset (COVID-19
Day 15) or until resolution of the COVID-19 episode, whichever comes last (see Section 8.1.2).
b
Per Golan-Tripto I et al 2018.
c
Per Goldstein B et al. 2005
d
Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 per CDC website:
https://www.cdc.gov/coronavirus/2019-ncov/daily-life-coping/children/mis-c.html. Accessed on 12 Nov 2020.
Note: the list of symptoms was adapted for neonates and infants.

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10.8.5. 
Neonates Case Definition for Mild COVID-19
 
A SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract
sample (eg, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other
sample;
AND at any time during the course of observationa:
 
One of the following symptoms: fever (≥38.0°C or ≥100.4°F), poor feeding, tachycardia,
lethargy, diarrhea, vomiting, cough, or rhinorrhea.
A case is considered clinically mild when it meets the above case definition but not the moderate
to severe/critical definition in Section 10.8.4.
10.8.6. 
Infants Case Definition for Mild COVID-19
 
A SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract
sample (eg, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other
sample;
AND at any time during the course of observationa:
 
bOne of the following symptoms: fever (≥38.0°C or ≥100.4°F) or chills, poor appetite or poor
feeding, mood behaviors (frequent crying, irritability), lethargy/tiredness, diarrhea, vomiting,
cough, wheezing, tachypnea, nasal congestion or runny nose,
A case is considered clinically mild when it meets the above case definition but not the moderate
to severe/critical definition in Section 10.8.4.
a 
Participants will be asked to undertake the COVID-19 procedures until 14 days after symptom onset (COVID-19
Day 15) or until resolution of the COVID-19 episode, whichever comes last (see Section 8.1.2).
b 
Source: 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. Accessed 03 December 2020.

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10.9. Appendix 9: Summary of Guidance from CDC Website on Underlying
Medical Conditions That Lead or Might Lead to Increased Risk for Severe
Illness From COVID-19
10.9.1. 
Appendix 9A: CDC Websitea Underlying Medical Conditions for Adults
People of any age with the conditions listed below are more likely to get severely ill from COVID-
19. COVID-19 vaccines (initial dose and boosters) and preventive measures for COVID-19 are
essential.
Approved and authorized COVID-19 vaccines (initial dose and boosters) are safe and effective
and should be administered to people at higher risk including people with  underlying medical
conditions.
This list does not include all possible conditions that place a higher risk of 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 are at increased risk  of severe illness from
COVID-19:
 
Cancer
 
Chronic kidney disease
 
Chronic liver disease
 
COPD (chronic obstructive pulmonary disease)
 
Heart conditions, such as heart failure, coronary artery disease or cardiomyopathies
 
Immunocompromised state (weakened immune system) from solid organ transplant
 
Obesity (BMI of 30 kg/m2 or higher but < 40 kg/m2)
 
Severe Obesity (BMI ≥ 40 kg/m2)
 
Pregnancy
 
Stroke or cerebrovascular disease
 
Sickle cell disease
 
Smoking
 
Diabetes (Type 1 or Type 2)
COVID-19 is a new disease. Data and information are still currently under investigation to better
understand the impact of underlying medical conditions and actual risks for severe illness from
COVID-19:
 
Asthma (moderate to severe)
 
Cerebrovascular disease (affects blood vessels and blood supply to the brain)

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 
Cystic fibrosis
 
Hypertension or high blood pressure
 
Immunocompromised state (weakened immune system) from blood or bone marrow
transplant, immune deficiencies, HIV, use of corticosteroids, or use of other immune
weakening medicines
 
Neurologic conditions, such as dementia
 
Liver disease
 
Overweight (BMI > 25 kg/m2, but < 30 kg/m2)
 
Pulmonary fibrosis (having damaged or scarred lung tissues)
 
Thalassemia (a type of blood disorder)
 
Type 1 diabetes mellitus
10.9.2. 
Appendix 9B: CDC Website Underlying Medical Conditions for
Children and Teens
CDC and partners are investigating a rare but serious medical condition associated with COVID-
19 in children called Multisystem Inflammatory Syndrome in Children (MIS-C). We do not yet
know what causes MIS-C and who is at increased risk for developing it.
Babies under 1 year old might be more likely to have severe illness from COVID-19. Other
children, regardless of age, with the following underlying medical conditions might also be at
increased risk of severe illness compared to other children:
 
Asthma or chronic lung disease
 
Diabetes
 
Genetic, neurologic, or metabolic conditions
 
Heart disease since birth
 
Immunosuppression (weakened immune system due to certain medical conditions or being on
medications that weaken the immune system)
 
Medical complexity (children with multiple chronic conditions that affect many parts of the
body who are often dependent on technology and other significant supports for daily life)
 
Obesity
This list does not include every underlying condition that might increase the risk for severe illness
in children. As more information becomes available, CDC will continue to update and share
information about risk for severe illness among children.

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10.10. Appendix 10: Symptoms of Coronavirus (US Centers for Disease Control
and Prevention)
10.10.1. 
Appendix 10A: Symptoms of Coronavirus (US Centers for Disease
Control and Prevention) in Adults
The following extract shows symptoms of coronavirus infection in adults as listed on the US CDC
website dated 09 November 2020 and were still accurate at the time of finalization of this protocol:
(https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html).
People with COVID-19 have had a wide range of symptoms reported - ranging from mild
symptoms to severe illness. Symptoms may appear 2-14 days after exposure to the virus. People
with these symptoms may have COVID-19:
 
Fever or chills
 
Cough
 
Shortness of breath or difficulty breathing
 
Fatigue
 
Muscle or body aches
 
Headache
 
New loss of taste or smell
 
Sore throat
 
Congestion or runny nose
 
Nausea or vomiting
 
Diarrhea

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10.10.2. 
Appendix 10B: Symptoms of Coronavirus (US Centers for Disease
Control and Prevention) in Neonates
The following extract shows symptoms of coronavirus infection in neonates as listed on the US
CDC website dated 23 October 2020 and were still accurate at the time of finalization of this
protocol:
(https://www.cdc.gov/coronavirus/2019-ncov/hcp/caring-for-newborns.html)
Note: Current evidence suggests that SARS-CoV-2 infections in neonates are uncommon. If
neonates do become infected, the majority have either asymptomatic infections or mild disease (ie,
do not require respiratory support), and they recover. Severe illness in neonates, including illness
requiring mechanical ventilation, has been reported but appears to be rare. Neonates with
underlying medical conditions and preterm infants (<37 weeks gestational age) may be at higher
risk of severe illness from COVID-19.
Reported signs among neonates with SARS-CoV-2 infection include:
 
Fever
 
Lethargy
 
Rhinorrhea
 
Cough
 
Tachypnea
 
Increased work of breathing
 
Vomiting
 
Diarrhea
 
Poor feeding
The extent to which SARS-CoV-2 infection contributed to the reported signs of infection and
complications is unclear, as many of these findings are common in term and preterm infants for
other reasons (eg, transient tachypnea of the neonate, neonatal respiratory distress syndrome).

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10.10.3. 
Appendix 10C: Symptoms of Coronavirus (US Centers for Disease
Control and Prevention) in Children
The following extract shows symptoms of coronavirus infection in infants and children as listed
on the US CDC website dated 17September 2020 (CDC 2020g) and were still accurate at the time
of finalization of this protocol:
(https://www.cdc.gov/coronavirus/2019-ncov/daily-life-coping/children/symptoms.html)
The most common symptoms of COVID-19 in children are fever and cough.
The symptoms of COVID-19 are similar in adults and children and can look like other common
illnesses, like colds, strep throat, or allergies. The most common symptoms of COVID-19 in
children are fever and cough, but children may have any of these signs or symptoms of COVID-19:
 
Fever or chills
 
Cough
 
Nasal congestion or runny nose
 
New loss of taste or smell
 
Sore throat
 
Shortness of breath or difficulty breathing
 
Diarrhea
 
Nausea or vomiting
 
Stomachache
 
Tiredness
 
Headache
 
Muscle or body aches
 
Poor appetite or poor feeding, especially in babies under 1 year old.

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10.11. Appendix 11: Thrombosis with Thrombocytopenia (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 post-vaccination 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
Dyspnea 
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:

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Hypertension                                                                       
Dehydration
Other significant medical comorbidities or risk factors for DVT, specify:
If yes to any of the above, provide details:
Provide Well’s score, if calculated:

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10.12. Appendix 12: Thrombotic Events to be Reported as Suspected AESIs
At the time of writing the current protocol Amendment 3, the list of thrombotic events to be
reported to the sponsor as suspected AESIs is provided below. Further guidance may become
available on thrombotic events of interest.a
 
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, CVST, 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 HIT 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, DVT, pulmonary embolism, MedDRA PTs for acute
myocardial infarction,b MedDRA PTs for strokeb
a 
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.
b 
*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

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10.13. Appendix 13: Visit Guidance in Case of Pregnancy Termination Before the
Completion of the Applicable Study Period Visits
General Guidance:
 
In the situation of a completion/termination of the pregnancy before the completion of the
applicable Study Period visits, the participant should follow the visits scheduled in the ‘Study
Period’ (except for the Monthly phone calls) AND the ‘Follow-up’ section of the schedule of
activities.
 
If the pregnancy is completed/ terminated before the completion of the Day 29 it should be
judged based on the participants health and safety if these visits can be performed. These visits
are associated to our primary objective and therefore of high interest to be completed.
 
If the delivery takes place in a hospital where the site staff does not have privileges, it is
expected that medical records are collected to collect the applicable protocol required
information.
Randomization General 
timing of 
birth 
Detailed 
timing 
of birth
Guidance for 
completion of visits
Protocol language
1-dose schedule Birth before 
completion 
Study 
Period visits 
Vaccination 
1 
Before 
start 
visit 
window 
of Day 
29 
Day 8 
If not yet performed,
visit can be skipped.
Please perform diary
review with participant
as soon as feasible
(phone is acceptable)
Day 15 
Day 29 
This visit should be
performed, based on
assessment of participant
health
Monthly phone calls 
Not applicable
During 
visit 
window 
of Day 
29 
Day 29 
If not yet performed,
visit can be skipped,
provided that PP1 has
occurred. If Day 29 nor
PP1 visit were
performed, Day 29 is
recommended to be
performed as soon as
possible based on
assessment of participant
health, as long as it does
not overlap with the
window of the next
scheduled visit.
Monthly phone calls 
Not applicable
After 
Day 29
Monthly phone calls 
Not applicable

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10.14. Appendix 14: Protocol Amendment History
Amendment 6 (05 May 2022)
Overall Rationale for the Amendment:
Safety data with Ad26.COV2.S when administered within 3 months before pregnancy as well as during
pregnancy have shown no safety concerns in the mother or child in over 500 reported pregnancies, with
over 100 reported pregnancy outcomes. In addition safety data with other Janssen adenovirus type 26
(Ad26)-based vaccines when administered within 3 months before pregnancy as well as during pregnancy
have shown no evidence of an increased risk of adverse outcomes in the mother or child in over
2200 reported pregnancies, with over 1400 reported pregnancy outcomes (IB 2022). Due to the safety data
accrued to date on the use of Ad26.COV2.S specifically and Ad26-based vaccines in general and taking
into account the rapid progression of national vaccination campaigns, which makes it difficult to recruit
‘non-previously vaccinated’ (vaccine naïve) pregnant women, the following changes were made to facilitate
enrollment: the possibility to recruit previously vaccinated and boosted women with several vaccination
regimens, and in order to complete the study to provide reactogenicity and immunogenicity data during
pregnancy the sample size has been decreased from 400 to approximately 240 participants.
In the current fluid coronavirus disease-2019 (COVID-19) environment, emergent recommendations for
primary vaccination schemes and booster vaccination campaigns have reduced the pool of eligible
participants for the study. Therefore, study groups have been modified to allow enrollment of participants
previously vaccinated and those who had received booster doses up to 4 months prior to the study
vaccination.
Changes made to the clinical protocol of study VAC31518COV2004 as part of Amendment 6 are listed
below, including the rationale for each change and a list of all applicable sections. Changes made as part of
Protocol Amendments 1 to 5 are listed in Appendix 10.14.
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis
1.2 Schema
4.1 Overall Design
6.3 Preparation/Handling/Storage/
Accountability
9.2 Sample Size Determination
9.2.1 Immunogenicity
9.5.2 Interim Analysis 2
The study design has been amended so that
the overall target number of participants is
reduced from N=400 to N=240 participants,
preferably distributed equally across groups
but at least 40 participants in Groups 1-3 and
at least 25 participants in Group 4.
The number of remaining participants
(excluding Sentinel and Safety Cohorts) is
N=218.
See overall rationale for
amendment.
1.1 Synopsis
1.2 Schema
1.3 Schedule of Activities
4.1 Overall Design
5.1 Inclusion Criteria
5.2 Exclusion Criteria
6.8Prestudy and Concomitant
Therapy
Inclusion criterion #11 and Exclusion
criterion #13 have been updated to reduce the
timeframe of last vaccination prior to study
vaccination to at least 4 months.
To align with recent
recommendations for
booster doses in certain
countries.

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Section Number
and Name
Description of Change 
Brief Rationale 
1.1 Synopsis 
4.1 Overall Design  
5.1 Inclusion Criteria 
Inclusion criterion #11 updated to clarify the
inclusion of participants that were vaccinated
with a COVID-19 vaccine beyond primary
regimen for Groups 1-3.
Group descriptions have been updated and
now indicates Groups 1 and 2 are including
participants that were also boosted with the
homologous vaccine. Group 3 would also be
recruiting boosted participants, irrespective
of the vaccine and regimen.
Change in eligibility criteria
to allow inclusion of
participants that were
vaccinated with a COVID-
19 vaccine beyond primary
regimen as most potential
study participants have now
received at least one booster
vaccination.
1.3 Schedule of Activities 
SARS-CoV-2 vaccination history in the
Schedule of Activities tables and footnotes
has been updated to COVID-19 vaccination
history to align with text in the body.
To align with text in the
body of the protocol.
1.1 Synopsis 
1.3.1.2 Vaccine Naïve Adult 
Participants (Group 4, Including 
Sentinel and, Safety Cohorts): 
Booster Vaccination Schedule
2.3.3 Benefit-Risk Assessment 
for Study Participation 
4.1 Overall Design
8.2.5 Breast Milk Production
Outcomes
8.3.2 Method of Detecting
Adverse Events, Adverse Events
of Special Interest, Serious
Adverse Events and Medically-
attended Adverse Events
Potential changes in (postpartum) breast milk
production (reduction) has been added as
part of the safety evaluation for Group 4
participants that receive a booster.
Changes in breast milk production has been
added to solicited systemic adverse events.
Potential subjective changes
in breast milk production in
lactating participants,
receiving the Janssen
vaccine as a booster
postpartum, is added as part
of the safety evaluations.
1.1 Synopsis 
1.3 Schedule of Activities 
3 OBJECTIVES AND 
ENDPOINTS
4.1 Overall Design  
8STUDY ASSESSMENTS AND 
PROCEDURES  
8.1 Immunogenicity Assessments 
9.2 Sample Size Determination  
9.4.3 Exploratory Endpoints(s) 
Wording updated regarding the PBMC
subset being specific to any group and not
vaccine naïve only.
The PBMC subset has been updated to
approximately 25 adult participants per
group, if operationally feasible. Additionally,
it was clarified that the objective relating to
PBMC sampling will only be tested if PBMC
collection is feasible in a sufficient
proportion of participants.
Table 4 has been updated when the
probabilities of observing at least one Th2
event given true Th2 rates if N=25.
PBMC collection has been
adjusted to include all
groups in the study (if
feasible), to additionally
allow for an assessment of
cellular immune responses
in participants who are
previously vaccinated, as
these are a relevant
population in the current
world setting.
2.3.1 Risks Related to Study 
Participation  
8.5 Genetics and 
Pharmacogenomics 
Genetic testing replaced with genomic
research to use language that is inclusive of
the intended gene expression analysis by
RNAseq transcript profiling.
Correction.
5.1 Inclusion Criteria 
Inclusion Criterion #3 Number of CD4 cells
required is updated to ≥300 cells/µL.
Alignment across
Ad26.COV2.S protocols

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Section Number 
and Name
Description of Change 
Brief Rationale
5.1 Inclusion Criteria 
Inclusion Criterion #3, clarifying that if a 
potential participant does not have HIV viral
load and CD4 cell count data in their medical
records from the last 6 months efforts will be
made to obtain the necessary data for
potential entry into the study. A laboratory
result within 6 months of screening does not
need to be repeated.
Clarification
5.2 Exclusion Criteria 
6.8Prestudy and Concomitant 
Therapy  
Wording for Exclusion Criterion #8 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. 
Alignment across
Ad26.COV2.S protocols.
Intraarticular steroids are
typically use as a single shot
indicated for 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.
1.1 Synopsis
2 INTRODUCTION
Updated text to define the clinical isolate of
Wuhan, 2019.
Clarification 
1.1 Synopsis
3 OBJECTIVES AND
ENDPOINTS
9.2.2 Safety
9.4.2 Primary/Secondary
Endpoint(s)
Endpoint has been revised to include “or
without” complications to term neonate and
preterm neonate.
Correction
1.3 Schedule of Activities
8.2.1 Physical Examinations
Post-pregnancy physical examination has 
been removed and aligned with the targeted
physical examinations.
Correction
1.1 Synopsis
1.2 Schema
1.3 Schedule of Activities
4.1 Overall Design
6.2 Booster Vaccination
It has been clarified for booster vaccinations 
the vaccine naïve participants (Group 4)
must not be pregnant or have received
another COVID-19 vaccine (eg, national
immunization program)
If so, the participant is not allowed to receive
the booster dose.
Correction
6.9 Study Vaccination Pausing
Rules
Clarified the medical monitor does not 
coordinate meetings with IDMC but will
trigger the process for pausing.
Clarification
1.1 Synopsis
8.1.1 Immunogenicity
Assessments
Clarified blood sampling information. 
Clarification

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Section Number 
and Name
Description of Change 
Brief Rationale
8.1.2 Procedures in the Event of 
(Suspected) COVID-19 
Clarified if a clinic visit is not feasible a 
home may be allowed if allowed per local
regulations and transfer of a nasal swab to
the study site as soon as possible after
collection (within 3 days).
Clarification
9.2 Sample Size Determination  
The probability of observing at least one 
adverse event given a true adverse event
incidence table (Table 3) has been updated to
reflect a smaller population.
Clarification
Throughout the protocol 
Minor errors and inconsistencies were 
corrected, and minor clarifications were 
added throughout the protocol. 
Correction of minor errors
and inconsistencies.
Addition of minor
clarifications.
Amendment 5 (18 March 2022)
Overall Rationale for the Amendment:
Modify the total sample size for the safety and reactogenicity evaluation of the Sentinels (n=5) and larger
Safety Cohort (n=17) from N=25 to N=22. Recruitment of vaccine naïve pregnant participants in the Safety
Cohort turned out to be severely impacted by ongoing vaccination campaigns. The sponsor approached the
IDMC to discuss whether the safety data accrued on 22 participants from the Sentinel and Safety Cohorts
(up to 26 February 2022) would allow a thorough and educated assessment by the IDMC. Due to a longer
recruitment time, in addition the originally planned at Day 8 (7days post-vaccination) data, meaningful
longer term safety data for the 22 participants had been collected to support the safety assessment).
Based on the review of the Sentinel and Safety Cohorts data (N=22), the IDMC advised that the safety and
reactogenicity profile of Ad26.COV2.S at 5×1010 vp was considered acceptable and no safety concerns
were identified in adult pregnant women. The remaining 375 planned participants will receive 1 dose of
Ad26.COV2.S at the 5×1010 vp at study entry. Subsequently, the 2 dose regimen of Ad26.COV2.S at the
lower dose level of 2.5×1010 vp was be removed from the main study as no longer needed.
Changes made to the clinical protocol of study VAC31518COV2004 as part of Amendment 5 are listed
below, including the rationale for each change and a list of all applicable sections. Changes made as part of
Protocol Amendments 1 to 4 are listed in Appendix 10.14.
Section Number
and Name
Description of Change 
Brief Rationale
1.1 Synopsis
1.2 Schema
2 INTRODUCTION
4.1 Overall Design
6.3 Preparation/Handling/Storage/
Accountability
6.5 Dose Modification
Text updated for the combined number of 
vaccine naïve adult pregnant women in the 
Sentinel and Safety Cohorts from N=25 to 
N=22. 
Text updated for the number of participants
in the Safety Cohort only from n=20 to n=17.
All applicable sections have been updated
accordingly.
Recruitment
challenges of
vaccine naïve
pregnant
participants

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Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis 
1.2 Schema 
1.3 Schedule of Activities 
2 INTRODUCTION  
3 OBJECTIVES AND ENDPOINTS  
4.1 Overall Design (including Figure 2) 
6.1 Study Vaccinations Administered 
6.2 Booster Vaccination 
6.3 Preparation/Handling/Storage/ 
Accountability
6.5 Dose Modification 
6.8Prestudy and Concomitant Therapy 
7.1 Discontinuation of Study Vaccination 
7.2 Delay or Discontinuation of Vaccination 
due to Pregnancy-Specific Complications
8STUDY ASSESSMENTS AND 
PROCEDURES  
8.2.1 Physical Examinations
9.2.1 Immunogenicity  
9.2.2 Safety  
9.4.2 Primary/Secondary Endpoints
9.4.3 Exploratory Endpoints
9.5.2 Interim Analysis 2
10.13 Appendix 13
10.5 Contraceptive Guidance
Text updated to indicate that following 
IDMC review of the Sentinel and Safety 
Cohorts (N=22), the safety and 
reactogenicity profile of 1 dose of
Ad26.COV2.S at 5×1010 vp was considered
acceptable and no safety concerns were
identified. The remaining 375 planned
participants will receive 1 dose of
Ad26.COV2.S at 5×1010 vp.
Removed information regarding 2 doses of
Ad26.COV2.S at 2.5×1010 vp, which
included deleting Section 1.3.3. Subsequent
subsections were renumbered accordingly.
Removed information regarding second dose
or second vaccination.
All applicable sections have been updated
accordingly.
See overall
rationale for
amendment
1.3 Schedule of Activities 
It has been clarified for booster vaccinations 
the vaccine naïve participants (Group 4) must
not have received another COVID-19
vaccine (eg, national immunization program)
If so, the participant is not allowed to receive
the booster dose.
Clarification
1.1 Synopsis 
3 OBJECTIVES AND ENDPOINTS  
8.3.1 Time Period and Frequency for 
Collecting Information Relating to Adverse
Events, Adverse Events of Special Interest, 
Serious Adverse Events and Medically- 
attended Adverse Events
8.3.3 Follow-up of Adverse Events, Serious
Adverse Events, Adverse Events of Special
Interest, Pregnancy-related AEs and
Medically-attended Adverse Events
9.2.2 Safety
9.4.2 Primary/Secondary Endpoints
To align with study objectives, pregnancy- 
related AEs throughout pregnancy have been
added.
All applicable sections have been updated
accordingly.
Clarification
1.1 Synopsis 
1.3 Schedule of Activities 
4.1 Overall Design
8.1.1 Immunogenicity Assessments
It has been clarified biomarker analysis will 
be in PAXgene® tubes.
Clarification
1.1 Synopsis 
8.3.1 Time Period and Frequency for 
Collecting Information Relating to Adverse 
Events, Adverse Events of Special Interest, 
Serious Adverse Events and Medically- 
attended Adverse Events
It has been clarified the investigator’s 
assessment of ongoing AEs at the time of
each participant’s last visit should be
documented and closed in the participant’s
medical chart.
Clarification

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Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis 
1.3 Schedule of Activities 
It has been clarified only the overall Apgar 
score is required to be documented in the
eDC.
Clarification
1.1 Synopsis 
9.2.1 Immunogenicity  
9.4.1 General Considerations
9.4.2 Primary/Secondary Endpoints
It has been clarified that baseline serostatus 
refers to SARS-CoV-2 baseline serostatus.
Clarification
1.3 Schedule of Activities 
It has been clarified in schedule of activities 
the physical examination is a full physical
examination.
It has been clarified that the physical
examination at PP1 will be a targeted
physical examination.
Clarification
1.1 Synopsis 
1.3.4. Procedures for Adult Participants 
With (Suspected) COVID-19, 
1.3.5. Procedures for Neonates and Infants
With (Suspected) COVID-19,
8.1.2. Procedures in the Event of
(Suspected) COVID-19
Clarification of the procedure to follow if a 
participant tests positive for SARS-CoV-2
infection.
Clarification
1.3 Schedule of Activities 
8.1.2 Procedures in the Event of 
(Suspected) COVID-19 
It has been clarified closure of a COVID-19 
episode should occur at the last study visit. If
the episode is ongoing, it should be marked
as such in the eCRF and followed by the
investigator and the outcome recorded in the
participant’s medical chart.
Clarification
Throughout the protocol 
Minor grammatical, formatting, or spelling 
changes were made. 
Minor errors were
noted
Amendment 4 (13 December 2021)
Overall Rationale for the Amendment:The main purpose of this amendment is to:
- Allow the inclusion of participants previously vaccinated with a COVID-19 vaccine, who
have completed a primary vaccine regimen at least 6 months prior to receiving the study
vaccine into the study. These participants will be offered a single booster vaccination of
the Ad26.COV2.S at the 5×1010 vp dose level. Note: throughout the protocol, previously
vaccinated participants refer to participants previously vaccinated with a COVID-19
vaccine.
- Participants who were vaccine naïve at study entry, will be offered an (optional) booster
vaccination of Ad26.COV2.S at the 5×1010 vp dose level. This booster should be
administered after delivery. The booster vaccination will be administered not earlier than
2 months after completion of the participant’s Ad26.COV2.S vaccination in the study. The
booster vaccination and the booster follow-up visit should not extend the study duration.
- If, after review of the Day 8 safety data of the Sentinels and Safety Cohort by the IDMC,
the safety and reactogenicity  profile is considered acceptable, the remaining 375

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participants will receive 1 dose of Ad26.COV2.S at the 5×1010 vp dose at study entry. The
arm of 2 doses of Ad26.COV2.S at the 2.5×1010 vp dose level (N 75) will be removed
from the main study.
- If the safety and reactogenicity profile is not considered acceptable, the remaining 375
participants will continue to receive 2 doses of Ad26.COV2.S at the 2.5×1010 vp. This
remains unchanged.
Rationale:
- Rationale for including participants previously vaccinated with a COVID-19 vaccine and
provide a single booster and rationale for offering participants who were vaccine naïve at
study entry a booster:
On October 20, 2021, the FDA authorized a single booster dose of the Janssen (Johnson
and Johnson) COVID-19 Vaccine administered at least 2 months after completion of the
single dose primary regimen to individuals 18 years of age and older. Also on October 20,
2021, the FDA authorized the use of a heterologous (or “mix and match”) booster dose for
currently available (ie, FDA authorized or approved) COVID-19 vaccines.
A single dose of Ad26.COV2.S vaccine is immunogenic and highly efficacious against
severe COVID-19 disease and COVID-19 related hospitalization and death. While
protection against variants of concern (such as the Beta and Mu variants in study COV3001
and the Delta variant in the Sisonke study[Gray 2021]) remains high against severe disease,
hospitalization, and death, this protection is lower against, eg, the Gamma variant
compared to the reference Wuhan strain.
A second dose of Ad26.COV2.S results in increases of humoral immune responses, and
was also shown to result in better protection against COVID-19, as shown in the primary
analysis of study COV3009 (Briefing Document 2021). Humoral immune responses
(including binding and neutralizing antibodies) have been shown to correlate with
protection against COVID-19 (Earle 20201; Khoury 2021; Goldblatt 2021). Vaccination
recommendation bodies (CDC 2021) have recently advised to give a booster vaccination
(FDA 2019; FDA 2021).
Should participants decide to receive an alternative vaccine outside the study participants
will be encouraged to remain in the study.
- Rationale for removing the 2-dose schedule of 2.5×1010 vp dose level (N 75) from the
main study:
The 5×1010 vp dose level was used in Janssen’s Phase 3 efficacy studies and has shown to
elicit strong immunogenicity with an acceptable safety profile. Therefore, if safety and
reactogenicity profile is considered acceptable, the lower dose will not be further explored.

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RATIONALE:
These and other changes made to the clinical protocol of study VAC31518COV2004 as part of
Protocol Amendment 4 are listed below, including the rationale for each change and a list of all
applicable sections. Changes made as part of Protocol Amendments 1 to 3 are listed in
Section 10.14.
Section Number
and Name
Description of Change 
Brief Rationale 
1.1 Synopsis 
1.2 Schema 
1.3.1 Adult Participants (Sentinels, 
Safety and Group 4): 1-dose Schedule 
1.3.1.1 Vaccine Naïve Adult Participants 
(Sentinel, Safety and Group 4): Booster 
Vaccination Visits 
1.3.1.2 Vaccine Naïve Adult Participants 
(Sentinels, Safety and Group 4): Booster
Vaccination Schedule 
1.3.2 Adult Participants: Group 1-3: 
previously vaccinated participants: dose 
1 Schedule 
2.3.1 Risks Related to Study 
Participation
2.3.2 Benefits of Study Participation 
1.3 OBJECTIVES AND ENDPOINTS  
1.4 STUDY DESIGN  
1.4.2 Justification for the Regimen and 
Dose 
5 STUDY POPULATION  
5.5 Criteria for Temporarily Delaying
Administration of Study Vaccination 
6.1 Study Vaccinations Administered 
6.2 Booster Vaccination  
81.8 STUDY ASSESSMENTS AND 
PROCEDURES
9 STATISTICAL CONSIDERATIONS  
10.2 Appendix 2: Clinical Laboratory 
Tests 
Text updated to indicate that a booster 
vaccination with a single dose of Ad26.COV2.S 
at 5×1010 vp will be offered to ongoing, 
consenting participants who were vaccine naïve
at study entry, and have completed pregnancy.
The booster vaccination will be administered
not earlier than 2 months after the participant’s
Ad26.COV2.S vaccination in the study.
Text updated to indicate that following IDMC
review, the remaining 375 participants will
receive either 1 dose of Ad26.COV2.S at 5×1010
vp if the safety profile is acceptable or 2 doses
of Ad26.COV2.S at 2.5×1010 vp if the safety
profile is not acceptable irrespective of
gestational age.
Adult Participants dose 1 schedule updated.
Post booster safety and immunogenicity will be
assessed 28 days post booster. Thereafter,
participants will be followed per the 1-dose
schedule of activities until the end of the study
(approximately 12 months postpartum).
Previously vaccinated pregnant women are now
included in the study, thus inclusion and
reference to previously vaccinated women was
added.
Information regarding the booster for previously
vaccinated participants (Groups 1-3) and
vaccine naïve participants (Group 4) was added.
Removed information regarding innate and
inflammatory subsets, as these will no longer be
included in this study.
Updated the text to indicate that 60 mL of blood
will be collected from participants who receive
the booster vaccination.
All applicable sections have been updated
accordingly.
See overall
rationale for
amendment.
2 INTRODUCTION  
Updates made to sections 2.1 and 2.2. 
Update.

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Section Number 
and Name
Description of Change 
Brief Rationale
1.3.5 Procedures for Adult Participants 
With (Suspected) COVID-19 
1.3.6 Procedures for Neonates and 
Infants With (Suspected) COVID-19 
1.3 OBJECTIVES AND ENDPOINTS
8.1.2.2 Procedures for Neonate and
Infant Participants in Case of Signs and
Symptoms of COVID-19
References to the collection of saliva samples in 
the modality of collection in the event of a
(suspected) COVID-19 infection were deleted
from the protocol.
Correction.
2.3.1 Risks Related to Study 
Participation  
Information regarding the risks related to the 
study participation has been updated (eg, 
information with regard to TTS and GBS). 
Alignment across
Ad26.COV2.S
protocols.
1.3.1 Adult Participants (Sentinels, 
Safety and Group 4): 1-dose Schedule 
1.1 Synopsis 
In the Schedule of Activities, it was erroneously 
indicated that the footnote: “To be repeated pre-
vaccination if the screening test was done more
than 4 days before Day 1” was applicable to the
Obstetric Ultrasound assessment performed at
Day 1 (vaccination day). This footnote is
applicable to the nasal swab sample taken on
Day 1 only.
Visits 3 and 4 were removed from the table.
Wording regarding the PBMC subset being
specific to vaccine naïve participants added to
the SoA.
Removed information regarding participants in
the innate and pro-inflammatory subsets, as
these will no longer be included in this study.
Correction.
1.1 Synopsis 
1.4 STUDY DESIGN  
3 OBJECTIVES AND ENDPOINTS  
8.4 Virology Assessments 
The possibility of performing sequencing if a 
sample is available has been added to the 
protocol. 
To identify
SARS-CoV-2
variants in
available samples.
1.1 Synopsis 
1.1.2 Schema 
1.4 STUDY DESIGN  
1.4.2 Justification for the Regimen and 
Dose
The staggered enrollment of participants, safety 
reviews and consequences of the safety review
outcome on the vaccine regimen that will be
studied has been clarified.
Clarification.
1.1 Synopsis 
9.5.2 Interim Analysis 2 
The timing of the interim analyses and the data 
in scope of the analyses has been clarified.
Clarification.
1.3.5 Procedures for Adult Participants 
With (Suspected) COVID-19 
1.3.6 Procedures for Neonates and 
Infants With (Suspected) COVID-19 
8.1.2.1 Procedures for Adult Participants 
in Case of Signs and Symptoms of 
COVID-19
8.1.2.2 Procedures for Neonate and
Infant Participants in Case of Signs and
Symptoms of COVID-19
Clarification was added that for participants 
with a positive test result for SARS-CoV-2
infection, a study visit will be conducted 28
days after symptom onset (ie, at the COVID-19
Day 29 visit) to assess the clinical course of the
infection.
Clarification.
1.3.7 Participants with a Suspected AESI 
- Pregnant Participants 
The naming ‘Janssen Adjudication Committee’ 
was corrected to ‘AESI Adjudication 
Consistency
throughout
protocol.

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Section Number 
and Name
Description of Change 
Brief Rationale
Committee’, in alignment with other places in
the protocol.
1.3.3 Adult Participants (Group 1-4, if 
applicable): 2-dose Schedule 
It has been clarified that the Day 85 visit of the 
2-dose schedule will be a phone call and, hence,
there will not be an assessment of vital signs or
physical examination at that time.
Correction.
8 STUDY ASSESSMENTS AND 
PROCEDURES  
4.1 Overall Design  
Blood volumes mentioned in Section 8, Table 1, 
and throughout the protocol have been corrected
to reflect the correct blood volumes taken for
the different participant (sub) groups.
Added information (Table 1 and throughout)
regarding vaccine-related biomarkers (whole
peripheral blood) PAX gene® and the booster
immunogenicity samples.
Added information indicating that PBMCs will
be collected for analysis of cellular
immunogenicity from a subset (N=50) of adult
participants who were vaccine naïve at study
entry.
Correction.
1.3.5 Procedures for Adult Participants 
With (Suspected) COVID-19 
1.3.6 Procedures for Neonates and 
Infants With (Suspected) COVID-19 
8 STUDY ASSESSMENTS AND 
PROCEDURES  
8.1.1 Immunogenicity Assessments
8.1.2.1 Procedures for Adult Participants 
in Case of Signs and Symptoms of 
COVID-19 
8.1.2.2 Procedures for Neonate and 
Infant Participants in Case of Signs and 
Symptoms of COVID-19
8.6 Biomarkers
Inconsistencies between the Schedule of 
Activities for participants with suspected
COVID-19 (both the SoAs for adults and the
SoAs for neonates/infants) and the section
outlining the procedures to be performed in case
of suspected COVID-19 have been aligned.
Removed information regarding participants in
the innate and pro-inflammatory subsets from
Table 1 and Table 2, and from Sections 8.1.1
and 8.6 and in the text, as this subset will no
longer be included in this study.
Corrections
1.3.3 Adult Participants (Group 1-4, if
applicable): 2-dose Schedule
It has been clarified that blood sampling at Day
57 (Visit 8 of the 2-dose schedule) must occur
pre-vaccination.
Clarification.
3 OBJECTIVES AND ENDPOINTS
1.1 Synopsis
The following exploratory objective, which was
erroneously omitted for the objectives for the
adult participants but was included for the
neonates/infants, has been added: To assess
SARS CoV2 viral load in SARS CoV2 infected
participants during a confirmed COVID 19
episode.
Added wording regarding vaccine naïve
participants and booster assessments for specific
endpoints.
Correction.
1.3.3 Adult Participants (Group 1-4, if
applicable): 2-dose Schedule1.3.3 Adult
Participants (Group 1-4, if applicable): 2-
dose Schedule
Footnote ‘a’ in the 2-dose Schedule of Activities
has been revised: In case of premature birth
before vaccination 2, the need for a second dose
should be evaluated by the investigator and the
mother. In case no second vaccination is
Correction.

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Section Number 
and Name
Description of Change 
Brief Rationale
received, the assessments of Visit 15 and the 12
months follow up phase will be initiated. In case
a second vaccination will be received, all Visits
(except Pregnancy Week 36 Follow up phone
call) will have to be completed.
1.3.7 Participants with a Suspected AESI 
- Pregnant Participants 
8.2.3.1 Hematology Clinical Laboratory 
Assessments 
It is clarified that also in the event of 
thrombocytopenia, laboratory assessments (to
be performed locally) are required to facilitate
diagnosis and determine treatment options,
including but not limited to platelet count and
anti-PF4 tests.
It is clarified that all local laboratory results
need to be encoded in the eCRF, including
platelet counts. Low platelet counts are to be
recorded as suspected AESI
(thrombocytopenia).
Clarification.
9 STATISTICAL CONSIDERATIONS  
9.5 Planned Analyses 
1.1 Synopsis 
Tables 3 and 5 were updated. 
The text throughout was updated to indicate that
analyses will be performed by group, and
overall.
Added text indicating that the SAP will detail
the 2 planned interim analyses, the primary
analysis and the final analysis, and that
additional unplanned interim analyses may be
performed for safety and/or immunogenicity to
facilitate decision making and for regulatory
purposes.
Added information in the Interim Analysis 2
regarding the outcomes if the safety profile in
the Sentinel and Safety Cohorts is considered
acceptable or not, per IDMC recommendation.
Updated the Final Analysis to indicate that it
will include safety and immunogenicity data.
Clarification.
11 REFERENCES  
The reference to the Brighton Collaboration 
case definition of thrombotic events and
thrombocytopenia was updated.
Additional references added to the list.
Update.
1.3.1 Adult Participants (Sentinels, 
Safety and Group 4): 1-dose Schedule 
1.3.3 Adult Participants (Group 1-4, if
applicable): 2-dose Schedule
1.1 Synopsis
The SoAs were updated to present the recording 
of AEs more accurately.
Clarification.
1.1 Synopsis 
It has been clarified that serological response to 
vaccination could also be measured by an assay
which is equivalent to ELISA.
Clarification.

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Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis 
1.3.1 Adult Participants (Sentinels, 
Safety and Group 4): 1-dose Schedule 
1.3.3 Adult Participants (Group 1-4, if 
applicable): 2-dose Schedule 
1.4 STUDY DESIGN  
1.6.3 Measures to Minimize Bias: 
1.2 Schema
6.5 Dose Modification 
It has been clarified that the Day 4 safety review 
following vaccination of the Sentinels was 
performed by the sponsor’s SRP and discussed
with the investigator, and that at the time of
writing of this amendment, this review was
completed and the safety and reactogenicity of
the single dose of Ad26.COV2.S at 5×1010 vp
was found to be acceptable. Hence, enrollment
of the Safety Cohort was initiated and
participants in this cohort will receive a single
dose of Ad26.COV2.S at 5×1010 vp.
Recruitment of previously vaccinated and
vaccine naïve participants has been updated to
the following groups: Comirnaty (Pfizer-
BioNTech) or SpikeVax (Moderna) (Group1),
Ad26.COV2.S (Janssen)(Group 2), other
COVID-19 vaccines (Group 3), and vaccine
naïve participants (Group 4).
Clarification and
update.
1.1 Synopsis
1.4 STUDY DESIGN
1.3.1 Adult Participants (Sentinels,
Safety and Group 4): 1-dose Schedule
1.3.2 Adult Participants: Group 1-3:
previously vaccinated participants: dose
1 Schedule
1.3.3 Adult Participants (Group 1-4, if
applicable): 2-dose Schedule
The text has been updated to indicate two
potential outcomes following IDMC review
depending on whether the safety profile of 1
dose of Ad26.COV2.S at 5×1010 is acceptable or
not.
If acceptable, the remaining 375 participants
will be enrolled and randomized to receive 1
dose of Ad26.COV2.S at 5×1010 vp. If not
acceptable, the remaining 375 participants will
receive 2 doses ofAd26.COV2.S at 2.5×1010 vp
administered with a 56 day interval. Previously
vaccinated participants (Group 1-3) should have
completed a primary vaccine regimen at least 6
months prior to receiving the study vaccine into
the study.
In addition, a row for the randomization of
participants has been added to the SoAs.
Correction.
1.1 Synopsis
1.4 STUDY DESIGN
It is clarified that the Day 8 safety review by the
IDMC will not only include the Day 8 data from
the Safety Cohort but also from the Sentinels.
Clarification.
5.1 Inclusion Criteria
5.2 Exclusion Criteria
Throughout the in- and exclusion criteria, it has
been indicated if changes were made to the
criteria through one of the previous (and
current) amendments.
Other inclusion and exclusion criteria were
amended in this protocol amendment
Removed exclusion criteria regarding
participants previously receiving coronavirus
vaccine.
Clarification.

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Section Number 
and Name
Description of Change 
Brief Rationale
6.9 Study Vaccination Pausing Rules 
Updated the list of events that will lead to a 
pause in further study vaccination. Added death
of an adult participant, considered related to
study vaccine or if the causal relationship to the
study vaccine cannot be excluded.
Update.
1.1 Synopsis 
1.3.1 Adult Participants (Sentinels, 
Safety and Group 4): 1-dose Schedule 
1.3.3 Adult Participants (Group 1-4, if 
applicable): 2-dose Schedule 
1.3.4 Neonate/Infants Schedule
1.4 STUDY DESIGN
Language with regard to the timing of the 
recording of SAEs, MAAEs, AEs leading to
discontinuation has been aligned across
sections.
Body temperature added to Neonate/Infants
Schedule.
Clarification.
1.1.1 Synopsis 
9.3 Populations for Analysis Sets 
It has been added that the PPI-NVN analysis set
will also exclude neonates/infants with major
protocol deviations that are expected to impact
the immunogenicity outcomes.
Correction.
1.1 Synopsis 
1.3 Schedules of Activities 
8 STUDY ASSESSMENTS AND 
PROCEDURES
9 STATISTICAL CONSIDERATIONS
Text regarding the collection of colostrum and
breast milk added to the Schedule of Activities
and updated in the remaining sections listed.
Clarification.
10.9.1 Appendix 9A: CDC Websitea 
Underlying Medical Conditions for 
Adults 
10.13 Appendix 13: Visit guidance in
case of pregnancy termination before the 
completion of the applicable Study 
Period visits 
Updated the list of underlying medical
conditions that adults are more likely to get
severely ill from COVID-19 in Appendix 9A.
Updated the visit guidance in case ofpregnancy
termination before the completion of Study
Period Visits in Appendix 10.13.
Throughout the protocol 
Throughout the protocol (including the
synopsis), sections/paragraphs, have been
moved to the most appropriate location and
redundant sections have been deleted for clarity
purposes.
Clarification.
Throughout the protocol 
Minor errors and inconsistencies were
corrected, and minor clarifications were added
throughout the protocol.
Correction of
minor errors and
inconsistencies.
Addition of minor
clarifications.
Throughout the protocol 
The naming ‘Janssen Adjudication Committee’
was corrected to ‘AESI Adjudication
Committee’, in alignment with other places in
the protocol.
Consistency
throughout
protocol.

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Amendment 3 (02 July 2021)
Overall Rationale for the Amendment: The main purpose of this amendment is to update the safety
procedures to include TTS as an AESI, based on spontaneous reports of extremely rare events of TTS
observed following administration of the Ad26.COV2.S vaccine under EUA in the US that suggest that
there may be an increased risk of a thrombotic event combined with thrombocytopenia associated with the
vaccine.
The study design has been amended so that a larger cohort of participants (N = 325) receive the selected
vaccine regimen for adults of a single dose of Ad26.COV2.S at 5×1010 vp, with a smaller cohort of
participants (N = 75) receiving 2-doses of Ad26.COV2.S at 2.5×1010 vp. The aim is to evaluate a dosing
schedule that has the potential for less reactogenicity, but at least comparable or potentially greater
immunogenicity. Enrollment will be staggered with the safety and reactogenicity evaluated in a group of
Sentinels (n=5) followed by a larger Safety Cohort (n=20), before proceeding to full enrollment. If the
safety profile of Ad26.COV2.S at 5×1010 vp is not acceptable in pregnant women, then the remaining
375 participants will be administered 2-doses at the lower dose of 2.5×1010 vp at a 56-day interval.
Section Number 
and Name
Description of Change 
Brief Rationale
1.1. Synopsis, 
1.3.1. Adult Participants: 1- 
dose Schedule, 
1.3.2. Adult Participants: 2- 
dose Schedule, 
1.3.6. Participants with a 
Suspected AESI - Pregnant 
Participants, 
2.3.1. Risks Related to Study  
Participation  
2.3.3. Benefit-Risk  
Assessment for Study  
Participation, 
3. OBJECTIVES AND
ENDPOINTS,
4.1. Overall Design,
6.8. Prestudy and Concomitant
Therapy,
6.9. Study Vaccination
Pausing Rules,
8.1.1. Immunogenicity
Assessments,
8.2.3.1. Hematology Clinical
Laboratory Assessments,
8.3. Adverse Events, Serious
Adverse Events, Adverse
Events of Special Interest, and
Other Safety Reporting,
8.3.1. Time Period and
Frequency for Collecting
Information Relating to
Adverse Events, Adverse
Events of Special Interest,
Serious Adverse Events and
Medically-Attended Adverse
Events,
8.3.2. Method of Detecting
Adverse Events, Adverse
Thrombosis 
with 
thrombocytopenia 
syndrome (TTS) will be considered an  
AESI. Follow-up assessments will be 
performed in the event of a suspected 
AESI. 
Participants will be asked daily via the 
eCOA if they have experienced any  
health concerns (including new onset of 
symptoms associated with TTS) within  
the 30 day time period post-vaccination, 
and if so, participants will be advised to
contact the study center.
Emerging data following use of the
Ad26.COV2.S vaccine under EUA
in the US suggest an increased risk
of TTS, with onset of symptoms
approximately 1-3 weeks after
vaccination. Therefore, additional
reporting and data collection
procedures are implemented to
follow-up thrombotic events and
thrombocytopenia and identify
cases of TTS.

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Section Number 
and Name
Description of Change 
Brief Rationale
Events of Special Interest,
Serious Adverse Events and
Medically-attended Adverse
Events,
8.3.3. Follow-up of Adverse
Events, Serious Adverse
Events, Adverse Events of
Special Interest and
Medically-Attended Adverse
Events,
8.3.5. Adverse Events of
Special Interest,
8.3.5.1. Thrombosis with
Thrombocytopenia Syndrome
(TTS),
9.4.2. Primary/Secondary
Endpoint(s),
10.2. Appendix 2: Clinical
Laboratory Tests
10.3.6. Safety Monitoring
Committees Structure,
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,
10.4.5. Procedures,
10.11. Appendix 11:
Thrombosis with
Thrombocytopenia (TTS)
AESI Form,
10.12. Appendix 12:
Thrombotic Events to be
Reported as Suspected AESIs,
11. REFERENCES
1.1. Synopsis, 
1.3.6. Participants with a 
Suspected AESI - Pregnant 
Participants, 
3. OBJECTIVES AND 
ENDPOINTS, 
8.2.3. Clinical Safety 
Laboratory Assessments, 
8.3.5. Adverse Events of 
Special Interest, 
10.2. Appendix 2: Clinical
Laboratory Tests
Serum and plasma samples obtained at 
baseline and post-vaccination will be 
used for retrospective analysis of 
coagulation-related parameters.
In the event of an AESI, coagulant factors
that are thought to be associated with
TTS, including anti-PF4 antibodies, lupus
anticoagulant, 
anti-β2 
glycoprotein,
D-dimer levels and anti-cardiolipin will
be assessed.
This was added to fully evaluate
coagulopathy-related parameters
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Section Number 
and Name
Description of Change 
Brief Rationale
1.1. Synopsis, 
1.3.1. Adult Participants: 
1-dose Schedule, 
1.3.2. Adult Participants: 
2-dose Schedule, 
3. OBJECTIVES AND 
ENDPOINTS,
8.3.1. Time Period and 
Frequency for Collecting 
Information Relating to 
Adverse Events, Adverse
Events of Special Interest, 
Serious Adverse Events and 
Medically-Attended Adverse 
Events, 
For the primary endpoints: 
Adverse evets, including solicited local 
and systemic AEs will be monitored for 
7days after (each) vaccination, or until
resolution.
Additional safety assessment at 14 days
post-vaccination (1-dose schedule and
first dose of 2-dose schedule).
Timepoints were specified for the
assessment of humoral immune response
28 days after the first vaccination and
14days after the second vaccination.
For the 2-dose schedule, the Day 85
(28days post-vaccination 2) visit will
become 
a 
phone 
call 
visit 
for
safety-follow-up.
Update timepoints for assessment of
humoral responses
post-vaccination 1 and
post-vaccination 2.
2. INTRODUCTION, 
2.1. Study Rationale 
Text updated to include data from the 
Reproduction 
and 
Developmental 
Toxicity Study for Ad26.COV2.S. 
Update 
relevant 
background
information 
to 
support 
study
rationale.
1.1. Synopsis, 
1.2. Schema, 
2. INTRODUCTION, 
3. OBJECTIVES AND 
ENDPOINTS, 
4.1. Overall Design, 
4.3. Justification for Dose, 
6.1. Study Vaccinations 
Administered, 
6.3. Measures to Minimize 
Bias: Randomization and 
Blinding, 
9.2.1. Immunogenicity, 
9.2.2. Safety, 
9.5.2. Interim Analysis 2
9.6. Independent Data
Monitoring Committee.
The study design has been amended so 
that a larger cohort of participants 
(N = 325) receive the selected vaccine 
regimen for adults of a single dose of 
Ad26.COV2.S at 5×1010 vp, with a 
smaller cohort of participants (N = 75) 
receiving 2-doses of Ad26.COV2.S at 
2.5×1010 vp. If the safety profile of 
Ad26.COV2.S at 5×1010 vp is not 
acceptable, then a 2-dose schedule of 
Ad26.COV2.S at a dose of 2.5×1010 vp 
will be administered to all remaining 
participants (N=375) at an interval of 
56 days.
To mitigate safety concerns relating
to 
potential 
reactogenicity
associated with the use of a 2-dose
schedule 
of Ad26.COV2.S 
at
5×1010 vp in pregnant women, all
participants will receive a single
dose of Ad26.COV2.S at 5×1010 vp,
unless the safety profile in the
Sentinels and Safety Cohort is not
acceptable, in which case all
participants will receive a 2-dose
schedule 
of Ad26.COV2.S 
at
2.5×1010 vp.
7.1. Discontinuation of Study 
Vaccination  
The following text was added: 
Participants who have previously 
experienced an event of TTS, including 
CVST, or HIT. 
Update
To ensure that a participant's study
vaccination must be discontinued if
the participant has experienced an
event of TTS, including CVST or
HIT after receiving the first dose of
vaccine (applicable to the 2-dose
schedule).
7.1. Discontinuation of Study 
Vaccination  
The following text was added: 
Participants who have previously 
experienced an event of CLS. 
Update
To ensure that a participant's study
vaccination must be discontinued if
the participant has experienced an
event of CLS after receiving the
first dose of vaccine (applicable to
the 2-dose schedule).

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Section Number 
and Name
Description of Change 
Brief Rationale
1.1. Synopsis, 
4.2. Scientific Rationale for 
Study Design, 
5.2. Exclusion Criteria 
Exclusion criterium added: 
Participant has a history of CLS. 
Update
To ensure that participants with a
risk of CLS are not included in the
clinical study
1.1. Synopsis, 
4.2. Scientific Rationale for 
Study Design, 
5.2. Exclusion Criteria 
Exclusion criterium added: 
TTS, including CVST, or HIT. 
Update
To ensure that a participant that has
a history of TTS, including CVST,
or HIT are not included in the
clinical study.
5.2. Exclusion Criteria 
7. 
Exclusion criterion relating to a 
participant that is an employee of the 
investigator or study site, with direct
involvement in the study, is reinstated.
Criterion reinstated for consistency
across studies.
1.1. Synopsis, 
1.3.1. Adult Participants: 
1-dose Schedule, 
1.3.2. Adult Participants: 
2-dose Schedule 
3. OBJECTIVES AND
ENDPOINTS,
4.1. Overall Design,
8.1.1. Immunogenicity
Assessments
8.6. Biomarkers
The exploratory objectives and endpoints 
were updated for adults and neonates. 
These updates are reflected in the Table 
of Summary of Humoral and Cellular 
Immunogenicity Assays. 
Update to include additional
exploratory objectives and
endpoints in line with other study
protocols within the clinical
program.
1.1. Synopsis,
1.3.1. Adult Participants:
1-dose Schedule,
1.3.2. Adult Participants:
2-dose Schedule,
3. OBJECTIVES AND
ENDPOINTS,
8.1.1. Immunogenicity
Assessments,
8.5. Genetics and
Pharmacogenomics
The text was updated to include
evaluation of innate, pro-inflammatory
and other relevant pathway responses to
Ad26.COV2.S vaccination in a subset of
participants (N=25 from each cohort) at
selected timepoints:
- Analysis of mRNA expression levels of
vaccine-induced innate responses,
including inflammatory and coagulation-
related mediators.
- Analysis of cytokines, chemokines, and
other protein-or lipid mediators of the
innate immune response.
Update 
to 
include 
additional
analysis of immunological pathways
associated 
with 
Ad26.COV2.S
vaccination.
1.1. Synopsis,
3. OBJECTIVES AND
ENDPOINTS,
The 
exploratory 
endpoint 
of
SARS-CoV-2 viral load during a
confirmed 
COVID-19 
episode 
in
neonates/infants born to adult participants
who have received Ad26.COV2.S during
the 2nd and/or 3rd trimester of pregnancy
was added.
Update to include SARS-CoV-2
viral load as an exploratory
endpoints.
1.3.1. Adult Participants: 1-
dose Schedule,
1.3.2. Adult Participants: 2-
dose Schedule,
1.3.3. Neonate/Infants
Schedule,
8.2.1. Physical Examinations
Text updated for clarification of
procedures that are related to the
pregnant mother and neonate, including:
Collection of breast milk and colostrum;
Safety assessments: Obstetric
examination (will not be performed at
PP1 visit), Physical examination; and
medical and obstetric history.
Clarification relating to procedures.

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Section Number 
and Name
Description of Change 
Brief Rationale
1.3.4. Procedures for Adult 
Participants With (Suspected) 
COVID-19, 
1.3.5. Procedures for Neonates 
and Infants With (Suspected)
COVID-19, 
8.1.2. Procedures in the Event 
of (Suspected) COVID-19 
Clarification in the footnotes that central 
laboratory testing for SARS-CoV-2 
infection will be done only after a local 
positive test.
Additional information added to support 
procedures in case a participant cannot 
attend the study site due to COVID-19. 
Clarification that in the event that sites 
cannot support collection of the nasal 
swab and saliva samples from the
participants home, that HCP visits will
be needed.
Clarification in relation to testing
for SARS-CoV-2 in the event a
local test is positive.
Clarification of procedures in case
of travel restrictions due to the
ongoing COVID-19 pandemic
Alignment with other Phase 3
protocols.
2.3.1. Risks Related to Study 
Participation  
Text has been added clarifying that 
genetic test results obtained during the 
course of this study are for exploratory 
research purposes and will not be 
provided to the participant.
Protect the participant from
disclosure of personal genetic
information gathered for
exploratory research purposes only.
1.3.1. Adult Participants: 1- 
dose Schedule; 
1.3.2. Adult Participants: 2- 
dose Schedule, 
8.1.1. Immunogenicity
Assessments,
Blood sampling timepoints and total 
blood volumes to be drawn were updated 
to align with other changes described in 
this table.
Blood sampling timepoints and total
blood volumes updated in line with
updates to study design.
9.5. Interim Analyses 
Interim Analysis 3 (optional) deleted. 
Not required
Throughout the protocol 
Minor grammatical, formatting, or 
spelling changes were made.
Minor errors were noted

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Amendment 2 (19 March 2021)
Overall Rationale for the Amendment: The main purpose of this amendment is to update the study design
based on health authority feedback. The design was updated from a 2- dose regimen to a 1- or 2- dose
regimen, thereby including the vaccination regimen with currently available supportive efficacy data and
authorized under EUA (US)/Conditional Marketing Authorization (EU). In addition, halting rules were
added for pregnancy-related complications; an additional interim analysis was added for a potential total of
3 interim analyses; exclusion of participants who are seropositive at baseline was removed; assessment of
neurodevelopmental status of neonates/infants born of participants that received the vaccine during the 2nd
and/or 3rd trimester of pregnancy was added; viral neutralizing antibody assay was added as a secondary
endpoint; plasma collection at different timepoints was added to allow adequate evaluation in case of
occurrence of a thromboembolic event.
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis;
1.2 Schema;
1.3.1Adult Participants: 1-
dose Schedule;
3 OBJECTIVES AND
ENDPOINTS;
4.1 Overall Design;
6.1 Study Vaccinations
Administered;
6.5 Dose Modification
Inclusion of a second group of
participants who will only receive 1 dose
of the vaccine at 5×1010 vp,
Inclusion of the vaccination
regimen with currently available
supportive efficacy data and
authorized under EUA
(US)/Conditional Marketing
Authorization (EU)
1.1 Synopsis;
4.1 Overall Design;
6.5 Dose Modification;
9.6 Independent Data
Monitoring Committee
Text was added to clarify that the fallback
regimen for unacceptable tolerability is a
2-dose schedule of Ad26.COV2.S at a
dose level of 2.5×1010 vp, and that if this
regimen 
is 
used, 
Sentinels 
and
participants in the Safety Cohort who
were 
randomized 
to 
receive
Ad26.COV2.S at a dose level 5×1010 vp
will not receive a second vaccination.
Clarification
1.1 Synopsis;
1.3 Schedules of Activities;
6.3 Measures to Minimize
Bias: Randomization and
Blinding
Text was revised from no randomization
to stratified randomization of participants
to the 1- or 2-dose regimen.
Inclusion of a second group of
participants who will only receive 1
dose of the vaccine at 5×1010 vp,
and inclusion of the pregnancy
stage stratification factor
1.1 Synopsis;
3 OBJECTIVES AND
ENDPOINTS
9.2.1 Immunogenicity;
9.4.3 Exploratory Endpoint(s)
Secondary objectives were grouped by
Adult Participants and Neonates/Infants.
For adult participants, humoral immune
response at 28 days post-vaccination was
moved from primary to secondary
objective; humoral immune response
based on ELISA and VNA titers were
made Secondary objectives.
To improve readability/clarity.
Based on health authority feedback,
assessment of neutralizing antibody
responses 28 days after each
vaccination in all adult participants
and their neonates (cord blood) is a
secondary objective; assessment at
other timepoints is exploratory.
1.1 Synopsis;
3 OBJECTIVES AND
ENDPOINTS;
9.2.1 Immunogenicity;
10.1 Appendix 1:
Abbreviations
Reference to “pseudoviron” and “wild-
type” VNA was deleted.
The type of VNA to be used will be
determined based on assay
performance.

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Section Number 
and Name
Description of Change 
Brief Rationale
2 INTRODUCTION  
Epidemiology data were updated for 
SARS-CoV-2 and toxicology data were
updated for Ad26.COV2.S.
Update
5.5 Criteria for Temporarily 
Delaying Administration of 
Study Vaccination; 
7.2 Delay or Discontinuation
of Vaccination due to
Pregnancy-Specific
Complications (added)
Addition of halting rules specific for 
pregnancy complications. 
To ensure the safety of participants
with 
pregnancy-related
complications
9.5.1 Interim Analysis 1; 
9.5.2 Interim Analysis 2; 
9.5.3 Interim Analysis 
3(added)
Text for Interim Analysis 1 was updated 
from “will take place” to “may take 
place.”
Interim Analysis 2 was updated to occur 
when all 400 participants have completed 
the Day 29 visit (28 days post-dose 1) and 
to include immunogenicity data.
Addition of Interim Analysis 3, which
may take place when all 400 participants
have completed the Day 85 visit (28 days
post Visit 5).
Interim Analysis 1 was made
optional.
To 
evaluate 
safety 
and
immunogenicity data periodically to
be able to inform Health Authorities
10.1 Appendix 1: 
Abbreviations; 
10.3.6 Safety Monitoring
Committees Structure
Deletion of the statistical support group 
(SSG). 
A separate SSG is not needed in the
context of an open-label study
5.1 Inclusion Criteria 
Inclusion criterion 10: A footnote was 
added to indicate that participants with
visual impairment are eligible and may
have caregiver assistance in completing
the eCOA questionnaires.
Clarification
5.2 Exclusion Criteria 
Exclusion criterion 17 was deleted. 
There is no need to exclude
employees or those involved with
the study in an uncontrolled open-
label design post Emergency Use
Authorization/Conditional
Marketing Authorization.
5.2 Exclusion Criteria 
9.4.1 General Considerations 
Exclusion criterion 23 was modified. 
Exclusion criterion 26 was deleted 
(redundant in view of the changes to 
criterion 23). 
Text was added to indicate that some 
descriptive analyses may be performed by  
serostatus at baseline. 
Seropositive 
participants 
will
provide informative safety data on
vaccination in this subpopulation of
pregnant 
women 
and 
their
neonates/infants, especially given
the 
increasing 
prevalence 
of
seropositive individuals over time.
Primary immunogenicity endpoints
will be summarized by baseline
serostatus to assess the impact of
preexisting immunity.

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Brief Rationale
1.1 Synopsis; 
3 OBJECTIVES AND 
ENDPOINTS; 
4.1 Overall Design; 
8.1.1 Immunogenicity 
Assessments; 
9.2 Sample Size 
Determination; 
9.4.3 Exploratory Endpoint(s) 
Neutralizing antibodies will be collected 
and assessed in all participants and their 
neonates/infants as a secondary endpoint; 
text related to a subset of participants for 
VNA was deleted from sample size 
determination. 
Current data suggest neutralizing
antibody levels may be informative
of protection, in addition to binding
antibodies. 
Inclusion 
of 
all
participants in this analysis will
provide more information and allow
for stratification between 2nd and 3rd
trimesters. 
Secondary
immunogenicity endpoints will be
summarized by baseline serostatus
to assess the impact of preexisting
immunity.
1.1 Synopsis; 
1.3.3 Neonate/Infants 
Schedule; 
3 OBJECTIVES AND 
ENDPOINTS; 
8.2.5 Neonatal Assessments; 
9.4.3 Exploratory Endpoint(s)
Inclusion of the Ages & Stages 
Questionnaire, 3rd edition to assess 
neurodevelopmental 
status 
in 
neonates/infants at 2, 6 and 12 months of
age as an exploratory endpoint. Section
title was updated.
To 
evaluate 
developmental
outcomes of the children of study
participants
1.3.2 Adult Participants: 2- 
dose Schedule 
Footnote was updated to indicate that the
baseline SIC should be completed prior to
the first vaccine administration. 
If the baseline SIC is not completed,
no eCOA scales will be triggered.
1.3.2 Adult Participants: 2- 
dose Schedule 
Blood draw for serologic testing at 
screening was removed; footnote was 
added that humoral immunogenicity 
samples at Day 1, Day 29, Day 85, birth, 
PP6 and PP12 will be used for baseline 
and subsequent serology testing. 
Other footnotes have been clarified. 
As we are including seropositives
and seronegatives, there is no need
for serological samples at screening.
The 
additional 
timepoints 
are
necessary to evaluate the occurrence
of asymptomatic infection.
Clarification
1.3.1 Adult Participants: 1- 
dose Schedule; 
1.3.2 Adult Participants: 2- 
dose Schedule; 
8.1.1 Immunogenicity 
Assessments; 
9.4.3 Exploratory Endpoint(s); 
10.2 Appendix 2: Clinical 
Laboratory Tests; 
10.3.5 Long-Term Retention 
of Samples for Additional 
Future Research  
Blood samples (7.5 mL) for plasma will 
be collected pre-dose on Day 1 and 
Day 57 (2-dose regimen) and at 7days 
and 28 days post-dose 1 and post-dose 2 
(if applicable); at delivery and at the 
postpartum Day 42 follow-up visit, to be 
stored for future testing to evaluate the 
impact of any potential thromboembolic 
events (if applicable) and possibly
additional. (Unused plasma samples may
be used for immunogenicity testing.)
Blood volumes were updated.
Due to concerns of a possible
association with adenoviral vector
based vaccines on the incidence of
thromboembolic 
events 
within
healthy 
participants 
and 
the
increased 
risk 
of 
these
thromboembolic events associated
with pregnancy.

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Brief Rationale
1.3.4 Procedures for Adult 
Participants With (Suspected) 
COVID-19; 
1.3.5 Procedures for Neonates 
and Infants With (Suspected)
COVID-19; 
8.1.2.1 Procedures for Adult 
Participants in Case of Signs 
and Symptoms of COVID-19; 
8.1.2.2 Procedures for
Neonate and Infant
Participants in Case of Signs
and Symptoms of COVID-19
Text 
was 
added 
to 
clarify 
the 
requirements for collection of nasal 
swabs and SIC, respectively, to close the 
COVID-19 episode for adult participants.
A note was added that if the participant is
unable to complete the SIC/PedSIC, the
reason for the missing assessment should
be recorded in the eCRF.
To reduce burden on participants
who continue to test positive after
symptom resolution
8.1.2.1 Procedures for Adult 
Participants in Case of Signs 
and Symptoms of COVID-19; 
8.1.2.2 Procedures for
Neonate and Infant
Participants in Case of Signs
and Symptoms of COVID-19
Clarification was added that COVID-19 
Day 29 procedures should be completed
even if nasal swabs are pending.
Clarification
4.3 Justification for Dose 
Text was added to inform about EUA/ 
Conditional Marketing Authorization of
the single dose regimen of Ad26.COV2.S
5×1010 vp.
Updated information
1.1 Synopsis; 
3 OBJECTIVES AND 
ENDPOINTS; 
6.8 Prestudy and Concomitant 
Therapy; 
8.3.1Time Period and 
Frequency for Collecting
Information Relating to
Adverse Events, Adverse
Events of Special Interest,
Serious Adverse Events ;
9.2.2 Safety;
9.4.2 Primary/Secondary
Endpoint(s)
Text was modified to clarify that AEs 
leading to discontinuation will be
reported for adult participants and
neonates/infants throughout the study, not
just medically-attended AEs leading to
discontinuation.
Clarification
4.4 End of Study Definition  
Text was revised to define premature 
discontinuation as not having completed 
Visit 12. 
Replaced reference to completion of
the 2-dose regimen, because not all
participants will receive 2 doses
9.4.1 General Considerations 
Text was updated that analyses may be 
performed by pregnancy stage, dose 
regimen, and/or by baseline serostatus. 
For neonates/infants, analyses may also 
be performed by vaccination regimen
received by the adult participant during
pregnancy.
To align with the randomized 1- or
2-dose study design and enrollment
of participants regardless of
baseline serostatus
10.5 Appendix 5: 
Contraceptive Guidance 
A footnote was added to hormonal 
contraception “or per physician 
preference/local standard of care in a 
woman who is breastfeeding.”
Introduces flexibility, as hormonal
contraception may be different in a
breastfeeding participant

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10.2 Appendix 2: Clinical 
Laboratory Tests 
Tables were added to outline tests 
performed on adult participants and
neonates/infants.
Consistency with body text
Throughout the protocol 
Minor grammatical, formatting, or 
spelling changes were made.
Minor errors were noted
Amendment 1 (28 February 2021)
Overall Rationale for the Amendment: Pregnancy is associated with an increased risk of severe illness
from COVID-19 and potential adverse birth outcomes. The main rationale for the protocol amendment is
to document changes to study design which, if implemented, will ensure that all participants enrolled in this
study benefit from the protection conferred by the Ad26.COV2.S vaccine. This is considered an ethical
imperative, in view ofthe rising disease burden associated with the current pandemic. The initial proposal
was for a randomized double-blind, placebo-controlled study to evaluate the safety and reactogenicity of 2
dose levels (2.5×1010 vp and 5×1010 vp) of Ad26.COV2.S versus placebo control, administered as a 1-dose
or 2-dose schedule, in adult participants during the 2nd and/or 3rd trimester of pregnancy. The current
proposal is for an open-label study to assess the safety and reactogenicity of Ad26.COV2.S, administered
at a single dose level of 5×1010 vp, as a 2-dose schedule (at a 56-day interval, if feasible) to all study
participants during the 2nd and/or 3rd trimester of pregnancy (or postpartum, if necessary). There will be no
placebo control group in this study. Interim Analysis will be performed when the first 200 enrolled adult
participants have completed the Day 29 visit (28 days post-dose 1) and Day 85 visit (28 days post-dose 2),
for the purpose of providing post-dose 1 safety and reactogenicity data for regulatory authorities, if
requested to do so.
Section Number 
and Name
Description of Change 
Brief Rationale
Section 1.1 Synopsis;
Section 1.2 Schema;
Section 1.3.1 Schedule of
Activities;
Section 3 Objectives and
Endpoints;
Section 4.1 Overall Design;
Section 4.3 Justification for
Dose
Change in vaccine dosing regimen: The
original proposal was for a randomized
double-blind, placebo-controlled study to
evaluate the safety and reactogenicity of
2-dose levels (2.5×1010 vp and 5×1010 vp)
of Ad26.COV2.S, administered as a 1
dose or 2-dose schedule.
- 
The 
current 
proposal 
(protocol
Amendment 1) is for an open-label study
to assess the safety and reactogenicity of
Ad26.COV2.S, administered at a single
dose level of 5×1010 vp, as a 2-dose
schedule (at a 56-day interval, if feasible)
to all study participants during the 2nd
and/or 3rd trimester of pregnancy (or
postpartum, if necessary). There will be
no 
placebo 
control 
group. 
The
Ad26.COV2.S (2.5×1010 vp) dose is not
retained in this protocol amendment as
the Ad26.COV2.S (5×1010 vp) dose
showed an acceptable reactogenicity
profile in adults 18years and older.
- To ensure that all participants
enrolled in the study are offered the
Ad26.COV2.S vaccine at the
selected dose of 5×1010 vp, using a
2-dose schedule.
- To ensure that there is flexibility
built into the dosing regimen, which
will allow for the second dose of
vaccine to be administered
postpartum, if necessary.
Section 1.1 Synopsis;
Section 4.1 Overall Design;
Section 5.1 Inclusion Criteria;
Section 9.2 Sample Size
Determination
The age range of adult participants
enrolled has been extended to ≥ 18years
to ≤45 years of age.
- The age range at which adult
participants are recruited has been
extended to reflect an increase in
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the age range of ≥40 years and
≤45 years.
Section 1.1 Synopsis; 
Section 3 Objectives and 
Endpoints; 
Section 4.1 Overall Design; 
Section 5.1 Inclusion Criteria; 
Section 6.1 Study Vaccination 
Administered; 
Section 9.4.2 
Primary/Secondary Endpoints 
The gestational age at enrollment has 
been extended from Weeks ≥20 to ≤36, 
with enrollment stratified by pregnancy 
stage at time of randomization to 
Weeks ≥16 to ≤38 (2nd or 3rd trimester of 
pregnancy), with no restriction placed on 
the number of participants, based on age 
of gestation (within the given range), or 
on the dosing regimen (ie, 1-dose or 
2-dose based on age of gestation). 
All participants will receive 2-doses of 
Ad26.COV2.S at the 5×1010 vp dose 
level, irrespective of gestational age. 
Depending on the stage of pregnancy at 
the time of enrollment, both the first and 
second dose of vaccine should be 
administered 
during 
pregnancy, 
if 
feasible, with the first dose of vaccination 
(Day 1) administered following the
screening period. The 2nd  dose of vaccine
will be administered on Study Day 57.
For those participants in later stages of
pregnancy (ie, 3rd trimester at enrollment)
and in those cases in which it is not
feasible to administer both vaccines
during 
pregnancy 
(eg, 
premature
delivery), the second dose of vaccine can
be administered postpartum.
- The gestational age of adult
participants at enrollment has been
extended to Weeks ≥16 to ≤38 (ie,
still within the 2nd or 3rd trimester of
pregnancy, but with an extended
gestational age range), to reflect the
real-world situation and the need to
provide protection for pregnant
women.
- Participants will no longer be
stratified by pregnancy stage to
receive either a 1-dose or 2-dose
schedule based on gestation age at
the time of randomization. All
participants will receive a 2-dose
schedule, with the second dose
administered 
postpartum, 
if
necessary.
Section 1.1 Synopsis;
Section 4.1 Overall Design;
Section 6.5 Dose
Modification;
Section 9.6 Independent Data
Monitoring Committee
The safety and tolerability of a single
dose of the Ad26.COV2.S vaccine at the
5×1010 vp dose level in pregnant women,
will be assessed in the first instance in 5
sentinels 
at 
Day 4 (3 days 
post-
vaccination) and if acceptable, in the
larger Safety Cohort (20 participants) at
Day 8 (7days post-vaccination), before
proceeding to full enrollment.
An IDMC  will review the open-label
safety and reactogenicity data:
Only after positive recommendations
from the IDMC following assessment of
the Day 8 safety and reactogenicity
profile in the Safety Cohort, will the
remaining 375 participants be enrolled to
received 2 doses of Ad26.COV2.S at
5×1010 vp.
If the safety profile after 1 dose of
Ad26.COV2.S at the 5×1010 vp dose in
the group of Sentinels and/or in the Safety
Cohort is not considered acceptable, all
remaining participants will receive 2
To ensure that the safety and
reactogenicity of the Ad26.COV2.S
vaccine at the 5×1010 dose level is
monitored and assessed by the
Sponsor and the IDMC in a Safety
Cohort 
of 
25 pregnant 
adult
participants (5 sentinels initially, and
a further 20 participants), before
proceeding to full enrollment, with
the aim of minimizing exposure in
pregnant women in the event of
safety concerns.

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Brief Rationale
doses of Ad26.COV2.S at the 2.5×1010 vp
dose level as shown in the figure below.
The sequential enrollment is depicted in
the figure below.
All participants (including sentinels and
those assigned to the Safety Cohort) will
receive 2-doses of Ad26.COV2.S.
Section 1.1 Synopsis; 
Section 1.3.1 Schedule of 
Activities 
Section 2.3.3 Benefit-Risk  
Assessment for Study 
Participation; 
Section 4.1 Overall Design; 
Section 8.3.2 Method of 
Detecting Adverse Events, 
Medically-attended Adverse 
Events, and Serious Adverse 
Events Information
Sentinels and participants in the Safety 
Cohort will be vaccinated at least 1 hour 
apart and will remain under observation at 
the site for at least 60 minutes to monitor
for the presence of any acute reactions
and solicited events. Participants in the
Sentinel and Safety Cohorts will continue
to be closely monitored for 7 days
post-vaccination and will be requested to
record solicited signs and symptoms in a
reactogenicity diary.
All other participants will remain under
observation at the study site for at least
30 minutes and will be requested to
record solicited signs and symptoms in a
reactogenicity diary for 7days post-
vaccination.
To ensure that the Safety and
reactogenicity is monitored
post-vaccination.
Section 6.3 Measures to 
Minimize Bias: 
Randomization and Blinding 
Section 6.6 Continued Access 
to Study Vaccine After the 
End of the Study; 
Section 10.3.6 Safety 
Monitoring Committee 
Structure 
In the original protocol, participants were 
randomized to Groups 1-4 (Safety Cohort 
including Sentinels) with the remaining 
participants randomized to Groups 5-10 
(stratified by number of weeks gestation 
and study regimen).
Based on the current study design,
randomization will not be used in this
study. Participants will no longer be
stratified by pregnancy stage. All
participants (including those in the
sentinel group and safety cohort) will be
assigned in an open-label manner to
receive 2 doses of the Ad26.Cov2.S
vaccine at a dose level of 5×1010 vp.
As an open-label study, blinding
procedures are no longer applicable.
Continued Access to Study Vaccine After
the End of the Study: Not applicable.
Clarification that participants will no
longer be assigned to separate study
groups based on randomization and
stratification by pregnancy stage and
study site.
Section 1.1 Synopsis; 
Section 4.1 Overall Design; 
Section 9.2 Sample 
Determination  
The change from a double-blind, placebo- 
controlled study to an open-label study
has had an impact on sample size
calculations, with a reduction in numbers
of participants enrolled: Based on the
proposed study regimen, a target of 400
adult participants will be enrolled (down
Clarification

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Section Number 
and Name
Description of Change 
Brief Rationale
from 824 adult participants in the original
study design).
Section 9.2.1 Safety 
(Endpoints); 
Section 9.3 Populations for 
Analysis Sets; 
Section 9.4.2 
Primary/Secondary Endpoints 
Section 9.5 Interim Analyses; 
Section 9.5.1 Interim 
Analysis 1; 
Section 9.5.2 Interim 
Analysis 2; 
Section 9.7Primary Analysis 
Statistical 
Consideration 
(including 
sample size, populations for analysis sets, 
statistical analysis, and safety endpoints) 
have been updated to reflect the impact of 
changing from a randomized double- 
blind, placebo-controlled study to an 
open-label study. 
- Interim analysis will now be performed 
on the 
first 
200 
enrolled 
adult 
participants, with Interim Analysis 1 
performed when the first 200 enrolled
adult participants have completed the
Day 29 visit (ie, 28 days post-dose 1), and
Interim Analysis 2 performed when the
first 200 enrolled adult participants have
completed the Day 85 visit (ie, 28 days
post-dose 2).
Primary/Secondary Safety Endpoints: 
- No formal statistical testing of safety 
data is planned. Safety data will be 
analyzed 
descriptively 
for 
adult
participants. Safety data for participants
who receive the second dose of vaccine
postpartum may be provided as a separate
descriptive analysis.
- Safety endpoints: updated in line with
revised 
definitions 
for 
pregnancy
outcomes 
and 
outcomes 
in
neonates/infants.
Clarification that primary analysis of
safety and immunogenicity will be
performed when all adult participants
have completed the visit that takes place
"approximately" 42 days postpartum.
Statistical Considerations include
Interim Analysis to take place when
the 
first 
200 
enrolled 
adult
participants have completed the
Day 29 visit (28 days post-dose 1)
and Day 85 visit (28 days post-dose
2), for the purpose of providing
post-dose 1 and post-dose 2 safety
and 
reactogenicity 
data 
for
regulatory authorities, if requested to
do so.
Statistical 
Considerations 
for
analysis of safety data for women
who receive the second dose of
vaccine postpartum.
Section 5.2 Exclusion Criteria;
Section 10.5 Appendix 5:
Contraceptive Guidance
Exclusion Criterium 28 added: At the
time of consenting, participants should
agree to practicing an acceptable effective
method of contraception postpartum and
agree to remain on such a method of
contraception following the birth of the
infant until 3 months after administration
of the second study vaccine. Participants
should 
follow 
contraceptive 
(birth
control) measures consistent with local
regulations regarding the acceptable
methods of contraception
To reflect the enrollment of
participants in the later stages of
pregnancy (ie, 3rd  trimester at
enrollment) and those cases in which
it is not feasible to administer both
vaccines during pregnancy (eg,
premature delivery), and the second
dose of vaccine can be administered
postpartum.

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Section Number 
and Name
Description of Change 
Brief Rationale
Appendix 5: Contraceptive Guidance
added.
Section 5.2. Exclusion Criteria Exclusion Criterium No. 25 deleted. 
A participant who is currently working in 
an occupation with a high-risk of 
exposure to SARS-CoV-2 infection or 
considered to be at increased risk to 
acquire COVID-19 for any other reason, 
will no longer be excluded from 
enrollment.
To reflect the fact that pregnant
women are unlikely to be working
in an occupation where they are at
increased risk of exposure to
SARS-CoV-2 infection; participants
who are at risk due to exposure in
the general population should not
be excluded from enrollment.
Section 1.3.1
Schedule of Activities
Footnote (bb) added to Schedule of
Activities: Urine pregnancy test should be
performed at Study Visit 5 (ie, prior to
Vaccination 2). This is only applicable to
women who are ≥6 weeks postpartum (ie,
only applies to women in those cases in
which the second dose of vaccine is to be
administered after birth).
To reflect the enrollment of
participants in the later stages of
pregnancy (ie, 3rd trimester at
enrollment) and those cases in which
it is not feasible to administer both
vaccines during pregnancy (eg,
premature delivery), and the second
dose of vaccine can be administered
postpartum (ie, there is a possibility
that the participant may become
pregnant prior to receipt of the
second dose).
Section 1.3.1
Schedule of Activities
Section 8.1.1 Immunogenicity
Assessments
All participants will be given the option
to provide breast milk and colostrum on a
voluntary basis (previously obtained from
a subset of participants [N=60]).
The volume of breast milk is adjusted to
approximately 10 mL (previously 5 mL).
To ensure that breast milk and
colostrum are provided by
participants on an optional basis.
Section 1.3.1
Schedule of Activities;
Section 8.1.1 Immunogenicity
Assessments
Blood samples for PBMC isolation for
assessment of cellular immunity will be
obtained from a subset of 60 participants
(previously, a subset of 260 participants).
The number of participants from
whom blood samples will be
collected for isolation of PBMC has
been adjusted to reflect the change
in study design.
Section 1.3.2
Schedule of Activities;
Section 1.3.4
Schedule of Activities;
Section 8.1.1 Immunogenicity
Assessments
Peripheral blood samples collected for
assessment of humoral immunity in
neonates/infants has been updated:
- Schedule of Activities 1.3.2: Blood
samples of 3.5 mL to be collected at
Study Visit 4 and Visit 8 (ie, at 2 months
and 6 months of age);
- Schedule of Activities 1.3.4: Blood
samples of 2.5 mL to be collected.
Cord blood samples to be collected for
assessment of humoral immunity in
neonates/infants: Approximately 15 mL
(minimum of 10 mL)
- Schedule of Activities 1.3.2 and
- Table 1. Immunogenicity Assessments
The peripheral blood volumes and
cord blood volumes to be collected
have been revised.

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Section 1.1 Synopsis; 
Section 3 Objectives and 
Endpoints; 
Section 4.1 Overall Design; 
Section 9.2.1 Safety 
(Statistical Considerations); 
Section 9.4.2 
Primary/Secondary Endpoints 
Definitions for Pregnancy outcomes and 
outcomes in neonates/infants updated as 
follows: 
- Pregnancy outcomes (including live
term birth live preterm birth, stillbirth,
and abortion).
- Outcomes in neonates and infants
(including, normal neonate, term neonate
with complications, preterm neonate
with complications, neonatal infection,
respiratory distress, congenital
anomalies, neonatal death, low birth
weight, and small for gestational age
measured from birth until approximately
12 months of age [non-exhaustive]).
To align with revised definition
used in the electronic Case Report
Form (eCRF).
Section 6.9 Study Vaccination 
Pausing Rules; 
Section 10.3.6 Safety 
Monitoring Committee 
Text relating to the Safety Monitoring 
Committee updated. 
Text relating to procedures to be 
performed in the event of a study pause 
added, specifying that "if following
appropriate safety review it is deemed
appropriate to restart dosing, the sponsor
must submit a request to restart dosing
with pertinent data to competent
authority as a request for a substantial
amendment, as required by local
regulations or authority request (eg,
MHRA). If needed, this will be followed
by a substantial amendment of the IB
and/or protocol."
Clarification on the procedures to
be followed to initiate vaccination
in the event that a study vaccination
pausing rule is met.
Section 1.3.1  
Schedule of Activities 
The following updates were made to the 
Schedule of Activities: 
- Obstetric ultrasound Day 1, visit 2
(pre-dose: vaccination 1): footnote 4
deleted
- Nasal swab Day 1 visit 2 (pre-dose):
footnote 5 deleted.
Correction of an error in the
original protocol.
Section 1.1 Synopsis; 
Section 3 Objectives and 
Endpoints 
Inclusion ofanalysis ofthe phenotype of 
antigen-specific T and B cells, assessed 
by single cell analysis.
Endpoint erroneously not listed in
the original protocol.

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Section Number 
and Name
Description of Change 
Brief Rationale
Section 1.1 Synopsis; 
Section 3 Objectives and 
Endpoints; 
Section 8.1.1 Immunogenicity 
Assessments 
Summary  of Humoral and Cellular 
Immunogenicity  Assays updated to 
include updates to the exploratory
endpoints for analysis of antibody
binding specificities:
- To assess in  adult participants, the
impact of preexisting humoral immunity
against coronavirus other than  SARS-
CoV-2 at baseline, on acquisition of
Ad26.COV2.S vaccine immunogenicity:
 Analysis of antibodies binding to
coronaviruses other than SARS-
COV-2 by ELISA or equivalent
assay, or to other respiratory
viruses (Meso Scale Discovery).
Endpoint erroneously not listed in
the original protocol.
Section 2 Introduction 
Text updated in line with the latest 
Investigator Brochure (dated 
19 February 2021) and published studies.
Inclusion of latest available
information.
Throughout the protocol 
Minor grammatical, formatting, or 
spelling changes were made.
Minor errors were noted
Original Protocol 
07 December 2020

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11. 
REFERENCES
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VAC31518 (JNJ-78436735) 
Clinical Protocol VAC31518COV2004 Amendment 7
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
215
Status: Approved, Date: 16 September 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 intervention, 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 course of 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
 
16-Sep-2022
07:31:52
(GMT)
Document Approval
PPD