IGHID 12107 - A Phase I Study to Evaluate the Safety and Immunogenicity of the ChAdOx1.HIVconsv62 - MVA.tHIVconsv4 (C62-M4) or, ChAdOx1.tHIVconsv1+C62 - MVA.tHIVconsv3+M4 (C1C62-M3M4) Prime-Boost Regimens in Persons With HIV-1 Suppressed on Antiretroviral Therapy
Phase: PHASE1
Conditions: HIV Vaccine, HIV-1-infection
Sponsor: University of North Carolina, Chapel Hill

IGHID 12107 - A Phase I Study to Evaluate the Safety and Immunogenicity of The 
ChAdOx1.HIVconsv62 - MVA.tHIVconsv4 (C62-M4) or, ChAdOx1.tHIVconsv1+C62 - 
MVA.tHIVconsv3+M4 (C1C62-M3m4) PRIME-BOOST REGIMENS in persons with HIV-1 
Suppressed on Antiretroviral Therapy – THE CM (HIV-CORE 008) STUDY 
NCT Number     
NCT05604209 
Document Date 
23Oct2023 
 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
Confidential
Page 1 of 143
 
 
IGHID 12107 - A PHASE I STUDY TO EVALUATE THE SAFETY AND 
IMMUNOGENICITY OF THE CHADOX1.HIVCONSV62 - 
MVA.THIVCONSV4 (C62-M4) OR, CHADOX1.THIVCONSV1+C62 - 
MVA.THIVCONSV3+M4 (C1C62-M3M4) PRIME-BOOST REGIMENS 
IN PERSONS WITH HIV-1 SUPPRESSED ON ANTIRETROVIRAL 
THERAPY –  
THE CM (HIV-CORE 008) STUDY 
 
DAIDS ES-ID Protocol Number: 38832 
National Clinical Trial (NCT) Identified Number:  TBD 
Grant Principal Investigator: Nilu Goonetilleke, PhD 
Protocol Principal Investigator: Cynthia Gay, MD, MPH 
IND Number: IND # 27352 
Funded by: National Institute of Health (NIH) 
Division of AIDS (DAIDS) 
Version Number: 3.0 
23 October 2023 
 
 
 
 
 
 
 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
Confidential
Page 2 of 143
 
IGHID 12107 - A Phase I Study to Evaluate the Safety and Immunogenicity of the 
ChAdOx1.HIVconsv62 - MVA.tHIVconsv4 (C62-M4) or, ChAdOx1.tHIVconsv1+C62 - 
MVA.tHIVconsv3+M4 (C1C62-M3M4) Prime-Boost Regimens in Persons with HIV-1 
Suppressed on Antiretroviral Therapy – The CM (HIV-CORE 008) Study 
THE CM (HIV- CORE 008) STUDY 
DAIDS ES-ID Protocol Number: 38832 
SIGNATURE PAGE 
I will conduct the study in accordance with the provisions of this protocol and all applicable 
protocol-related documents. I agree to conduct this study in compliance with United States (US) 
Health and Human Service regulations (45 CFR 46); applicable U.S. Food and Drug 
Administration regulations; standards of the International Conference on Harmonization 
Guideline for Good Clinical Practice (E6); Institutional Review Board/Ethics Committee 
determinations; all applicable in-country, state, and local laws and regulations; and other 
applicable requirements (e.g., US National Institutes of Health, Division of AIDS) and 
institutional policies.  
 
 
 
Protocol Principal Investigator: _______________________________________________  
Print/Type  
 
 
Signed: ___________________________________ Date: ____________________  
 
Title: _____________________________________ 
 
 
 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
Confidential
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PROTOCOL TEAM ROSTER 
Grant Principal Investigator  
Nilukshi (Nilu) Goonetilleke, PhD  
Associate Professor  
Dept. Microbiology & Immunology / Medicine University of 
North Carolina  
120 Mason Farm Road, CB# 7042 2023 (Office 2017), Genetic 
Medicine Building  
Chapel Hill, NC 27599-7042  
Phone: (919) 962-3129  
Email: nilu_goonetilleke@med.unc.edu  
 
Protocol Principal Investigator  
Cynthia Gay, MD, MPH  
Associate Professor  
Medical Director UNC HIV Cure Center  
University of North Carolina  
Division of Infectious Diseases  
130 Mason Farm Road,  
2135 Bioinformatics Building, CB# 7030  
Chapel Hill, North Carolina 27599-7030  
Phone: (919) 843-2726  
Fax: (919) 966-8928  
Email: cynthia_gay@med.unc.edu  
Co-Investigator  
Joseph Eron, MD  
Professor of Medicine,  
School of Medicine  
Chief, Division of Infectious Diseases 
Director, Clinical Core, UNC Center for AIDS Research  
University of North Carolina  
130 Mason Farm Road,  
2110 Bioinformatics Building, CB# 7030  
Chapel Hill, North Carolina 27599-7030  
Phone: (919) 966-2536  
Fax: (919) 966-6714  
Email: joseph_eron@med.unc.edu  
Co-Investigator  
David Margolis, MD  
Professor of Medicine, Microbiology & Immunology, 
and Epidemiology  
University of North Carolina  
120 Mason Farm Road,  
2016 Genetic Medicine Building, CB# 7042 Chapel 
Hill, NC 27599-7042  
Phone: (919) 966-6388  
Email: david_margolis@med.unc.edu  
 
Clinical Program Director  
Susan Pedersen, RN  
UNC HIV Cure Center  
University of North Carolina  
130 Mason Farm Road,  
2100 Bioinformatics Building, CB# 7030  
Chapel Hill, NC 27599-7030  
Phone: (919)-966-6713 
Fax: (919) 843-7625  
Email: susan_pedersen@med.unc.edu 
  
Co-Investigator 
Monica Diaz, M.D., M.S. 
Assistant Professor 
Department of Neurology, University of North Carolina 
194 Finley Golf Course Road Suite 200 
Chapel Hill, NC 57517 
Phone: (984) 974-4401 
Email: monica.diaz@neurology.unc.edu 
 
Co-Investigator 
Nancie M. Archin, Ph.D.  
Assistant Professor  
University of North Carolina Division of Infectious Diseases  
120 Mason Farm Rd, CB# 7042  
2060 Genetic Medicine Building  
Chapel Hill, NC, 27599-7042  
Phone: (919) 962-0180  
Email: nancie_archin@med.unc.edu   
Co-Investigator  
Tomáš Hanke, PhD  
Professor of Vaccine Immunology, Distinguished 
Professor 
University of Oxford, Nuffield Department of Medicine  
The Jenner Institute  
ORCRB Roosevelt Drive, Oxford OX3 7DQ United 
Kingdom  
Phone: +44 1865 617630  
Email: tomas.hanke@ndm.ox.ac.uk 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
Confidential
Page 4 of 143
 
Co-Investigator  
Emmanuel Benjamin Walter, MD 
Professor of Pediatrics 
Duke University, Duke Global Health Institute 
Duke Clinical Research Institute, Duke Human Vaccine Institute 
27 Parmer Way, Box 106008, Dvtu- Rtp, Parmer 3rd Floor, 
Bldg.3 
Durham, NC 27703 
Phone: (919) 620-5374 
Email: walte002@mc.duke.edu 
Co-Investigator  
Mehri McKellar, MD 
Duke University Medical Center 
P.O. Box 102359 
Durham, NC 27710 
Phone: 919-613-6129 
Fax: 919-684-8902 
Email: mehri.mckellar@duke.edu 
Statistician  
Michael Hudgens, PhD  
Professor,  
Department of Biostatistics Director,  
Center for AIDS Research (CFAR) Biostatistics Core  
3107C McGavran-Greenberg Hall CB#7420 
Chapel Hill, NC 27599-7042 
Phone: (919) 966-7253  
Email: mhudgens@bios.unc.edu 
Statistician  
Ann Marie Weideman, MS  
University of North Carolina 
Center for AIDS Research (CFAR) Biostatistics Core 
3104A McGavran-Greenberg Hall 
Chapel Hill, NC 27599-7042 
Phone: (410) 858-6447 
Email: anndo1@live.unc.edu 
Statistician  
Melissa Mischell 
University of North Carolina 
Center for AIDS Research (CFAR) Biostatistics Core 
3105 McGavran-Greenberg Hall 
Chapel Hill, NC 27599-7042 
Phone: (609) 235-5837 
Email: mmischel@unc.edu 
DAIDS Program Officer  
Steve Smiley, PhD  
Program Officer  
Therapeutics Research Program  
Division of AIDS, NIAID, NIH, DHHS  
5601 Fishers Lane, Room 9E59  
Bethesda, MD 20892-9830  
Phone: 240-627-3071  
Fax: 240-627-3106  
Email: stephen.smiley@niaid.nih.gov 
DAIDS Medical Officer  
Lawrence Fox, MD, Ph.D.  
Captain, US Public Health Service  
Senior Medical Officer,  
HIV Research Branch Division of AIDS, NIAID, NIH, DHHS  
phone: 240-627-3069  
FAX: 240-627-3106  
Email: LFOX@niaid.nih.gov  
  
 
 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
Confidential
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TABLE OF CONTENTS 
SIGNATURE PAGE ..........................................................................................................2 
PROTOCOL TEAM ROSTER ........................................................................................3 
TABLE OF CONTENTS ..................................................................................................5 
TABLE OF TABLES .........................................................................................................9 
TABLE OF FIGURES .......................................................................................................9 
TABLE OF APPENDICES ...............................................................................................9 
STATEMENT OF COMPLIANCE ...............................................................................10 
1 
PROTOCOL SUMMARY .......................................................................................11 
1.1 
Synopsis .................................................................................................................11 
1.2 
Schema ..................................................................................................................15 
1.3 
Schedule of Activities (SoA) ................................................................................16 
2 
INTRODUCTION ....................................................................................................19 
2.1 
Study Rationale ....................................................................................................19 
2.2 
Background ..........................................................................................................20 
2.2.1 
T Cell Correlates and HIV Control ..............................................................20 
2.2.2 
Overview of the Vaccines ..............................................................................21 
2.2.3 
The Immunogens ............................................................................................22 
2.2.4 
The Viral Vectors ...........................................................................................26 
2.2.5 
Simian adenovirus viral vectors ...................................................................26 
2.2.6 
MVA Vaccine Vectors ...................................................................................33 
2.2.7 
Simian Adenovirus- and MVA Prime Boost Vaccination ..........................36 
2.3 
Risk/Benefit Assessment ......................................................................................37 
2.3.1 
Known Potential Risks of C1 and C62 Vaccines .........................................37 
2.3.2 
Known Potential Risks of M3 and M4 vaccines ..........................................39 
2.3.3 
Known Potential Risks Common to Both ChAdOx1-vectored and 
MVA-vectored Vaccines ................................................................................40 
2.3.4 
Known Potential Risks of Overdose .............................................................40 
2.3.5 
Known Potential Risks of Syncope ...............................................................41 
2.3.6 
Known Potential Risks of Blood Drawing ...................................................41 
2.3.7 
Known Potential Risks of Leukapheresis ....................................................41 
2.3.8 
Unknown Risks...............................................................................................42 
2.3.9 
Known Potential Benefits ..............................................................................42 
2.3.10 
Assessment of Potential Risks and Benefits .................................................42 
3 
OBJECTIVES AND ENDPOINTS .........................................................................42 
4 
STUDY DESIGN ......................................................................................................45 
4.1 
Overall Design ......................................................................................................45 
4.2 
Scientific Rationale for Study Design .................................................................46 
4.3 
Justification for Dose ...........................................................................................47 
4.4 
End of Study Definition .......................................................................................48 
5 
STUDY POPULATION ...........................................................................................48 
5.1 
Inclusion Criteria .................................................................................................48 
5.2 
Exclusion Criteria ................................................................................................52 
5.3 
Screening ...............................................................................................................55 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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5.3.1 
Re-Screening ...................................................................................................55 
5.3.2 
Screen Failures ...............................................................................................56 
5.4 
Strategies for Recruitment and Retention .........................................................56 
5.4.1 
Co-Enrollment Guidelines.............................................................................56 
6 
STUDY INTERVENTION ......................................................................................57 
6.1 
Study Intervention(s) Administration ................................................................57 
6.1.1 
Study Intervention Description ....................................................................57 
6.1.2 
Dosing and Administration ...........................................................................57 
6.2 
Preparation/Handling/Storage/Accountability .................................................59 
6.2.1 
Acquisition and Accountability ....................................................................59 
6.2.2 
Formulation, Appearance, Packaging, and Labeling .................................60 
6.2.3 
Product Storage and Stability .......................................................................60 
6.2.4 
Preparation .....................................................................................................61 
6.3 
Measures to Minimize Bias: Randomization and Blinding..............................62 
6.3.1 
Randomization ...............................................................................................62 
6.3.2 
Un-blinding .....................................................................................................62 
6.4 
Study Intervention Compliance ..........................................................................63 
6.5 
Concomitant Therapy ..........................................................................................63 
6.5.1 
Required Medications ....................................................................................63 
6.5.2 
Prohibited Medications .................................................................................63 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ...............................................................64 
7.1 
Discontinuation of Study Intervention ...............................................................64 
7.1.1 
Premature Treatment Discontinuation Evaluations...................................64 
7.1.2 
Discontinuation of Antiretroviral Therapy .................................................65 
7.2 
Participant Discontinuation/Withdrawal from the Study ...............................65 
7.2.1 
Enrolled Participants, who are Not Randomized and Do Not Start Study 
Treatment .......................................................................................................65 
7.2.2 
Evaluations for Randomized Participants Who Do Not Start Study 
Treatment .......................................................................................................66 
7.2.3 
Evaluations for Randomized Participants Who Received Study Product 
and are Discontinued or Withdrawn from Study Participation ................66 
7.2.4 
Participant May Withdraw or be Withdrawn from the Study..................66 
7.3 
Premature Study Discontinuation (D/C) Evaluations ......................................67 
7.4 
Lost to Follow-Up .................................................................................................67 
8 
STUDY ASSESSMENTS AND PROCEDURES ...................................................67 
8.1 
Exclusion Efficacy Assessments ..........................................................................67 
8.1.1 
Remote Data Collection .................................................................................67 
8.1.2 
Visit windows ..................................................................................................67 
8.1.3 
Medical History ..............................................................................................68 
8.1.4 
Medication History ........................................................................................69 
8.1.5 
Clinical Assessments ......................................................................................70 
8.1.6 
Laboratory Studies ........................................................................................72 
8.1.7 
Research Assays .............................................................................................72 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
Confidential
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8.2 
Safety and Other Assessments ............................................................................73 
8.2.1 
Screening .........................................................................................................73 
8.2.2 
Participant Enrollment ..................................................................................73 
8.2.3 
Leukapheresis .................................................................................................74 
8.2.4 
Randomization ...............................................................................................75 
8.2.5 
Study Unblinding ...........................................................................................75 
8.2.6 
Unscheduled Visits .........................................................................................76 
8.2.7 
Vaccine and Placebo Administration Visit ..................................................76 
8.2.8 
Administration of study vaccine/Post Vaccine/Injection management .....76 
8.2.9 
Post Vaccination Symptom Diary.................................................................77 
8.2.10 
Solicited AE Assessments ..............................................................................77 
8.2.11 
Severity Assessment of Solicited AEs ...........................................................77 
8.2.12 
End of Study ...................................................................................................78 
8.2.13 
Vaccination Information Card .....................................................................78 
8.2.14 
Laboratory Evaluations.................................................................................78 
8.3 
Adverse Events and Serious Adverse Events ....................................................80 
8.3.1 
Definition of Adverse Events (AE) ...............................................................81 
8.3.2 
Definition of Serious Adverse Events (SAE) ...............................................81 
8.3.3 
Definition of Medically Attended Adverse Events (MAAEs) ....................82 
8.3.4 
Definition of Adverse Events of Special Interest (AESIs) ..........................82 
8.4 
Time Period and Frequency for Collecting AE and SAE Information...........83 
8.4.1 
Classification of an Adverse Event ...............................................................83 
8.4.2 
Time Period and Frequency for Event Assessment and Follow-Up .........84 
8.4.3 
Clinical Laboratory Assessments: ................................................................86 
9 
CLINICAL MANAGEMENT .................................................................................87 
9.1 
Toxicities ...............................................................................................................87 
Table 21  
Expedited Reporting Guidelines .............................................................88 
9.1.1 
Grade 1 and Grade 2 Toxicities ....................................................................90 
9.1.2 
Grade 3 and Grade 4 Toxicities ....................................................................90 
9.2 
AESI ......................................................................................................................91 
9.2.1 
Potential blood clots AESIs and Thrombosis with Thrombocytopenia 
Syndrome (TTS) .............................................................................................91 
9.2.2 
Potential Neurological AESIs........................................................................92 
9.2.3 
Delayed Dose...................................................................................................93 
9.2.4 
Consideration for SARS-CoV-2 Pandemic ..................................................93 
9.3 
Adverse Event Reporting ....................................................................................93 
9.3.1 
Local or Systemic Reactions to Vaccine/Placebo Injections ......................94 
9.3.2 
Allergic or Hypersensitivity Reactions.........................................................95 
9.3.3 
Monitoring HIV RNA levels .........................................................................95 
9.4 
Serious Adverse Event Reporting.......................................................................95 
9.5 
AESI reporting .....................................................................................................97 
9.6 
Other Reporting Situations .................................................................................97 
9.6.1 
Reporting to DAIDS ......................................................................................97 
9.6.2 
Reporting Events to Participants .................................................................97 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Page 8 of 143
 
9.6.3 
Reporting of Pregnancy .................................................................................98 
9.6.4 
Pregnancy Outcomes and Reporting ...........................................................98 
9.6.5 
Product Quality ..............................................................................................99 
9.7 
New Safety Information ......................................................................................99 
9.7.1 
Definition of New Safety Information (NSI) ................................................99 
9.8 
NSI Reporting.....................................................................................................100 
9.9 
Reporting NSI to Participants ..........................................................................101 
10 STATISTICAL CONSIDERATIONS ..................................................................101 
10.1 
Statistical Hypotheses ........................................................................................101 
10.2 
Endpoints ............................................................................................................101 
10.3 
Sample Size Determination ...............................................................................101 
10.4 
Procedure for missing and invalid data ...........................................................102 
10.5 
Study Duration and Accrual .............................................................................102 
10.6 
Randomization ...................................................................................................102 
10.7 
Statistical Analyses.............................................................................................103 
10.7.1 
General Approach ........................................................................................103 
10.7.2 
Analysis of the Primary Safety Endpoint(s) ..............................................103 
10.7.3 
Analysis of the Secondary Safety Endpoints .............................................103 
10.7.4 
Analysis of Secondary Immunogenicity Endpoints ..................................104 
10.7.5 
Safety Analyses .............................................................................................105 
10.7.6 
Baseline Descriptive Statistics .....................................................................106 
10.7.7 
Planned Interim Analyses ...........................................................................106 
10.7.8 
Tabulation of Individual participant Data ................................................106 
10.7.9 
Exploratory Analysis ...................................................................................106 
11 SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..............................................................................................107 
11.1 
Regulatory, Ethical, and Study Oversight Considerations ............................107 
11.1.1 
Informed Consent Process ..........................................................................107 
11.1.2 
Study Discontinuation and Closure ............................................................107 
11.2 
Confidentiality ....................................................................................................108 
11.2.1 
Confidentiality and Privacy ........................................................................108 
11.2.2 
Certificate of Confidentiality ......................................................................109 
11.3 
Future Use of Stored Specimens and Data ......................................................109 
11.4 
Key Roles and Study Governance ....................................................................110 
11.5 
Safety Oversight .................................................................................................110 
11.5.1 
Safety Pause ..................................................................................................111 
11.6 
Clinical Monitoring ............................................................................................111 
11.6.1 
Clinical Monitoring Procedures .................................................................112 
11.6.2 
Quality Assurance and Quality Control ....................................................112 
11.6.3 
Data Handling and Record Keeping ..........................................................112 
11.7 
Protocol Deviations ............................................................................................113 
11.8 
Publication and Data Sharing Policy ...............................................................113 
11.9 
Conflict of Interest Policy ..................................................................................114 
12 ABBREVIATIONS .................................................................................................115 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Page 9 of 143
 
13 PROTOCOL AMENDMENT HISTORY ............................................................120 
14 REFERENCES .......................................................................................................121 
TABLE OF TABLES 
Table 1 
Vaccines Vectored by Engineered Simian Adenovirus ChAdOx1 ......21 
Table 2 
Vaccines Vectored by Poxvirus Modified Vaccinia Virus Ankara .....22 
Table 3 
Characteristics of individual HIVconsvX immunogens .......................25 
Table 4 
Summary of Safety Data for Recombinant ChAdOx1 Studies at 5 x 1010 
Virus Particles ..........................................................................................29 
Table 5  
Adverse reactions reported following vaccination with AZD1222 COVID-19 
Vaccine1 .....................................................................................................32 
Table 6 
Safety Data for selected Recombinant MVA Studies expressing HIV 
immunogens, given IM at 1-2 x 108 vpu .................................................35 
Table 7 
Summary of M&M Trial Safety data.....................................................35 
Table 8 
Summary of Safety Data for vaccination with a ChAdOx11 prime followed by 
MVA boost2...............................................................................................36 
Table 9 
Common Local Reactions........................................................................37 
Table 10 
Common Systemic Reactions ..................................................................37 
Table 11 
Local Reactions to MVA vaccine ............................................................39 
Table 12 
Systemic Reactions to MVA vaccine ......................................................40 
Table 13 
Objectives and Endpoints for the Clinical Study ..................................43 
Table 14 
Study Randomization ..............................................................................45 
Table 15 
Vaccine Doses ...........................................................................................47 
Table 16 
Adequate Organ Function Values for Inclusion ...................................52 
Table 17  
Study Treatment Administration ...........................................................58 
Table 18 
Medication Complete History or Timeframe ........................................70 
Table 19 
Blood Volumes Associated with Study Visits ........................................80 
Table 20 
Criteria for Grading the Severity of an AE ...........................................83 
Table 21  
Expedited Reporting Guidelines .............................................................88 
Table 22 
Key Roles for Clinical Study .................................................................110 
TABLE OF FIGURES 
Figure 1 
Overview of HIVconsvX Vaccine Immunogens ....................................23 
Figure 2 
Immunogenicity Data from the M&M Study ........................................24 
TABLE OF APPENDICES 
Appendix 1 
Rationale for Protocol Version 3.0 .......................................................136 
Appendix 2 
Assessment for Post C62 and C1C62 Vaccine Adverse Reactions ....138 
Appendix 3 
 SARS-CoV-2 Pandemic Considerations .............................................139 
Appendix 4  Neurology Testing ..................................................................................141 
Appendix 5  Diagnosis and Management ..................................................................142 
Appendix 6  MedDRA Preferred Terms (PTs) for TTS ..........................................143 
 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Page 10 of 143
 
 
STATEMENT OF COMPLIANCE 
The conduct of this clinical trial will be in accordance with International Conference on 
Harmonization Good Clinical Practice (ICH GCP) and the following: 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR 
Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812) 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training. 
The Institutional Review Board (IRB) will review and approve the protocol, informed consent 
form(s), recruitment materials, and all participant materials submitted. Approval of both the 
protocol and the consent form must be obtained before any participant is enrolled. Any 
amendment to the protocol will require review and approval by the IRB before the changes are 
implemented to the study. In addition, all changes to the consent form will be IRB-approved; a 
determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form. 
 
 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
Confidential
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1  PROTOCOL SUMMARY 
1.1 
Synopsis  
Title: 
IGHID 12107 - A Phase I Study to Evaluate the Safety and Immunogenicity 
of the ChAdOx1.HIVconsv62 - MVA.tHIVconsv4 (C62-M4) or, 
ChAdOx1.tHIVconsv1+C62 - MVA.tHIVconsv3+M4 (C1C62-M3M4) 
Prime-Boost Regimens in Persons with HIV-1 Suppressed on Antiretroviral 
Therapy – The CM (HIV-CORE 008) Study 
 
Study 
Description: 
Phase 1, double blind, randomized, placebo-controlled, parallel design study 
to evaluate the safety and immunogenicity of vaccines C62 followed by M4 
or C62 and C1 together (C1C62) followed by M4 and M3 together (M3M4). 
Serial vaccination will be denoted as C62-M4 or C1C62-M3M4. 
 
Hypotheses:  
Intramuscular (IM) vaccination with C62-M4 or C1C62-M3M4 in persons 
with HIV-1 (PWH) on suppressive antiretroviral therapy (ART) will be safe 
and increase HIV-1-specific T cell responses targeting conserved regions of 
HIV-1.  
Administration of C1C62-M3M4 will result in a greater increase in the 
breadth of HIV-1-specific T cells targeting conserved regions of HIV-1 than 
C62-M4. 
Objectives: 
 
Primary Objective:  
Evaluate the safety of vaccination with i) C62-M4 and ii) C1C62-M3M4 in 
PWH on ART through 28 days after the last vaccination or placebo.  
 
Secondary Objectives: 
1. Evaluate the safety of vaccination through the end of study 
2. Compare the within-participant relative change in magnitude of 
HIV-1-specific T cell responses following vaccination with C62-M4 or 
C1C62-M3M4. 
3. Compare the between-arm change in breadth of HIV-1-specific T cell 
responses following vaccination C62-M4 or C1C62-M3M4. 
 
 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Page 12 of 143
 
Other Objectives: 
1. Compare the change in function and phenotype of HIV-1-specific T cell 
responses in participants from pre-vaccination to post-vaccination with 
C62-M4 or C1C62-M3M4. 
2. Evaluate the kinetics of immunologic responses in participants post-
vaccination with C62-M4 or C1C62-M3M4. 
3. Evaluate the kinetics of CD8+ T cell mediated HIV inhibition pre- and 
post-vaccination following vaccination with C62-M4 or C1C62-M3M4. 
4. Explore cellular activation of total CD4+ and CD8+ T cells pre- and post-
vaccination with C62-M4 or C1C62-M3M4. 
5. Explore the impact of vaccination with C62-M4 or C1C62-M3M4 on 
low-level plasma viremia.  
6. Explore the impact of vaccination with C62-M4 or C1C62-M3M4 on 
cell-associated HIV RNA in CD4+ T cells. 
7. Explore the impact of vaccination with C62-M4 or C1C62-M3M4 on 
total HIV DNA in CD4+ T cells 
8. Assess the long-term safety and tolerability of vaccination with C62-M4 
and C1C62-M3M4 
Study 
Population: 
PWH, inclusive of men and women ≥ 18 and ≤ 70 years of age and all 
ethnicities, with viral suppression on ART and a CD4 cell count ≥ 350 
cells/mm3 at screening. 
Phase: 
Phase 1  
Description 
of Sites 
Enrolling 
Participants: 
The University of North Carolina, Chapel Hill, North Carolina, USA 
Duke University Health System, Durham, North Carolina, USA 
 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Description 
of Study 
Intervention 
Double blind, randomized, placebo-controlled, parallel design study in which 
18 participants with durable viral suppression are randomly assigned to 
receive vaccination with:  
1. C62 followed by M4  
2. C1C62 combined followed by M3M4 combined, or  
3. Placebo (normal saline)  
Participants will be randomized 8:8:2 to one of three study arms, and receive 
study treatment or placebo at Days 0 and 28.  
A maximum of 2 participants will receive the Day 0 vaccination per week. 
Study Schema 
Arm 
N Day 
Treatment 
Total 
Dose 
(vp) 
Route 
Day 
Treatment 
Total 
Dose 
(pfu) 
Route 
1 
8 
0 
C62 
5×1010 
IM 
28 
M4 
1.8×108 
IM 
2 
8 
0 
C1C62* 
5×1010 
IM 
28 
M3M4# 
1.9×108 
IM 
3 
2 
0 
Placebo◊ 
- 
IM 
28 
Placebo◊ 
- 
IM 
C6= ChAdOx1.HIVconsv62 (mosaic 2) 
C1 = ChAdOx1.tHIVconsv1 (mosaic 1) 
M4 = MVA.tHIVconsv4 (mosaic 2) 
M3 = MVA.tHIVconsv3 (mosaic 1) 
vp = virus particles 
pfu = plaque forming units  
IM = intramuscular 
*2.5×1010 vp, each vaccine 
# 0.9×108 pfu M4; 1.0×108 pfu M3 
◊ normal saline 
Primary 
Endpoint 
Statistics 
 
  
If zero of 8 participants experience a safety event, a 95% 1-sided exact 
binomial upper confidence limit for the probability of a safety event will be 
31%. If one participant experiences a safety event, the corresponding 95% 
1-sided upper confidence limit will be 47%. Each safety endpoint will be 
estimated with an exact binomial 95% 1-sided upper confidence limit. If no 
safety events are observed in the two vaccine arms and data is pooled across 
arms (n=16), then the upper limit of the exact, 1-sided 95% confidence 
interval will be 0.17.  

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Page 14 of 143
 
Study 
Duration 
The study will take approximately 2.0 years from the time the study opens to 
enrollment until completion of data analyses. 
Participant 
Duration: 
 
Each participant will complete the study in approximately 36 weeks (9 
months). 

16.1.1 Protocol 
IGHID-12107 - The CM (CORE008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ ChAdOx1.tHIVconsv1 boosted with 
M4+MVA.tHIVconsv3 (M3)  
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1.2 
Schema 
DAY 0 
Screen         Enroll     Baseline 
          Day 28                   D56               D84             D140            D196
Baseline Clinical and
Research Labs 
Continues ART Therapy 
Leukapheresis
Leukapheresis
Enrollment → Day 0
Vaccination
Arm 2 
M4 + M3
n=8
Arm 3 
Placebo
n=2
Continues ART Therapy
Arm 1 
M4
n=8
Randomization 
& Vaccination 
Arm 1 
C62
n=8
Arm 3
Placebo
n=2
Arm 2
C62 + C1
n=8

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Page 16 of 143
 
 
1.3 
Schedule of Activities (SoA)  
 
Screening 
 
Enrollment and 
Baseline  
Day 0             
Vaccination 
Day 2 
Day 7 
Day 14 
Day 28            
Vaccine Booster 
Day 30 
Day 35 
Day 42 
Day 56 
Day 84 
Day 140 
Day 196              
EOS 
D = days      
W = weeks 
D-60 
 
0 
 
W1 
W2 
W4 
 
W5 
W6 
W8 W12 W20 
W28 
Visit window  
 
≤ 60 D 
Visit 1 
≤ 10 D 
Visit 2 
 
 
+/-  
2 D 
+/-  
2 D 
 
 
+/- 
2 D 
 +/-   
2 D 
+/-    
7 D 
+/-      
7 D 
+/-   
14 D 
Visit  
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
Clinical Procedures  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility and 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Locator Information 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PID Assignment  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
SID Assignment  
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
RID Assignment 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical and 
Medication History  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete PE 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Targeted PE  
 
 
X 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
Vital Signs (VS) 
X 
X 
X 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
Height  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review ART 
Adherence 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Targeted Reproductive 
History 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Updated Medical 
History  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
medication review and 
update 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
Confidential
Page 17 of 143
 
 
 
Screening 
 
Enrollment and 
Baseline  
Day 0             
Vaccination 
Day 2 
Day 7 
Day 14 
Day 28            
Vaccine Booster 
Day 30 
Day 35 
Day 42 
Day 56 
Day 84 
Day 140 
Day 196              
EOS 
Assess AEs 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assess SAEs, MAAEs 
and AESIs 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Study Treatment or 
Placebo 
 
 
X 
 
 
 
X 
 
 
 
 
 
 
 
Post-vaccine 
assessment  
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Complete post-vaccine 
symptom diary 
 
 
 
X 
X 
 
 
X 
X 
 
 
 
 
 
Telephone Assessment1  
 
 
 
X 
 
 
 
X 
 
 
 
 
 
 
Leukapheresis 
 
X2 
 
 
 
 
 
 
 
 
X3 
 
 
 
Clinical Laboratory  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CBC with differential 
X 
X 
 
 
X 
X 
 
 
X 
 
X 
X 
X 
X 
Chemistries 
X 
X 
 
 
X 
X 
 
 
X 
 
X 
 
X 
X 
Serum Pregnancy test  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine Pregnancy – 
POCT - WOCBP only 
 
 
X 
 
 
 
X 
 
 
 
 
 
 
 
Coagulation Tests 
(PT/INR/ APTT)  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV Ag/Ab Test  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
CD4+/CD8+ T Cell 
Differential Panel  
X 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
HIV-1 RNA PCR  
X 
 
 
 
X 
 
X 
 
X 
 
 
 
 
X 
RPR 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
HBsAg & HCV Ab 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
PF4 antibody ELISA 
(serum) 
 
X4 
 
 
 
 
 
 
 
 
 
 
 
 
COVID-19 RT-PCR 
(nasal swab) 
 
X 
X 
 
 
 
X 
 
 
 
 
 
 
 
Research Laboratory  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HLA Typing  
 
X 
 
 
 
 
 
 
 
 
 
 
 
 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Page 18 of 143
 
 
 
Screening 
 
Enrollment and 
Baseline  
Day 0             
Vaccination 
Day 2 
Day 7 
Day 14 
Day 28            
Vaccine Booster 
Day 30 
Day 35 
Day 42 
Day 56 
Day 84 
Day 140 
Day 196              
EOS 
CMV and EBV Test  
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
COVID-19 Antibody 
Test  
 
X5 
X5 
 
X5 
X5 
X5 
 
X5 
X5 
X5 
 
X5 
 
Plasma and PBMC for 
Immunologic and 
Virologic Studies  
X 
X6 
X 
 
X 
X 
X 
 
X 
X 
X 
X7 
X 
X 
Table Legend 
1 See Appendix 2 detailing additional telephone assessments at Days 5, 10, 18 and 22. 
2 Leukapheresis should be scheduled as close to the screening visit as feasible.  
3 See Section 8.1.2. 
4 Collect and store sample at enrollment. All other testing (if required) will be performed in real time. 
5 Test only retrospectively from stored plasma if immune response data suggest need. 
6  Collect separate research PBMCs samples at Enrollment.  
7 Collect sample only if participant completed Day 56 leukapheresis.  If participant completed large blood draw 
instead of leukapheresis, do not collect sample. 
AE=adverse events; AESI = AE of special interest; EOS = end of study; MAAE = medically attended AE; 
PE=physical exam; PID=participant ID; POCT=point of care test; RID=randomization ID; SAE=serious AE; 
SID=study ID; WOCBP=woman of childbearing potential 
 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Page 19 of 143
 
 
2 INTRODUCTION 
2.1 
Study Rationale  
ART has transformed human immunodeficiency virus type 1 (HIV) from a fatal disease to a 
chronic condition for the 37 million PWH. However, ART must be taken life-long as interruption 
of therapy in PWH mostly results in viral rebound within weeks (1-4). This rebound results from 
cells harboring HIV proviral DNA that is integrated into the host genome. While >95% of 
proviral DNA is replication-incompetent, the remaining fraction that we define as the ‘HIV 
reservoir’, retains the capacity to produce infectious virus particles, either stochastically (5-8), or 
through interventions to induce coordinated reactivation (9-12). The HIV reservoir is highly 
stable, with an estimated half-life of 44 months (13, 14). Natural decay of the HIV reservoir 
would take >70 years. Therefore, to enable PWH to cease ART, additional strategies are 
required. 
Current strategies permitting PWH to stop ART without viral rebound aim to either eliminate all 
HIV-1 infected cells harboring persistent, replication-competent virus (HIV eradication), or to 
achieve a state of durable HIV-1 suppression without rebound (HIV remission). Both approaches 
could harness CD8+ T cell immunity to achieve reservoir reduction or elimination. Clearance of 
reactivated, HIV infected cells by CD8+ T cells has been demonstrated with in vitro studies (15, 
16). These observations are consistent with the extensively documented role of CD8+ T cells in 
control of HIV in untreated infection (17-24), as well as more recent studies suggesting CD8+ T 
cells contribute to control of HIV reactivation and/or virus rebound (25-27). 
The frequency and quality of memory T-cells induced by vaccination are to a large extent 
determined by the vaccine vectors and modalities employed to deliver the HIV-derived 
immunogens (28-31). While live, replication-competent virus vectors elicit more vigorous 
immune responses (32), their immunogenicity has to be balanced with safety. Like replicating 
vaccines, non-replicating vaccines deliver the immunogen to the major histocompatibility 
complex (MHC) class I presentation pathway either directly or by cross-presentation, (33-35) 
however, no infectious vaccine progeny are produced (36). This increase in safety does lessen 
immunogenicity (37, 38) that cannot be easily enhanced by repeated boosts with the same 
vaccine, because of a build-up of anti-vector immunity, particularly humoral immunity, which 
dampens insert-specific T-cell induction (39, 40).   
Serial vaccinations are an established approach to increase the frequency of vaccine-induced 
immune responses. In both pre-clinical and clinical testing, heterologous vaccination with 
different viral vectors expressing common or highly related immunogens has been consistently 
demonstrated to induce higher frequencies of T cells against the immunogen than homologous 
vaccination with the same viral vector (41-46). Previous studies have shown that vaccination 
with rChAdV followed by rMVA consistently induces high frequencies of T cells against the 
vaccine immunogen; this includes studies in HIV seropositive and seronegative participants.  
The goal of this clinical study is to increase the frequency of circulating CD8+ T cell responses 
against HIV in PWH on ART. This will be achieved by vaccination with heterologous, 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Page 20 of 143
 
 
attenuated viral vectors expressing highly related HIV immunogens spanning conserved regions 
of the virus. 
2.2 
Background 
2.2.1 
T Cell Correlates and HIV Control 
HIV-specific CD8+ T cells contribute to control of HIV in untreated PWH, however the level of 
contribution across individuals is highly variable. A small minority of PWH are able to maintain 
long-term control of HIV (<50 copies/ml) without ART (47). Certain MHC Class I alleles such 
as B*27:05, B*57:01 and B*81:01 are highly overrepresented in these ‘elite-controllers’. HIV 
elite controllers maintain high frequencies of HIV-specific CD8+ T cells that are broadly 
functional, including mediating strong in vitro suppression of HIV-infected CD4+ T cells. Large 
cohort studies have consistently observed an inverse correlation between higher breadth (number 
of epitopes targeted) of IFN-γ producing CD8+ T cells targeting the HIV Gag protein measured 
by ELISpot assay and virus load in untreated individuals (48). These studies in humans are 
supported by studies of SIV in non-human primates in which CD8+ T cell depletion have defined 
a clear contribution of CD8+ T cells, particularly those targeting Gag, against HIV.  
Virus escape from CD8+ T-cell immune pressure is a major and highly successful immune 
evasion mechanism for HIV-1 and the resulting HIV-1 genetic variability constitutes the biggest 
roadblock for HIV vaccine development. In natural infection, mutations in and around T cell 
epitopes emerge within weeks of primary T cell responses, limiting CD8+ T cell detection and 
clearance of virus-infected cells (21). Virus escape occurs are different rates and at different 
regions across the HIV proteome. This is largely because different HIV proteins have different 
levels of tolerance of mutations. Envelope and regions of Nef tolerate higher levels of virus 
mutation than Gag and Pol proteins. HIV fitness is associated with sequence variation (22). More 
conserved mutations in Gag and Pol are more likely to induce fitness costs in the virus (49). The 
higher level of Gag conservation is consistent with the observed association between T cell 
targeting of Gag and lower HIV viremia.  
An additional challenge is that T cell responses targeting structurally/functionally conserved 
regions of HIV-1 proteins are often subdominant relative to T cells targeting highly variable 
regions such as Env. Circulating T cells in PWH on ART are no exception. Mapping of HIV-
specific T cell responses in PWH on ART by our group and others found very similar patterns of 
T cell targeting to untreated infection (50).  Specifically, CD8+ T cells consistently target Gag 
but also highly variable regions in Env and Nef. Of note, in these studies, we also observed that 
PWH on ART had a higher proportion T cells targeting Pol.  
While ART prevents virus escape, the persistent HIV reservoir in PWH ‘archives’ previous virus 
escape mutations (50, 51). Deep sequencing of replication-competent HIV-1 recovered from 
resting CD4+ T cells in durably suppressed individuals found that, similar to untreated infection, 
approximately one in three circulating T cells harbor escape variants in the HIV reservoir (52).  
Following virus reactivation (e.g. after treatment interruption), these escape mutations likely 
limit the effectiveness of circulating HIV-specific T cell responses.  An important observation 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
Confidential
Page 21 of 143
 
 
from these studies was that virus escape occurred less frequently in low entropy or more 
conserved regions of HIV (50, 51). These observations indicate that, while T cell escape occurs 
in the replication competent HIV reservoir, it is not ubiquitous and some CD8+ T cell 
populations still effectively detect and clear virus infected cells, consistent with the sustained 
functionality of HIV-specific CD8+ T cells observed over time (53). The implications of these 
data for HIV-1 cure strategies is an optimal vaccine regimen will need to preferentially boost T-
cell responses from which there is no pre-existing escape and/or induce strong de novo CD8+ T-
cell responses. 
Altogether, these data indicate HIV vaccine regimens in PWH should (re)focus T-cell responses 
on the protective, structurally/functionally conserved regions of HIV-1 proteins, which are often 
subdominant.  
2.2.2 
Overview of the Vaccines 
Simian adenovirus-vectored ChAdOx1.tHIVconsv1 (C1) and ChAdOx1.HIVconsv62 (C62) 
vaccines (Table 1) have been designed to be given serially with replication-deficient poxvirus 
Modified vaccinia virus Ankara (MVA)-vectored vaccines MVA.tHIVconsv3 (M3) and 
MVA.tHIVconsv4 (M4) vaccines (Table 2). All vaccines express highly-related HIV-derived 
conserved immunogens designed to maximize vaccine immunogenicity, maximize coverage of 
HIV viral diversity and minimize the effects of viral escape.  
Table 1 
Vaccines Vectored by Engineered Simian Adenovirus ChAdOx1 
Vaccine 
Manufacturer 
Description 
ChAdOx1.tHIVconsv1 
(C1) 
ADVAXIA 
BIOLOGICS 
SRL1 
The ChAdOx1.tHIVconsv1 vaccine Drug Product has a genome size 
of 32,906 bp and is a slightly opaque frozen liquid, essentially free 
from visible particulates. The appearance is dependent upon the 
concentration of the virus.  
ChAdOx1.HIVconsv62  
(C62) 
ADVAXIA 
BIOLOGICS 
SRL1 
The ChAdOx1.HIVconsv62 vaccine Drug Product has a genome size 
of 32,846 bp and is a slightly opaque frozen liquid, essentially free 
from visible particulates. The appearance is dependent upon the 
concentration of the virus.  
1Manufacturing authorization MIA aM42/2018, ADVAXIA BIOLOGICS SRL, Via Pontina Km 30.600-00071 
Pomezia, Italy 
 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Table 2 
Vaccines Vectored by Poxvirus Modified Vaccinia Virus Ankara 
Vaccine 
Manufacturer 
Description 
MVA.tHIVconsv3 
(M3)  
IDT Biologika 
GmbH (IDT)1 
The MVA.tHIVconsv3 vaccine Drug Product a genome size of 
approximately 181, 000 bp and is a white to light brownish opaque 
homogeneous suspension. 
MVA.tHIVconsv4 
(M4)  
IDT Biologika 
GmbH (IDT)1 
The MVA.tHIVconsv4 vaccine Drug Product a genome size of 
approximately 181, 000 bp and is a white to light brownish opaque 
homogeneous suspension. 
1Manufacturing authorization DE-ST-01_MIA_2016_0017/604.41501.A.18 Dessau-Rosslau, Germany 
2.2.3 
The Immunogens 
2.2.3.1 
Rationale for Design of HIVconsvX 
HIVconsvX is was designed in silico using full-genome sequences of group M HIVs in the Los 
Alamos National Laboratory HIV Sequence Database (LANL-HSD), as of September 2013 (54). 
HIVconsvX is comprised of six conserved regions of the Gag (region 1 and 2) and Pol (regions 
3-6) of HIV computed into two complementary amino acid sequences, Mosaic-1 and Mosaic-2 
(Figure 1A). Mosaic-1 and -2 differ in about 10% of amino acids and between them, maximize 
the match of the vaccine to the global circulating HIV-1 isolates (Figure 1B). Each of the four 
vaccines in this study uses a different order of the six conserved regions to minimize induction of 
T cell responses to potential newly formed and, therefore, irrelevant non-HIV epitopes generated 
by joining two adjacent regions together (Figure 1C). 
The six regions in Gag and Pol in HIVconsvX contain a high number of previously identified 
CD8+ T cell epitopes against HIV, restricted by 84 different HLA I alleles (54). These regions 
maximize epitopes associated with control of HIV viremia and minimize epitopes associated 
with poor HIV control (55). The conserved nature of these regions not only increase the 
likelihood of a match between the immunogens and infecting virus/es but also decreases the 
effects of virus escape, including pre-existing escape in the HIV reservoir (52).  
The potential immunogenicity and efficacy of HIVconsvX has been tested in cohort studies. First 
in a cohort of treatment naïve PWH, higher magnitude and breadth of CD8+ T-cell responses 
reactive to HIVconsvX-derived peptides correlated with higher CD4+ T-cell count and lower 
viral load (54). More recently, our group used empirical methods to identify whether virus 
variants in the HIV reservoir could escape circulating T cell responses in PWH on ART. Epitope 
mapping and HIV sequencing of a cohort of 25 PWH on ART, found that 32% of T cell epitopes 
harbored escape variants in the HIV reservoir (50). On average, participants’s T cells targeted 3 
epitopes within HIVconsvX (0-6), suggesting that therapeutic vaccination of HIVconsvX will 
successfully increase circulating HIV-specific T cell responses (50).  Importantly, T cell escape 
in regions corresponding to HIVconsvX was 2.5-fold lower than escape outside of the 
immunogen (15.3% vs 43.5%) (50).   

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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These data are consistent with observations to date in the ongoing Phase I M&M Study 
examining the safety and immunogenicity of M3 and M4 vaccines given alone or in combination 
in PWH on ART (NCT03844386). The M&M study closed to enrolment in December 2021 and 
blinded safety data are summarized in Section 2.2.6.2. T cell responses to HIVconsvX, mosaic-1 
and mosaic-2 immunogens have been measured in 16 participants to date. Blinded results 
consistent increase in T cell breadth to peptides spanning either the Mosaic-1 or Mosaic-1 
immunogens following vaccination.  In 12 of 16 participants, T cell magnitude also increased ≥ 
2-fold following vaccination when compared to baseline (average of pre-vaccination visits) 
(Figure 2).  
Figure 1 
Overview of HIVconsvX Vaccine Immunogens  
 
(A) The HIVconsvX immunogens are comprised of six (1-6) conserved regions of HIV. (B) The vaccine design is 
bivalent, consisting of Mosaic-1 (872aa) and Mosaic-2 (872aa) immunogens that together increase the vaccine 
match to all the circulating HIV strains globally. (C) The regions in each Mosaic were re-ordered to generate four 
immunogens that were inserted into vaccines, C1, C62, M3 and M4. The goal of the re-ordering is to minimize 
exposure of participants to non-natural junctions between HIV regions. t= tPA-leader sequence in C1, M3 and M4, 
Pk= a C-terminal mAb tag, which facilitates protein detection in C62, black arrow= inversion of sections 1-103 aa 
and 104-231 aa of region 1(p24 Gag) in HIVconsv62 
 
 
Pol
Six highly functionally conserved regions of the HIV-1 proteome
Computed bi-valent mosaic
Mosaic 1
Mosaic 2
Mosaic 2
Reshuffled regions for synthetic immunogen genes
Gag
1
3
2
6
4
5
1
3
2
6
4
5
1
2
3
5
6
t
tHIVconsv1
1
2
6
t
4
5
3
tHIVconsv3
tHIVconsv4
HIVconsv62
1
3
4
5
6
1
2
3
4
5
6
3
4
5
6
t
t
1
2
3
5
6
1
2
t
Pk
4
2
1
1
2
Pk
C1
C62
M3
M4
6
5
4
3
90.4% 
sequence
identity
A.
B.
C.

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Figure 2 
Immunogenicity Data from the M&M Study 
 
 
 
 
 
PWH on ART received a single vaccination of M3, M4, M3+M4, or placebo in a 7:7:7:2 distribution. (A) T cell 
responses to the HIV immunogens, Mosaic-1 (M3) and Mosaic-2 (M4) and to Env, Nef and Acc (Rev, Vif, Vpr, 
Vpu, Tat) proteins not found in the vaccine immunogen in one participant. (B) T cell responses to peptides spanning 
Mosaic-1 (M3) or Mosaic-2 (M4) were measured pre- and post- the vaccination visit.  Analysis of unblinded datas 
suggests that vaccination increased in T cell breadth to vaccine immunogens (C) Twelve of 16 participants show a 
≥2 increase in T cell response to either or both mosaic immunogens at D7 post-vaccination.  
2.2.3.2 
Individual Immunogens 
tHIVconsv1 was inserted into ChAdOx1 to generate the C1 vaccine. The tHIVconsv1 
immunogen uses Mosaic-1 and the regions are ordered as 1-2-3-4-5-6. tHIVconsv1 does not 
harbor a Pk tag described in (Table 3). tHIVconsv3 contains a human tissue plasminogen 
activator leader sequence (tPA-LS) described in Section 2.2.3.3.  
tHIVconsv3 was inserted into MVA to generate the M3 vaccine. The tHIVconsv3 immunogen 
was generated using Mosaic-1 sequences. tHIVconsv3 differs from tHIVconsv1 only in the 
order of its 6 conserved regions which are 3-6-2-5-1-4 (Table 3). tHIVconsv3 does not harbor a 
Pk tag described in Section  2.2.3.3. tHIVconsv3 contains a tPA-LS described in Section 2.2.3.3.  
HIVconsv62 was inserted into ChAdOx1 to generate the C62 vaccine. The HIVconsv62 
immunogen uses Mosaic-2 and the regions are ordered as 6-5-4-3-2-1/1. It uses the same amino 
acids and is immunologically equivalent to a previous design HIVconsv6, but uses different 
codons and has a rearranged region 1 (p24 Gag) (Table 3). Also, region 1 (p24, 231 amino acids) 
has been inverted, with sub-region 104-231 now followed by amino acids 1-103. The inverted 
region 1 is identified as 1/1. These changes increased the stability of the immunogen during virus 
propagation (ChAdOx1.HIVconsv62 IB). HIVconsv62 harbors a Pk tag but does not contain a 
tPA-LS. 
The tHIVconsv4 immunogen was generated using Mosaic-2 sequences. The amino acid 
sequence of tHIVconsv4 differs from HIVconsv62 only in the order of its 6 conserved regions 
which are 4-1-5-2-6-3 (Table 3). Region 1 in tHIVconsv4 is not inverted (see Figure 1). 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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tHIVconsv4 does not harbor a Pk tag described in Section 2.2.3.3. tHIVconsv4 contains a 
tPA-LS described in Section 2.2.3.3. 
Table 3 
Characteristics of individual HIVconsvX immunogens 
Immunogen 
Vaccine 
Parent Mosaic 
(M) 
Region Order 
Pk Tag1 
tPA-leader 
sequence1 
tHIVconsv1 
C1 
M-1 
1-2-3-4-5-6 
- 
+ 
tHIVconsv3 
M3 
M-1 
3-6-2-5-1-4 
- 
+ 
HIVconsv62 
C62 
M-2 
6-5-4-3-2-1/1 
+ 
- 
tHIVconsv4 
M4 
M-2 
4-1-5-2-6-3 
- 
+ 
1 +, in vaccine construct; -, not in vaccine construct 
HIVconsv62 differs from the other 3 immunogens in that it is flanked by a C-terminal 
monoclonal antibody epitope Pk (IPNPLLGLD) derived from the P and V proteins of the 
paramyxovirus of simian virus 5 (SV5) family (56). The Pk tag was included to facilitate 
detection of the full-size HIVconsv62 protein expression from the vaccine during manufacture 
and vaccine quality control.  
HIV-MVA and HIV-DNA vaccines harboring the Pk tag were safely administered to 492 HIV-
negative adults, 97 HIV-negative 20-week-old infants and 30 HIV-positive adults (42, 57-59). In 
these studies, no SAEs related to vaccine products were observed in any study participants. 
2.2.3.3 
tPA-LS 
C62 differs from the other 3 immunogens in that it does not contain a human tPA-LS; the ‘t’ in 
the tHIVconsvX nomenclature (Figure 1). The tPA-LS was included in the first three 
immunogens because it had been shown to increase in vitro expression of the vaccine 
immunogen (60). The presumption was that increased expression of the immunogen would 
enhance the immune response following vaccination. However, subsequent work found that the 
tPA-LS only enhances T cell induction for recombinant DNA vaccines (54, 60), not viral-
vectored vaccines (54), and therefore is not included in the generation of C62. 
Note, the prior eight Phase1/2a clinical studies using vector derived from simian adenovirus 
serotype 63 (ChAdV63) and MVA vectors expressing first-generation conserved HIV 
immunogens did not include tPA-LS (reviewed in (61). These studies were conducted in HIV 
seropositive and seronegative participants in Europe and Africa (62-65). In these clinical trials, 
ChAdV63/MVA vaccination induced consistent and strong T-cell responses in people, including 
in PWH on ART (61, 63-70). Murine studies also demonstrated that the inclusion of tPA-LS in 
viral vectors did not lessen immunogenicity in mouse models (54). 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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2.2.4 
The Viral Vectors  
Prime-boost regimens describe sequential vaccination with two different recombinant vaccine 
vectors expressing a common immunogen, an approach which focuses the immune response on 
the common immunogen (71). Prime-boost heterologous regimens have consistently induced 
higher frequencies of T cells against the immunogen than homologous vaccine boosting. This is 
likely because homologous vaccination induces anti-vector immunity, limiting the 
immunogenicity of the boosting vaccination. One of the most promising prime boost 
combinations is a recombinant adenovirus vector (rAdV) prime followed by MVA boost. These 
regimens have demonstrated immunogenicity that has translated across mice, non-human 
primates and humans. Both clinical and animal data clearly show that rAdV/MVA prime-boost is 
more immunogenic than either vaccine alone (64). One limitation with adenoviral vectored 
vaccination is high, pre-existing immunity for some serotypes. Approximately 40% of the US 
population are seropositive for the HAdV-5 serotype, and seropositivity is substantially higher in 
sub-Saharan Africa (72). In response, two approaches have been taken. The first approach 
involves the development of human adenoviral vectors (HAdVs) which are genetically distinct 
from HAdV-5 and against which the prevalence of pre-existing immunity is considerably lower. 
The second approach employed herein, uses recombinant simian adenoviruses (SAdV) against 
which pre-existing human adenovirus immunity has no impact. Animal testing and subsequent 
clinical studies demonstrate that SAdV vectors are almost, if not equally, immunogenic as 
HAdVs (73). 
2.2.5 
Simian adenovirus viral vectors 
Chimpadenoviruses (ChAdV) were developed as vaccine vectors following concerns that 
pre-existing immunity to HAdv serotypes could limit future widespread use of these vaccine 
vectors. ChAdV and HAdV are not phylogenetically distinguishable and fall into the same eight 
adenovirus groups. ChAdOx1 is replication-deficient in vaccinated animals or humans due to 
deletion of the essential E1 gene region. ChAdOx1 can only propagate in cells complementing 
the E1 functions that are used for manufacture (ChAdOx1.HIVconsv62 IB Section 2.1). 
ChAdOx1 is closely related to ChAd63 which has been extensively tested as a vaccine vector 
including as a HIV vaccine in PWH (74).  
Like all adenoviruses, ChAdVs possess a stable genome such that inserts of foreign genes are not 
deleted. ChAdVs and the transgene information remains extra-chromosomal, thus avoiding any 
potential for insertional mutagenesis.  
2.2.5.1 
Generation of C1 and C62 vectors 
Full details of the generation of the C1 and C62 vaccine vectors are provided in 
ChAdOx1.tHIVconsv1 IB, and ChAdOx1.HIVconsv62 IB.  
Description of ChAdOx1.tHIVcons1 (C1) ChAdOx1.tHIVconsv1 vaccine consists of the 
replication-deficient simian adenovirus vector ChAdOx1, which carries a transgene coding for 
the leader sequence of tPA-LS fused to a chimeric protein assembled from 6 conserved regions 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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of the HIV-1 proteome expressed under the control of the CMV promoter. These regions have no 
biological or enzymatic activities and are delivered solely for the purpose of inducing T-cell 
responses. 
Description of ChAdOx1.HIVconsv62 (C62): ChAdOx1.HIVconsv62 vaccine consists of the 
replication-deficient simian adenovirus vector ChAdOx1, which carries a transgene coding for a 
chimeric protein assembled from 6 conserved regions of the HIV-1 proteome expressed under 
the control of the CMV promoter. These regions have no biological or enzymatic activities and 
are delivered solely for the purpose of inducing T-cell responses. 
2.2.5.2 
Clinical Experience with ChAdV-Vectored Vaccines 
Sixteen clinical trials testing nine different ChAdOx1 vaccines have been or are in clinical 
testing (n> 22,000 participants) (ChAdOx1.HIVconsv62 IB Section 6, (75)). This includes 
peer-reviewed data from 12,082 healthy volunteers who received at least one dose of either low 
dose or standard dose ChAdOx1 nCoV-19 vaccine in the COV001 and COV002 clinical trial in 
the United Kingdom (UK) (EudraCT 2020-001228-32), the COV003 trial conducted in Brazil 
(ISRCTN89951424), and the COV005 trial conducted in South Africa reported in (75). Across 
the four clinical trials with 12,021 participants receiving ChAdOx1 nCoV-19 were included in 
safety analyses. Across this group, there were 79 SAEs (0.7%) (Table S6, supplement, (75), <1% 
occurrence of anaphylactic reactions. Only two events were considered possibly related to 
vaccination with ChAdOx1 nCoV-19, including a case of transverse myelitis reported 14 days 
after ChAdOx1 nCoV-19 booster vaccination, which an independent neurological committee 
determined was most likely due to an idiopathic, short segment, spinal cord demyelination. A 
potentially vaccine-related SAE related to fever to 40°C was reported 2 days post-vaccination in 
a participant in South Africa who recovered rapidly without an alternative diagnosis and was not 
admitted to hospital; this participant remains blinded and received a second dose of allocated 
vaccine without a similar reaction. There were two additional cases of transverse myelitis 
originally reported as potentially related but later determined unlikely to be related to vaccination 
by an independent committee of neurological experts. There was one non-COVID-19 death 
reported across the studies in the ChAdOx1 nCoV-19 arm that was considered unrelated to the 
vaccine. 
Safety and some immunogenicity data for recombinant ChAdOx1 vaccines have been reported 
across several clinical trials for 6,596 participants with detailed safety data available for 755 
study participants receiving at least one IM dose of 5×1010 virus particles (vp); the same dose 
and route of vaccination proposed for this CM Study (Section 1.1). Data are summarized in 
Table 4 (76). In these studies, solicited AEs have mostly been mild or moderate with unsolicited 
AEs mostly classed as mild/Grade 1. 
As noted above, ChAdOx1 is highly related to the ChAd63 (=ChAdV63) vector which has also 
undergone extensive clinical testing. Participants (n=1,367) received recombinant ChAd63 
vaccines given IM at a dose of 5x1010 vp, mostly in prime-boost combination with MVA-
vectored vaccines. Vaccination has been safe and well tolerated with no SAEs reported 
(ChAdOx.tHIVconsv1 IB Section 6.5, ChAdOx1.HIVconsv62 IB Section 6).  

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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In summary, recombinant ChAdOx1 vaccines have an established and good safety record in the 
vast majority of humans. Based on this information the Sponsor does not consider toxicology 
testing of C1 or C62 will generate novel safety or reactogenicity to further inform this proposed 
vaccination regimen.  
 
 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Table 4 
Summary of Safety Data for Recombinant ChAdOx1 Studies at 5 x 1010 
Virus Particles 
Country 
Trial 
Vaccine 
Age 
n 
Summary of Results 
UK1 
FLU004 
ChAdOx1 NP+M1 
18-50 
6 
AEs probably associated with vaccination were 
experienced by most vaccinees in the 7 days 
following vaccination. AEs were mostly mild 
and all were self-limiting.  No SAEs were 
reported.  
UK1 
CHIK001 
ChAdOx1Chik 
18-50 
9 
The majority of local and systemic solicited 
AEs were mild or moderate in nature. No SAEs 
were reported. All solicited local and systemic 
AEs resolved within 1-6 days. 
UK1 
MERS001 
ChAdOx1 MERS 
18-50 
9 
AEs probably associated with vaccination were 
all experienced by vaccinees in the 7 days 
following vaccination. Local and systemic AEs 
were mostly moderate and all were self-
limiting. Unsolicited AEs in the 28 days 
following vaccination considered related to 
ChAdOx1 MERS were predominantly mild and 
resolved. No SAEs were reported. 
UK1 
COV001 
ChAdOx1 nCoV-19 
18-55 
543 
AEs probably associated with vaccination were 
experienced by the majority of vaccinees in the 
7 days following vaccination and were mostly 
mild and all self-limiting. Prophylactic 
paracetamol decreased AEs. Unsolicited AEs in 
the 28 days following vaccination considered 
related to ChAdOx1 nCoV-19 were 
predominantly mild/moderate and resolved. No 
SAEs related to ChAdOx1 nCoV-19 were 
recorded. 
10 participants received a second ChAdOx1 
nCoV-19 booster. AEs related to vaccination 
were in the 7 days following booster 
vaccination and were mostly mild and all self-
limiting.  No SAEs related to ChAdOx1nCoV-
19 recorded. 
UK2, 3 
COV002 
ChAdOx1 nCoV-19 
(2·2 × 10¹⁰ vp 
followed by 3·5–6·5 
× 10¹⁰ vp 
or MenACWY) 
18-55 
56-69 
≥70 
50 
30 
46 
No severe local symptoms were reported. No 
SAEs related to ChAdOx1nCoV-19 recorded.    
UK2, 3 
COV002 
ChAdOx1 nCoV-19 
(2 doses of 3·5–6·5 
× 10¹⁰ vp or 
MenACWY) 
18-55 
56-69 
≥70 
49 
30 
49 
No severe local symptoms were reported. No 
SAEs related to ChAdOx1 nCoV-19 recorded.  
 
 
 
Total 
821 
 
1 Source: ChAdOx.tHIVconsv1 IB Section 6 and ChAdOx1.HIVconsv62 IB Section 6,  
2 Source: Voysey et al Lancet 2021 (75), Ramasamy et al Lancet 2021 (76) 
3 Post emergency use authorization clinical data relating to ChAdOx1 nCoV-19 are detailed in Table 5. 
 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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2.2.5.3 
COVID-19 Adenovirus Vectors  
The COVID-19 pandemic resulted in emergency use authorization from the FDA for several 
COVID-19 vaccines, including the Janssen/J&J Ad26COVS1 vaccine as a single dose 
recombinant HAd26 vector (77). Other adenovirus-vectored COVID-19 vaccines are authorized 
for use in other countries, including AZD1222-ChAdOx1 nCoV-19 (75) and the Russian Gam 
COVID-Vacc, a heterologous HAd26-HAd5 prime-boost (78). Overall, there is increased 
likelihood that some potential study participants may have received an adenovirus-based vaccine.  
Pre-existing humoral immunity has been shown to interfere with vaccine-induced immunity, 
including the induction of T cell immunity to autologous adenoviruses. The best example 
includes Ad5 which is a group C virus. Pre-existing Ad5-specific NAb titers impaired the Merck 
Ad5 vector expressing HIV immunogens (72, 79, 80). Similarly, autologous antibodies to rhesus 
adenoviruses were shown to interfere with T cell immunity in mice models (81). By contrast, 
studies in humans, animal models and in vitro cell models, have shown that pre-existing Ab titers 
to adenoviruses from phylogenetically different groups do not impair induction of immunity to 
adenovirus vaccination (82). For example, high Ad5 antibody titers did not impair T cell 
responses following vaccination of macaques with Ad26 (group D)-RhAd prime-boost regimens 
in NHP (81). Lastly, sera from ChAd63 (Group E) vaccinated individuals did not neutralize 
ChAdOx1 (Group E) infection (74); though no data are available regarding impact on immune 
responses. Pre-existing Ad26 and Ad35 (Group B) antibodies did not impact the induction of 
vaccine-specific immune responses following Ad26-Ad35 heterologous vaccination in healthy 
adults in the US, East and South Africa (83). Altogether, these studies suggest that adenoviral 
vaccination with phylogenetically different groups will not impede the induction of T cell 
responses to C1 and or C62 vaccines.  
More data are needed on interactions between adenoviruses within the same phylogenetic group. 
As such, prior vaccination with Group E vaccine vectors, including the COVID-19 vaccine 
AZD1222, will be an exclusion criterium for this study. By contrast, prior vaccination with the 
Janssen Ad26COVS1 COVID-19 vaccine (and Gam COVID-Vacc) will not be exclusionary. 
Conversely, C62 and, or C1C62 vaccination could impede subsequent vaccination with 
AZD1222.  
2.2.5.4 
Post-authorization experience with Adenovirus Vectored COVID-19 
vaccines 
As of July 2021, over 110 million doses of AZD1222-ChAdOx1 nCoV-19 had been given across 
Europe, including the UK. Post-authorization experience identified new possible AEs. Given 
these AEs are reported voluntarily, it is not possible to estimate frequency or as yet establish a 
causal relationship following vaccine exposure. These AEs are listed in the AZD122 and 
Ad26COVS1 packet inserts as either very rare frequency (< 1in 10,000) (Table 5, 
ChAdOx.tHIVconsv1 IB Section 6.2, ChAdOx.HIVconsv62 IB Section 6.2) . Post-authorization 
clinical reporting is addressed in the Risk/Benefit Assessment in Section 2.3. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Blood and lymphatic system disorders: Review of clinical data in the 4 week window following 
the first AZ1222 vaccination in the UK and European Union (EU) AZ1222 programs (>49 
million Europeans, 09 April 2021) identified rare cases of unusual thromboses associated with 
thrombocytopenia in people without previous history of prothrombotic medical conditions (84, 
85), https://www.ema.europa.eu/en/news/astrazeneca-covid-19-vaccine-review-very-rare-cases-
unusual-blood-clots-continues, ChAdOx.tHIVconsv1 IB Section 7.2, ChAdOx.HIVconsv62 IB 
Section 7.2, Table 5). Specifically thromboses with thrombocytopenia occurring in the first 3.5 
weeks of vaccination, median of < 2 weeks post-vaccination (84, 85). Thromboses with 
thrombocytopenia were also reported in a smaller number of individuals vaccinated with the 
Janssen Ad26COVS1 COVID-19 vaccine. The majority of patients tested to date harbored 
antibodies against platelet factor 4 suggesting immune-related events, independent of heparin-
therapy (84-86). At present, no specific risk factors, such as age, gender or a previous medical 
history of clotting disorders have been identified for these very rare events. A summary of 
findings reported to the European Medicines Agency (EMA) are reported in Table 5.  
Immune system disorders: Events of anaphylaxis following AZ1222 vaccination have been 
reported (https://www.ema.europa.eu/en/documents/prac-recommendation/prac-
recommendations-signals-adopted-8-11-march-2021-prac-meeting_en.pdf, Table 5).   
Vascular Disorders: Very rare cases of capillary leak syndrome (CLS) have been reported in the 
first days after vaccination with AZD1222 and the Janssen Ad26COVS1 vaccine. A history of 
CLS was apparent in some of the cases. Fatal outcome has been reported. CLS is a rare disorder 
characterized by acute episodes of edema mainly affecting the limbs, hypotension, 
hemoconcentration, and hypoalbuminemia (ChAdOx.tHIVconsv1 IB Section 7.2, 
ChAdOx.HIVconsv62 IB Section 7.2, Table 5). 
Nervous System Disorders: Very rare events of neuroinflammatory disorders have been reported 
following vaccination with AZ1222/Vaxzevria. A causal relationship has not been established 
(ChAdOx.tHIVconsv1 IB Section 7.1, ChAdOx.HIVconsv62 IB Section 7.1, Table 5).  
 
 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Table 5  
Adverse reactions reported following vaccination with AZD1222 COVID-19 
Vaccine1 
 
Very 
Common 
≥1 per 10 
Common 
≥1 per 100 to <1 
per 10 
Uncommon 
≥1 per 1,000 to 
<1 per 100 
Rare 
≥1 per 
10,000 
to <1 
per 
1000 
Very Rare 
< 1 per 10,000 
Not Known 
(cannot be 
estimated 
from post-
authorization 
data) 
Blood and 
lymphatic 
system 
disorders 
 
thrombocytopenia 
lymphadenopathy 
 
Thrombosis in 
combination with 
thrombocytopenia2 
 
Metabolic and 
Nutrition 
system 
disorders 
 
 
Decreased 
appetite 
 
 
 
Nervous system 
disorders 
Headache 
 
Dizziness, 
somnolence 
 
 
Guillian-
Barré 
syndrome 
Vascular 
system 
disorders 
 
 
 
 
Thrombosis in 
combination with 
thrombocytopenia2 
Capillary 
Leak 
Syndrome 
Gastrointestinal 
disorders 
Nausea 
Vomiting, 
diarrhea 
 
 
 
 
Skin and 
subcutaneous 
tissue disorders 
 
 
Hyperhidrosis, 
pruritus, rash 
 
 
 
Musculoskeletal 
and connective 
tissue disorders 
Myalgia 
arthralgia 
 
 
 
 
 
Immune System 
Disorders 
 
 
 
 
 
Allergic 
reactions 
including 
anaphylaxis 
General 
disorders and 
administration 
site conditions 
Fatigue, 
malaise, 
feverishness, 
chills, 
injections 
site 
tenderness, 
pain, 
warmth, 
pruritus, 
bruising 
Fever 3, injection 
site erythema, 
injection site 
swelling, 
Injection site 
hematoma 
 
 
 
1Source: Product Information Vaxzevria, COVID-19 Vaccine ANNEX 1, https://www.ema.europa.eu/ 
https://www.ema.europa.eu/en/documents/product-information/vaxzevria-previously-covid-19-vaccine-astrazeneca-
epar-product-information_en.pdf, Table 1 and EMA EPITT no.19683  

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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2 Severe and very rare cases of thrombosis in combination with thrombocytopenia have been reported post-
marketing. These included venous thrombosis such as cerebral venous sinus thrombosis (CVST), splanchnic vein 
thrombosis, as well as arterial thrombosis. 
3 Measured fever > 38°C  
2.2.5.5 
Pre-Clinical Experience with ChAdV-Vectored Vaccines 
Eight ChAdOx1-vectored vaccines have been examined in seven Good Laboratory Practice 
(GLP) toxicology studies in BALB/c mice conducted at ENVIGO (formerly Huntingdon Life 
Science) (ChAdOx.tHIVconsv1 IB 5.3 and ChAdOx1.HIVconsv62 IB 5.3)   
As an overview, adult mice (male and female) typically received two doses of the recombinant 
ChAdOx1 vaccine 14 days apart with up to a 14-day observation window. Across toxicology 
studies, IM doses calculated to be >500-fold the proposed clinical dose of ChAdOx1 (5×1010 vp) 
were tested. All of these studies uniformly concluded IM delivery of the ChAdOx1-vectored 
vaccines was well tolerated and was not associated with any adverse effects. Non-adverse effects 
observed were attributable to inflammatory and immune responses at the IM injection site and 
induction of immune responses often reflected as changes in the spleen, drainage and/or 
increased cellularity in lymph nodes, and slight increases in white blood cell count and/or protein 
concentrations. Of note, one GLP toxicity study (Study TX05CW) described in 
ChAdOx1.HIVconsv62 IB Section 5.3.2, tested ChAdOx1.HTI and another experimental 
rChAdOx1 vaccine with very similar HIV transgene called HTI (87). For the purposes of 
toxicity, the HIV-1-derived vaccine inserts (=immunogens=transgene products) of HIVconsv, 
tHIVconsv1, tHIVconsv3, tHIVconsv4, HIVconsv62 and HTI employed by experimental 
vaccines are very similar and the regions partially overlap among the different immunogen 
designs. They are assembled from small regions of HIV-1 proteins, have no known biological or 
enzymatic activity, and are joined into a chimeric protein of 872 amino acids for the sole purpose 
of inducing CD4+ and CD8+ T-cell responses.  
In two of the seven GLP toxicology studies described, ChAdOx1 vaccinations were boosted with 
MVA vaccines. Both of these studies tested two IM doses with one study testing a third IV dose 
of either ChAdOx1 and/or MVA. In both combination studies, >500-fold the proposed clinical 
dose of ChAdOx1 were tested. Study GG05TY used a combination regimen similar to the 
proposed C62-M4 and C1C62-M3M4 regimens. Similar to the toxicity studies testing ChAdOx1 
alone, both studies with ChAdOx1 plus MVA booster concluded that ChAdOx1 and MVA were 
well tolerated and not associated with any adverse effects. Non-adverse effects included local 
inflammatory responses at the IM injection site and induction of immune responses. 
 
2.2.6 
MVA Vaccine Vectors 
MVA is a vaccinia virus strain which was attenuated by serial passage in chick embryo 
fibroblasts (CEF). It has lost 15% of the parental genome, including cytokine and chemokine 
receptor genes (88). It replicates well in CEFs and baby hamster cells but is unable to replicate 
efficiently in human and most other mammalian cells (89). The replication defect occurs at a late 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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stage of virion assembly such that the early viral and transgene expression is unimpaired. This 
makes MVA an efficient single-round-expression vaccine vector that is itself incapable of 
replication and spread in most mammalian cells. The DNA sequence of the entire MVA genome 
has been determined (90). 
2.2.6.1 
Generation of M3 and M4 vectors 
Full details of the generation of the M3 and M4 vaccine vectors are provided in IND 18368, 
Investigator Brochures. 
MVA.tHIVconsv3 (M3): The M3 vaccine is a second-generation HIV-1 conserved-region 
multi-component vaccine employing tHIVconsv3 immunogens comprised of Mosaic-1 regions. 
MVA.tHIVconsv3 is a recombinant, non-replicating MVA expressing six conserved sub-protein 
regions (regions 1-6) of HIV-1 as one chimeric protein designated tHIVconsv3 (Table 2). 
MVA.tHIVcons4 (M4): The M4 vaccine is a second-generation HIV-1 conserved-region multi-
component immunization regimen employing tHIVconsv4 immunogens comprised of Mosaic-2 
regions. MVA.tHIVconsv4 is a recombinant, non-replicating MVA expressing six conserved 
sub-protein regions (regions 1-6) of HIV-1 as one chimeric protein designated tHIVconsv4 
(Table 2).  
2.2.6.2 
Clinical Experience with MVA-Vectored Vaccines including M3 and M4 
Vaccines 
Despite the high level of attenuation, MVA has been shown to induce strong cellular immune 
responses. MVA was administered to more than 120,000 previously unvaccinated individuals as 
part of the smallpox eradication campaign in a field study in Germany in the 1970s. 
MVA-vectored candidate vaccines for AIDS, malaria, tuberculosis, influenza, hepatitis C, cancer 
and Ebola have been tested extensively in previous clinical trials by The Jenner Institute, 
University of Oxford (UOXF) and other laboratories resulting in considerable cumulative safety 
data on recombinant MVAs over the last four decades (42, 58, 88, 91-117) (See IND 18368, 
Investigator Brochures). 
Over 4000 people have received this MVA vector, which has been shown to be safe and 
immunogenic. The first MVA vaccine from the University of Oxford, MVA.HIVA was 
administered to over 400 healthy seronegative and PWH volunteers in the UK, Europe and 
Africa, including 60 twenty-week-old African infants in clinical trials. The first generation 
conserved-region MVA.HIVconsv was administered to over 224 participants. The candidate 
vaccine against TB, MVA85A, was safely injected into 2,400 participants including adults, 
adolescents, children and 1500 infants. See Table 6. 
 
 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Table 6 
Safety Data for selected Recombinant MVA Studies expressing HIV 
immunogens, given IM at 1-2 x 108 vpu  
Site 
Trial 
Vaccine 
Age 
n 
Summary of Results 
Spain 
BCN01ROMI 
NCT02616874 
MVA.HIVconsv 
(2 doses) 
18-
65yr 
15 
No SAE relative to vaccination.  
Grade 4 SAE: CPK elevation; total of 10 Grade 3 
AEs: local pain at injection site, headache, fever 
myalgia, anorexia, abdominal pain 
Spain 
BCN01 
NCT01712425 
MVA.HIVconsv 
18-
65yr 
24 
No SAE relative to vaccination.  
4 Grade 3 SAE: pain at site of injection, 3x intense 
tiredness myalgia 
US 
GV-TH-01 
NCT01378156 
MVA62B 
(2 doses) 
18-
50yr 
9 
No SAE relative to vaccination.  
No SAE reported 
Spain 
RisVac 03 
NCT01571466 
MVAHIV-B 
(3 doses) 
18-
65yr 
14 
No SAE relative to vaccination. 
4 Grade 3 AEs: hyperglycemia, pneumonia, 
influenza, renal colic 
Twenty-two participants have been randomized to receive M3, M4, M3M4 or placebo given IM 
into the arm in a 7:7:7:3 ratio at final dose of 2×108 pfu in the M&M Study (NCT03844386; IND 
18368) conducted at the University of North Carolina at Chapel Hill (UNC). Safety data for 24 
participants are summarized in Table 7. Consistent with the broad literature summarizing MVA 
clinical safety profiles, data to date indicate vaccination with M3 and M4, given alone or in 
combination, is safe and well tolerated with vaccine-related AEs resolving within 48 hours. 
Table 7 
Summary of M&M Trial Safety data 
Site 
Trial 
Vaccine 
Age 
n 
Summary of Results 
UNC- 
Chapel 
Hill 
M&M 
M3, M4, 
M3M4, placebo 
21-60 
241 
• 
192 solicited AEs at least probably 
associated with vaccination were experienced 
by 23 participants in the 28 days following 
vaccination.  
• 
91% were Grade 1-2  and 9% were Grade 
3and all resolved within 48 hours.  
• 
4 participants reported 17 Grade 3AEs 
(Section 2.3.2) 
• 
65 unsolicited AEs were experienced by 22 
participants. No unsolicited Grade 3AEs 
were related to study product.   
 
1 Blinded data summary of 24 participants who have progressed to D28 post-vaccination or beyond. 18 participants 
have completed the study through D168 post-vaccination.  

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Page 36 of 143
 
 
2.2.6.3 
Pre-Clinical Experience with MVA-Vectored Vaccines 
Formal GLP-compliant acute toxicity and biodistribution studies of M3 and M4 was not required 
for Phase I testing of M3 and M4 vaccines. Both vaccines demonstrated to be safe, non-toxic and 
immunogenic in over 1,000 mice during routine experimental immunizations (representative 
immunogenicity data published in (54, 118), MVA.tHIVconsv3 IB Section 2.3, 
MVA.tHIVconsv4 IB Section 2.3).  
Toxicity studies have been performed by the early generation HIV MVA vaccine, MVA.HIVA 
also generated by the UOXF. No significant toxic effects, either local or systemic, were seen in 
SCID mice receiving two doses of MVA.HIVA by the intradermal (ID)route in study MRC/015 
or in BALB/c mice receiving two doses of MVA.HIVA by IM or the subcutaneous route in study 
MRC/018 (119, 120). The toxicity and persistence of MVA.HIVA in macaques infected with 
pathogenic strains of SIV (SIVmac) was evaluated in a GLP safety and biological clearance 
study. In SIV-infected macaques, no MVA.HIVA DNA was detected in any organ examined 
(testes, epididymis, ovary, blood, brain, heart, spleen, kidney, liver, mesenteric lymph node, 
draining axillary lymph node, skin and muscle at the site of injection) up to 9 weeks after ID 
immunization. SIV infection did not enhance the risk of target organ toxicity or persistence of 
MVA.HIVA or transfer of vaccine genomic DNA into germ cells in these animals (120). 
2.2.7 
Simian Adenovirus- and MVA Prime Boost Vaccination 
2.2.7.1 
Clinical Experience with Chimpadenovirus OX1 AND MVA-Vectored 
Vaccines 
Heterologous vaccination with simian adenovirus- and MVA-vectors has been tested in multiple 
humans studies (91, 92, 121-126), including PWH on ART (64, 65). In these trials, MVA has 
been mostly delivered as boosting vaccination 2 or 4 weeks after ChAd-vaccination. In all 
studies, combination vaccination was well-tolerated with few SAEs reported.  Table 8 
summarizes safety data of ChAd0x1/MVA vaccine regimens.  
Table 8 
Summary of Safety Data for vaccination with a ChAdOx11 prime 
followed by MVA boost2 
Site 
Trial 
Vaccine 
Age 
n 
Summary of Results 
UK 
NCT02390063 
ChAdOx1 5T4-
MVA-5T4 
≥18 
40 
No SAE related to vaccination. 
UK 
NCT01818362 
ChAdOx1NP+M1 
-MVA NP+M1 
18->50 
73 
No SAE related to vaccination. 
UK 
NCT01829490 
ChAdOx185A-
MVA85A 
18-55 
24 
No SAE related to vaccination. 
1 ChAdOx1 dose 2.5x1010vp given IM 
2 MVA dose 1.0-2.0 x108pfu given IM 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Page 37 of 143
 
 
2.2.7.2 
Clinical Experience with Simian Adenovirus 63 AND MVA-vectored 
Vaccines 
Over 1,200 participants have received rChAd63/rMVA expressing a range of immunogens, 
including vaccination of 700 infants (5-17 months) (66, 92, 103, 124, 126-130). All clinical 
studies, including those expressing conserved HIV immunogens, have shown that heterologous 
ChAdV/MVA vaccination is safe and well tolerated. Heterologous vector delivery with rChAdV 
(ChAdv63) and rMVA vaccines expressing first generation conserved HIV immunogens has 
been tested in 154 humans, including PWH on ART. Consistent with all other ChAdV/MVA 
studies, vaccination was safe and well-tolerated (ChAdOx1.HIVconsv62 IB Section 6.5). 
2.2.7.3 
Pre-clinical Experience with Simian Adenovirus 63 AND MVA-Vectored 
Vaccines 
Two additional GLP toxicity studies were performed using first generation HIVconsv vaccines 
using boosting regimens of ChAdV63 or MVA. In both studies, there was 14 days between 
ChAd63 and MVA boosts. The HIVconsv vaccines were well-tolerated and not associated with 
any adverse effects. The only effects of treatment seen were those attributable to inflammatory 
and immune responses at the IM injection site, lymph nodes, and the spleen  
(ChAdOx1.HIVconsv62 IB and ChAdOx1.tHIVconsv1 IB). 
2.3 
Risk/Benefit Assessment   
2.3.1 
Known Potential Risks of C1 and C62 Vaccines 
Previous experience with other simian adenovirus viral vectored vaccines suggests AEs provided 
in Table 9 and Table 10 are expected to occur in some participants after vaccination with C1, 
C62 or C1C62 vaccines.  
Table 9 
Common Local Reactions 
Injection site erythema  
Injection site pruritus  
Injection site pain  
Injection site swelling 
Injection site warmth 
 
Table 10 
Common Systemic Reactions 
Arthralgia  
Fatigue  
Malaise  
Headache 
Nausea 
Fever (>37.7°C or 99.9°F) 
Myalgia  
Feverishness 
 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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These AEs are primarily mild in severity, however occasionally moderate or severe events have 
been reported. These events usually occur within 24 hours of vaccination and resolve within 24 
to 48 hours. Given existing data for ChAdOx1-vectored vaccines, it is anticipated that the 
majority of systemic AEs post C1, C62, or C1C62 will be mild in intensity 
(ChAdOx1.tHIVconsv1 IB and ChAdOx1.HIVconsv62 IB). 
Transient lymphopenia has been observed in the recent HIVCORE 0052 trial and previously in 
trials of other ChAdOx1-vectored vaccines. This is asymptomatic and resolves spontaneously 
within a week (ChAdOx1.tHIVconsv1 IB and ChAdOx1.HIVconsv62 IB).  Complete blood cell 
counts will be monitored throughout the study. 
Severe allergic reactions including anaphylaxis may occur, as with receipt of any vaccine or 
medication. Participants will be vaccinated in a clinical area equipped to provide immediate 
advanced life support. Rare Side-effects: Some rare side effects have been observed following 
vaccination with AztraZeneca COVID-19 vaccine (AZD1222) (Table 5) and the Janssen vaccine 
(Ad26COVS1) COVID-19 vaccine with an estimated 1 case per 100,000 – 250,000 vaccine 
recipients. These side effects are:  
1. A combination of thrombosis and thrombocytopenia known as Thrombosis with 
Thrombocytopenia Syndrome (TTS), also termed vaccine-induced prothrombotic immune 
thrombocytopenia (VIPIT)  
2. New onset neurological disease (i.e. Guillain-Barre syndrome or GBS) 
3. Systemic CLS. Cases of TTS have occurred within the first twenty-four days (range 5-42 
days) following vaccination and occurred mostly in women under 60 years of age (84). This 
includes rare severe cases presenting as venous thrombosis, including unusual sites such as 
CVST, splanchnic vein thrombosis, deep vein thrombosis and pulmonary embolism, as well 
as arterial thrombosis, concomitant with thrombocytopenia with some cases resulting in 
death. Participants to date have mostly harboured antibodies against the Platelet Factor 4 
which is released by activated platelets (84, 85). 
 
There have been very rare cases of CLS reported in the first days after vaccination. CLS is a rare 
disorder characterised by acute episodes of edema mainly affecting the limbs, hypotension, 
concentrated blood and hypoalbuminemia. Investigation of some these cases indicated a history of 
CLS. Some cases were fatal.  
Participants in this study will be followed using a combination of phone calls (n=5) and in-
person visits (n=2) for the development of symptoms associated with the development of new 
onset blood clots and neurological deficits (Appendix 2) for the 28 days following C62 or 
C1C62 vaccination. All participants will be advised to seek immediate medical attention should 
they develop symptoms. CBC will be performed to examine platelet levels at Day 7 and 14 post-
vaccination. Participants will be provided with a vaccination information card (Section 8.2.13), 
describing the study vaccine and the need to consider TTS if clinically warranted. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
Confidential
Page 39 of 143
 
 
As with any other vaccine, rare events of GBS or immune mediated reactions that can lead to 
organ damage may occur. Rare cases of GBS have been reported in individuals who received the 
AstraZeneca and the Johnson and Johnson COVID-19 vaccines. In a few individuals who 
received the AstraZeneca COVID-19 vaccine (ChAdOx1), a variant of GBS with significant 
facial weakness has been described. 
 
2.3.2 
 Known Potential Risks of M3 and M4 vaccines 
The M&M study conducted at UNC is the first human clinical trial using M3 and M4. To date, 
there have been no SAEs among 23 PWH on ART who received either M3, M4, M3M4 or 
placebo (Table 7). Ninety-one percent of AEs reported as related to the study product were grade 
1 or 2 (solicited). Four participants reported 17 Grade 3 events (solicited) and included arthralgia 
(1), headache (1), unexplained diaphoresis (1), myalgia (2), chills (3), fatigue (3), flu-like 
symptoms (3), malaise (3)felt to be treatment related, which resolved in 24 hours without 
intervention. All AEs resolved within 24 – 48 hours of vaccination.  
The safety profile of M3, M4 or M3M4 in the M&M Study is consistent with safety data from 
other MVA-vectored vaccines, including those given to PWH. Local and systemic reactions are 
summarized in Table 11 and Table 12 respectively (See IND 18368, Serial 0004).   
Altogether we anticipate AEs to M4 and M3M4 in this study will be mild in severity involving 
transient Grade 1 and 2 local reactions such as pain or erythema at the injection site in addition to 
headache, malaise, and fever (See IND 18368 Serial Number 0004).   
Standard local (Table 11) and systemic reactions (Table 12) can occur, with most appearing 
within the first 24 hours and usually subsiding within 48 – 72 hours. 
Table 11 
Local Reactions to MVA vaccine  
Injection site erythema (redness) 
Injection site pruritus (itching) 
Injection site tenderness  
Injection site swelling 
Injection site warmth  
Skin discoloration 
Injection site pain  
Skin damage (vesiculation or ulceration) 
Induration (hardening or formation of a crust or scab) 
 
 
 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Page 40 of 143
 
 
Table 12 
Systemic Reactions to MVA vaccine  
Vomiting 
Fatigue (extreme tiredness)  
Malaise  
Headache 
Flu like symptoms  
Temperature (fever >37.7°C or 99.9°F) 
Sweating (diaphoresis)  
Chills  
Diarrhea 
Abdominal pain 
Dizziness 
Myalgia (muscle pain) 
Anorexia 
Nausea 
Arthralgia  
Decreased appetite 
Syncope 
Hypertension 
2.3.3 
 Known Potential Risks Common to Both ChAdOx1-vectored and 
MVA-vectored Vaccines 
Viral Reversion: A potential concern regarding the safety of live, attenuated viral vaccines is the 
possibility of pathogenesis caused by viral mutation and replication. Any potential risk in this 
respect arising from the administration of M3 or M4 is thought to be very small, due to the 
avirulence and restricted replication of the parental virus MVA and the recombinant vaccine 
viruses M3 and M4 in human cells. 
Pregnancy: Animal reproduction studies have not been performed and human data on use during 
pregnancy are not available. Therefore, the vaccine should not be administered to pregnant 
women or women with the intention to become pregnant. 
Allergy: Serious allergic reactions including anaphylaxis may occur as with any vaccine. The 
incidence of this is unknown but is estimated at one per 105 to 106 vaccinations. Participants will 
be vaccinated in a clinical area that has the capacity to administer medications and utilize 
emergency equipment for the management of serious adverse reactions. 
2.3.4 
 Known Potential Risks of Overdose 
A drug overdose is defined as the accidental or intentional use of a drug or medicine or an 
administration error in an amount that is higher than is normally used. Given all doses of C1, 
C62, M3 and M4 will be provided and administered by licensed study staff only and as prepared 
by the manufacturing facilities, overdose is not anticipated. 
Overdose in this study is specifically defined as any dose greater than the intended protocol dose. 
In the unlikely event of overdose, it is recommended that the participant be monitored for any 
signs or symptoms of adverse reactions or effects and appropriate symptomatic treatment be 
administered immediately. Note that administration of the “wrong” vaccine is a protocol 
deviation, but not, in the absence of associated AE, an SAE. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Page 41 of 143
 
 
Any overdose must be reported to the protocol team and sponsor within 24 hours of awareness. 
Only overdoses associated with a clinical SAE needs to be reported as an SAE. The quantity and 
duration of the excess dose should be documented.  
2.3.5 
 Known Potential Risks of Syncope 
Syncope (fainting) can occur before or following any vaccination as a stress response to the 
needle injection. 
2.3.6 
 Known Potential Risks of Blood Drawing 
Blood drawing may cause pain and bruising and may infrequently cause a feeling of 
lightheadedness or fainting. Rarely, it may cause infection at the site where the blood was drawn. 
We minimize risk by using sterile technique and universal precautions. 
2.3.7 
Known Potential Risks of Leukapheresis 
These include common side effects similar to blood draws. However, more serious side effects 
could occur such as flushing, infection due to contaminated equipment, and damage to red blood 
cells. These serious side effects occur in less than 1 in 10,000 procedures. No such SAEs have 
occurred in our prior studies, including more the 500 cell collections from PWH as donors at 
UNC.   
The following are the most common risks: 
• Pain or bruising at the site of needle sticks, 
• Phlebitis,  
• Citrate toxicity (10%), 
• Oral paresthesia,  
• Paresthesia, 
• Stiffness in the arms due to the immobilization during donation, 
• Fatigue, 
• Temporary fluctuations in heart rate, and 
• Temporary increases in blood pressure. 
 
Less common: 
• Infiltration the tissue,  
• Muscle aches or cramps, 
• Chills,  
• Fever, 
• Nausea or vomiting, 
• Lightheadedness or headache, and 
 
• Vasovagal reaction. 
 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
Confidential
Page 42 of 143
 
 
Rare: 
• Seizures or fainting, 
• Transient weight gain, ankle swelling, or increased urination for 24 hours due to fluid 
retention, 
• Infection due to contamination of equipment, 
• Skin rashes, flushing, or other allergic responses, 
• Damage to or loss of red blood cells due to machine malfunction, and  
• Remote possibility of air entering the vein and causing chest pains, shortness of breath or 
shock or death. 
2.3.8 
 Unknown Risks 
New therapies can lead to unexpected, incidental finding that could have a potential effect on the 
participant’s health. Upon confirmation of a potential health or reproductive effect, the study 
team will notify participants impacted by the new information and will advise. 
2.3.9 
 Known Potential Benefits    
The addition of the C62 and C1 vaccines boosted by M4, or combined M3M4 to a person’s 
ART regimen and the donation of one’s blood cells to this research study provides no direct 
medical benefits to participants. However, participation contributes to ongoing HIV research, 
potentially resulting in new treatments for HIV infection.   
2.3.10 
Assessment of Potential Risks and Benefits 
Interventions with the potential to improve HIV-specific T-cell responses and limit viremia 
should be tested. Therapies that improve clearance of persistently HIV-1-infected cells will 
likely be a necessary component of any HIV remission or eradication strategy. Based on the data 
outlined above, there is sufficient expectation that the proposed treatment vaccines will be safe 
and well tolerated. Although participants in this early phase study will receive no direct benefit 
for their participation, there remains a strong desire among PWH, and the HIV community at-
large, to pursue HIV preventative and therapeutic vaccine strategies. The potential adverse 
effects, stigmatization, and financial costs encountered by PWH receiving life-long ART along 
with the potential harm of persistent immune activation are strong reasons to pursue HIV vaccine 
research. In short, an HIV cure or sustained remission in the absence of ART would have 
substantial benefits for many individuals if achieved. An effective HIV vaccine represents a key 
strategy for both HIV prevention and cure. 
Participants will be informed of potential adverse events associated with study products at the 
time of informed consent by a study investigator and will be encouraged to talk with other 
providers and family/significant others as needed prior to signing the informed consent.  
3 OBJECTIVES AND ENDPOINTS 
The objectives and endpoints for the clinical study are provided in Table 13. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
Confidential
Page 43 of 143
 
 
Table 13 
Objectives and Endpoints for the Clinical Study 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
Primary 
 
 
Evaluate the safety of 
vaccination through 28 days 
after the last vaccination or 
placebo with:  
C62-M4 
C1C62-M3M4 
in PWH on ART 
Occurrence of at least one ≥ Grade 3 AE 
including signs/symptoms, lab toxicities, 
and/or clinical events, that is possibly or 
definitely related to study treatment from 
the first day of treatment (D0) through 28 
days following the boost vaccination or D 
56. 
NOTE: The occurrence of a Grade 3 
elevated blood pressure during a study-
related leukapheresis that resolves 
following completion of the procedure will 
not be included as a primary safety 
endpoint. 
 
In previous clinical studies of 
ChAdOx1 and MVA modalities, 
given alone or in combination, all 
observed vaccine related AEs 
occurred within 28 days of 
vaccination. 
The study will use standard safety 
grades used in HIV clinical trials. 
Should these grades be exceeded, it 
is currently felt that such risks 
would be unacceptable in a 
research study of this nature.   
Secondary 
 
 
Evaluate the safety of 
vaccination through the end of 
study  
 
 
 
 
 
 
 
 
 
 
 
 
Occurrence of any ≥ Grade 1 AE including 
signs/symptoms, lab toxicities, and/or 
clinical events, that is possibly, or definitely 
related to study treatment any time from the 
first day of treatment (D0) through D196 
(Week 28). 
NOTE: The occurrence of a Grade 3 
elevated blood pressure during 
leukapheresis that resolves following 
completion of the procedure will not be 
included as a secondary safety endpoint. 
Safety data will include local and systemic 
signs and symptoms, laboratory measures of 
safety/toxicity, and all adverse and serious 
adverse events. Safety data will be routinely 
collected throughout the study.   
The study will use standard safety 
grades used in HIV clinical trials. 
Should these grades be exceeded, it 
is currently felt that such risks 
would be unacceptable in a 
research study of this nature.   
Compare the within-
participant relative change in 
magnitude of HIV-1-specific 
T cell responses following 
vaccination with C62-M4 or 
C1C62-M3M4. 
Relative change in magnitude of T cell 
responses to HIV-1 conserved regions from 
baseline (before C62 or C1C62 
vaccination) to post-boost vaccination at 
D35 and D42. 
Vaccination of PWH on ART with 
MVA vaccines expressing HIV 
immunogens, given alone or as a 
boosting vaccination, induced the 
peak HIV-specific T cell responses 
at day 7 or day 14 post-vaccination 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Page 44 of 143
 
 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
Compare the between-arm 
change in breadth of HIV-1-
specific T cell responses 
following vaccination C62-
M4 or C1C62-M3M4. 
 
Change in breadth of T cell responses 
targeting HIV conserved regions from 
baseline (before C62 or C2C62 
vaccination) to post-boost vaccination 
measured at D56. 
 
The mosaic immunogen design is 
predicted to broaden the number 
reactive HIV epitope variants (i.e. 
breadth) detected by CD8+ T cells 
in vaccinees. T cell breadth is 
maintained over time, enabling 
measurement at D56 providing 
economical use of participant 
samples. 
Assess the long-term safety 
and tolerability of study 
vaccines  
Incidence and severity of SAEs, MAAEs, 
and AESIs through EOS. 
Multiple post-vaccination 
timepoints needed to evaluate the 
longer-term safety of the C1 and/or 
C62 vector. 
Tertiary/Exploratory  
 
 
Compare the change in 
function and phenotype of 
HIV-1-specific T cell 
responses in participants from 
pre- to post-vaccination with 
C62-M4 or C1C62-M3M4. 
Change in function of T cell responses 
targeting HIV conserved regions from 
baseline (before C62 or C1C62 
vaccination) to post-boost vaccination at 
D35 or D42. 
Vaccination is expected to induce 
temporal changes in memory 
phenotype and breadth of function 
Evaluate the kinetics of 
immunologic responses in 
participants pre- and post-
vaccination with C62-M4 or 
C1C62-M3M4. 
Relative change in magnitude of T cell 
responses to HIV-1 conserved regions at 
multiple pre- (minimum 2) and post-
vaccination (D35 or D42) timepoints. 
Multiple pre- and post-vaccination 
timepoints are needed to evaluate 
the stability of any change 
observed. 
Evaluate the kinetics of CD8+ 
T cell mediated HIV inhibition 
pre- and post-vaccination with 
C62-M4 or C1C62-M3M4. 
Relative change in magnitude of T cell 
responses to HIV-1 conserved regions at 
multiple pre- (minimum 2) and post-
vaccination (D35 or D42) timepoints. 
Anticipate greatest change in T cell 
virus inhibition will occur at peak-
magnitude of T cell response. 
Explore cellular activation 
status of total CD4+ and CD8+ 
T cells pre- and post-
vaccination with C62-M4 or 
C1C62-M3M4. 
Relative change in magnitude of T cell 
responses to HIV-1 conserved regions at 
multiple pre- (minimum 2) and post-
vaccination (include D35, D42) timepoints. 
Anticipate greatest change in T cell 
activation status to occur at peak-
magnitude of T cell response.  
Explore the impact of 
vaccination with C62-M4 or 
C1C62-M3M4 on low-level 
plasma viremia.  
Relative change in low-level viremia at 
multiple pre- (minimum 2) and post-
vaccination (minimum 2) timepoints. 
Multiple pre- and post-vaccination 
timepoints are needed to evaluate 
the stability of any change 
observed. 
Explore the impact of 
vaccination with C62-M4 or 
C1C62-M3M4 on cell-
associated HIV RNA in CD4+ 
T cells. 
Relative change in cell-associated RNA at 
multiple pre- (minimum 2) and post-
vaccination (minimum 2) timepoints. 
 
Multiple pre- and post-vaccination 
timepoints needed to evaluate the 
stability of any change observed. 
Explore the impact of 
vaccination with C62-M4 or 
C1C62-M3M4 on total HIV 
DNA in CD4+ T cells. 
Relative change in cell-associated RNA at 
multiple pre- (minimum 2) and post-
vaccination (minimum 2) timepoints. 
 
Multiple pre- and post-vaccination 
timepoints needed to evaluate the 
stability of any change observed. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Page 45 of 143
 
 
4 STUDY DESIGN  
4.1 
Overall Design 
This is a Phase 1, pilot study with a double blind, randomized, placebo-controlled, parallel 
design to evaluate safety and immunogenicity of C62 followed by M4 or, C1C62 given in 
combination followed with M3M4 given in combination.   
The participants will be PWH suppressed on ART with plasma HIV-1 RNA <50 copies/mL. 
We hypothesize that C62 followed by M4 or, C1C62 given in combination followed with 
M3M4 given in combination will be safe and increase HIV-1-specific T cell responses targeting 
conserved regions of HIV-1. We also hypothesize that administration of C1C62-M3M4 will 
result in a greater increase in the breadth of HIV-1-specific T cells targeting conserved regions of 
HIV-1 than C62-M4 vaccination. 
Vaccine and placebo doses will be administered to all participants as 2 separate IM injections in 
the deltoid muscle of each arm. Participants continue baseline ART regimen throughout the 
study. 
Participants will be randomized 8:8:2 to one of three study arms and receive study treatment or 
placebo at D0 and D28 as in Table 14.  
Table 14 
Study Randomization 
Arm 
N 
Day 
Treatment 
Total Dose 
(vp) 
Route 
Day 
Treatment 
Total Dose 
(pfu) 
Route 
1 
8 
0 
C62 
5×1010 
IM 
28 
M4 
1.8×108 
IM 
2 
8 
0 
C1C62 
5×1010 
IM 
28 
M3M4 
1.9×108  
IM 
3 
2 
0 
Placebo 
(saline) 
- 
IM 
28 
Placebo 
(saline) 
- 
IM 
 
The primary safety outcome is the occurrence of at least one ≥ Grade 3 Adverse Event (AE) 
including signs/symptoms, lab toxicities, and/or clinical events that are possibly, or definitely 
related to study treatment. The period of observation is from the day of ChAdV vaccination at 
D0 through to D56 which is 28 days following the MVA vaccination or placebo. The primary 
safety analysis will be blinded until D56 or 28 days following the MVA vaccination or placebo 
in the last study participant. 
Participants will be followed and monitored for clinical events that are possibly, or definitely 
related to study treatment per the SoA. All participants will be informed about potential 
contraindications and risks associated with the study vaccines.  

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Safety will be assessed for the duration of the study. Solicited AEs will be recorded for 28 days 
after each dose of study intervention (through Day 57), and SAEs, MAAEs, and AESIs will be 
recorded through the EOS.  
 
Study analysis plans are discussed in the Statistical Analyses Section 10.7. 
 
4.2 
Scientific Rationale for Study Design 
The scientific rationale of this study is that vaccination that shifts CD8+ T cell targeting (breadth 
and magnitude) away from variable HIV epitopes and towards conserved HIV regions enabling 
better T cell mediated control of HIV-reactivation.  
Vaccine Vectors: Immunogenicity - We are testing serial vaccination with two live-attenuated 
vaccine modalities ChAdOx1 and MVA expressing complementary immunogens. This 
heterologous vector approach is often termed, prime-boost vaccination. Vaccination with 
heterologous viral vectors consistently elicits higher frequencies of immune responses against 
the vaccine immunogen than homologous vaccination regimens (131).  Safety: As detailed 
above, Both ChAdOx1 and MVA vectored vaccines given IM either alone or serially have been 
safe and well tolerated. Altogether, the immunogenicity and safety profiles of these vaccines 
support their choice in this study.  
Immunogens: The HIVconsvX design targets regions of HIV that are both conserved and harbor 
high numbers of T cell epitopes associated with control of HIV viremia. T-cell epitopes in the 
HIVconsvX immunogen are also significantly less-likely to harbor virus escape variants in either 
vRNA or the latent HIV reservoir. We therefore hypothesize these conserved immunogens will 
induce consistent and significant increases in circulating T cell-mediated immunity in 
participants. We will compare bivalent mosaic (C1C62-M3M4) and monovalent mosaic (C62-
M4) immunogens. We hypothesize that following vaccination, the bivalent mosaic immunogens 
will induce a greater breadth of T-cell response than the monovalent immunogen.    
Cohort: Individuals chronically infected prior to ART treatment will be prioritized for 
enrollment.  
We and others have documented that individuals treated in chronic infection have sustained and 
detectable HIV specific T-cell responses (132). This compares with ART initiated in acute 
infection where treatment may blunt the induction of T cell responses against HIV. Studies in 
individuals treated in chronic infection will allow us to better address our study hypothesis which 
focuses on shifting T cell dominance away from variable epitopes to immunogenic, but more 
conserved epitopes that are less subject to escape. Accordingly, our endpoint assays are designed 
to also examine de novo induction of HIV-specific T cell responses.  
Our exploratory objectives will examine whether vaccination decreases the size of the HIV 
reservoir. Therefore, we are targeting chronically HIV-infected participants who harbor a 
detectable, complex and relatively stable reservoir.  

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Durable Suppression: The inclusion criterion of > 2 years of durable suppression has been 
included for two reasons. First, we have shown that HIV T cell responses in durably suppressed 
participants are highly stable, providing a reliable baseline to examine changes in T cell 
frequencies (132).  Second, the size of the HIV reservoir stabilizes after 2 years providing a 
stable baseline to examine change in virologic measurements (65).  
Placebo Controls: Two placebo controls are included in this study. Powering calculations 
described Section 10.3 are independent of a placebo arm. Placebos have been included to ensure 
real-time objectivity in recording study AEs. Placebo-associated safety and immunogenicity data 
in this study will be combined with data collected from placebos (n=3) from our current trial 
IGHID 11810 (The M&M Study), giving a final n=5 of placebo controls.  
4.3 
Justification for Dose 
The vaccine doses to be used in the clinical study are provided in Table 15. 
Table 15 
Vaccine Doses 
Group 
Vaccine 
Dose 
Route 
1 
C62 
C62 = 5 x 1010 virus particles (vp)  
IM 
 
M4 
M4 = MVA.tHIVconsv4 = 1.8 x 108 plaque-forming units (pfu) 
IM 
2 
C1C62 
C1 = 2.5 x 1010 vp 
C62 = 2.5 x 1010 vp 
IM 
 
M3M4 
M4 = MVA.tHIVconsv4 = 0.9 x 108 pfu 
M3 = MVA.tHIVconsv3 = 1 x 108 pfu 
IM 
3 
Placebo  
Normal saline injection  
IM  
Justification for ChAdOx1 vaccine dose: Fourteen clinical trials testing 10 different ChAdOx1 
vaccines have been or are in clinical testing (n=872 participants) (ChAdOx.tHIVconsv1 IB 
Section 6, ChAdOx1.HIVconsv62 IB Section 6). Safety and immunogenicity data are available 
for 789 participants with 567 study participants receiving an IM dose of 5×1010 vp; the same 
dose and route of vaccination proposed for this CM Study. The safety profiles of ChAdOx1 
vectors have been well tolerated to date. Solicited AEs have mostly been mild or moderate with 
unsolicited AEs mostly classed as mild/Grade 1 (ChAdOx.tHIVconsv1 IB Section 6, 
ChAdOx1.HIVconsv62 IB Section 6).  
ChAdOx1 is highly related to the ChAd63 vector which has also undergone extensive clinical 
testing. Participants (n=1,367) have received recombinant ChAd63 vaccines given IM at a dose 
of 5×1010 vp, mostly in prime-boost combination with MVA-vectored vaccines. Vaccination has 
been safe and well tolerated (ChAdOx.tHIVconsv1 Section 7, ChAdOx1.HIVconsv62 IB Section 
7). This dose has also been consistently immunogenic, either inducing or increasing the 
frequency of circulating T cells against the vaccine immunogen. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Page 48 of 143
 
 
Justification of the MVA vaccine dose: M4 vaccination will be given at a dose of 1.8×108 pfu 
and M3M4 given at a final dose of 1.9×108 pfu.  We anticipate dosing to be immunogenic, well 
tolerated but also provide economical use of M4 Good Manufacturing Practice (GMP) vaccine. 
In the ongoing UNC Study NCT03844386 (IND 18368), M3 and M4 given IM to PLW on ART 
at a final dose of 2×108 pfu has been safe and well tolerated in 21 participants (Table 7). These 
data are consistent with other studies in which recombinant MVA has proven to be safe and 
tolerated when delivered IM at a dose of 2×108 pfu (Table 6) (92, 97). The AEs reported in prior 
studies were mild (Grade 1) and moderate (Grade 2) local and systemic reactions. Most reactions 
were reactogenic, involving pain at the injection site (local) and malaise and myalgia (systemic) 
(See IND 18368, Investigator Brochures).  
Based on data from all studies, there were very few treatment-related SAEs reported following 
MVA vaccination (See IND 18368, Investigator Brochures) (93). In a study of MVA expressing 
influenza antigens delivered as an IM injection (n=8), fewer local adverse events were observed 
than with intradermal (ID) injection (n=12) (133). Systemic adverse events (AEs) were similar 
for both IM and ID injection.  
Blinded data to date also suggests that both the M3 and M4 vaccines given at similar doses are 
likely to be immunogenic (Figure 2). These immunogenicity data (NCT03844386; IND 18368) 
are supported by other studies in which doses of MVA from 5×107 to 2×108 have been 
immunogenic, including in PWH (66, 97, 102, 134, 135). Across those studies stronger 
immunogenicity has been observed at doses between 1-2×108 pfu (66, 97, 102).  
4.4 
End of Study Definition 
A participant is considered to have completed the study if he or she has completed all study 
required visit including the last visit per Section 1.3. 
5 STUDY POPULATION 
5.1 
Inclusion Criteria 
1. HIV infection documented by any licensed rapid HIV test or HIV enzyme or 
chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and 
confirmed by a licensed Western blot or a second antibody test by a method other than 
the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral assay. 
 
A reactive initial rapid test should be confirmed by either another type of rapid assay or 
 
an E/CIA that is based on a different antigen preparation and/or different test principle 
 
(e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load. 
NOTE: The term “licensed” refers to a US FDA-approved kit, which is required for all  IND 
studies. WHO (World Health Organization) and CDC (Centers for Disease Control and 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Prevention) guidelines mandate that confirmation of the initial test result must use a test that is 
different from the one used for the initial assessment.  
2. Ages ≥ 18 to ≤ 70 years old 
3. Able and willing to give written informed consent. 
4. Able and willing to provide adequate locator information.  
5. Able and willing to comply with all study requirements through D196/Week 28. 
6. Continuous ART prior to screening, defined as not missing more than 14 total days and 
never more than 7 consecutive days in the last 3 months prior to screening. 
7. No change in any ART medication in the 30 days prior to screening.  
Permitted ART regimens include:  
a. At least 3 ART agents (not counting ritonavir or cobicistat as one of the agents if 
less than a 200 mg total daily dose). One of the agents must include an integrase 
inhibitor, NNRTI (Non-Nucleoside Reverse Transcriptase Inhibitors), or a 
boosted-PI (protease inhibitor).  
OR 
b. Two (2) ART agents in which one of the agents is either a boosted protease 
inhibitor or an integrase inhibitor. 
NOTE: Other potent fully suppressive antiretroviral combinations will be considered on a case-
by-case basis.  
NOTE: Changes in drug formulation or dose are allowed (e g, TDF to TAF, ritonavir to 
cobicistat or separate ART agent dosing to fixed-dose combination), but none within 30 days 
prior to screening.  
NOTE: Prior changes in, or elimination of, medications for easier dosing schedule, intolerance, 
toxicity, an improved side effect profile or within a drug class are permitted if an alternative 
suppressive regimen was maintained, but not within 30 days prior to screening. 
8. Ability and willingness of participant to continue ART throughout the study. 
9. Plasma HIV-1 RNA <50 copies/mL at 2 time points in the 24 months prior to screening 
and never ≥50 copies/mL on 2 consecutive time points in the last 24 months.  
NOTE: Plasma HIV-1 RNA must be performed by any US laboratory that has a Clinical 
Laboratory Improvement Amendments (CLIA) certification or its equivalent. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Page 50 of 143
 
 
10. 
Documented plasma HIV-1 RNA result <50 copies/mL ≥24 months but ≤ 36 months 
prior to screening. 
11. 
Plasma HIV-1 RNA level <50 copies/mL on an FDA-approved HIV RNA assay 
performed at a US CLIA Certified Laboratory (or its equivalent) at screening.  
12. 
CD4 cell count ≥ 350 cells/mm3 performed at any US laboratory that has a CLIA 
certification or its equivalent at screening. 
13. 
Completion of COVID-19 vaccine dosing at least 14 days prior to enrollment (see 
exclusion criterion regarding COVID-19 vaccination). 
14. 
Hepatitis C (HCV) antibody negative result at screening or, if the participant is HCV 
antibody positive, a negative HCV RNA at screening. 
15. 
Hepatitis B surface antigen (HBsAg) negative at screening.  
16. 
Adequate vascular access for leukapheresis.  
17. 
Able and willing to receive IM injections in both arms without difficulty.  
18. 
All women must have a negative serum pregnancy test with a sensitivity of a least 25 
U/mL at screening regardless of reproductive potential.  
19. 
All participants must agree not to participate in a conception process (e.g., active 
attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization, 
egg donation) while on study.  
NOTE: Women of child-bearing potential is defined as women who have not been post-
menopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 
24 months, or women who have not undergone surgical sterilization, specifically hysterectomy 
and/or bilateral oophorectomy or bilateral salpingectomy 
20. 
All men and women participating in sexual activity that could lead to pregnancy must 
agree to consistently use at least one of the following forms of birth control for at least 
21 days prior to Visit 3 (D0) and for 4 months after their last vaccination: 
a. Condoms (male or female) with or without a spermicidal agent  
b. Diaphragm or cervical cap with spermicide 
c. Intrauterine device (IUD) 
d. Tubal ligation 
e. Hormone-based contraceptive 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
Confidential
Page 51 of 143
 
 
NOTE: For female participants receiving ritonavir or cobicistat, estrogen-based contraceptives 
are not reliable and an alternative method should be suggested. 
21. 
Men and women not of reproductive potential are eligible without requiring the use of 
contraceptives. Acceptable documentation detailing sterilization and menopause are 
specified below. 
NOTE: Men who have sex with men only will not be required to use contraception.  
NOTE: Women who have sex with women only will not be required to use contraception.  
NOTE: Written/oral documentation communicated by clinician/clinician’s staff of one of the 
following: 
a. Physician report/letter 
b. Operative report or other source documentation in the patient record (a laboratory 
report of azoospermia is required to document successful vasectomy) 
c. Discharge summary 
d. Follicle stimulating hormone-release factor (FSH) measurement elevated into the 
menopausal range as established by the reporting laboratory 
22. Agrees not to enroll on another study of an investigational agent during the study period, 
defined as any unlicensed investigational drug not yet approved for use in humans.  
23. Willingness to defer routine vaccination, including influenza, from 14 days prior to 
enrollment through Day 56 of the study.  
NOTE: Individuals who require vaccination will delay enrollment until 14 days after 
vaccination.  
24. Agrees to refrain from blood donation during the course of the study. 
25. Participants with Type 2 diabetes must have a hemaglobin A1C <8 within 12 months 
prior to screening. 
26. Adequate organ function as indicated by the laboratory values provided in Table 16. 
 
 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
Confidential
Page 52 of 143
 
 
Table 16 
Adequate Organ Function Values for Inclusion 
System 
Laboratory Value 
Hematological 
Absolute neutrophil count 
≥ 1,000 /mcL 
Platelets 
≥ 150,000 / mcL 
Hemoglobin 
≥ 12 g/dL (male) and ≥ 11.5 g/dL (females)  
Coagulation 
Prothrombin Time or INR 
<1.1 x ULN  
Chemistry 
Serum potassium levels 
WNL 
Serum magnesium levels 
>LLN1   
Glucose 
Screening serum glucose ≤ Grade 1 (fasting or non-fasting)  
Renal 
Creatinine clearance determined by the 2021 
CKD-Epi equation found at: 
https://www.mdcalc.com/calc/3939/ckd-epi-
equations-glomerular-filtration-rate-gfr 
eGFR > 60mL/min 
Hepatic 
Serum total bilirubin 
Total bilirubin <1.5 x ULN.  
If elevated, direct bilirubin must be <2 x ULN 
If on atazanavir –containing therapy, a direct bilirubin should 
be measured instead and must be ≤1.0mg/dL.  
AST (SGOT) and ALT (SGPT) 
<1.5 X ULN 
Alkaline Phosphatase  
<1.5X ULN 
1 LLN for Mg++ per the clinical laboratory’s normal range used for this study is a grade 1 event per the DAIDS 
Toxicity Table and is allowed for eligibility. 
 
ULN = upper limit of normal 
LLN = lower limit of normal  
WNL = within normal limits 
5.2 
Exclusion Criteria 
1. Women of childbearing age/potential who are breast feeding, pregnant, or planning 
pregnancy from enrollment to 4 months after the last vaccination. 
2. Untreated syphilis infection defined as a positive rapid plasma reagin (RPR) without clear 
documentation of treatment. 
NOTE: Potential participants may rescreen with documentation of adequate treatment. 
Participants reporting symptoms consistent with syphilis infection between the screening visit 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
Confidential
Page 53 of 143
 
 
and the vaccination visit should be assessed to determine the need for repeat testing prior to 
vaccination. 
3. Current treatment for HCV or HCV treatment within 6 months prior to enrollment. 
4. HIV RNA ≥150 copies/mL in the 6 months prior to screening. 
5. Received any infusion blood product or hematopoetic growth factors within 6 months 
prior to enrollment. 
NOTE: receipt of COVID convalescent plasma ≥ 90 days prior to enrollment is not exclusionary. 
6. Use of any of the following agents within 90 days prior to enrollment: 
immunomodulatory, cytokine, or growth stimulating factors such as systemic cytotoxic 
chemotherapy or immune globulin. 
7. Intent to use immunomodulatory treatment during the study. 
8. Use of systemic corticosteroids or topical steroids over a total area exceeding 225 cm2 
within 30 days prior to enrollment, or anticipated need for periodic use of systemic 
corticosteroids during the study. 
NOTE: Participants receiving stable physiologic doses of glucocorticoids, defined as the 
equivalent of prednisone ≤10 mg/day, will not be excluded. Participants receiving inhaled, 
intranasal, topical (as defined), intermittent intra-articular corticosteroids, or topical imiquimod 
will not be excluded.  
NOTE: Concomitant use of oral/systemic /intra-articular/inhaled/intranasal corticosteroids is 
prohibited for participants receiving ritonavir or cobicistat. 
9. Use of any investigational HIV vaccine or HIV immunotherapy. 
NOTE: Exceptions allowed per PI review and approval. 
10. Any experimental non-HIV vaccination within the 6 months prior to enrollment.  
NOTE: receipt of FDA or EUA approved or licensed COVID-19 vaccines is not exclusionary if 
≥ 14 days prior to enrollment on a case by case review by PI or designee. 
11. Prior receipt of any adenovirus Group E-vectored vaccines including those for COVID-
19 (i.e. AZD1222/AstraZeneca). 
NOTE: Prior immunization with smallpox vaccine is not exclusionary.  
NOTE: Janssen Ad26COVS1 COVID-19 vaccine is not exclusionary. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Page 54 of 143
 
 
12. Prior receipt of a live vaccine within 60 days prior to enrollment (i.e. varicella, measles, 
mumps, rubella (MMR), and yellow fever).  
NOTE: Individuals who require live vaccination will delay enrollment until 60 days after 
vaccination. 
NOTE: Receipt of Mpox vaccine is not exclusionary as long as the last Mpox vaccination is 
received at least 60 days prior to enrollment. 
13. Use of any other investigational treatment within 6 months prior to enrollment, with the 
exception of Phase II or higher studies of antiretroviral agents. 
NOTE: Co-enrollment with other studies under an IND using an FDA approved medication that 
are not otherwise listed as prohibited will be considered on a case-by-case basis.     
14. For any serious illness requiring systemic treatment or hospitalization, the participant 
must either complete therapy or be clinically stable on therapy, in the opinion of the site 
investigator, for at least 90 days prior to enrollment.  
15. History of inflammatory diseases involving the peripheral or central nervous system, 
including but not limited to GBS, myasthenia gravis, optic neuritis, multiple sclerosis, 
transverse myelitis, neuromyelitis optica spectrum disorder (NMOSD) and chronic 
inflammatory demyelinating polyneuropathy (CIDP), that in the opinion of the 
investigator would preclude participation. 
16. History of pregnancy, head trauma or major surgery within 90 days prior to enrollment, 
that in the opinion of the investigator would preclude participation. 
NOTE: Minor surgery within 90 days prior to enrollment and not resulting in reduced mobility 
will be assessed on a case-by-case basis.     
17. Any clinically significant acute or chronic medical condition, other than HIV infection, 
that in the opinion of the investigator would preclude participation. 
18. History of malignancy within the last 3 years. 
NOTE: History of non-melanoma skin cancer (e.g., basal cell carcinoma or squamous cell skin 
cancer) is not exclusionary with documentation of resolution per topical treatment or complete 
resection as determined by a dermatologist at least 3 months prior to enrollment. 
19. Immune deficiency other than that caused by HIV infection. 
20. Any medical, psychiatric, substance abuse, occupational or other condition that, in the 
judgment of the investigator, would interfere with, or serve as a contraindication to, 
protocol adherence or assessment of safety. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Page 55 of 143
 
 
21. Blood pressure consistently > 150 mm Hg systolic and >100 mm Hg diastolic.  
NOTE: Elevated BP during leukapheresis procedures is not exclusionary. Isolated elevations 
must be noted as acceptable and signed by study PI or designee.  
22. History of seizure(s) within the past 3 years.  
23. History of splenectomy. 
24. Bleeding disorder including factor deficiency, coagulopathy or platelet disorder that 
requires special precautions (easy bruising without a formal diagnosis is not 
exclusionary) or on chronic anticoagulation 
25. Allergy to eggs and/or egg products. 
26. History of anaphylaxis or severe adverse reaction to prior vaccines including symptoms 
such as hives, respiratory difficulty, angioedema, and/or abdominal pain. 
27. History of hereditary angioedema, acquired angioedema or idiopathic angioedema. 
28. Known allergy/sensitivity or hypersensitivity to components of study vaccines. 
29. Unstable asthma (e.g. sudden acute attacks occurring without an obvious trigger) or 
asthma requiring: 
a. Daily steroid or long-acting beta-agonist prevention 
b. Hospitalization in the last two years 
30. Active chronic skin problems such as eczema or psoriasis not controlled with topical 
treatments.  
31. Inability to communicate effectively with study personnel. 
5.3 
Screening 
Labs and/or procedures completed within the 14 days preceding the screening visit can be used 
to qualify the participant upon approval of the study PI (or designee). 
Screening evaluations must occur prior to the participant starting any medications, treatments, or 
interventions. Screening visit can occur up to 60 days prior to Enrollment/Baseline Visit. 
5.3.1 
Re-Screening 
Potential participants who are unable to meet protocol-defined eligibility criteria at the Screening 
Visit may be eligible to re-screen again at the investigator’s (or designee’s) discretion. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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If a screen failure or the failure to enroll or proceed to Day 0 is due to the inability to meet one of 
the laboratory parameters (hematology, chemistry, HIV RNA level, or CD4+ T cell count), a 
retest of the failed criteria may be performed one time only. 
5.3.2 
Screen Failures  
Screen failures are defined as participants who consent to participate in this study but are not 
subsequently randomly assigned to the study intervention or entered in the study.  
Demographic, clinical, and laboratory data is collected on persons at screening. The information 
collected on persons who fail screening and do not enroll will be retained in the screen failure 
section of the study file.  
5.4 
Strategies for Recruitment and Retention 
There are several venues for recruitment available to the study team: 
• In the UNC and Duke ID Clinics and/or other local HIV clinics, there is a large pool of 
patients with long-term viral suppression on ART interested in participating in research.  
Many have previously participated in clinical research studies. These individuals will be 
provided with the opportunity to discuss this study with their provider and the study 
coordinator. 
• Individuals who signed the UNC CFAR database consent, as well as those who signed 
the consent for the UNC Cure and PHI studies/database, will be identified and 
approached about the study. Primary care providers or the study coordinator, after 
consultation with their primary care provider, will provide information about the study 
and participation. 
• Advertisements and flyers in local clinics and with UNC and Duke HIV Community 
Outreach Organizations. 
5.4.1 
Co-Enrollment Guidelines 
Co-enrollment on other studies will be addressed on a case-by-case basis with the study team. 
Due the potential interference with monitoring for the effects of this study’s treatments, 
participants will not be able to participate on other studies that provide medications, with the 
exception of Phase 2 or greater ARV studies. 
Co-enrollment in the ACTG 5332 REPRIEVE study (NCT023442900) using FDA approved 
pitavastatin is permitted provided the participant has taken the study provided medication ≥ 4 
months. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Although not a study, some FDA or EUA sanctioned COVID-19 treatments and vaccines are 
permitted (see eligibility criteria) but must be addressed on a case-by-case basis with the study 
team. 
6 STUDY INTERVENTION 
6.1 
Study Intervention(s) Administration 
6.1.1 
Study Intervention Description  
Double blind, randomized, placebo-controlled, parallel design, study in which 18 participants 
with durable viral suppression are randomly assigned to receive vaccination with C62-M4, 
C1C62-M3M4, or placebo.  
Participants will be randomized 8:8:2 to one of three study arms and receive study treatment or 
placebo at D0 and D28. 
6.1.1.1 
Manufacture of C62 AND C1 
The ChAdOx1.tHIVconsv1 (C1) drug substance has a genome size of 32,906 bp and is supplied 
as a slightly opaque frozen liquid, essentially free from visible particulates. The appearance is 
dependent upon the concentration of the virus (Table 1). C1 was manufactured in accordance 
with GMP by ADVAXIA BIOLOGICS S.r.l., Via Pontina km 30.600, 00071 Pomezia, Rome, 
Italy. The code name for the Drug Substance is ChAdOx1.tHIVconsv1. There is no 
recommended International Non-proprietary Name (INN). 
The ChAdOx1.HIVconsv62 drug substance has a genome size of 32,846 bp and is supplied as a 
slightly opaque frozen liquid, essentially free from visible particulates. The appearance is 
dependent upon the concentration of the virus (Table 1). C62 was manufactured accordance with 
GMP by ADVAXIA BIOLOGICS S.r.l., Via Pontina km 30.600, 00071 Pomezia, Rome, Italy. 
The code name for the Drug Substance is ChAdOx1.HIVconsv62. There is no recommended 
INN. 
6.1.1.2 
Manufacture of M3 + M4  
The drug substance/investigational medicinal product for M3 and M4 was manufactured in 
accordance with GMP by IDT Biologika GmbH (IDT), Am Pharmapark, 06861, Dessau-
Rosslau, Germany. 
6.1.2 
Dosing and Administration  
For further information on Dosing and Administration please see Section 4.1. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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6.1.2.1 
Dosing  
All participants will receive vaccine/placebo administered on D0 and a booster vaccine/placebo 
administered at D28. Participants will be randomized to Arms 1, 2 or 3, respectively.   
For the purpose of this study and safety management, a maximum of 2 study participants can be 
vaccinated in one week. 
6.1.2.2 
Study Treatment Administration 
C1, C62, M3 and M4 vaccines should be thawed to room temperature and administered within 
60 minutes of removal from the freezer. Vaccination will be performed, and the study product 
handled according to the relevant SOPs. 
Administer all vaccines/placebo doses at D0 and D28. 
Administer all vaccine/placebo doses as an IM injection in the deltoid muscle (Table 17). 
Table 17  
Study Treatment Administration 
STUDY ARM  
DAY 
Deltoid - 1 
Deltoid - 2 
1. C62-M4 
0 
C62 (2.5 ×1010 vp) 
C62 (2.5 ×1010vp) 
 
28 
M4 (0.9 ×108 pfu) 
M4 (0.9 ×108 pfu) 
2. C1C62-M3M4 
0 
C62 (2.5 ×1010 vp) 
C1 (2.5 ×1010 vp) 
 
28 
M4 (0.9 ×108 pfu) 
M3 (1.0 ×108 pfu) 
3. PLACEBO 
0 
Saline  
Saline  
 
28 
Saline  
Saline  
The study DOES NOT ALLOW any modifications to any vaccine doses. 
6.1.2.2.1 
C1 and C62  
Study Arm 1: Half of the C62 vaccine will be administered into the deltoid muscle of each arm, 
with the dose prepared for administration by the site Investigational Drug Service (IDS). The 
IDS will direct which arm (left or right) each syringe will go into as assigned by the 
randomization schedule. 
Study Arm 2: C1 will be delivered in the deltoid of one arm and C62 will be delivered to the 
other arm. The dose of both products will be prepared for administration by the site IDS. The 
IDS will direct which arm (left or right) each vaccine will go into as defined by the 
randomization schedule.  

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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6.1.2.2.2 
M3 and M4  
Study Arm 1: Half of the M4 vaccine will be administered into the deltoid muscle of each arm, 
with the dose prepared for administration by the site IDS. The IDS will direct which arm (left or 
right) each syringe will go into as assigned by the randomization schedule. 
Study Arm 2: M3 will be delivered in the deltoid of one arm and M4 will be delivered to the 
other arm. The dose of both products will be prepared for administration by the site IDS. The 
IDS will direct which arm (left or right) each syringe will go into as defined by the 
randomization schedule. 
6.1.2.2.3 
Saline Placebo 
Study Arm 3:  Saline will be administered into the deltoid muscle of each arm, prepared for by 
the site IDS. The IDS will direct which arm (left or right) each syringe will go into as assigned 
by the randomization schedule. 
6.1.2.2.4 
Rescheduled Booster Vaccination  
Participants whose D28 vaccination is delayed due to toxicity or other unanticipated event; that 
has been reviewed and approved by the PI (or designee) will have post D28 visits at the 
timepoints per the original schedule of events. This means booster vaccination will remain Visit 
7 but will be re-named to represent the number of days post prime vaccination (D0). 
Consequently, Visit 8 will occur 2 days after booster vaccination, Visit 9 - 7 days, Visit 10 – 14 
days, and so on. Post D28 procedures will take place per schedule of events based on the date of 
D28. The events will be renamed to match actual day. (i.e. D28 will remain as Visit 7 but will 
become actual day booster vaccine given post D0).  
New day numbers and timelines will be documented appropriately in study records.  
6.2 
Preparation/Handling/Storage/Accountability 
6.2.1 
Acquisition and Accountability 
The C1, C62, M3 and M4 vaccines will be used as supplied by the manufacturer. It will be 
prepared, dispensed and administered according to Pharmacy Manual and site-specific SOPs.   
Normal saline use for placebo will be obtained by the site, supplied by site IDS. 
The C1, C62, M3 and M4 vaccines will be stored, distributed from, and accountability 
maintained in the site IDS at UNC and Duke.  
The primary IDS pharmacist at each site will be responsible to the Protocol Principal Investigator 
for maintaining study drug accountability, reconciliation, and record maintenance during the 
study, including documentation of the amount of both study treatments (C1, C62, M3 and M4) 
received in IDS and the amount administered to each participant.  

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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6.2.2 
Formulation, Appearance, Packaging, and Labeling 
ChAdOx1.tHIVconsv1 vaccine (C1) was manufactured in formulation buffer at a target 
concentration of >1.1x1011 vp/mL. It is supplied at a concentration of 1.3 x1011 vp/mL. The fill 
volume is 0.65 mL. 
ChAdOx1.HIVconsv62 vaccine (C62) was manufactured in formulation buffer at a target 
concentration of >1.1x1011 vp/mL. It is supplied at a concentration of 1.6 x1011 vp/mL. The fill 
volume is 0.65 mL. 
MVA.tHIVconsv3 vaccine (M3) is a white cloudy solution, formulated in Tris-saline buffer at a 
concentration of 3.4x108 pfu/ml. The extractable fill volume is 500 µl. The product is supplied 
in sterile rubber-stopped glass vials.  
MVA.tHIVconsv4 vaccine (M4) is a white cloudy solution, formulated in Tris-saline buffer at a 
concentration of 1.8x108 pfu/ml. The extractable fill volume is 500 µl. The product is supplied 
in sterile rubber-stopped glass vials. 
C1, C62, M3 and M4 vaccines will be packaged and labeled at the manufacturing facilities.  
The vaccines will be labelled or have accompanying documentation indicating compliance with 
GMP and other regulatory requirements. The minimum information provided by the 
manufacturer includes:  
1. Study product name 
2. Concentration 
3. Manufacturer 
4. Date of manufacture 
5. Lot number 
6. Volume 
6.2.3 
Product Storage and Stability 
The investigational vaccines are shipped from manufacturing site to study site IDS pharmacy 
with temperature monitoring capacity. Once received at the IDS Pharmacy, the study vaccines 
are transferred to temperature-monitored storage.   
Vaccine accountability, storage and shipment will be in accordance with Pharmacy Manual, site 
IDS SOPs (as applicable) and DAIDS requirements.   
6.2.3.1 
C1 and C62 
The vaccines are supplied as frozen liquids in glass vials for IM administration and are stored at -
75°C ± 15°C in a secure freezer. The freezers are temperature monitored and if outside 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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designated range appropriate action is taken in accordance with Pharmacy Manual, site IDS 
SOPs (as applicable) and DAIDS requirements.  
6.2.3.2 
M3 and M4 
The study vaccines are kept in temperature-monitored storage at -75 °C ± 15°C in a locked 
freezer (See IND 18368, Investigator Brochures). The freezers are temperature monitored and if 
outside designated range appropriate action is taken in accordance with Pharmacy Manual, site 
IDS SOPs (as applicable) and DAIDS requirements.  
6.2.3.3 
Saline 
The placebo (normal saline) will be stored at room temperature.   
6.2.4 
Preparation 
6.2.4.1 
Dilution of C1 and C62  
Refer to Pharmacy Manual. 
6.2.4.2 
Dispensing and Handling 
1. The vaccine will be dispensed according to Study Specific Pharmacy Manual and/or study-
specific SOPs.  
2. All vaccines will be used as supplied by the manufacturer and prepared per pharmacy manual 
guidelines. 
3. The vaccines will be thawed to room temperature. 
4. The required dose volume will be drawn into the appropriate syringe and C1, C62, M3 and 
M4 vaccines will be administered within 1 hour of thawing. C1, C62, M3 and M4 vaccines 
will be dispensed from the UNC or Duke IDS Pharmacy, where only the pharmacist(s) will 
be un-blinded. 
5. All syringes (vaccine and placebo) will prepared per research site’s IDS Pharmacy 
procedures to maintain blinding. 
NOTE: When preparing the placebo, sodium chloride for injection 0.9% should be used in 
place of C1, C62, M3 or M4. 
Any unused portion of entered vials and expired pre-filled syringes should be disposed of in 
accordance with institutional or pharmacy policy. 
6.2.4.3 
Labeling  
Label the prepared study product or placebo with the following to maintain blinding: 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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1. Participant identifier(s) 
2. Study Product Name  
3. Route 
4. Site (L or R deltoid) to be administered. 
5. Expiration time or beyond use date and time.  
6. Any additional information required by IDS.  
7. Caution: New Drug—Limited by Federal (or United States) law to investigational use 
6.3 
Measures to Minimize Bias: Randomization and Blinding 
6.3.1 
Randomization 
The 18 study participants will be randomly assigned to receive one vaccination with C62-M4 
(n=8) or C1C62-M3M4 (n= 8) or placebo (n=2) through a blinded randomization schedule as 
further described in Section 8.2.5. When participant eligibility is confirmed, study specific 
identification numbers (SIDs) are assigned sequentially for each participant at the Enrollment 
Visit. Vaccine and placebo product will be indistinguishable and clearly labeled with the 
administration site: left deltoid or right deltoid muscle. Site and laboratory personnel and 
participants will be blinded with respect to the allocation of vaccine or placebo. A double-blind 
placebo-controlled, permuted-block design has been chosen to minimize bias in the reporting of 
safety and immunological data. 
Participants will be randomized and assigned a Randomization ID (RID) on D0 by study data 
staff prior to vaccine/placebo administration.   The institutional or site IDS will be provided a 
clearly decoded key of the three study arms in a separate file that will be maintained in a secure 
location. The randomization schedule will be generated centrally by the study statisticians at the 
UNC CFAR using computer software and will be kept concealed from study personnel. 
6.3.2 
Un-blinding 
Un-blinding of an individual participant is indicated in the event of a medical emergency where 
the clinical management would be altered by knowledge of the group assignment. Procedures 
and contact details for un-blinding procedures will specified in a unit SOP. Reference Section 
8.2.5. 
 
Unblinding may occur in response to a specific request from any regulatory agency to unblind 
the study. Blinding information will be shared with study staff who will then contact participants 
to inform them of the treatment they received. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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6.4 
Study Intervention Compliance 
Participants will keep a daily diary of solicited AEs for local and systemic symptoms for 7 days 
after both vaccine/placebo administrations. 
6.5 
Concomitant Therapy 
Whenever a concomitant medication is initiated or the dose is changed for all participants after 
receipt of vaccine/placebo at D0 through D56 of the study, the PI (or designees) must review the 
concomitant medications’ most recent package inserts, investigator’s brochures, or updated 
information from DAIDS to obtain the most current information on drug interactions, 
contraindications, and precautions. 
6.5.1 
Required Medications 
1. All participants will be required to have durable HIV suppression on ART for ≥ 24 months 
prior to study screening and maintain ART therapy throughout the entire study. The study 
will not provide ART medications.  
2. The study team will consider alternate ART regimens on a case-by-case basis prior to 
enrollment per eligibility criteria. The study permits the use of all approved PIs, NNRTIs, 
NRTIs, and fusion and integrase inhibitors. Also permitted are changes to the participants’ 
ART during the study for dosing simplification, tolerability issues, and improved side effect 
profile or at the investigator’s discretion. If a participant develops toxicity related to his/her 
previously stable ART, consult the protocol team (preferably before appropriate therapy 
modification) 
6.5.2 
Prohibited Medications 
1. Ongoing use of investigational ART with the exception of Phase II or higher studies of 
antiretroviral therapy.  
2. Concomitant use with oral or parental corticosteroids, immunosuppressive agents (including 
but not limited to azathioprine, and cyclosporine) or any immunotherapy or 
immunomodulatory agents. 
3. Inhalers or nasal sprays containing steroids from 14 days prior to first vaccination through 
Day 42, 14 days after the second vaccination.  
4. Antihistamines from 7 days prior to vaccination through Day 35. 
5. Standard vaccines (e.g., pneumococcal, Hepatitis A, Hepatitis B, influenza) are prohibited 14 
days prior to enrollment through Day 56.    

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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6. Available COVID-19 vaccines are prohibited 14 days prior to enrollment through Day 56. 
NOTE: receipt of adenoviral vectored vaccines (i.e. AstraZeneca, Janssen) should be 
deferred until 3 months after the last dose of the ChAdOx1.tHIVconsv1 vaccine (Day 90). 
7. Live vaccinations (e.g., varicella, measles, mumps, rubella, MMR, yellow fever, oral polio) 
are prohibited from 60 days prior to enrollment through Day 56, reference Sections 5.1 and 
Section 5.2;  
8. Mpox vaccinations are prohibited from 60 days prior to enrollment through D56. 
NOTE: Administration of live vaccine for Mpox is allowed at any time after enrollment if 
indicated for post-exposure prophylaxis.  
9. Any agent that suppresses lymphocytes or monocyte function. 
10. Chemotherapeutic agents, growth factors, cytokines, or chemokines, white lineage colony 
stimulating factors (e.g., granulocyte-colony stimulating factor [G-CSF] and GM-CSF).  
11. Chronic use of topical corticosteroids applied to large areas of the skin (exceeding the 
cumulative area of the palm of the participant’s hand). 
12. Sporadic topical use of corticosteroids (e.g. creams) to small areas of the skin (<225 cm2) for 
participants who are receiving ritonavir or cobicistat as part of their current ART regimen. 
13. Any form of corticosteroid or antihistamine medications at or near the injection site, 
including for treatment of injection site reactions. 
14. Refer to exclusion criteria in Section 5.2. 
7 STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1 
Discontinuation of Study Intervention 
7.1.1 
Premature Treatment Discontinuation Evaluations 
Study treatment intervention will occur at D0 and D28. The collection of safety labs, virologic, 
immunologic, SCA, and the 2nd leukapheresis will continue to be collected per SoA, Section 1.3.  
Participants who do not complete both vaccine/placebo D0 and D28 injections will be replaced, 
provided the inability to complete the D28 vaccination visit is not due to a study-related AE. 
Participants who complete both vaccine/placebo D0 and D28 injections but do not complete the 
D35 study visit will be replaced, provided the inability to complete the D35 visit is not due to a 
study-related AE. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
Confidential
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Participants who receive at least one dose of vaccine/placebo but are unable to complete either 
the D28 vaccination, the D35 visit, the 2nd leukapheresis or the D56 visit should be encouraged 
to continue on study for safety assessments per the SoA, Section 1.3.  
7.1.2 
 Discontinuation of Antiretroviral Therapy  
If the participant discontinues ART prior to D0, DO NOT give the vaccine/placebo injection.  
If the participant discontinues ART at any time after the first vaccine or placebo administration, 
the participant should continue on study for safety follow-up as noted in the SoA, Section 1.3. 
Collection of virologic, immunologic, SCA, and the 2nd leukapheresis samples will be 
determined on a case-by-case basis in discussion with the protocol team. This participant may be 
replaced. 
7.2 
Participant Discontinuation/Withdrawal from the Study 
7.2.1 
 Enrolled Participants, who are Not Randomized and Do Not Start Study 
Treatment  
Participants who withdraw or who are withdrawn from the study after the Enrollment Visit but 
prior to receipt of vaccine/placebo: 
DO NOT re-use the SID.  
REPLACE the participant. 
A participant who is unable to complete the leukapheresis procedure or has less than 20 ml of 
leukapheresis product collected prior to D0 may be terminated from the study as determined by 
the PI.  
If terminated:  
DO NOT re-use the SID.  
REPLACE the participant. 
Termination can also occur due to complications at the leukapheresis procedure as determined by 
the Clinical PI (or designee) and the Apheresis Medical Director and can include 
contraindications for further leukapheresis procedures. 
Participants who complete the first leukapheresis procedure pre-vaccine but do not want to do 
the second leukapheresis procedure may be withdrawn from the study as determined by the PI.  
If terminated: 
DO NOT re-use the SID.  
REPLACE the participant. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
Confidential
Page 66 of 143
 
 
7.2.2 
 Evaluations for Randomized Participants Who Do Not Start Study 
Treatment 
Participants who withdraw or are withdrawn after randomization but prior to starting study 
treatment (vaccine or placebo) will have no further evaluations or follow-up.  
• DO NOT re-use the RID.  
• DO NOT re-use the SID.  
• REPLACE the participant.  
7.2.3 
 Evaluations for Randomized Participants Who Received Study Product 
and are Discontinued or Withdrawn from Study Participation  
Participants who withdraw or are withdrawn after randomization and prior to D28, will have no 
further research evaluations.  Continue follow-up for safety through D28 (based on review by 
PIs) will be encouraged and if participant is unable to continue for visits through D28, they will 
be asked to complete EOS safety evaluation visit.  
• DO NOT re-use RID.  
• DO NOT re-use the SID.  
• REPLACE the participant. 
7.2.4 
 Participant May Withdraw or be Withdrawn from the Study 
• Request by the participant to withdraw from the study and study procedures. 
• Development of an illness that requires treatment with medications prohibited in the study. 
• Change in the participant’s medical condition that might make continuation in the study 
harmful to participant. 
• Participant does not continue to meet eligibility requirements. 
• Participant does not complete D7 or D35 visit.  
• Request of the participant’s primary care provider if she/he thinks the study is no longer in 
the best interest of the participant. 
• Participant judged by the study PI (or designee) to be at significant risk of failing to comply 
with the provisions of the protocol, as to cause harm to self or seriously interfere with the 
validity of the study results. 
• At the discretion of the IRB/Ethics Committee, FDA, NIH, and other government agencies as 
part of their duties, Principal Investigator (designee), or vaccine. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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7.3 
Premature Study Discontinuation (D/C) Evaluations  
Participants who prematurely discontinue study participation after completing the 
vaccine/placebo prime (D0) and boost (D28) but before D196 will have premature study 
discontinuation (D/C visit) evaluations performed per the SoA for D196.  
7.4 
Lost to Follow-Up 
Participants classified as lost to follow-up (LTFU) need to meet both of the following criteria:  
1. Failure to respond or reply to 3 documented phone contact attempts, followed by  
2. Failure to respond to a certified letter sent to the address provided by the participant.  
In scenarios in which a participant is relocated after 3 failed attempts, the study PI will address 
continued participation on a case-by-case basis.  
8 STUDY ASSESSMENTS AND PROCEDURES 
8.1 
Exclusion Efficacy Assessments  
8.1.1 
Remote Data Collection 
Study visits may be conducted remotely (e.g., telephone, facetime) in the following situations: 
a. a participant is unable to attend a visit because of a debilitating illness; the site must inform 
the protocol team in advance. 
b. the site is temporarily unable to conduct non-essential visits in the clinic per University 
policies at the time of the visit; the site must inform the protocol team in advance. 
c. at the discretion of the protocol team if the risk of an on-site visit is felt to pose more risk 
than potential benefit to the participant; a message from the team will be sent to the study 
team. 
Regardless of the situation, the study team should designate which visits were conducted 
remotely and attempt to obtain as much of the visit-specific required information, based on the 
Schedule of Events, and record it on the relevant study specific checklist. The reason for 
conducting the visit remotely must also be recorded and documented in the participant’s study 
file. 
8.1.2 
 Visit windows  
a. Perform visits per window listed in SoA, Section 1.3. There is no window around the D2, 
D7, D30, and D35 visits. There is a ± 2 days window around the visits at Days 14, 28, 42 
and 56.  

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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b. There is a ± 1 day window around the telephone call assessments at Days 5, 10, 18 and 22. 
See Appendix 2.  
c. There is a ± 7 days window around the visits at Days 84 and 140. D196 has a ± 14 days 
window. Please reference SoA, Section 1.3 and Sections 4.1 and 8.2.3. 
d. Post D28 visits are scheduled based on the date of D28 booster vaccination.  Consequently, 
D30 will occur exactly 2 days after booster vaccination, D35 will occur exactly 7 days after, 
D42 will occur 14 days (+/- 2 days) after, and so on.  
e. Window for D56 leukapheresis is – 7/+21 days with preference for the procedure to be 
completed as close to Day 56 as possible. If unable to complete the D56 leukapheresis and 
upon review and approval of the protocol PI, a large blood draw can be completed between 
14 – 21 days after D56 (Days 70-77). This large blood draw will be completed as close to 21 
days after D56 as possible (Section 8.2.3) 
8.1.3 
 Medical History  
The medical history includes all signs, symptoms and diagnoses regardless of grade within 
the 30 days prior to entry and any significant medical conditions noted in medical records 
(e.g., hospitalizations, surgeries, prior medical history). Assessment and documentation of 
the medical history evaluation occurs at the screening visit. Update to medical history will 
occur at all clinical visits. 
 Document: 
a. 
All allergies to any medications and their formulations 
b. 
Date of birth, gender, race and ethnicity of participant   
c. 
HIV history, including acute status at ART initiation and HIV-1 RNA 
suppression, if available  
d. 
Nadir CD4 and pre-ART/peak HIV-1 RNA level, if available (if documentation is 
not available, collect and record participant recall) 
e. 
Targeted Reproductive Assessment includes:  
- For women and men participating in activities that could lead to pregnancy, 
verify use of birth control for a minimum of 21 days prior to first vaccination 
date (see Section 5.1) through the 4 months following the last vaccination date. 
- Assess the date of the last menstrual period (LMP) for all women of 
childbearing potential (WOCBP) at all study visits as part of the complete PE 
or the targeted assessment. 

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ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
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8.1.4 
 Medication History 
Complete a medication history, include medication start and stop dates. Document the 
vaccine/placebo administration as indicated Table 18. 
 

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Table 18 
Medication Complete History or Timeframe 
Medication Category  
Complete History or Timeframe 
Antiretroviral Therapy  
Complete History  
Immune-based Therapy  
Current & within 90 days prior to screening.   
HCV antiviral therapy  
Complete history  
Prescription Drugs  
Within 30 days prior to screening 
Systemic Corticosteroids  
Within 30 days prior to screening 
HIV-1 related vaccines 
Complete History 
Experimental non-HIV vaccine  
Within the 6 months prior to screening 
Vaccines  
Within 60 days prior to screening (For Covid-19 
and Mpox vaccines, complete history) 
Experimental treatment for COVID-19 illness   
Within the 90 days prior to screening  
IgG therapy or immunization w/experimental Abs 
Within 90 days prior to screening 
Non-prescription drugs (OTC)  
Within 30 days of enrollment 
8.1.5 
 Clinical Assessments  
a. 
Complete Physical Exam (PE): A complete PE will be performed at screening and 
D196. This complete PE is to include at a minimum an examination of the skin, head, 
mouth, and neck; auscultation of the chest; cardiac exam; abdominal exam; and 
examination of the lower extremity for edema. The complete PE will also include signs 
and symptoms, diagnosis, weight (kg), temperature (T°C, oral), respiratory rate (RR), 
pulse (P), and blood pressure (BP). 
b. 
Targeted Physical Assessment: A targeted physical assessment is done at all 
identified visits and includes vital signs. The targeted or directed physical assessment 
addresses any previously identified or new event that the participant experiences since the 
last study visit or any unresolved signs or symptoms previously experienced. In addition 
to the vital signs, this assessment includes updates to signs and symptoms, and clinical 
assessment of HIV disease. 
c. 
Vital Signs (VS): Perform VS at all clinical visits. VS include P, BP, RR, T, and 
weight. Measurement of weight is required at check in only.  
On vaccination days, vital sign measurements will be collected before vaccination. If 
individual vital sign measurements are considered clinically significant by the 
investigator, vaccination may be withheld that day (or, as noted for BP, delayed briefly 
pending a calming period), and participants may return on a subsequent day for re-
evaluation and vaccination, ideally, within the allowed visit window (SoA, Section 1.3).  

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ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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d. 
Height: Measurement of height (cm) that is required at the screening visit should 
be performed with shoes off. 
e. 
ART Adherence Assessment: This protocol requires participants take all required 
doses of ART. Document all missed doses, even if the reason/s for missing the doses are 
outside the participant’s control. Report missed doses to study PI (or designee). Study 
participation can be terminated if HIV medication is missed.  
f. 
Assess and document any missed doses while on study and discuss missed ART 
doses with study PI (or designee). Continuation on study will be contingent on adherence. 
g. 
Antiretroviral Medication Assessments: During the study, all modifications to the 
participant’s ART regimen, including any ARV interruptions, dose modifications, 
formulations modifications, starts, and permanent discontinuations since the last study 
visit or at the study visit must be recorded. This will be checked along with the 
concomitant medications at each visit.  
h. 
Post Vaccine Assessment: Assess for any injection site reactions and systemic 
reactions. Record any reportable events. 
i. 
Signs and Symptoms Assessments: At entry, all signs and symptoms, regardless 
of grade, that occurred within the 30 days before entry must be recorded.  
j. 
Solicited Adverse Events  
Local and systemic predefined solicited AEs for reactogenicity assessment (Section 
8.2.10) will be collected in a Participant Symptom Diary for 7 days following the 
administration of each dose of study product. In addition, assessments of solicited AEs 
will occur at study visits through 28 days following administration of each dose of study 
product. 
Solicited AEs should not be reported as unsolicited AEs (see Section 8.3). However, 
solicited AEs should be reported as SAEs, MAAEs or AESIs if they meet criteria 
(Sections 8.3.2, 8.3.3 and 8.3.4 respectively).  
k. 
Unsolicited Adverse Events  
Active solicitation of AEs will be done at every study visit. Post-entry signs and 
symptoms, Grade ≥ 2, will be recorded. All signs or symptoms, definitely or possibly 
related to study interventions will be recorded, regardless of grade. Additionally, all signs 
and symptoms that lead to a change in study treatment or change in ART or 
discontinuance of the leukapheresis procedure, regardless of grade, must be recorded.  
l. 
Diagnoses: After entry, record all diagnoses identified. 

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m. 
Concomitant Medication Assessments: At screening, record all medications taken 
per medical history guidelines. Thereafter, record all new or discontinued concomitant 
medications, including prescription, dietary supplements, and over-the-counter 
medications taken or stopped since the last visit. 
8.1.6 
 Laboratory Studies  
a. 
CD4+/CD8+: All study required absolute CD4+/CD8+ count and percentages and 
CD4/CD8 ratio must be obtained from a laboratory that possesses a CLIA certification or 
equivalent. Eligibility will be determined based on a CD4+ ≥ 350 cells/µL at screening. 
b. 
Plasma HIV-1 RNA: All study required HIV-1 RNA assays must be performed by 
a laboratory that possesses a CLIA certification or equivalent. Eligibility will be 
determined based on an HIV-1 RNA value <50 at screening. 
c. 
Heparin Platelet Factor (PF) 4 Antibody: A test for heparin-induced 
thrombocytopenia (HIT) antibody, also called heparin-PF4 antibody, is performed to 
detect antibodies that develop in some people who have been treated with heparin. It is 
used to help establish a diagnosis of immune-mediated heparin-induced 
thrombocytopenia (HIT type II) when you have a low platelet count (thrombocytopenia) 
and excessive clotting (thrombosis). 
This serum sample will be collected at enrollment and processed and stored in the 
research lab for testing should participant develop a clotting adverse event. 
8.1.7 
 Research Assays  
Blood will be collected for the following research laboratory evaluations: 
a. Human Leukocyte Antigen (HLA) Typing: HLA testing will be performed; however, if 
HLA type is available in the medical record, it does not need to be repeated. The result 
will be used for research purposes. 
b. CMV Testing: Cytomegalovirus (CMV) is a common virus that usually causes no 
symptoms or only mild illness. CMV testing detects antibodies in the blood that the body 
produces in response to the infection or detects CMV directly. In the United States, as 
many as 60% of people have been exposed to CMV at some point in their life. If positive 
CMV antibody results are available in the medical record, it does not need to be repeated.  
c. EBV Testing: The Epstein-Barr virus (EBV), also known as human herpesvirus 4, is a 
gamma herpes virus that occurs only in humans. Laboratory testing can help distinguish 
whether someone is susceptible to EBV infection or has a recent or past infection.  
The Anti-VCA IgG appears in the acute phase of EBV infection, peaks at two to four 
weeks after onset, declines slightly then persists for the rest of a person’s life. If positive 
EBV antibody results are available in the medical record, it does not need to be repeated.  

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ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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d. COVID-19 RT-PCR Testing: The COVID-19 RT-PCR test is a real-time reverse 
transcription polymerase chain reaction (rRT-PCR) test for the qualitative detection of 
nucleic acid from SARS-CoV-2 collected as upper respiratory specimens (such as 
nasopharyngeal or oropharyngeal swabs, nasal swabs, or mid-turbinate swabs). 
Participants testing positive by RT-PCR at enrollment would delay progression on study 
until 30 days from date of diagnosis if asymptomatic or 30 days from resolution of mild 
to moderate symptoms related to COVID-19.  
e. COVID-19 Antibody Testing: COVID-19 nucleocapsid antibody testing on stored 
plasma as indicated per the SoA, Section 1.3.  
f. Plasma/PBMC for Immunology Studies: Plasma and cryopreserved PBMC will be 
stored for analysis of low-level viremia, T-cell specificity, phenotype and function of 
immune cells, and virologic measurements per the SoA, Section 1.3. Specific testing will 
include the following: 
1) Measurement of T cell responses pre- and post-treatment 
2) Measurement of T cell virus inhibition pre- and post-treatment 
3) Phenotyping of both total and specific CD4+ and CD8+ T cell activation, homing 
and memory differentiation using flow cytometry pre- and post- treatment 
4) Functional analysis (e.g., anti-viral cytokine and lytic molecule release) of both 
total and specific T cells pre- and post-treatment  
5) Low-level HIV-1 RNA assays pre- and post-treatment 
NOTE: Site laboratory standardized protocols will guide the performance of all research assays.  
NOTE: See Section 7.1 regarding collection of stored Plasma/PBMC for Immunology Studies 
for participants who discontinue ART or do not complete study treatment. 
8.2 
Safety and Other Assessments 
8.2.1 
Screening  
Screening takes place in a stepwise manner and includes the completion of inclusions and 
exclusion prior to enrollment. 
8.2.2 
 Participant Enrollment  
Enrollment occurs within the 60 days following screening. Participants not meeting eligibility 
requirements will not continue on study.   
Once eligibility is confirmed, participant study identification numbers (SIDs) will be assigned 
sequentially as each participant enters the study.  

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Participants testing RT-PCR positive for COVID-19 at enrollment, will delay vaccination 
following enrollment (See Section 8.1.7D above), determined by PI (or designee) on a case by 
case basis. Labs obtained at the original enrollment will not need to be repeated unless requested 
by PI after review.  
Visit 2 and all associated procedures, inclusive of leukapheresis, will occur within 60 days of 
Visit 1. If required for scheduling, the leukapheresis visit can occur separately from Visit 2 but 
within 60 days of Visit 1 and after the Enrollment/Baseline visit. Safety labs (chemistry, 
hematology, and COVID-19 RT-PCR) and vital signs assessment will be done at the last visit 
prior to vaccination and D0 will be scheduled within the 10 days of that visit.   
8.2.3 
 Leukapheresis 
Participants undergo 2 leukapheresis procedures. The first leukapheresis occurs at or after 
Enrollment/Baseline (Visit 2) but prior to D0. This leukapheresis provides cells needed to 
perform baseline research assays and measurements required to establish pre-treatment immune 
responses. 
Participants will be provided with institutional instructions to prepare for the procedure. 
1. Baseline Leukapheresis  
This procedure can occur at any time point within the 60 days following the Screening visit. 
It can occur at or after the Enrollment/Baseline (Visit 2).  
If leukapheresis is scheduled on a date other than the Enrollment/Baseline visit: 
• The procedure should be scheduled after the Enrollment/Baseline visit.  
• If the leukapheresis is the last procedure done within the 60 days of screening and 
prior to the vaccination, perform safety labs (chemistry, hematology, and COVID-19 
RT-PCR) and vital signs assessment and schedule the D0 visit within 10 days of the 
leukapheresis.  
• CBC with differential is required for the completion of the leukapheresis facility and 
will be obtained per facility policies and procedures. 
• If the leukapheresis procedure is done at the Enrollment visit, collect the leukapheresis 
product in addition to the research labs. (See Study Specific Lab Manual.) 
2. Day 56 (Visit 8) Leukapheresis 
If cannot be done within the D56 Visit window due to scheduling conflicts or unforeseen issues, 
reference procedure window in Section 8.1.2.  

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ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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The preference would be the completion of a second leukapheresis, however, if unable to 
perform leukapheresis, after review and approval by PI, a large blood draw can be completed. 
The amount to be drawn will be determined by total blood volume required by the study and will 
not exceed blood volumes allowed per site SOP. Total volume will not exceed 150 mL for this 
collection.  
8.2.4 
Randomization  
The 18 study participants will be randomly assigned to C62-M4 (n=8) or C1C62-M3M4 (n=8) 
or placebo (n=2) through a blinded randomization schedule. The randomization schedule will be 
generated in SAS version 9.4 or higher (Cary, NC) using a permuted-block design to ensure 
balance cumulatively. Each assignment will be given a consecutive randomization ID (RID: 
1001-1018). 
The administration of the first vaccination or placebo designates D0, and the remaining visits are 
calculated by consecutive days starting with D0. Participants will be randomized to Study Arm, 
and will receive secondary randomization with respect to vaccine administration sites (left and 
right deltoid muscles). The randomization to vaccine administration sites that takes place at D0 
will dictate the vaccine administration sites at D28.  
Within C1C62-M3M4, exactly half of the participants will be randomized to receive C62 in the 
left deltoid and C1 in the right deltoid muscle at D0, followed by M4 in the left deltoid and M3 
in the right deltoid muscle at D28. The remaining half of participants will receive C62 in the 
right deltoid and C1 in the left deltoid muscle at D0, followed by M4 in the right deltoid and M3 
in the left deltoid muscle at D28.  Although no randomization to administration site is required 
for Study Arms C62-M4 or Placebo since the vaccine/placebo will be split between the left and 
right deltoid muscles, an administration site (right or left deltoid) will be designated on these 
prepared syringes to guarantee blinding. 
8.2.4.1 
Participants Randomized and Do Not Receive Study Product 
Participants randomized to receive study product but who do not receive the vaccine/placebo are 
withdrawn from the study (Sections 7.2 and Section 7.3) and will be replaced. A new 
randomization ID (RID) will be generated and appended to the end of the randomization 
schedule, so that any replacements are randomized at the end of the study. 
8.2.5 
 Study Unblinding 
Study un-blinding of the research team can occur 28 days after the last participant receives their 
vaccine/placebo booster injection and following completion of an independent SMC review.   
Unblinding of study participants can commence days after all participants have completed the 
last study visit and all queries and outstanding protocol implementation requirements have been 
resolved. 

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8.2.5.1 
 Emergency Unblinding 
If, in the judgment of the protocol PI or in the judgment of the participant’s medical provider and 
the site PI, a medical event is of sufficient extreme severity that it requires the immediate 
unblinding of a participant, the site PI may proceed with unblinding a participant per the 
instructions in the study specific SOP.  The decision to un-blind will be taken in conjunction 
with the independent members of the Study Monitoring Committee (SMC). Emergency 
unblinding is expected to be extremely rare. It should only occur in the setting of a potentially 
life-threatening clinical event, and if knowing the participant’s treatment assignment would 
affect decisions regarding the participant’s immediate medical management. Both conditions 
must be satisfied.  The site personnel will ensure that the reasons for un-blinding are documented 
in the clinical research chart. 
8.2.6 
Unscheduled Visits  
Visit windows are defined in the protocol (Section 8.1.2) and SoA, Section 1.3. For a visit not 
performed within the window period, the interim visit will be completed and documented as a 
protocol deviation. If there is a missed visit that requires safety assessments or local safety labs, 
study staff should attempt to bring the participant in for an interim visit as soon as possible. 
Safety evaluations should be completed per SoA, Section 1.3 for the missed visit. 
8.2.7 
 Vaccine and Placebo Administration Visit  
First vaccine (C62 or C1C62) or placebo injections are given at D0 and second vaccine (M4 or 
M3M4) or placebo injections at D28.  
1. Complete required pre-vaccine/placebo assessments and blood draws (Section 1.3) prior to 
the administration of the vaccine/placebo. 
2. At D0 and D28, record the RID and the vaccine/placebo injection, including dose and time of 
administration. Record where the injection was given (location). If unable to administer the 
entire dose for any reason, notify the study PI (or designee) and document the reason. 
8.2.8 
 Administration of study vaccine/Post Vaccine/Injection management 
1. Observe participant and injection site for 30 minutes following each vaccine/placebo 
injection for clinical AEs per SOP. 
2. Instruct participant to contact the study coordinator immediately with any concerns about the 
injection site after leaving the clinic. 
3. Provide post vaccination symptom diary and instructions for completion prior to leaving the 
clinic per SOP: Completion of Post Vaccination Symptom Diary. 
4. Contact participant two days after the injection in the manner pre-determined by the study 
coordinator and participant for AE assessment. 

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ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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5. Following receipt of vaccine/placebo, participants will be followed with study visits through 
D196 after D0 
8.2.9 
Post Vaccination Symptom Diary  
Solicited AEs will be captured in the post vaccination symptom diary given to each participant 
following each vaccination. Reference Table 9, Table 10, Table 11, and Table 12 for a complete 
list of the predefined solicited AEs for reactogenicity assessment.   
8.2.10 
Solicited AE Assessments 
Participants will be given a Post Vaccination Symptom Diary, an oral thermometer and tape 
measure along with an emergency 24-hour telephone number to contact the on-call study 
physician, if needed.  
Following administration of each dose of study product, participants will be instructed to record 
for 7 days the timing and severity of local and systemic solicited AEs, if applicable and whether 
medication was taken to relieve the symptoms. 
Participants will be instructed to take their temperature once daily, starting with the day of both 
injections (D0 and D28), after leaving the clinic and through D7 post-injection. Temperature 
should be taken orally in the evening whenever possible. If more than one measurement is made 
in a day (for example due to feeling unwell), then the highest temperature taken that day should 
be recorded. Study staff will follow new or unresolved solicited AEs to resolution. In general, 
participants reporting any post-injection reaction greater than mild should to be evaluated by the 
study PI (or designee) within 72 hours after onset, unless the reaction is improving and/or has 
completely resolved. 
Initiate appropriate countermeasures, including medical intervention or procedures, if clinically 
indicated. 
8.2.11 
Severity Assessment of Solicited AEs 
Severity will be assessed for solicited AEs by the participant according to toxicity grading scales 
provided in the Post Vaccination Symptom Diary.  
Participants experiencing any severe symptoms, will be instructed to call study coordinator or on 
call study physician for evaluation.  
Following the administration of the first vaccine/placebo, the study coordinator will contact the 
participant on D2, D5, D10, D18, D22 and D28 to review symptoms and any issues they may be 
experiencing. The Post Vaccination Symptom Diary is reviewed with the participant for 
accuracy and completeness on D7 and D35. Assessment of local and systemic unsolicited AEs 
will be done at every visit. Participants will be asked to contact the study team should they 

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ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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experience AEs, especially those listed as emergent on their Vaccine Information Card and in the 
Post Vaccination Symptom Diary, at any time point during the study.   
8.2.12 
End of Study  
The End of Study (EOS) Visit will occur 6 months following the last vaccination. Throughout 
the protocol and study documents, this last required visit will be referred to as the EOS visit, 
EOS, Day 196 or D196.  
8.2.13 
Vaccination Information Card  
Participants will be provided with a vaccination information card listing the signs and symptoms 
associated with TTS and general instructions for care should they need to seek care outside the 
study for the development of AEs associated with clotting disorders, neurological disorders or 
other AESIs.   
8.2.14 
Laboratory Evaluations  
Details of specimen collection are in the Lab Procedures Manual.   
The study PI (or designee) assesses the results of all clinical laboratory tests to determine 
continuing eligibility or AE relatedness at specified visits. Lab results or values outside the 
normal reference range require the investigator (or designee) to determine if the abnormal value 
is clinically significant and/or related to a study intervention. All confirmed abnormal laboratory 
values that the investigator deems clinically significant and/or related to a study intervention 
must be reported as AEs, regardless of grade. Post-entry laboratory values, Grade ≥2, will be 
recorded. Participants and/or their primary care provider will be informed of any clinically 
significant laboratory test result or clinical event that occurs throughout the study. Participants 
will be referred for care when appropriate. 
1. Hematology: Perform hemoglobin, hematocrit, white blood cell count (WBC), differential 
WBC, absolute neutrophil count (ANC), and platelet count in real time at the local 
laboratory. 
a. CBC with differential for leukapheresis procedures per collection agency policy:  
1. A STAT CBC with differential is required prior to each leukapheresis performed at 
the UNC Apheresis Lab unless results completed within 24 hours of the procedure 
are available to the Apheresis Lab performing the procedure.  
2. Leukapheresis procedures performed at a local apheresis collection center require a 
CBC within 30 days of procedure, neutrophil count (ANC), and platelet count in 
real time at the local laboratory. 
2. Blood Chemistries:  Perform the following:  

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ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
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a. Electrolytes (sodium, chloride, potassium, CO2/bicarbonate), glucose, blood urea 
nitrogen (BUN), creatinine, calcium, and magnesium, in real time at the local laboratory.  
b. Liver function test: (total bilirubin, AST (SGOT), ALT (SGPT), and alkaline 
phosphatase) in real time at the local laboratory. 
Note: For participants on ritonavir boosted atazanavir, total and direct bilirubin should be 
measured. 
3. Creatinine and Creatinine Clearance: The creatinine clearance (eGFR) will be required for 
study enrollment eligibility. The study assesses serum creatinine level at all the safety lab 
checks and uses the serum creatinine value for toxicity grading.  
Creatinine clearance (eGFR) calculations will use the 2021 CKD-EPI equation. This 
calculation can be found at https://www.mdcalc.com/calc/3939/ckd-epi-equations-
glomerular-filtration-rate-gfr  
The creatinine clearance (eGFR) value reported as part of the lab report of serum creatinine 
level will be re-assessed and re-calculated if incidental finding indicates a value ≥ Grade 3. 
The re-calculated value using the 2021 CKD-EPI equation will be used to determine the 
severity of the lab abnormality.  
4. Pregnancy Test - Serum or Urine beta-HCG per SOE:  A negative serum pregnancy test 
(to rule out pregnancy) is required on all women at screening. A negative urine POCT 
pregnancy test on D0 and D28 will be completed on all women of childbearing potential. 
Urine test must have a sensitivity of <25 mIU/mL.  
NOTE: Confirmation of a negative urine POCT pregnancy test within 7 days of a 
leukapheresis at the American Red Cross is required on all women of childbearing potential. 
The use of the POCT urine pregnancy test as confirmation of negative pregnancy status is 
acceptable for vaccination visit at D0 and D28, unless pregnancy is suspected. If pregnancy 
is suspected, a serum pregnancy test must be done to rule out pregnancy. The test must be 
negative within 48 hours of the dose.  
In addition, a POCT pregnancy test should be performed at any visit post vaccination, if 
pregnancy is suspected. Because the study has no direct clinical benefit, this added protection 
is warranted. 
The study will use the date of LMP to rule out suspected pregnancy. Pregnancy will be 
suspected if >35 days since first day of last menstrual period in pre-menopausal women has 
elapsed. 
5. Hepatitis Screen: Both hepatitis tests (HCV AB and HBsAg) must be negative or non-
detected to be included on the study. A positive HCV AB test reflexed to Hepatitis C RNA 

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ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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revealing a negative result is acceptable.  If participant has history of Hepatitis C with prior 
positive HCV AB, perform RNA test only. 
6. RPR: Participants diagnosed with syphilis at screening may rescreen following a minimum 
of 14 days following documentation of adequate treatment of syphilis.  
7. HIV Ag/Ab Test: Complete HIV testing at screening if documentation of HIV infection is 
not available from prior records. 
8. Prothrombin time (PT), INR, and APTT: Evaluate at the Screening Visit.  
9. PF4 Antibody ELISA: A sample will be collected and stored at enrollment and collected per 
clinical management of suspected clotting AESI. (Section 8.1.6)  
10. Estimated Blood Volumes: The estimated blood volumes associated with each study visit 
are provided Table 19. 
Table 19 
Blood Volumes Associated with Study Visits 
Day # 
Approximate Blood 
Volume (mL) 
Day # 
Approximate Blood Volume 
(mL) 
Screen 
103 
Day 35 
88 
Enrollment/Baseline 
78 
Day 42 
60 
Baseline Leukapheresis  
20 
Day 56  
42 
Day 0 
77 
D56 Leukapheresis 
20 
Day 7 
88 
Large Blood Draw 1 
150 
Day 14 
60 
Day 84 2 
88 
Day 28 
57 
Day 140 
99 
Day 30  
0 
Day 196 
105 
1 Large blood to be completed only on approval of PI if unable to complete D56 leukapheresis (Section 8.1.2) 
2 If leukapheresis at D56 occurs, blood is drawn at D84. If large blood draw is scheduled, then no D84 research blood 
draw is performed. 
8.3 
Adverse Events and Serious Adverse Events 
 
The PI is responsible for ensuring that all staff involved in the study are familiar with the content 
of this section. 
 
All AEs are considered to be unsolicited AEs (collected by ‘open question’ at study visits) unless 
categorized as solicited AEs (Reference Table 9, Table 10, Table 11, and Table 12). 
 
Solicited AEs are local or systemic predefined events for assessment of reactogenicity. Solicited 
AEs will be reported by the participant and collected in a Post Vaccination Symptom Diary 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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(Section 8.2.9). Solicited AEs will be assessed separately from the unsolicited AEs collected 
during the study visits or telephone assessments. 
 
General information for AEs in this protocol excludes solicited AEs.  
 
The PI and any designees are responsible for detecting, documenting, and recording 
events that meet the definition of an AE. 
8.3.1 
Definition of Adverse Events (AE) 
Adverse event means any untoward medical occurrence associated with the use of an 
intervention in humans, whether or not considered intervention-related (21 CFR 312.32 (a)). 
An adverse event can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding, for example), symptom, or disease temporally associated with the use of a 
medicinal product, whether or not considered related to the medicinal product. 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. 
8.3.2 
 Definition of Serious Adverse Events (SAE) 
An adverse event (AE) or suspected adverse reaction is considered "serious" if, in the view of 
either the investigator or sponsor, it results in any of the following outcomes:  
1. Results in death – the cause of death is the AE; death is an outcome.  
2. A life-threatening adverse event – The term ‘life-threatening’ in the definition of ‘serious’ 
refers to an event in which the participant was at risk of death at the time of the event. It does 
not refer to an event, which hypothetically might have caused death, if it were more severe.    
3. Inpatient hospitalization or prolongation of existing hospitalization - In general, 
hospitalization signifies that the participant has been detained (usually involving at least an 
overnight stay) at the hospital or emergency ward for observation and/or treatment that 
would not have been appropriate in the physician’s office or outpatient setting. 
Complications that occur during hospitalization are AEs. If a complication prolongs 
hospitalization or fulfils any other serious criteria, the event is serious. When in doubt as to 
whether ‘hospitalization’ occurred or was necessary, the AE should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an SAE. 
4. A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions - The term disability means a substantial disruption of a person’s ability 
to conduct normal life functions. This definition is not intended to include experiences of 
relatively minor medical significance such as uncomplicated headache, nausea, vomiting, 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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diarrhea, influenza, and accidental trauma (e.g., sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption.  
5. A congenital anomaly/birth defect.  
6. Important medical events – Important medical events that may not result in death, be life-
threatening, or require hospitalization may be considered serious when, based upon 
appropriate medical judgment, they may jeopardize the participant and may require medical 
or surgical intervention to prevent one of the outcomes listed in this definition. Examples of 
such medical events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias, or convulsions that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse. 
8.3.3 
 Definition of Medically Attended Adverse Events (MAAEs) 
MAAEs are defined as AEs leading to medically-attended visits that were not routine visits for 
physical examination or vaccinations, such as an emergency room visit, or an otherwise 
unscheduled visit to from medical personnel (medical doctor) for any reason. AEs, including 
abnormal vital signs, identified on a routine study visit or during the scheduled illness visit will 
not be considered MAAEs.  
8.3.4 
 Definition of Adverse Events of Special Interest (AESIs)  
An AESI (serious or non-serious) is one of scientific and medical concern specific to the 
sponsor’s product or program, for which ongoing monitoring and rapid communication by the 
investigator to the sponsor can be appropriate. Such an event might warrant further investigation 
in order to characterize and understand it. Depending on the nature of the event, rapid 
communication by the trial sponsor to other parties (e.g., regulators) might also be warranted. 
AESIs will be collected according to the timepoints in the SoA (Section 1.3). 
An AESI can be serious or non-serious. All AESIs will be recorded in the participant chart and 
the database.  
Serious AESIs will be recorded and reported as per Section 9.5.  
AESI for this protocol include those listed below.  
1. Grade 3 or greater Injection Site Reactions  
2. Immune-related AEs of any grade 
3. Blood clot related events any grade (as per Section 9.2.1) 
4. New onset neurological diseases of any grade (as per Section 9.2.2)  

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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NOTE: Participants with an ongoing AESI at EOS should be followed until the AESI has 
resolved or stabilized in the opinion of the study team. 
8.4 
Time Period and Frequency for Collecting AE and SAE Information  
8.4.1 
Classification of an Adverse Event 
8.4.1.1 
Severity of Event 
 
Event severity will be assigned according to the PI’s (or designee’s) assessment. The grading 
system for drug toxicities is located in the Division of AIDS Table for Grading the Severity of 
Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 
2017, which can be found on https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-
grading-tables  
Severity Grade for Parameters Not Identified in the Grading Table:  
Table 20 should be used to grade the severity of an AE that is not specifically identified in the 
grading table. In addition, all deaths related to an AE are to be classified as Grade 5. 
Table 20 
Criteria for Grading the Severity of an AE 
PARAMETER  
GRADE 1 MILD  
GRADE 2 
MODERATE  
GRADE 3 
SEVERE  
GRADE 4 
POTENTIALLY 
LIFE-
THREATENING  
Clinical adverse 
event NOT 
identified 
elsewhere in the 
grading table  
Mild symptoms 
causing no or 
minimal 
interference with 
usual social & 
functional activities 
with intervention 
not indicated  
Moderate 
symptoms causing 
greater than 
minimal 
interference with 
usual social & 
functional 
activities with 
intervention 
indicated  
Severe symptoms 
causing inability to 
perform usual 
social & functional 
activities with 
intervention or 
hospitalization 
indicated  
Potentially life-
threatening symptoms 
causing inability to 
perform basic self-care 
functions with 
intervention indicated 
to prevent permanent 
impairment, persistent 
disability, or death  
8.4.1.2 
Relationship to Study Intervention 
Attribution/Assessment of Causality is a determination that describes the relationship or 
association of the study product with an adverse event.  
The PI or designee must assess the relationship between vaccine/placebo and each occurrence of 
each AE/SAE using their clinical judgement. This assessment of causality or relationship of AEs 
to the study product is determined by 1) temporal relationship of the event to the administration 
of study product, 2) whether an alternative etiology has been identified, and 3) biological 
plausibility.  

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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The causality assessment categories that will be used for this study are described below. 
• Causality assessments that are considered not related to study product: 
1. Not related: 
The event is related to an etiology other than the study product (the alternative etiology 
must be documented in the participant’s medical record). 
If an SAE is considered "unrelated" to study product, the Investigator should offer his/her 
clinical opinion as to what factor(s), agent(s), or process(s) were the likely causative 
mechanism for the event.  
• Causality assessments that are considered related to study product: 
1. Possible: 
 
There is an association between the event and the administration of the study product and 
there is a plausible mechanism for the event to be related to study product; but there may 
also be alternative etiology, such as characteristics of the participant’s clinical status or 
underlying disease. 
2. Definite: 
There is an association between the event and the administration of study product; a 
plausible mechanism for the event to be related to the study product, causes other than the 
study product have been ruled out, and/or the event re-appeared on re-exposure to the 
study product. 
8.4.1.3 
Expectedness  
The PI (or designee) will be responsible for determining whether an adverse event (AE) is 
expected or unexpected.  An AE will be considered unexpected if the nature, severity, or 
frequency of the event is not consistent with the risk information previously described for the 
study intervention or is not listed in the most current IBs for the study intervention. 
8.4.2 
Time Period and Frequency for Event Assessment and Follow-Up 
The occurrence of an adverse event (AE) or serious adverse event (SAE) may come to the 
attention of study personnel during study visits and interviews of a study participant presenting 
for medical care, or upon review by a study monitor. 
AEs will be assessed and recorded from the time the participant is enrolled on the study through 
the date of the last participant required contact. Reference SoA, Section 1.3 and Appendices for 
enhanced assessments that will be done during the 28 days following administration of study 
product.  

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Solicited AEs will be assessed and recorded for 28 days following each dose of study product. 
SAEs will be assessed and recorded from the time the participant is enrolled on the study through 
the date of the last participant required contact  
MAAEs and AESIs will be assessed and recorded starting on Day 0 (vaccine/placebo 
administration), through all post treatment visits, and through the date of last participant required 
contact.  
All unsolicited AEs not meeting the criteria for SAEs will be captured in the research record on 
the appropriate form. Information collected includes: 
1. event description,  
2. time of onset,  
3. PI’s (or designees) assessment of: 
○ severity,  
○ relationship to study product,  
○ expectedness, 
4. time of resolution/stabilization of the event.  
All AEs occurring while on study must be documented appropriately regardless of relationship.  
Any study related AE that is unresolved at the participant’s last study visit should be followed up 
by the investigator or designee for as long as medically indicated, but without further recording 
in the database. All study-product related AEs should be followed to adequate resolution unless 
in the investigator’s opinion, the AE is unlikely to resolve and has become a chronic underlying 
disease. AE outcomes will be documented as one of the following:  
1. Recovered/resolved. 
2. Recovering/resolving 
3. Not recovered/not resolved 
4. Recover with sequelae/resolved with sequelae. 
5. Fatal  
6. Unknown 
The action taken with the vaccine/placebo due to the AE should be recorded using one of the 
following: 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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1. No action taken. 
2. Next dose delayed. 
3. Permanently discontinued/withdrawn from further study vaccination (with date). 
4. Not applicable.  
Any medical condition that is present at the time that the participant is screened will be 
considered baseline and not reported as an AE. However, if the study participant’s condition 
deteriorates at any time during the study, it will be recorded as an AE.  
Changes in the severity of an AE will be documented to allow an assessment of the duration of 
the event at each level of severity to be performed. AEs characterized as intermittent require 
documentation of onset and duration of each episode. 
The research coordinator will record all reportable AEs with start dates occurring any time on or 
after the enrollment visit through the last participant required contact. At each study visit, the 
research coordinator will inquire about the occurrence of AEs and SAEs since the last visit. 
Starting with Day 0, in addition to AEs and SAEs evaluations, the study coordinate will 
additionally assess for MAAEs and AESIs.  
If the investigator becomes aware of an SAE or AESI with a suspected causal relationship to the 
study intervention that occurs after the end of the clinical study in a treated participant, the 
investigator shall, without undue delay as described in Table 21. 
8.4.3 
Clinical Laboratory Assessments:  
Safety laboratory assessments will be carried out at UNC, Duke, or local Lab Corp and evaluated 
by the investigator to ensure participant safety. The investigator is responsible for reviewing the 
results of all laboratory tests as they become available.  
a. Laboratory values that fall outside of a clinically accepted reference range or differ 
significant from previous values must be evaluated for clinical significance by the PI (or 
designee). The PI (or designee) may repeat the laboratory test or request additional tests to 
verify the results of the original laboratory tests.  
b. If the PI (or designee) determines the laboratory value to be of clinical significance for that 
participant, it is considered an AE.  
c. Generally, Grade 1 and Grade 2 laboratory findings need not be reported as AEs unless 
deemed clinically significant by the PI (or designee).  
d. Consistent with the DAIDS designation of Grade 3 events as severe or medically significant 
and Grade 4 events as life-threatening, Grade 3 and Grade 4 laboratory findings should be 
reported as AEs or SAEs, as appropriate.  

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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e. The test result or finding should be reported as the AE. Such laboratory values should 
generally be recorded as “increased” or “decreased” (e.g., change from baseline potassium of 
5.0 to 3.5 mEq/L = potassium decreased). 
9 CLINICAL MANAGEMENT  
9.1 
Toxicities 
Adverse events will be graded according to the DAIDS AE Grading Table. The PI (or designee) 
is responsible for appropriate reporting of AEs to the regulatory authorities. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Table 21  
Expedited Reporting Guidelines  
Entity 
(Notification Method) 
Protocol Team 
(Email1) 
SMC 
(Email) 
NIH DAIDS and 
DAIDS MO 
 
University of 
Oxford 
(Email) 
UNC IRB 
(PRI) 
FDA2  
Personnel Responsible for 
Reporting 
Site PI 
Protocol PI 
Site PI 
Protocol PI 
Protocol PI 
Protocol PI 
Grade 3 AEs (including 
local or systemic reactions) 
Within 24 hours of site 
awareness 
(report again within 24 
hours if AE does not return 
to ≤G2 after 14 days) 
As determined per 
protocol team 
(report again within 24 
hours if AE does not 
return to ≤G2 after 14 
days) 
 
 
 
 
Grade 4 AEs (including 
local or systemic reactions) 
Within 24 hours of site 
awareness 
(report again within 24 
hours if AE does not return 
to ≤G2 after 14 days) 
Within 24 hours of 
protocol team awareness 
(report again within 24 
hours if AE does not 
return to ≤G2 after 14 
days) 
Within 3 days of site 
awareness 
Within 3 days of site 
awareness 
Report according to 
UNC IRB Promptly 
Reportable Information 
SOPs (SOPs 1401, 
1402)  
Report according to 
FDA requirements for 
IND reporting 
Grade 3 or 4 allergic or 
hypersensitivity reactions 
at least possibly related to 
study treatment 
Within 24 hours of site 
awareness 
Within 24 hours of 
protocol team awareness 
Within 3 days of site 
awareness 
Within 3 days of site 
awareness 
Report according to 
UNC IRB Promptly 
Reportable Information 
SOPs (SOPs 1401, 
1402)  
Report according to 
FDA requirements for 
IND reporting 
AESIs  
Within 24 hours of site 
awareness 
(AESI Clotting Form)  
Within 24 hours of site 
awareness 
Within 24 hours of 
site awareness 
Within 3 days of site 
awareness 
Report according to 
UNC IRB Promptly 
Reportable Information 
SOPs (SOPs 1401, 
1402)  
Report according to 
FDA requirements for 
IND reporting 
SAEs NOT related to 
study treatment 
Within 24 hours of site 
awareness 
As determined per 
protocol team 
Within 3 days of site 
awareness 
Within 3 days of site 
awareness 
 
 
Report according to 
FDA requirements for 
IND reporting 
SUSARs  
(SAEs at least possibly 
related to study treatment) 
Within 24 hours of site 
awareness 
Within 24 hours of 
protocol team awareness 
Within 3 days of site 
awareness 
Within 3 days of site 
awareness 
Report according to 
UNC IRB Promptly 
Reportable Information 
SOPs (SOPs 1401, 
1402)  
Report according to 
FDA requirements for 
IND reporting 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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1 Email the protocol team at UNC_IGHID12107@med.unc.edu.    
2 Reference IGHID 12107 CQMP for additional details.  Report according to FDA requirements for IND reporting: https://www.fda.gov/drugs/investigational-new-drug-ind-application/ind-
application-reporting-safety-reports 
 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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9.1.1 
Grade 1 and Grade 2 Toxicities 
Participants who develop a Grade 1 or Grade 2 AE or regardless of relationship to study product  
may complete study treatment at the discretion of the site PI. Grade 1 or Grade 2 AEs that may 
be related to the vaccine/placebo injection will be handled according to standard clinical practice 
and documented. The adverse event will be monitored closely.  
9.1.2 
 Grade 3 and Grade 4 Toxicities 
For participants who develop a Grade 3 or Grade 4 AE following administration of 
vaccine/placebo, the site PI or designee must be notified within 24 hours. Grade 3 or Grade 4 
AEs should be reported as described in Table 21.   
Grade 3 events 
If a participant develops a Grade 3 AE, the participant may not receive further study product 
until:  
• Written consultation and approval from the study PI (and SMC, as needed)  
• The AE has returned to baseline or ≤ Grade 2 and determined clinically stable by the site 
PI (or designee).  
If any grade 3 AE has not returned to baseline or ≤ Grade 2 within the D28 window, the vaccine 
can only proceed after consultation with the protocol team.  Ideally, the booster vaccination is 
administered within 30 days of the Day 28 visit window but can be delayed up to 60 days after 
Day 28 visit window.  
Grade 4 events 
Grade 4 events at least possibly related to study treatment will result in permanent 
discontinuation of study product for the participant. 
If a participant develops a Grade 4 AE not related to study treatment, the participant may not 
receive further study product until: 
• Written consultation and approval from the study PI (and SMC, as needed)  
• The AE has returned to baseline or ≤ Grade 2 and determined clinically stable by the site 
PI (or designee).  
Ideally, the booster vaccination is administered within 30 days of the Day 28 visit window but 
can be delayed up to 60 days after Day 28 visit window 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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9.2 
AESI  
9.2.1 
Potential blood clots AESIs and Thrombosis with Thrombocytopenia 
Syndrome (TTS) 
A high index of suspicion for blood clots should be maintained in participants who develop 
symptoms or diagnoses associated Thrombosis with Thrombocytopenia Syndrome (TTS), after 
receiving vaccine/placebo on study. The PI and study team must be notified immediately of all 
suspected cases. Signs and symptoms include: shortness of breath; chest pain; blurred vision or 
other vision changes; swelling, pain or erythema in a limb; severe or persistent abdominal pain; 
nausea or vomiting; dizziness; mental status changes; seizure, severe or persistent headache; easy 
bruising and/or bleeding; microhemorrhage beside the site of vaccination. If a participant 
experiences new onset (acute or subacute) symptoms listed above, there should be prompt 
evaluation, and consideration of prompt imaging to evaluate for the diagnoses listed below and 
hematology consultation. Associated diagnoses include: 
• 
Deep vein thrombosis (DVT) – symptoms depend on location of thrombosis such 
as: swelling, pain, warmth of an extremity; headache, visual disturbances, seizures 
for sinus vein thrombosis; abdominal pain for intraabdominal thrombosis 
• 
Pulmonary thromboembolism – sudden onset of shortness of breath, pleuritic chest 
pain, sudden death/pulseless electrical activity arrest 
• 
Stroke or cerebral venous sinus thrombosis  
• 
Myocardial infarction 
• 
Arterial thrombosis 
Initial evaluation should include the following:  
• 
CBC with manual count 
• 
D-dimer 
• 
PT/INR 
• 
PF4 antibody ELISA 
• 
Fibrinogen 
For any suspected TTS, WITHOLD further doses of vaccine/placebo until diagnostic evaluation 
has been completed and etiology of the signs and symptoms has been determined.  
In cases of concern for TTS, see Appendix 5 for a recommended testing algorithm. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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For this study, Vaccine-induced immune thrombotic thrombocytopenia (VITT) will be defined as 
the following: 
• 
Platelet count <150 x 109/L with a confirmatory peripheral smear showing reduced 
platelets with no evidence of clumping (that could indicate falsely low platelet 
count) 
• 
Presence of thrombosis/thromboembolism (refer to the list of MedDRA Preferred 
Terms proposed by the CDC; See Appendix 6) confirmed by: 
1) Imaging (i.e. ultrasound, CT scan, magnetic resonance imaging or venography or 
arteriography, echocardiogram, perfusion V/Q scan, conventional angiography, etc) 
2) Surgical Procedure (confirming presence of thrombus), i.e. thrombectomy 
Pathologic examination, i.e. biopsy or autopsy 
PFA antibody positive 
Study staff will complete an AESI clotting form using the list of MedDRA Preferred Terms 
(Appendix 6) to ensure complete documentation of the event. 
If evaluation provides evidence that TTS is unlikely, it is important to document the scientific 
evidence for and treat per standard clinical practice. Participants may continue study procedures 
unless clinically contraindicated. 
If TTS is confirmed or probable, the participant should not receive additional vaccine/placebo, 
but should be followed for safety per the SOA and as clinically indicated. See Section 9.1 for 
expedited reporting as an AESI. 
9.2.2 
Potential Neurological AESIs 
The PI and study team must be notified immediately of all suspected cases of neurological 
diseases. Neurological diseases are most commonly based on clinical symptoms.  
If a participant experiences new onset (acute or subacute) motor or sensory disturbances (i.e., 
weakness, numbness, dysarthria, dysphagia, paresthesias, hypoesthesia, hyperesthesia, 
dysesthesias), bowel/bladder dysfunction, gait impairment, visual disturbance, or any event of 
myelitis, encephalomyelitis, transverse myelitis, or other sudden neurological deficit, there 
should be prompt neurological evaluation, including referral to a neurology specialist for further 
evaluation, testing and treatment, as clinically indicated. In cases of concern for spinal cord 
disease, see Appendix 4 for a recommended testing algorithm which would be shared with 
providers caring for the participant. 
For new onset neurological symptoms, proceed with the following: 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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• 
WITHHOLD further doses of vaccine/placebo until clinical and laboratory 
evaluation are completed and etiology of the symptoms or laboratory abnormalities 
are defined  
• 
Consultation with neurology immediately 
If neurological disease is confirmed or probable, the participant should not receive additional 
vaccine/placebo, but should be followed for safety per the SOA and as clinically indicated. See 
Section 9.5 for expedited reporting as an AESI. 
9.2.3 
 Delayed Dose  
In the event of acute illness or inability to return for Day 28, the booster vaccination can be 
delayed. The booster vaccine should ideally be given within 30 days after the Day 28 visit 
(booster vaccine dose) but can be extended up to 60 days, if needed. See Section 9.1.2 for 
additional instructions regarding delayed doses for Grade 3 or Grade 4 AEs. 
9.2.4 
 Consideration for SARS-CoV-2 Pandemic 
See Appendix 3 for guidance about participant follow-up during periods of restrictions of in-
person study visits due to local SARS-CoV-2 transmission. Participants should be tested for 
SARS-CoV-2 infection at the discretion of the site investigator according to any applicable local 
guidelines or SOC. 
9.3 
Adverse Event Reporting  
The study will monitor participants for adverse events. Safety endpoints will include all adverse 
experiences, in addition to laboratory safety assessments, and vital signs. All AEs will be 
recorded on the appropriate study form.  
AEs will be recorded in the database if any of the following criteria have been met:   
1. Study treatment related Grade ≥ 1 AE  
2. Grade ≥ 2 AEs  
3. Autoimmune-related AEs regardless of grade 
4. MAAEs regardless of grade  
5. AESIs regardless of grade 
6. HIV viral loads ≥ 50 copies/mL 
7. Injection Reactions regardless of grade  

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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8. AEs that led to a change in study treatment/intervention regardless of grade 
9. AEs meeting SAE definition  
 
9.3.1 
 Local or Systemic Reactions to Vaccine/Placebo Injections 
9.3.1.1 
Grade 1 or 2  
Local reactions of Grade 1 or Grade 2 severity will usually resolve spontaneously. If needed, 
they may be managed with local application of cold packs, oral acetaminophen, oral non-
steroidal anti-inflammatory agents, or a combination of these measures as appropriate. 
NOTE: Topical steroids should not be applied to the injection site. 
9.3.1.2 
Grade 3 or 4  
Grade 3 or Grade 4 local reactions (Table 9 and Table 11) should be reported as described in 
Table 21 (AESI per definition in Section 8.3.4). For Grade 4 local reactions, notify site PI or 
designee immediately (or Emergency response team, as appropriate) as definitive medical and/or 
surgical intervention should be undertaken as appropriate.  
Grade 3 and Grade 4 systemic reactions (Table 10 and Table 12) should be reported as described 
in Table 21. The common systemic adverse events usually seen with ChAdV-vectored vaccines 
and MVA-vectored vaccines are listed in Section 2.3.2 (Table 9, Table 10, Table 11, and Table 
12). These events usually occur within 24 hours of vaccination and will resolve within the 
following 48 hours.  It is anticipated that the majority of systemic adverse events post 
vaccination will be mild in intensity. However, there is a possibility of moderate or severe 
headache or malaise. 
9.3.1.3 
Injection Site Reaction 
Injection Site Erythema or Redness and Injection Site Induration or Swelling will not be 
considered an AE if there is no interference with usual social and functional activities such that:  
1. Grade 1: 2.5 to < 5 cm in diameter OR 6.25 to < 25 cm2 surface area;  
2. Grade 2: ≥ 5 to < 10 cm in diameter OR ≥ 25 to < 100 cm2 surface area;  
3. Grade 3: ≥ 10 cm in diameter OR ≥ 100 cm2 surface area OR Ulceration OR Secondary 
infection OR Sterile abscess OR Drainage;  
4. Grade 4: Potentially life-threatening consequences (e.g., abscess, exfoliative dermatitis, 
necrosis involving dermis or deeper tissue) 

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ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
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9.3.2 
Allergic or Hypersensitivity Reactions 
Record all allergic and hypersensitivity reactions with both grade severity and attribution.  
Serious allergic or hypersensitivity reactions (≥ Grade 3) that are deemed possibly related to the 
study treatment by the PI (or designee) will be reported as described in Table 21 and as detailed 
at https://www.fda.gov/drugs/investigational-new-drug-ind-application/ind-application-reporting-safety-
reports.  
9.3.3 
 Monitoring HIV RNA levels 
In the event of viremia of ≥ 50 copies/mL the following should occur per standard of care: 
a. Adherence to ART should be carefully assessed and documented.  
b. A standard HIV RNA assay should be repeated within 1-4 weeks. 
c. HIV resistance testing will be performed at the time of drawing a confirmatory sample 
and as indicated for persistent viremia. 
d. For HIV RNA confirmed >200 copies/mL on repeat testing, stored samples may be tested 
for the presence of one or more ARV drugs in the participant’s regimen. 
e. HIV RNA will be repeated every 2 weeks, or sooner as clinically indicated, until <50 
copies/mL and the participant can continue on study. 
f. In the event of confirmed viremia and documented adherence to ART, ART should be 
managed by the primary care provider in discussion with the study team. The results of 
the HIV resistance tests will be shared with the participants and their care providers. 
The protocol team will monitor the conduct and safety of the study via monthly meetings and 
regular summaries. Accrual, baseline characteristics, conduct of the study (including premature 
study discontinuations), any interruptions of ART, virologic failures, and all reported toxicities 
and events will be monitored during the study and discussed monthly with the protocol team or 
more frequently, if needed.  
The protocol team will review the individual safety data monthly to assess relation of all reported 
toxicities and AEs to the study treatment. A study unique independent Safety Monitoring 
Committee (SMC) will receive quarterly study progress and safety monitoring reports. Study 
feasibility and the achievement of study milestones will be assessed in these reports. The DAIDS 
program and medical officers will review and assess the monthly safety reports, as well as SAE 
reports for potential impact on the study participant safety and protocol conduct as per DAIDS 
policies, guidance documents, and SOPs, as applicable. 
9.4 
Serious Adverse Event Reporting  
All SAEs at least possibly related to study treatment will be considered unexpected and be 
reported as SUSARs within the regulatory timelines outlined in Table 21.  
 

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ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
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All SAEs at least possibly related to study treatment occurring during the study must be reported 
to the UNC IRB per the UNC IRB reporting requirements. A written report will be submitted to 
the FDA as outlined in Table 21. Additional information will be supplied as requested.  
 
All SAEs occurring during the study will be reported to DAIDS as outlined in Table 21. 
All SAEs considered possibly related to study product must be followed until recovery to 
baseline or stabilization with the date of resolution or stabilization recorded in the source 
documents. In addition, the investigator should report all follow-up for reportable SAEs to the 
UNC IRB. Resolution of an event is defined as the return to pre-treatment status or stabilization 
of the condition with the expectation that it will remain chronic. 
All SAEs determined as possibly related to the vaccine/placebo that have not resolved by the end 
of the study, or that have not resolved upon discontinuation of the participant's participation in 
the study, must be followed until any of the following occurs: 
1. The event resolves. 
2. The event stabilizes. 
3. The event returns to baseline, if a baseline value/status is available. 
4. The event can be attributed to etiology other than the vaccine/placebo or to factors unrelated 
to study conduct. 
5. It becomes unlikely that any additional information can be obtained (participant’s or health 
care practitioner’s refusal to provide additional information, or lost to follow-up after 
demonstration of due diligence with follow-up efforts) 
Any event requiring hospitalization (or prolongation of hospitalization) that occurs during the 
course of a participant's participation in a study must be reported as an SAE, except 
hospitalizations for the following: 
1.  Hospitalizations not intended to treat an acute illness or adverse event (e.g., social reasons 
such as pending placement in long-term facility) 
2. Surgery or procedure planned before entry into the study (must be documented in the source 
document) 
The protocol PI (or designee) will be responsible for notifying the UNC IRB, FDA, the 
University of Oxford, and DAIDS of any unexpected fatal or life-threatening SAEs as soon as 
possible, but in no case later than the timelines described in Table 21.  In addition, the PI must 
notify the FDA in an IND safety report of potential serious risks, from clinical trials or any other 
source, as soon as possible, but in no case later than 15 calendar days after the sponsor 
determines that the information qualifies for reporting. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
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9.5 
AESI reporting 
If an AESI occurs, the study coordinator, in collaboration with the site PI or designee, will 
evaluate the severity and seriousness of the AE and the relationship to the study treatment, and 
will document the findings. The protocol team should be contacted within 24 hours of 
notification of any AESIs (reference Section 8.3.4). 
All AESIs occurring during the study must be reported to the UNC IRB per the UNC IRB 
reporting requirements. A written report will be submitted to the DAIDS MO and the IRB 
within 24 hours of site becoming aware of the AESI. Additional information will be supplied 
as requested.  
All AESIs, serious and non-serious, must be reported using the same reporting process as for 
SAE reporting.  
9.6 
Other Reporting Situations  
9.6.1 
 Reporting to DAIDS  
The Protocol Team will be responsible for reporting to DAIDS the following information via 
email to DAIDSRSCSafetyOffice@tech-res.com.  
a. Monthly listing of all AEs within 5 business days of the 1st of each month. 
b. Monthly Line listing of SAEs including suspected unexpected serious adverse reactions 
(SUSARs) within 5 business days of the 1st of each month.  
c. All safety reports submitted to the FDA within 48 hours of submission.  
d. All IND submissions within 5 business days of submission. 
e. All FDA communications within 5 business days of the communication. 
f. Notification that the study is halted or put on clinical hold by the PI, IRB, FDA or other 
regulatory entity within 24 hours of notification that the study was halted or put on hold.  
g. All annual reports to FDA within 5 business days of the submission. 
h. Open SMC or DSMC summary reports within 5 business days of open report finalization.  
9.6.2 
 Reporting Events to Participants  
We are engaged in a number of similar studies of novel immunotherapies for HIV, persistent 
HIV infection, monoclonal antibodies, latency reversing agents, and other interventions. We 
report the scientific findings of our work in the literature and have regular (annual or more 
frequent) presentations with the local and national HIV-infected and affected community. Due to 

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IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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the lack of evidence thus far that our studies have a clinical impact, we discuss the scientific 
findings in a general way with each participant after EOS visits. Our studies have extremely 
stringent stopping criteria, and thus far, we have had no relevant or study-related SAEs to report. 
We would inform all study participants by letter or electronic messaging of any AEs determined 
by the External Study SMC to merit such notice. 
9.6.3 
 Reporting of Pregnancy  
If the participant becomes pregnant during the study, vaccine/placebo will not be administered. 
Although not considered an adverse experience, it is the responsibility of investigators or their 
designees to report any pregnancy in a participant or participant’s partner (spontaneously 
reported to them) that occurs during the study or within 4 months after vaccination. All 
participants or their partners who become pregnant must be followed to the 
completion/termination of the pregnancy. If the pregnancy continues to term, the outcome 
(health of infant) must also be reported the UNC IRB, the DAIDS Medical Officer, and the FDA 
(US Food and Drug Administration). 
If a male participant impregnates his partner while he is participating in this study, the pregnancy 
must be reported and the study PI (or designee) should make a concerted effort to follow the 
pregnancy and outcome. The study PI (or designee) will make every effort to obtain a medical 
release and a separate pregnancy outcome consent from the pregnant partner granting permission 
to follow the health of both the pregnant partner and her unborn child to the UNC IRB, DAIDS, 
study product sponsor, and FDA without delay and within 24 hours if the outcome is an SAE 
(e.g. death, abortion, congenital anomaly, or other disabling or life-threatening complication to 
the mother or newborn). 
Pregnancy and pregnancy outcome will be recorded. Pregnancies that occur on study should be 
reported prospectively to the Antiretroviral Pregnancy Registry. More information is available at 
www.apregistry.com. Telephone: 800-258-4263; Fax: 800-800-1052.  
9.6.4 
 Pregnancy Outcomes and Reporting 
If a woman has completed the study or chooses to discontinue from the study before the end of 
the pregnancy, then site study staff should request permission via a separate pregnancy outcome 
consent to contact her regarding pregnancy outcomes at the end of pregnancy. If the information 
is obtained, pregnancy outcomes will be submitted at the end of the pregnancy. 
Pregnant women will discontinue study treatment and will be encouraged to continue on study 
and complete the evaluations included in the post-treatment evaluation section. At the end of the 
pregnancy, outcome and adverse events for participant and infant will be recorded. If pregnancy 
is suspected in a woman on study after study treatment, then a pregnancy test should be obtained. 
If pregnancy is confirmed, then further study treatment will be discontinued and the woman 
should continue on study (off study product) safety follow-up visits as noted in the SOE. Stored 
plasma/PBMC for stored plasma for virologic studies should not be obtained to minimize blood 
volume. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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The site study staff should request permission via a separate pregnancy outcome consent to 
contact her regarding pregnancy outcomes at the end of pregnancy. A visit 6 months following 
the end of pregnancy will be conducted to assess for evidence of adverse events (AEs) in the 
participant and infant and documented. 
9.6.5 
 Product Quality  
Any suspected transmission of an infectious agent via a medicinal product or other product 
quality issue that results in an event of clinical consequence are AEs. The product quality issue 
must be reported within 1 business days after being made aware of the event.  
A product quality complaint (PQC) is any written, electronic or oral communication that states 
possible deficiencies of a study product related to manufacturing, labeling, or packaging, i.e., any 
dissatisfaction relative to the identity, quality, durability, or reliability of a product, including its 
labeling or package integrity. A PQC may have an impact on the safety and efficacy of the 
product. Timely, accurate, and complete reporting and analysis of PQC information from studies 
is crucial for investigators, the manufacturer and IND sponsor UNC, and for the protection of the 
participants’ rights, welfare and well-being; and is mandated by regulatory agencies worldwide. 
UNC has established procedures in conformity with regulatory requirements to ensure 
appropriate reporting of PQC information and all trials will be conducted in accordance with 
those procedures. 
All initial PQCs must be reported to DAIDS by the study-site personnel within 1 business day 
after being made aware of the event.  
If the complaint is combined with an SAE, the study-site personnel must report the PQC to 
DAIDS the sponsor according to the SAE reporting timelines (refer to Section 9.4, SAEs). A 
sample of the suspected product should be maintained under correct storage conditions for 
further investigation if requested by DAIDS. 
UNC must report any self-identified or site personnel-reported PQC to DAIDS within one 
business days of being made aware of the complaint and include notifications regarding 
immediate action taken.  
9.7 
New Safety Information  
9.7.1 
 Definition of New Safety Information (NSI) 
The Office for Human Research Protections (OHRP) considers new safety Information involving 
risks to participants or others as NSI and this includes, in general, any incident, experience, or 
outcome that meets all of the following criteria: 
1. Unexpected in terms of nature, severity, or frequency given (a) the research procedures/study 
treatment that are described in the protocol-related documents, such as the IRB-approved 

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IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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research protocol, the informed consent document, and IB; and (b) the characteristics of the 
participant population being studied. 
2. Related or possibly related to participation in the research (“possibly related” means there is 
a reasonable possibility that the incident, experience, or outcome may have been caused by 
the procedures/treatment involved in the research); and 
3. Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized. 
4. Please reference the UNC Office for Human Research Ethics SOP 1401 to address Promptly 
Reportable Information. This SOP provides definitions and procedures for the reporting 
promptly reportable information to the UNC-Chapel Hill IRB. 
9.8 
NSI Reporting  
The investigator will report NSI to the UNC IRB. The NSI report will include the following 
information: 
1. Protocol identifying information: protocol title and number, PI’s name, and the IRB project 
number. 
2. A detailed description of the event, incident, experience, or outcome.  
3. An explanation of the basis for determining that the event, incident, experience, or outcome 
represents an NSI;  
4. A description of any changes to the protocol or other corrective actions that have been taken 
or are proposed in response to the NSI. 
To satisfy the requirement for prompt reporting, NSI reports will be reported using the following 
timeline:  
1. NSI that are SAEs will be reported to the IRB and the DAIDS MO within 3 business days of 
the investigator becoming aware of the event.  
2. Any other NSI will be reported to the IRB and to the DAIDS MO within 7 business days of 
the investigator becoming aware of the event.  
3. All NSI should be reported to appropriate institutional officials (as required by an 
institution’s written reporting procedures), the NIH MO (or designee), and the OHRP within 
30 business days of the IRB’s review and determination that the report of the problem from 
the investigator imposed a safety risk. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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9.9 
Reporting NSI to Participants  
We would inform all study participants by letter or electronic messaging of any NSI if it is 
determined by the UNC IRB to merit such notice. 
10 STATISTICAL CONSIDERATIONS  
10.1 Statistical Hypotheses 
1. Vaccination with either C62-M4 or C1C62-M3M4 will be safe and well tolerated  
2. Both C62-M4 and C1C62-M3M4 vaccination will increase the frequency of circulating HIV-
specific T cells  
3. C1C62-M3M4 will induce a greater breadth of T cells targeting conserved regions of HIV 
than C62-M4 
 
10.2 Endpoints 
Primary Safety Endpoint:  
• Occurrence of at least one ≥ Grade 3 Adverse Event (AE) including signs/symptoms, lab 
toxicities, and/or clinical events, that is possibly or definitely related to study treatment any 
time from the first day of treatment (D0) through 28 days following the boost vaccination or 
D56. 
Secondary Efficacy Endpoint(s): 
• Occurrence of any ≥ Grade 1 AE including signs/symptoms, lab toxicities, and/or clinical 
events, that is possibly or definitely related to study treatment any time from the first day of 
treatment (D0) through D196 (Week 28). 
Secondary Immunogenicity Endpoint(s): 
• Relative change in magnitude of T cell responses to HIV-1 conserved regions from baseline 
(before C62 or C1C62 vaccination) to post-boost vaccination at D35 and D42. 
• Change in breadth of T cell responses targeting HIV conserved regions from baseline (before 
C62 or C1C62 vaccination) to post-boost vaccination at D56. 
10.3 Sample Size Determination 
The proposed number of 8 vaccinees per arm and 2 placebo controls was determined to be 
sufficient to evaluate the risk of common SAEs or severe local or systemic reactions based on 

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IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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early phase trials of simian adenovirus- and MVA-vectored vaccines, given alone or serially (59, 
64, 92-94, 97, 121, 125-128, 136-139).  
Enrollment into the trial will be suspended if two or more participants experience a study 
treatment-related AE of Grade 3 or higher or if one or more participants experience an SAE 
possibly related to study treatment. 
If zero of 8 participants experience a safety event, an exact one-sided binomial 95% upper 
confidence limit for the probability of a safety event will be 31%. If one participant experiences 
a safety event, the corresponding one-sided 95% upper confidence limit will be 47%. If no safety 
events are observed in the two vaccine arms and data is pooled across arms (n=16), then the 
exact one-sided 95% upper confidence limit will be 17%. 
10.4 Procedure for missing and invalid data 
There is very little missing or invalid data in our concurrent study using MVA-vectored vaccines 
(NCT03844386; IND 18368), so it is anticipated that this study will be similar. Due to the small 
sample size, formal imputation methods will not be used. However, if there is concern that key 
findings are sensitive to missing data, missing values can be replaced with the best (worst) rank 
in the C62-M4 arm and the worst (best) rank in the C1C62-M3M4 arm to determine if findings 
are sensitive to missingness.  
Safety analyses will include all evaluable participants regardless of whether they are replaced or 
missing for additional endpoints. In order to achieve the planned evaluable sample size, 
participants who do not receive both sets of vaccines at D0 and D28 will be replaced. 
10.5 Study Duration and Accrual  
Participants will be screened approximately 60 days prior to vaccination and will be followed for 
196 days after vaccination. The total study duration from screening to completion of follow-up 
per participant will be approximately 36 weeks (approximately 9 months). Given the focus of 
this study is on safety and potential adverse events, accrual will be staggered such that a 
maximum of up to 2 participants per week will receive the Day 0 vaccination.   
10.6 Randomization 
Following enrollment, the 18 study participants will be randomly assigned to receive vaccination 
with either C62-M4 (n=8), C1C62-M3M4 (n=8), or placebo (n=2) through a double-blinded, 
randomized block design. As detailed in (Section 7.2.1), participants who do not receive both 
sets of vaccines at D0 and D28 will be replaced. In cases such as these, the unblinded statistician 
will generate a new randomization ID that will serve as a replacement for the investigational 
product assigned to the dropout.   

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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10.7 Statistical Analyses 
10.7.1 
General Approach 
This is a Phase 1 study with a small sample size chosen to evaluate safety and the primary 
efficacy outcome. Exact methods that do not rely on large sample assumptions will be used for 
statistical inference and presented with descriptive statistics and/or data visualization. When 
feasible, graphs will present data at the participant-level with summary statistics. Emphasis will 
be placed on descriptive summaries and estimated effect sizes.  
For inferential tests, a significance level of 0.05 will be employed. However, this study recruits a 
small number of participants and thus may not detect scientifically meaningful effects at a 
significance level of 0.05. Since this is a small study with multiple exploratory endpoints, 
adjustment for multiple hypothesis testing will not be performed. Results should be interpreted 
within the context of the protocol-defined eligibility criteria and the target population available 
and willing to participant in this double-blinded, placebo-controlled, randomized clinical trial. 
10.7.2 
Analysis of the Primary Safety Endpoint(s) 
The probability of a primary safety event (≥ Grade 3 AE) from D0 through D56 (or 28 days 
following the second vaccination) will be estimated with a proportion and corresponding one-
sided exact binomial 95% upper confidence limit. These estimates will be calculated separately 
for C62 (D0) followed by M4 (D28) and C1C62 (D0) followed by M3M4 (D28) in PWH on 
ART. 
NOTE: The occurrence of a Grade 3 elevated blood pressure during a study-related 
leukapheresis that resolves following completion of the procedure will not be included as a 
primary safety endpoint. 
10.7.3 
Analysis of the Secondary Safety Endpoints 
The probability of a secondary safety event (≥ Grade 1 AE) from D0 through D196 will be 
estimated with a proportion and corresponding one-sided exact binomial 95% upper confidence 
limit. These estimates will be calculated separately for C62 (D0) followed by M4 (D28) and 
C1C62 (D0) followed by M3M4 (D28) in PWH on ART. 
 
NOTE: Safety events include incidence and grade of all reportable unsolicited and solicited 
adverse events including SAEs, MAAEs, and AESIs post first dose of C1 and/or C62 through 
Day 196. 
 

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ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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10.7.4 
Analysis of Secondary Immunogenicity Endpoints 
10.7.4.1 
T cell magnitude 
To evaluate changes in HIV-1 epitope-specific CD8+ T cell responses detected in IFN-γ ELISpot 
assays from baseline (pre-vaccination) to post-boost vaccination (D35 and D42), the relative 
change within participants will be estimated using a geometric mean ratio (GMR, also known as 
fold change) and evaluated with an exact two-sided Wilcoxon signed-rank test for within-arm 
comparisons and an exact two-sided Wilcoxon rank-sum test for between-arm comparisons. The 
Wilcoxon signed-rank test assumes symmetry of the change in natural log-transformed summed 
HIV-1 specific T cell response (estimated by GMR) under the null. If this assumption is violated, 
then a sign test will be conducted as a sensitivity analysis. 
10.7.4.2 
Power Calculations  
To compute power for a continuous covariate, such as T cell magnitude, a meaningful effect size 
must be determined ahead of time. Comparing T-cell responses within participants, an average 
fold change of at least 2 (GMR ≥ 2) is anticipated to be scientifically meaningful. Baseline HIV-
specific T cell responses from HIV-infected durably-suppressed PWH (53) were used to inform 
power calculations. A between-participant standard deviation of 0.8 was estimated using this 
data and the same standard deviation is assumed pre- and post-vaccination.  
Assuming the natural, log-transformed, HIV-specific T cell responses follow a normal 
distribution with between-participant standard deviation of 0.8 and a within-participant Pearson 
correlation of 0.9 for pre- and post-vaccine measurements, using 10,000 simulated datasets for 
n=8 participants provides 87% power to detect a GMR of 2 or greater. For a smaller within-
participant correlation of 0.8, there is >95% power to detect a GMR of 2 or greater. 
10.7.4.3 
T cell Breadth 
To evaluate change in breadth in the number of T cell responses targeting HIV-conserved 
regions from baseline (pre-vaccination) to post-vaccination (D56),  
an exact two-sided Wilcoxon signed-rank test will be used for within-arm comparisons and an 
exact two-sided Wilcoxon rank-sum test will be used for between-arm comparisons. 
.  
10.7.4.4 
Power Calculations for T cell Breath 
Baseline HIV-specific T cell breadth from durably-suppressed PWH were used to inform power 
calculations (50). In this study, reactive HIV T cell epitopes in the HIV proteome (Clade B 
consensus and autologous reservoir virus) were defined in 25 PWH on ART.  
For the C62-M4 and C1C62-M3M4 arms, we anticipate that vaccination will induce a change of 
breadth (the detection of a new reactive T cell epitope) ranging from 0-3 epitopes and 2-6 
epitopes, respectively.  

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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• We anticipate that C62-M4 will induce a change in breadth with the following frequency 
distribution: 0 (20% of participants), 1 (50%), 2 (20%), and 3 (10%).  
• We anticipate that C1C62-M3M4 will induce a change in breadth with the following 
frequency distribution: 2 (30% of participants), 3 (40%), 4 (15%), 5 (10%), and 6 (5%).  
Given these assumptions, n=8 evaluable participants per treatment arm provides 95% power to 
detect a difference between arms using an exact two-sided Wilcoxon rank-sum test (at a 0.05 
significance level). 
10.7.5 
Safety Analyses 
For the safety endpoints, we will describe all study treatment-related AEs through D56 (primary 
endpoint) and the end of study at D196 or 24 weeks following the second vaccination (secondary 
endpoint). AEs will be coded per the Medical Dictionary for Regulatory Activities (MedDRA). 
Events prior to treatment (e.g., due to study-related procedure) will be listed separately in an 
appendix to the final clinical study report. The following tables of AE data will be created to 
summarize the number and percent of participants who experience at least one event of each of 
the following types:  
• Study treatment-related AEs by severity grade 
• All SAEs (this may be a listing if there are few events) 
• Study treatment-related SAEs 
• Fatal AEs (this may be a listing if there are few events) 
• AEs that result in study discontinuation or study treatment discontinuation 
• AESIs 
• MAAEs 
• AEs with severity Grade 3 or greater 
• Study treatment-related AEs with severity Grade 3 or greater 
• All treatment-related AEs with severity Grade 1 or greater 
All of these tables will display the number and percent of participants that experience the given 
event and will display events by System Organ Class (SOC) and Preferred Term (PT). Events 
will be displayed alphabetically for SOC and in descending order of overall PT incidence within 
each SOC. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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10.7.6 
Baseline Descriptive Statistics 
Participant data will be summarized using the following baseline characteristics: gender, 
ethnicity, race (% Hispanic or Latino), onset of ART (number of acute versus chronic), age, CD4 
nadir, and years of ART suppression. 
10.7.7 
Planned Interim Analyses  
There are no planned formal interim analyses.  
10.7.8 
Tabulation of Individual participant Data 
Individual participant data will be listed by measure and time point. 
10.7.9 
Exploratory Analysis 
Other objectives or exploratory analysis can be grouped into additional immunological measures 
and virologic measures. 
10.7.9.1 
Immunologic Measures  
Kinetic data will be analyzed by descriptive statistics and data visualization. Other observed 
immunologic measurements, such as virus inhibition, may not be normally distributed or may be 
partially censored due to assay limits of quantification (LoQ). Thus, an exact two-sided 
Wilcoxon signed-rank test will be used for within-participant comparisons. If the assumption of 
symmetry of differences (required for the Wilcoxon signed-rank test) is violated, then a sign test 
will be conducted as a sensitivity analysis. For censored data, we will impute half the limit of 
detection. 
10.7.9.2 
Virologic Measures 
Virologic measures such as cell-associated HIV-1 RNA will be log-transformed prior to 
analyses. The analysis method chosen for plasma HIV-1 RNA SCA will depend on the number 
of results that fall below the assay limit of quantification. For example, if a substantial fraction 
(~50%) are below the assay limit of quantification, the analysis will focus on estimating the 
proportion of participants with SCA above the LoQ at various time points and comparison 
between arms will use Fisher’s exact test. Otherwise, changes within participants will be 
summarized and compared between arms using Wilcoxon rank-sum tests. 

16.1.1 Protocol 
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11 SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
11.1 Regulatory, Ethical, and Study Oversight Considerations 
11.1.1 
Informed Consent Process 
11.1.1.1 Consent and Other Informational Documents Provided to Participants 
Consent forms describing in detail the study intervention, study procedures, and risks are given 
to the participant and written documentation of informed consent is required prior to any 
screening procedures and prior to starting study intervention/administering study intervention.   
11.1.1.2 Consent Procedures and Documentation 
Informed consent is a process initiated prior to individuals agreeing to participate in the study 
and continues throughout the individual’s study participation. The consent forms are UNC IRB -
approved and the participant will be asked to read and review the document. The study 
investigator (or designee) and/or study coordinator will explain the research study to the 
participant and answer any questions that may arise. A verbal explanation will be provided in 
terms suited to the participant’s comprehension of the purposes, procedures, and potential risks 
of the study and of their rights as research participants. Participants will have the opportunity to 
carefully review the written consent form and ask questions prior to signing. The participants are 
provided the opportunity to discuss the study with their family, primary care provider, or 
significant other or to just think about the study and its requirements prior to agreeing to 
participate. The participant signs the informed consent document prior to any procedures being 
done specifically for the study. Participants are informed that participation is voluntary and that 
they may withdraw from the study at any time, without prejudice. A copy of the informed 
consent document will be given to the participants.  
The informed consent process will be conducted and documented in the source document, and 
the consent form signed, before the participant undergoes any study-specific procedures. The 
study PI (or designee) or the research coordinator will inform participants that the quality of their 
medical care will not be adversely affected if they decline to participate in this study, thus 
emphasizing the protection of the rights and welfare of the participants. 
11.1.2 Study Discontinuation and Closure 
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause.  Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to study participants, 
funding agency (NIH), the FDA, the University of Oxford, and the UNC IRB. If the study is 
prematurely terminated or suspended, the study PI (or designee) will promptly inform study 
participants, the UNC IRB, and DAIDS and will provide the reason(s) for the termination or 

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suspension.  Study participants will be contacted, as applicable, and be informed of changes to 
the study visit schedule. 
Circumstances that may warrant termination or suspension include but are not limited to: 
1. Determination of unexpected, significant, or unacceptable risk to participants 
2. Demonstration of efficacy that would warrant stopping    
3. Insufficient compliance to protocol requirements 
4. Data that are not sufficiently complete and/or evaluable 
5. Determination that the primary endpoint has been met 
6. Determination of futility 
Study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the sponsor, the UNC IRB, DAIDS, and/or the Food and Drug 
Administration (FDA). 
11.2 Confidentiality 
11.2.1 
Confidentiality and Privacy  
Participant confidentiality and privacy is strictly held in trust by the participating investigators, 
their study staff, and the sponsor(s)/funding source(s) and their representatives. This 
confidentiality is extended to cover testing of biological samples and genetic tests in addition to 
the clinical information relating to participants. Therefore, the study protocol, documentation, 
data, and all other information generated will be held in strict confidence. No information 
concerning the study or the data will be released to any unauthorized third party without prior 
written approval of the sponsor.  
All research activities will be conducted in as private a setting as possible. 
The study monitor, other authorized representatives of the sponsor, representatives of the UNC 
IRB, regulatory agencies, or pharmaceutical company supplying study product may inspect all 
documents and records required to be maintained by the study PI, including but not limited to, 
medical records and IDS pharmacy records for the participants in this study. The clinical study 
site will permit access to such records. 
The study participants’ contact information will be securely stored at the clinical study site for 
internal use during the study. At the end of the study, all records will continue to be kept in a 
secure location for as long a period as dictated by the reviewing IRB, Institutional policies, or 
sponsor requirements. 

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Study participant research data, which is for purposes of statistical analysis and scientific 
reporting, will be stored at the Goonetilleke Laboratory located on the campus of UNC in Chapel 
Hill. This will not include the participants’ contact or identifying information. Rather, individual 
participants and their research data will be identified by a unique study identification number. 
The study data entry and study management systems used by the clinical staff of the UNC HIV 
Cure Center and by research staff will be secured and password protected. At the end of the 
study, all study databases will be de-identified and archived. 
11.2.2 
Certificate of Confidentiality  
To further protect the privacy of study participants, a Certificate of Confidentiality will be issued 
by the NIH.  This certificate protects identifiable research information from forced disclosure. It 
allows the investigator and others who have access to research records to refuse to disclose 
identifying information on research participation in any civil, criminal, administrative, 
legislative, or other proceeding, whether at the federal, state, or local level. By protecting 
researchers and institutions from being compelled to disclose information that would identify 
research participants, Certificates of Confidentiality help achieve the research objectives and 
promote participation in studies by helping assure confidentiality and privacy to participants. 
11.3 Future Use of Stored Specimens and Data  
Data collected for this study will be analyzed and stored at the Goonetilleke Laboratory at UNC, 
Chapel Hill. After the study is completed, the de-identified, archived data will be stored in the 
UNC Database, for use by the Goonetilleke Research Laboratory and their collaborators. 
Permission to transmit data to researchers outside the study collaboratory team will require 
review and approval by the UNC IRB. In some circumstances, we will need to obtain additional 
consent from participants to share samples collected for the purpose of this study.   
With the participants’ approval and as approved by the UNC IRB, de-identified biological 
samples will be stored at the Goonetilleke Laboratory on the campus of UNC Chapel Hill. These 
samples could be used to research the causes of HIV cure for which individuals with HIV 
infection can greatly benefit. These samples may also be used for genetic testing. The 
Goonetilleke Research Laboratory will also be provided with a code-link that will allow linking 
the biological specimens with the phenotypic data from each participant, maintaining the 
blinding of the identity of the participant. 
During the conduct of the study, an individual participant can choose to withdraw consent to 
have biological specimens stored for future research. However, withdrawal of consent with 
regard to biological sample storage may not be possible after the study is completed.  
When the study is completed, access to study data and/or samples will be provided through the 
Goonetilleke Laboratory. 

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11.4 Key Roles and Study Governance 
Provided in Table 22 are the key roles for the study governance. 
Table 22 
Key Roles for Clinical Study 
Protocol Principal Investigator 
Grant Principal Investigator 
Cynthia Gay, MD, MPH 
Nilu Goonetilleke, PhD 
Associate Professor, Medical Director HIV Cure 
Center 
Assistant Professor, Dept. of Microbiology & 
Immunology/Medicine 
University of North Carolina at Chapel Hill  
University of North Carolina at Chapel Hill  
130 Mason Farm Road, Suite 2112 Bioinformatics 
Building, Campus Box 7030  
120 Mason Farm Road, 2017 Genetic Medicine Building, 
Campus Box 7042 
Chapel Hill, NC 27599-7030 
Chapel Hill, NC 27599-7042 
11.5 Safety Oversight 
Safety oversight will be under the direction of a SMC composed of individuals with the 
appropriate expertise. Members of the SMC are independent from the study conduct and free of 
conflict of interest.   
The SMC advises the study PI and protocol team for this First in Man, Phase I study. The 
primary responsibility of the SMC is to monitor human subject safety. The SMC considers 
study-specific data as well as relevant background information about the disease, test agents, and 
target population under study. 
During the trial, the SMC will review:   
1. Real-time and cumulative safety data for evidence of study-related adverse events;  
2. Adherence to the protocol;  
3. Factors that might affect the study outcome or compromise the trial data (such as protocol 
violations, losses to follow-up, etc.). 
4. Review the achievement of enrollment benchmarks  
The SMC will receive quarterly reports via email for review and comments. The SMC will be 
contacted directly via email (and possibly via teleconferencing) for any event or situation that 
impacts participant safety throughout the study and specified interventions or study participation 
will be suspended or terminated dependent on the response of the SMC. 
The study will undergo review at least annually by the SMC. The SMC will review information 
on accrual, baseline characteristics, conduct of the study (including premature study 

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discontinuations and premature study treatment discontinuations), AEs by treatment arm 
(including protocol team assessment of relationship to study treatment), virologic failures, and 
HIV-1 RNA levels over time, and completeness of follow-up. 
11.5.1 
Safety Pause 
Enrollment into the study and treatment injections will be temporarily suspended and the Study 
Monitoring Committee (SMC), unblinded to treatment assignment, will be asked to review all 
safety data. Review will include the relation to study treatment of the event(s) thought by the 
blinded core team to be a primary safety outcome, if any of the following occur: 
1. Two or more participants experience a primary safety outcome measure that is a Grade ≥3 
AE possibly related to study treatment (as judged by the core team, blinded to treatment 
arm); or  
2. One or more participants experience an SAE possibly related to study treatment (as judged 
by the core team, blinded to treatment arm). 
Following the review, the SMC will recommend if and how the study should proceed with 
respect to resuming enrollment and continuing study treatment. 
11.6 Clinical Monitoring  
To ensure the safety of participants in the study, compliance with applicable regulations, and to 
ensure accurate, complete, and reliable data, the protocol PI will keep records of laboratory tests, 
clinical notes, and participant medical records in the participant files as source documents for the 
study. 
An independent study monitor will monitor the study on a regular basis throughout the study 
period according to the study monitoring plan. The protocol PI (or designee) will allocate 
adequate time for such monitoring activities. The study monitor periodically will conduct a 
review of a sample of the participant data recorded on source documents at the study site. The 
protocol PI (or designee) will also ensure that the monitor is given access to all the above noted 
study-related documents, source documents (regardless of media), and study-related facilities 
(e.g., IDS pharmacy, etc.), and has adequate space to conduct the monitoring visit. Queries may 
be raised if any datum is unclear or contradictory. The protocol PI and site study personnel must 
address all queries in a timely manner. 
Participation as an Investigator in this study implies acceptance of the potential for inspection by 
the study Funder and its Representatives, US or non-US government regulatory authorities, IRB, 
and applicable compliance and quality assurance offices. The protocol PI (or designee) will 
permit study-related audits and inspections and will provide access to all study-related 
documents (e.g., source documents, regulatory documents, data collection instruments, study 
data, etc.). The protocol PI will ensure the capability for inspections of applicable study-related 
facilities (e.g., IDS pharmacy, CTRC, etc.). 

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11.6.1 
Clinical Monitoring Procedures 
Procedures to minimize risk to participants in the conduct of this study include:  
1. Informing participants about risks so they can recognize and report harms in partnership with 
the study team;  
2. respecting local/national blood draw limits;  
3. direct observation of participants after vaccine/placebo administration and collection of 
information regarding side effects for several days post product administration; 
4. having study staff properly trained in administering study procedures that may cause physical 
harm or psychologic distress, such as blood draws and injections; and 
5. providing study monitoring. 
11.6.2 
Quality Assurance and Quality Control 
UNC will perform internal quality management of study conduct, data and biological specimen 
collection, documentation, and completion.  A quality management plan was developed to 
describe the quality management program. 
UNC follows Standard Operating Procedures (SOPs) for quality management. Clinical research 
files verify and insure that the clinical trial is conducted per protocol and that data is generated 
and biological specimens collected, documented (recorded), and reported in compliance with the 
protocol, International Conference on Harmonization Good Clinical Practice (ICH GCP), and 
applicable regulatory requirements (e.g., GLP, GMP). Data Quality is monitored per the data 
quality management plan with routine and specific research chart review. 
The study staff will be educated on the protocol and training will be provided as needed to 
implement protocol procedures. The study data management team will be responsible for 
addressing QA issues (e.g., correcting procedures that are not in compliance with the protocol) 
and QC issues (e.g., correcting errors in data entry). Documentation, as required, will be 
maintained in the regulatory files. 
UNC will provide direct access to all trial-related sites, source data/documents, and reports for 
the purpose of monitoring and auditing by the funding sponsor, and inspection by local and 
regulatory authorities. 
11.6.3 
Data Handling and Record Keeping  
11.6.3.1 
Data Collection and Management Responsibilities  
The clinical research staff is responsible for data collection under the supervision of the site 
study PI (or designee). The study PI (or designee) is responsible for ensuring the accuracy, 
completeness, legibility, and timeliness of the data reported. 

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All source documents should be completed in a neat, legible manner to ensure accurate 
interpretation of data.   
Hard copies of the study visit worksheets will be provided for use as source document 
worksheets for recording data for each participant enrolled in the study.  Data recorded in the 
electronic case report form derived from source documents should be consistent with the data 
recorded on the source documents.  
Clinical data (including adverse events (AEs), concomitant medications, and expected adverse 
reactions data) and clinical laboratory data will be entered into a UNC School of Medicine 
Database housed in Advarra Electronic Data Capture (EDC). EDC includes password protection. 
Clinical data will be entered directly from the source documents. 
11.6.3.2 
Study Records Retention  
Per ICH guidelines, all essential documents, including source documents (regardless of media), 
signed ICFs, and laboratory test results, should be retained by the study PI (or designee) for at 
least 2 years after 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 formal discontinuation of clinical development of the investigational products. 
11.7 Protocol Deviations  
A protocol deviation is any noncompliance with the clinical trial protocol, International 
Conference on Harmonization Good Clinical Practice (ICH GCP), or Manual of Procedures 
(MOP) requirements. The noncompliance may be on the part of the participant, the investigators, 
or the study site staff. As a result of deviations, corrective actions will be developed and 
implemented promptly, when necessary.  
These practices are consistent with ICH GCP:  
It is the responsibility of the site PI (or designee) to use continuous vigilance to identify and 
report deviations at the annual renewal of the protocol, provided there is no impact on participant 
safety as a result of the deviation. All deviations must be addressed in study source documents. 
Protocol deviations are sent to the UNC IRB per their policies. The site PI is responsible for 
knowing and adhering to reviewing the IRB requirements. Further details about the handling of 
protocol deviations will be included in the SOP. 
11.8 Publication and Data Sharing Policy 
This study will be conducted in accordance with the following publication and data sharing 
policies and regulations: 
1. National Institutes of Health (NIH) Public Access Policy, which ensures that the public has 
access to the published results of NIH-funded research. It requires scientists to submit final 

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peer-reviewed journal manuscripts that arise from NIH funds to the digital archive PubMed 
Central upon acceptance for publication. 
2. NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial 
Information and the Clinical Trials Registration and Results Information Submission rule. As 
such, this trial will be registered at ClinicalTrials.gov, and results information from this trial 
will be submitted to ClinicalTrials.gov, if required.  
3. NIH Genomic Data Sharing Policy, which applies to all NIH-funded research that generates 
large-scale human or non-human genomic data, as well as the use of these data for 
subsequent research. Large-scale data include genome-wide association studies (GWAS), 
single nucleotide polymorphisms (SNP) arrays, and genome sequence, transcriptomic, 
epigenomic, and gene expression data. 
11.9 Conflict of Interest Policy 
The University of North Carolina at Chapel Hill recognizes that conflicts of interest will arise 
from the research enterprise, from technology transfer activities, and from the many facets of our 
investigators’ professional activities. UNC seeks to identify and manage these conflicting 
relationships, restricting activities where necessary, to preserve transparency, independent 
decision-making, protection of research participants, and integrity of the educational experience. 
UNC’s Conflict of Interest Program will have oversight over this study. 
 
 

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12 ABBREVIATIONS 
4A4OA 
4-anilino-4 oxobutanoic acid 
Ab 
Antibody 
ACD 
Acid Citrate Dextrose 
ACE 
Angiotension Converting Enzyme 
ADC 
Apparent Diffusion Coefficient 
AE 
Adverse Event 
AESI 
Adverse Event of Special Interest 
AHA 
Autoimmune Hemolytic Anemia 
AHI 
Acute HIV Infection  
Alk Phos 
Alkaline Phosphatase 
ALT 
Alanine Transaminase 
ANA 
Antinuclear Antibody 
ANC  
Absolute Neutrophil Count 
ANCA 
Antineutrophil Cytoplasmic Antibodies 
ANCOVA 
Analysis of Covariance 
Anti-dsDNA 
Anti-double-stranded DNA, IgG 
APTT 
Activated Partial Thromboplastin Time 
AQP4 
Aquaporin 4 
ART 
Antiretroviral Therapy  
AST 
Aspartate Transaminase 
ATI 
Analytic Treatment Interruption 
AUC 
Area Under the Curve 
BP  
Blood Pressure 
BUN 
Blood Urea Nitrogen 
C1 
ChAdOx1.tHIVconsv1 
C62 
ChAdOx1.HIVconsv62 
CBF 
Clinical Biomanufacturing Facility 
CBC 
Complete Blood Count 
CEF 
Chicken Embryo Fibroblast 
CFAR 
Center for AIDS Research  
CFR 
Code of Federal Regulations 
ChAdV 
Simian Adenovirus of chimpanzee origin 
CIDP 
Chronic Inflammatory Demyelinating Polyneuropathy 
CLIA 
Clinical Laboratory Improvement Amendments 
CLS  
Capillary Leak Syndrome 
CMP 
Clinical Monitoring Plan 
CMV 
Cytomegalovirus 
CNS 
Central Nervous System 
COC 
Certificate of Confidentiality 
CONSORT 
Consolidated Standards of Reporting Trials 
CPK 
Creatine Phosphokinase or Creatine Kinase (CK) 
CRF 
Case Report Form 
CRP 
C-Reactive Protein 
CSF 
Cerebral Spinal Fluid 

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CSRC 
(DAIDS) Clinical Science Review Committee 
CT 
Computed Tomography 
CTRC 
Clinical and Translational Research Center 
CVST 
Cerebral Venous Sinus Thrombosis 
D196 
Day 196 or End of Study  
DAIDS 
Division of AIDS 
D/C 
Discontinue 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DNCB 
Dinitrochlorobenzene 
DSMB 
Data Safety Monitoring Board 
DRE 
Disease-Related Event 
DVT 
Deep Vein Thrombosis 
DWI 
Diffusion Weighted Image 
 
 
EBV 
Epstein-Barr Virus 
E/CIA 
Enzyme or Chemiluminescence Immunoassay 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Forms 
eGFR 
Estimated Glomerular Filtration Rate 
ED 
Emergency Department 
EMA  
European Medicines Agency 
ENA 
Extractable Nuclear Antigen Antibodies 
EOS 
End of Study or Day 196  
ESR 
Erythrocyte Sedimentation Rate 
EU  
European Union  
FLAIR 
Fluid Attenuated Inversion Recovery 
FNA 
Fine Needle Aspiration 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act of 2007 
FFR 
Federal Financial Report 
FSH 
Follicle Stimulating Hormone 
GBS 
Guillain-Barré Syndrome 
G-CSF 
Granulocyte-Colony Stimulating Factor  
GM-CSF 
Granulocyte Macrophage-Colony Stimulating Factor 
GCP 
Good Clinical Practice 
GFP 
Green Fluorescent Protein 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
GRE 
Gradient Echo 
GWAS 
Genome-Wide Association Studies 
HBsAg 
Hepatitis B Surface Antigen 
HCV 
Hepatitis C Virus 
HCVAb 
Hepatitis C Virus Antibody 
HIPAA 
Health Insurance Portability and Accountability Act  

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HIV 
Human Immunodeficiency Virus 
HIVconsv 
1st generation conserved-region immunogen 
HLA 
Human Leukocyte Antigen 
HSV 
Herpes Simplex Virus 
IB 
Investigator’s Brochure 
IBC 
Institutional Biosafety Committee 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization  
ICMJE 
International Committee of Medical Journal Editors 
ID 
Intradermal 
ID Clinic 
Infectious Diseases Clinic 
IDS 
Investigational Drug Service 
IgG 
Immunoglobulin G 
IFN-γ 
Interferon gamma 
IgG 
Immunoglobulin G 
IDS 
Investigational Drug Services  
IL-1 
Interleukin - 2 
IL-12 
Interleukin - 12 
IM 
Intramuscular 
IND 
Investigational New Drug Application 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
ISO 
International Organization for Standardization 
ITT 
Intention-To-Treat 
IUD 
Intrauterine device 
IV 
Intravenous  
LANL-HSD 
Los Alamos National Laboratory HIV Sequence Database 
LDH 
Lactate Dehydrogenase 
LDL 
Low Density Lipoprotein 
LMP  
Last Menstrual Period 
LRA 
Latency Reversing Agent 
LSMEANS 
Least-Squares Means 
LTFU 
Lost to Follow-up 
M3 
MVA.tHIVconsv3 
M4 
MVA.tHIVconsv4 
MAAEs 
Medically Attended Adverse Events 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg/dL 
milligram per deciliter 
ml/min. 
milliliter per minute 
mm Hg 
millimeters of mercury 
MMR 
Measles, Mumps, Rubella 
MO 
Medical Officer 
MOG 
Myelinoligodendrocyte Glycoprotein 
MOI 
Multiplicity of Infection 
MOP 
Manual of Procedures 

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MSDS 
Material Safety Data Sheet 
MRI 
Magnetic Resonance Image 
MVA 
Modified Vaccinia virus (Ankara strain) 
MVA.HIVA 
MVA expressing the HIVA immunogen, comprising clade A p24 
and HIV epitope string 
MVA.HIVconsv 
MVA expressing the 1st generation conserved HIV immunogen, 
HIVconsv  
MVA.tHIVconsv3 
MVA expressing a 2nd generation conserved HIV immunogen, 
tHIVconsv3  
MVA.tHIVconsv4 
MVA expressing a 2nd generation conserved HIV immunogen, 
tHIVconsv4 
NCT 
National Clinical Trial 
NIH  
National Institutes of Health 
NIH IC 
NIH Institute or Center 
NMOSD 
Neuromyelitis Optica Spectrum Disorder  
NNRTI 
Non-nucleoside Reverse Transcriptase Inhibitor 
NRTI 
Nucleoside Reverse Transcriptase Inhibitor 
NSI 
New Safety Information  
OHRP 
Office for Human Research Protections 
OSP 
Office of Science Policy 
OTC 
Over the Counter 
P 
Pulse 
PBMC 
Peripheral Blood Mononuclear Cells 
PCR 
Polymerase Chain Reaction 
PE 
Physical Exam 
PF4 antibody ELISA Platelet Factor 4 antibody ELISA 
pfu 
Plaque-forming units 
PHI 
Primary HIV Infection 
PI 
Principal Investigator 
PID 
Participant Identification Number 
PI 
Protease Inhibitor 
POCT 
Point of Care Test 
PQC 
Product Quality Complaint 
PT 
Preferred Term  
PT 
Prothrombin time  
QA 
Quality Assurance 
QC 
Quality Control 
RID  
Randomization Identification Number 
rMVA 
Recombinant MVA 
RF 
Rheumatoid Factor  
RFP 
Red Fluorescent Protein 
RPR 
Rapid Plasma Reagent 
RR 
Respiratory Rate 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SFU 
Spot-forming units 

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SID 
Study Identification Number 
SMC 
Safety Monitoring Committee 
SNP 
Single Nucleotide Polymorphism  
SoA 
Schedule of Activities 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
STIR 
Short T1 Inversion Recovery  
SUSAR 
Serious Unexpected Serious Adverse Reaction 
SWI 
Susceptibility-Weighted Imaging 
T 
Temperature 
TAF 
Tenofovir Alafenamide 
TDF 
Tenofovir 
TM 
Transverse Myelitis 
TNF 
Tumor Necrosis Factor 
TSH 
Thyroid Stimulating Hormone  
TTS 
Thrombosis with Thrombocytopenia Syndrome 
tPA-LS 
Human tissue activator sequence  
UK 
United Kingdom 
ULN 
Upper Limit of Normal 
UNC 
University of North Carolina  
UOXF 
University of Oxford 
UP 
Unanticipated Problem 
US 
United States 
VDRL  
Venereal Disease Research Laboratories 
VITT 
Vaccine-Induced Immune Thrombotic Thrombocytopenia 
VS 
Vital Signs 
VZV 
Varicella Zoster Virus 
WHO 
World Health Organization  
WOCBP 
Women of Child Bearing Potential 
 
 
 
 
 
 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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13 PROTOCOL AMENDMENT HISTORY 
The table below is intended to capture changes of IRB-approved versions of the protocol, 
including a description of the change and rationale. A Summary of Changes table for the current 
amendment is located in Appendix 1.  
 
Version 
Date 
Description of Change  
Brief Rationale 
1.0 
14-Jan-2022 
Original Version 
Original Version 
2.0 
28-Oct-2022 
Updated Protocol Team Roster, Section 1.3, 
Section 3, Section 5.1, Section 5.2, Section 
6.1.2, Section 6.2.4, Section 6.3, Section 
6.5.2, Section 7.2.2, Section 7.2.3, Section 
8.1, Section 8.2, Section 8.4.3, Section 10.2, 
Section 10.7.4, Section 11.5, Section 11.6.3, 
Appendix 1, Appendix 2 
Modified exclusion criterion #12 to 
adjust timing of live vaccines prior to 
enrollment and address monkeypox 
vaccines, provide clarification and 
resolve discrepancies. 
3.0 
12-Jun-2023 
Updated Section 1.1, Section 2.2, Section 
2.3, Section 5.1, Section 5.2, Section 6.1, 
Section 6.5.2, 8.1, Section 8.3, Section 8.4, 
Section 9.1, Section 9.2, Section 9.3, 
Section 9.4, Section 9.5, Section 10.5, 
Section 11.4, Appendix 2 
Updated C1-C62 risks section per C1 
IB v4 dated 09-Dec-2022 and C62 IB 
v3 dated 09-Dec-2022. Incorporated 
CM#1 dated 27-Feb-2023. Removed 
contradictory language for allowable 
Mpox vaccine window. Clarified AE 
and SAE reporting guidelines.  Provide 
clarification and resolve discrepancies. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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14 REFERENCES  
1. 
Davey RT, Jr., Bhat N, Yoder C, Chun TW, Metcalf JA, Dewar R, Natarajan V, 
Lempicki RA, Adelsberger JW, Miller KD, Kovacs JA, Polis MA, Walker RE, Falloon J, 
Masur H, Gee D, Baseler M, Dimitrov DS, Fauci AS, Lane HC. 1999. HIV-1 and T cell 
dynamics after interruption of highly active antiretroviral therapy (HAART) in patients 
with a history of sustained viral suppression. Proc Natl Acad Sci U S A 96:15109-14. 
2. 
Crowell TA, Colby DJ, Pinyakorn S, Sacdalan C, Pagliuzza A, Intasan J, Benjapornpong 
K, Tangnaree K, Chomchey N, Kroon E, de Souza MS, Tovanabutra S, Rolland M, Eller 
MA, Paquin-Proulx D, Bolton DL, Tokarev A, Thomas R, Takata H, Trautmann L, Krebs 
SJ, Modjarrad K, McDermott AB, Bailer RT, Doria-Rose N, Patel B, Gorelick RJ, 
Fullmer BA, Schuetz A, Grandin PV, O'Connell RJ, Ledgerwood JE, Graham BS, 
Tressler R, Mascola JR, Chomont N, Michael NL, Robb ML, Phanuphak N, 
Ananworanich J, Group RVS. 2019. Safety and efficacy of VRC01 broadly neutralising 
antibodies in adults with acutely treated HIV (RV397): a phase 2, randomised, double-
blind, placebo-controlled trial. Lancet HIV 6:e297-e306. 
3. 
Bar KJ, Sneller MC, Harrison LJ, Justement JS, Overton ET, Petrone ME, Salantes DB, 
Seamon CA, Scheinfeld B, Kwan RW, Learn GH, Proschan MA, Kreider EF, Blazkova J, 
Bardsley M, Refsland EW, Messer M, Clarridge KE, Tustin NB, Madden PJ, Oden K, 
O'Dell SJ, Jarocki B, Shiakolas AR, Tressler RL, Doria-Rose NA, Bailer RT, 
Ledgerwood JE, Capparelli EV, Lynch RM, Graham BS, Moir S, Koup RA, Mascola JR, 
Hoxie JA, Fauci AS, Tebas P, Chun TW. 2016. Effect of HIV Antibody VRC01 on Viral 
Rebound after Treatment Interruption. N Engl J Med 375:2037-2050. 
4. 
Buzon MJ, Martin-Gayo E, Pereyra F, Ouyang Z, Sun H, Li JZ, Piovoso M, Shaw A, 
Dalmau J, Zangger N, Martinez-Picado J, Zurakowski R, Yu XG, Telenti A, Walker BD, 
Rosenberg ES, Lichterfeld M. 2014. Long-term antiretroviral treatment initiated at 
primary HIV-1 infection affects the size, composition, and decay kinetics of the reservoir 
of HIV-1-infected CD4 T cells. Journal of virology 88:10056-65. 
5. 
Chun TW, Carruth L, Finzi D, Shen X, DiGiuseppe JA, Taylor H, Hermankova M, 
Chadwick K, Margolick J, Quinn TC, Kuo YH, Brookmeyer R, Zeiger MA, Barditch-
Crovo P, Siliciano RF. 1997. Quantification of latent tissue reservoirs and total body viral 
load in HIV-1 infection. Nature 387:183-8. 
6. 
Finzi D, Hermankova M, Pierson T, Carruth LM, Buck C, Chaisson RE, Quinn TC, 
Chadwick K, Margolick J, Brookmeyer R, Gallant J, Markowitz M, Ho DD, Richman 
DD, Siliciano RF. 1997. Identification of a reservoir for HIV-1 in patients on highly 
active antiretroviral therapy. Science 278:1295-300. 
7. 
Siliciano JD, Kajdas J, Finzi D, Quinn TC, Chadwick K, Margolick JB, Kovacs C, Gange 
SJ, Siliciano RF. 2003. Long-term follow-up studies confirm the stability of the latent 
reservoir for HIV-1 in resting CD4+ T cells. Nat Med 9:727-8. 
8. 
Eisele E, Siliciano RF. 2012. Redefining the viral reservoirs that prevent HIV-1 
eradication. Immunity 37:377-88. 
9. 
Archin NM, Liberty AL, Kashuba AD, Choudhary SK, Kuruc JD, Crooks AM, Parker 
DC, Anderson EM, Kearney MF, Strain MC, Richman DD, Hudgens MG, Bosch RJ, 
Coffin JM, Eron JJ, Hazuda DJ, Margolis DM. 2012. Administration of vorinostat 
disrupts HIV-1 latency in patients on antiretroviral therapy. Nature 487:482-5. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Page 122 of 143
 
 
10. 
Sogaard OS, Graversen ME, Leth S, Olesen R, Brinkmann CR, Nissen SK, Kjaer AS, 
Schleimann MH, Denton PW, Hey-Cunningham WJ, Koelsch KK, Pantaleo G, 
Krogsgaard K, Sommerfelt M, Fromentin R, Chomont N, Rasmussen TA, Ostergaard L, 
Tolstrup M. 2015. The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo. PLoS 
Pathog 11:e1005142. 
11. 
Elliott J, Solomon A, Wightman F, Smith M, Palmer S, Prince M, Watson J, Hoy J, 
McMahon M, Lewin S. The Safety and Effect of Multiple Doses of Vorinostat on HIV 
Transcriptoin in HIV-Infected Patients receiving Combination Antiretroviral Therapy, p. 
In (ed),   
12. 
Bruner KM, Hosmane NN, Siliciano RF. 2015. Towards an HIV-1 cure: measuring the 
latent reservoir. Trends Microbiol 23:192-203. 
13. 
Crooks AM, Bateson R, Cope AB, Dahl NP, Griggs MK, Kuruc JD, Gay CL, Eron JJ, 
Margolis DM, Bosch RJ, Archin NM. 2015. Precise Quantitation of the Latent HIV-1 
Reservoir: Implications for Eradication Strategies. J Infect Dis doi:10.1093/infdis/jiv218. 
14. 
Siliciano JD, Siliciano RF. 2005. Enhanced culture assay for detection and quantitation of 
latently infected, resting CD4+ T-cells carrying replication-competent virus in HIV-1-
infected individuals. Methods Mol Biol 304:3-15. 
15. 
Shan L, Deng K, Shroff NS, Durand CM, Rabi SA, Yang HC, Zhang H, Margolick JB, 
Blankson JN, Siliciano RF. 2012. Stimulation of HIV-1-specific cytolytic T lymphocytes 
facilitates elimination of latent viral reservoir after virus reactivation. Immunity 36:491-
501. 
16. 
Sung JA, Lam S, Garrido C, Archin N, Rooney CM, Bollard CM, Margolis DM. 2015. 
Expanded Cytotoxic T-cell Lymphocytes Target the Latent HIV Reservoir. J Infect Dis 
doi:10.1093/infdis/jiv022. 
17. 
Borrow P, Lewicki H, Wei X, Horwitz MS, Peffer N, Meyers H, Nelson JA, Gairin JE, 
Hahn BH, Oldstone MB, Shaw GM. 1997. Antiviral pressure exerted by HIV-1-specific 
cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid 
selection of CTL escape virus. Nat Med 3:205-11. 
18. 
Borrow P, Lewicki H, Hahn BH, Shaw GM, Oldstone MB. 1994. Virus-specific CD8+ 
cytotoxic T-lymphocyte activity associated with control of viremia in primary human 
immunodeficiency virus type 1 infection. J Virol 68:6103-10. 
19. 
Price DA, Goulder PJ, Klenerman P, Sewell AK, Easterbrook PJ, Troop M, Bangham 
CR, Phillips RE. 1997. Positive selection of HIV-1 cytotoxic T lymphocyte escape 
variants during primary infection. Proc Natl Acad Sci U S A 94:1890-5. 
20. 
Koup RA, Safrit JT, Cao Y, Andrews CA, McLeod G, Borkowsky W, Farthing C, Ho 
DD. 1994. Temporal association of cellular immune responses with the initial control of 
viremia in primary human immunodeficiency virus type 1 syndrome. J Virol 68:4650-5. 
21. 
Goonetilleke N, Liu MK, Salazar-Gonzalez JF, Ferrari G, Giorgi E, Ganusov VV, Keele 
BF, Learn GH, Turnbull EL, Salazar MG, Weinhold KJ, Moore S, B CCC, Letvin N, 
Haynes BF, Cohen MS, Hraber P, Bhattacharya T, Borrow P, Perelson AS, Hahn BH, 
Shaw GM, Korber BT, McMichael AJ. 2009. The first T cell response to 
transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection. J 
Exp Med 206:1253-72. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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22. 
Liu MK, Hawkins N, Ritchie AJ, Ganusov VV, Whale V, Brackenridge S, Li H, Pavlicek 
JW, Cai F, Rose-Abrahams M, Treurnicht F, Hraber P, Riou C, Gray C, Ferrari G, 
Tanner R, Ping LH, Anderson JA, Swanstrom R, B CC, Cohen M, Karim SS, Haynes B, 
Borrow P, Perelson AS, Shaw GM, Hahn BH, Williamson C, Korber BT, Gao F, Self S, 
McMichael A, Goonetilleke N. 2013. Vertical T cell immunodominance and epitope 
entropy determine HIV-1 escape. J Clin Invest 123:380-93. 
23. 
Goulder PJ, Phillips RE, Colbert RA, McAdam S, Ogg G, Nowak MA, Giangrande P, 
Luzzi G, Morgan B, Edwards A, McMichael AJ, Rowland-Jones S. 1997. Late escape 
from an immunodominant cytotoxic T-lymphocyte response associated with progression 
to AIDS. Nat Med 3:212-7. 
24. 
Carrington M, O'Brien SJ. 2003. The influence of HLA genotype on AIDS. Annu Rev 
Med 54:535-51. 
25. 
Smith NM, Mlcochova P, Watters SA, Aasa-Chapman MM, Rabin N, Moore S, Edwards 
SG, Garson JA, Grant PR, Ferns RB, Kashuba A, Mayor NP, Schellekens J, Marsh SG, 
McMichael AJ, Perelson AS, Pillay D, Goonetilleke N, Gupta RK. 2015. Proof-of-
Principle for Immune Control of Global HIV-1 Reactivation In Vivo. Clin Infect Dis 
doi:10.1093/cid/civ219. 
26. 
Apetrei C, Sumpter B, Souquiere S, Chahroudi A, Makuwa M, Reed P, Ribeiro RM, 
Pandrea I, Roques P, Silvestri G. 2011. Immunovirological analyses of chronically 
simian immunodeficiency virus SIVmnd-1- and SIVmnd-2-infected mandrills 
(Mandrillus sphinx). J Virol 85:13077-87. 
27. 
Cartwright EK, Spicer L, Smith SA, Lee D, Fast R, Paganini S, Lawson BO, Nega M, 
Easley K, Schmitz JE, Bosinger SE, Paiardini M, Chahroudi A, Vanderford TH, Estes 
JD, Lifson JD, Derdeyn CA, Silvestri G. 2016. CD8(+) Lymphocytes Are Required for 
Maintaining Viral Suppression in SIV-Infected Macaques Treated with Short-Term 
Antiretroviral Therapy. Immunity 45:656-668. 
28. 
Appay V, Dunbar PR, Callan M, Klenerman P, Gillespie GM, Papagno L, Ogg GS, King 
A, Lechner F, Spina CA, Little S, Havlir DV, Richman DD, Gruener N, Pape G, Waters 
A, Easterbrook P, Salio M, Cerundolo V, McMichael AJ, Rowland-Jones SL. 2002. 
Memory CD8+ T cells vary in differentiation phenotype in different persistent virus 
infections. Nat Med 8:379-85. 
29. 
Estcourt MJ, McMichael AJ, Hanke T. 2004. DNA vaccines against human 
immunodeficiency virus type 1. Immunol Rev 199:144-55. 
30. 
Harari A, Rozot V, Cavassini M, Bellutti Enders F, Vigano S, Tapia G, Castro E, Burnet 
S, Lange J, Moog C, Garin D, Costagliola D, Autran B, Pantaleo G, Bart PA. 2012. 
NYVAC immunization induces polyfunctional HIV-specific T-cell responses in 
chronically-infected, ART-treated HIV patients. Eur J Immunol 42:3038-48. 
31. 
Honda M, Wang R, Kong WP, Kanekiyo M, Akahata W, Xu L, Matsuo K, Natarajan K, 
Robinson H, Asher TE, Price DA, Douek DC, Margulies DH, Nabel GJ. 2009. Different 
vaccine vectors delivering the same antigen elicit CD8+ T cell responses with distinct 
clonotype and epitope specificity. J Immunol 183:2425-34. 
32. 
Peng B, Wang LR, Gomez-Roman VR, Davis-Warren A, Montefiori DC, Kalyanaraman 
VS, Venzon D, Zhao J, Kan E, Rowell TJ, Murthy KK, Srivastava I, Barnett SW, Robert-
Guroff M. 2005. Replicating rather than nonreplicating adenovirus-human 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Page 124 of 143
 
 
immunodeficiency virus recombinant vaccines are better at eliciting potent cellular 
immunity and priming high-titer antibodies. J Virol 79:10200-9. 
33. 
Norbury CC, Basta S, Donohue KB, Tscharke DC, Princiotta MF, Berglund P, Gibbs J, 
Bennink JR, Yewdell JW. 2004. CD8+ T cell cross-priming via transfer of proteasome 
substrates. Science 304:1318-21. 
34. 
Shen L, Rock KL. 2004. Cellular protein is the source of cross-priming antigen in vivo. 
Proc Natl Acad Sci U S A 101:3035-40. 
35. 
Wolkers MC, Brouwenstijn N, Bakker AH, Toebes M, Schumacher TN. 2004. Antigen 
bias in T cell cross-priming. Science 304:1314-7. 
36. 
Moss B, Carroll MW, Wyatt LS, Bennink JR, Hirsch VM, Goldstein S, Elkins WR, 
Fuerst TR, Lifson JD, Piatak M, Restifo NP, Overwijk W, Chamberlain R, Rosenberg 
SA, Sutter G. 1996. Host range restricted, non-replicating vaccinia virus vectors as 
vaccine candidates. Adv Exp Med Biol 397:7-13. 
37. 
Buchbinder SP, Mehrotra DV, Duerr A, Fitzgerald DW, Mogg R, Li D, Gilbert PB, Lama 
JR, Marmor M, Del Rio C, McElrath MJ, Casimiro DR, Gottesdiener KM, Chodakewitz 
JA, Corey L, Robertson MN, Step Study Protocol T. 2008. Efficacy assessment of a cell-
mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, 
placebo-controlled, test-of-concept trial. Lancet 372:1881-93. 
38. 
Casimiro DR, Bett AJ, Fu TM, Davies ME, Tang A, Wilson KA, Chen M, Long R, 
McKelvey T, Chastain M, Gurunathan S, Tartaglia J, Emini EA, Shiver J. 2004. 
Heterologous human immunodeficiency virus type 1 priming-boosting immunization 
strategies involving replication-defective adenovirus and poxvirus vaccine vectors. J 
Virol 78:11434-8. 
39. 
Bridgeman A, Roshorm Y, Lockett LJ, Xu ZZ, Hopkins R, Shaw J, Both GW, Hanke T. 
2009. Ovine atadenovirus, a novel and highly immunogenic vector in prime-boost studies 
of a candidate HIV-1 vaccine. Vaccine 28:474-83. 
40. 
Thorner AR, Lemckert AA, Goudsmit J, Lynch DM, Ewald BA, Denholtz M, Havenga 
MJ, Barouch DH. 2006. Immunogenicity of heterologous recombinant adenovirus prime-
boost vaccine regimens is enhanced by circumventing vector cross-reactivity. J Virol 
80:12009-16. 
41. 
Amara RR, Villinger F, Altman JD, Lydy SL, O'Neil SP, Staprans SI, Montefiori DC, Xu 
Y, Herndon JG, Wyatt LS, Candido MA, Kozyr NL, Earl PL, Smith JM, Ma HL, Grimm 
BD, Hulsey ML, Miller J, McClure HM, McNicholl JM, Moss B, Robinson HL. 2001. 
Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA 
vaccine. Science 292:69-74. 
42. 
Hanke T, Goonetilleke N, McMichael AJ, Dorrell L. 2007. Clinical experience with 
plasmid DNA- and modified vaccinia virus Ankara-vectored human immunodeficiency 
virus type 1 clade A vaccine focusing on T-cell induction. J Gen Virol 88:1-12. 
43. 
Hanke T, Blanchard TJ, Schneider J, Hannan CM, Becker M, Gilbert SC, Hill AV, Smith 
GL, McMichael A. 1998. Enhancement of MHC class I-restricted peptide-specific T cell 
induction by a DNA prime/MVA boost vaccination regime. Vaccine 16:439-45. 
44. 
Letourneau S, Im EJ, Mashishi T, Brereton C, Bridgeman A, Yang H, Dorrell L, Dong T, 
Korber B, McMichael AJ, Hanke T. 2007. Design and pre-clinical evaluation of a 
universal HIV-1 vaccine. PLoS One 2:e984. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Page 125 of 143
 
 
45. 
Santra S, Sun Y, Korioth-Schmitz B, Fitzgerald J, Charbonneau C, Santos G, Seaman 
MS, Ratcliffe SJ, Montefiori DC, Nabel GJ, Ertl HC, Letvin NL. 2009. Heterologous 
prime/boost immunizations of rhesus monkeys using chimpanzee adenovirus vectors. 
Vaccine 27:5837-45. 
46. 
Vuola JM, Keating S, Webster DP, Berthoud T, Dunachie S, Gilbert SC, Hill AV. 2005. 
Differential immunogenicity of various heterologous prime-boost vaccine regimens using 
DNA and viral vectors in healthy volunteers. J Immunol 174:449-55. 
47. 
Deeks SG, Walker BD. 2007. Human immunodeficiency virus controllers: mechanisms 
of durable virus control in the absence of antiretroviral therapy. Immunity 27:406-16. 
48. 
Kiepiela P, Ngumbela K, Thobakgale C, Ramduth D, Honeyborne I, Moodley E, Reddy 
S, de Pierres C, Mncube Z, Mkhwanazi N, Bishop K, van der Stok M, Nair K, Khan N, 
Crawford H, Payne R, Leslie A, Prado J, Prendergast A, Frater J, McCarthy N, Brander 
C, Learn GH, Nickle D, Rousseau C, Coovadia H, Mullins JI, Heckerman D, Walker BD, 
Goulder P. 2007. CD8+ T-cell responses to different HIV proteins have discordant 
associations with viral load. Nat Med 13:46-53. 
49. 
Crawford H, Prado JG, Leslie A, Hue S, Honeyborne I, Reddy S, van der Stok M, 
Mncube Z, Brander C, Rousseau C, Mullins JI, Kaslow R, Goepfert P, Allen S, Hunter E, 
Mulenga J, Kiepiela P, Walker BD, Goulder PJ. 2007. Compensatory mutation partially 
restores fitness and delays reversion of escape mutation within the immunodominant 
HLA-B*5703-restricted Gag epitope in chronic human immunodeficiency virus type 1 
infection. J Virol 81:8346-51. 
50. 
Warren J. 2020. The HIV-1 Latent Reservoir Is Largely Sensitive to Circulating T Cells. 
51. 
Deng K, Pertea M, Rongvaux A, Wang L, Durand CM, Ghiaur G, Lai J, McHugh HL, 
Hao H, Zhang H, Margolick JB, Gurer C, Murphy AJ, Valenzuela DM, Yancopoulos 
GD, Deeks SG, Strowig T, Kumar P, Siliciano JD, Salzberg SL, Flavell RA, Shan L, 
Siliciano RF. 2015. Broad CTL response is required to clear latent HIV-1 due to 
dominance of escape mutations. Nature 517:381-5. 
52. 
Warren JA, Zhou S, Xu Y, Moeser MJ, MacMillan DR, Council O, Kirchherr J, Sung 
JM, Roan NR, Adimora AA, Joseph S, Kuruc JD, Gay CL, Margolis DM, Archin N, 
Brumme ZL, Swanstrom R, Goonetilleke N. 2020. The HIV-1 latent reservoir is largely 
sensitive to circulating T cells. Elife 9. 
53. 
Xu Y, Trumble IM, Warren JA, Clutton G, Abad-Fernandez M, Kirchnerr J, Adimora 
AA, Deeks SG, Margolis DM, Kuruc JD, Gay CL, Archin NM, Mollan KR, Hudgens M, 
Goonetilleke N. 2019. HIV-Specific T Cell Responses Are Highly Stable on 
Antiretroviral Therapy. Mol Ther Methods Clin Dev 15:9-17. 
54. 
Ondondo B, Murakoshi H, Clutton G, Abdul-Jawad S, Wee EG, Gatanaga H, Oka S, 
McMichael AJ, Takiguchi M, Korber B, Hanke T. 2016. Novel Conserved-region T-cell 
Mosaic Vaccine With High Global HIV-1 Coverage Is Recognized by Protective 
Responses in Untreated Infection. Mol Ther 24:832-42. 
55. 
Mothe B, Llano A, Ibarrondo J, Daniels M, Miranda C, Zamarreno J, Bach V, Zuniga R, 
Perez-Alvarez S, Berger CT, Puertas MC, Martinez-Picado J, Rolland M, Farfan M, 
Szinger JJ, Hildebrand WH, Yang OO, Sanchez-Merino V, Brumme CJ, Brumme ZL, 
Heckerman D, Allen TM, Mullins JI, Gomez G, Goulder PJ, Walker BD, Gatell JM, 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Page 126 of 143
 
 
Clotet B, Korber BT, Sanchez J, Brander C. 2011. Definition of the viral targets of 
protective HIV-1-specific T cell responses. J Transl Med 9:208. 
56. 
Hanke T, Szawlowski P, Randall RE. 1992. Construction of solid matrix-antibody-
antigen complexes containing simian immunodeficiency virus p27 using tag-specific 
monoclonal antibody and tag-linked antigen. J Gen Virol 73 ( Pt 3):653-60. 
57. 
Afolabi MO, Ndure J, Drammeh A, Darboe F, Mehedi SR, Rowland-Jones SL, 
Borthwick N, Black A, Ambler G, John-Stewart GC, Reilly M, Hanke T, Flanagan KL. 
2013. A phase I randomized clinical trial of candidate human immunodeficiency virus 
type 1 vaccine MVA.HIVA administered to Gambian infants. PLoS One 8:e78289. 
58. 
Goonetilleke N, Moore S, Dally L, Winstone N, Cebere I, Mahmoud A, Pinheiro S, 
Gillespie G, Brown D, Loach V, Roberts J, Guimaraes-Walker A, Hayes P, Loughran K, 
Smith C, De Bont J, Verlinde C, Vooijs D, Schmidt C, Boaz M, Gilmour J, Fast P, 
Dorrell L, Hanke T, McMichael AJ. 2006. Induction of multifunctional human 
immunodeficiency virus type 1 (HIV-1)-specific T cells capable of proliferation in 
healthy subjects by using a prime-boost regimen of DNA- and modified vaccinia virus 
Ankara-vectored vaccines expressing HIV-1 Gag coupled to CD8+ T-cell epitopes. J 
Virol 80:4717-28. 
59. 
Njuguna IN, Ambler G, Reilly M, Ondondo B, Kanyugo M, Lohman-Payne B, Gichuhi 
C, Borthwick N, Black A, Mehedi SR, Sun J, Maleche-Obimbo E, Chohan B, John-
Stewart GC, Jaoko W, Hanke T. 2014. PedVacc 002: a phase I/II randomized clinical 
trial of MVA.HIVA vaccine administered to infants born to human immunodeficiency 
virus type 1-positive mothers in Nairobi. Vaccine 32:5801-8. 
60. 
Weiss R, Durnberger J, Mostbock S, Scheiblhofer S, Hartl A, Breitenbach M, Strasser P, 
Dorner F, Livey I, Crowe B, Thalhamer J. 1999. Improvement of the immune response 
against plasmid DNA encoding OspC of Borrelia by an ER-targeting leader sequence. 
Vaccine 18:815-24. 
61. 
Hanke T. 2019. Aiming for protective T-cell responses: a focus on the first generation 
conserved-region HIVconsv vaccines in preventive and therapeutic clinical trials. Expert 
Rev Vaccines 18:1029-1041. 
62. 
Mohamed YS, Borthwick NJ, Moyo N, Murakoshi H, Akahoshi T, Siliquini F, Hannoun 
Z, Crook A, Hayes P, Fast PE, Mutua G, Jaoko W, Silva-Arrieta S, Llano A, Brander C, 
Takiguchi M, Hanke T. 2020. Specificity of CD8(+) T-Cell Responses Following 
Vaccination with Conserved Regions of HIV-1 in Nairobi, Kenya. Vaccines (Basel) 8. 
63. 
Borthwick NJ, Lane T, Moyo N, Crook A, Shim JM, Baines I, Wee EG, Hawkins PN, 
Gillmore JD, Hanke T, Pepys MB. 2018. Randomized phase I trial HIV-CORE 003: 
Depletion of serum amyloid P component and immunogenicity of DNA vaccination 
against HIV-1. PLoS One 13:e0197299. 
64. 
Mothe B, Rosas-Umbert M, Coll P, Manzardo C, Puertas MC, Moron-Lopez S, Llano A, 
Miranda C, Cedeno S, Lopez M, Alarcon-Soto Y, Melis GG, Langohr K, Barriocanal 
AM, Toro J, Ruiz I, Rovira C, Carrillo A, Meulbroek M, Crook A, Wee EG, Miro JM, 
Clotet B, Valle M, Martinez-Picado J, Hanke T, Brander C, Molto J, Investigators BCNS. 
2020. HIVconsv Vaccines and Romidepsin in Early-Treated HIV-1-Infected Individuals: 
Safety, Immunogenicity and Effect on the Viral Reservoir (Study BCN02). Front 
Immunol 11:823. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
Confidential
Page 127 of 143
 
 
65. 
Fidler S, Stohr W, Pace M, Dorrell L, Lever A, Pett S, Kinloch-de Loes S, Fox J, Clarke 
A, Nelson M, Thornhill J, Khan M, Fun A, Bandara M, Kelly D, Kopycinski J, Hanke T, 
Yang H, Bennett R, Johnson M, Howell B, Barnard R, Wu G, Kaye S, Wills M, Babiker 
A, Frater J, group Rts. 2020. Antiretroviral therapy alone versus antiretroviral therapy 
with a kick and kill approach, on measures of the HIV reservoir in participants with 
recent HIV infection (the RIVER trial): a phase 2, randomised trial. Lancet 395:888-898. 
66. 
Mothe B, Manzardo C, Sanchez-Bernabeu A, Coll P, Moron-Lopez S, Puertas MC, 
Rosas-Umbert M, Cobarsi P, Escrig R, Perez-Alvarez N, Ruiz I, Rovira C, Meulbroek M, 
Crook A, Borthwick N, Wee EG, Yang H, Miro JM, Dorrell L, Clotet B, Martinez-
Picado J, Brander C, Hanke T. 2019. Therapeutic Vaccination Refocuses T-cell 
Responses Towards Conserved Regions of HIV-1 in Early Treated Individuals (BCN 01 
study). EClinicalMedicine 11:65-80. 
67. 
Hartnell F, Brown A, Capone S, Kopycinski J, Bliss C, Makvandi-Nejad S, Swadling L, 
Ghaffari E, Cicconi P, Del Sorbo M, Sbrocchi R, Esposito I, Vassilev V, Marriott P, 
Gardiner CM, Bannan C, Bergin C, Hoffmann M, Turner B, Nicosia A, Folgori A, Hanke 
T, Barnes E, Dorrell L. 2018. A Novel Vaccine Strategy Employing Serologically 
Different Chimpanzee Adenoviral Vectors for the Prevention of HIV-1 and HCV 
Coinfection. Front Immunol 9:3175. 
68. 
Hancock G, Moron-Lopez S, Kopycinski J, Puertas MC, Giannoulatou E, Rose A, 
Salgado M, Hayton EJ, Crook A, Morgan C, Angus B, Chen F, Yang H, Martinez-Picado 
J, Hanke T, Dorrell L. 2017. Evaluation of the immunogenicity and impact on the latent 
HIV-1 reservoir of a conserved region vaccine, MVA.HIVconsv, in antiretroviral 
therapy-treated subjects. J Int AIDS Soc 20:21171. 
69. 
Mutua G, Farah B, Langat R, Indangasi J, Ogola S, Onsembe B, Kopycinski JT, Hayes P, 
Borthwick NJ, Ashraf A, Dally L, Barin B, Tillander A, Gilmour J, De Bont J, Crook A, 
Hannaman D, Cox JH, Anzala O, Fast PE, Reilly M, Chinyenze K, Jaoko W, Hanke T, 
Hiv-Core 004 Study Group T. 2016. Broad HIV-1 inhibition in vitro by vaccine-elicited 
CD8(+) T cells in African adults. Mol Ther Methods Clin Dev 3:16061. 
70. 
Borthwick N, Ahmed T, Ondondo B, Hayes P, Rose A, Ebrahimsa U, Hayton EJ, Black 
A, Bridgeman A, Rosario M, Hill AV, Berrie E, Moyle S, Frahm N, Cox J, Colloca S, 
Nicosia A, Gilmour J, McMichael AJ, Dorrell L, Hanke T. 2014. Vaccine-elicited human 
T cells recognizing conserved protein regions inhibit HIV-1. Mol Ther 22:464-75. 
71. 
Schneider J, Gilbert SC, Blanchard TJ, Hanke T, Robson KJ, Hannan CM, Becker M, 
Sinden R, Smith GL, Hill AV. 1998. Enhanced immunogenicity for CD8+ T cell 
induction and complete protective efficacy of malaria DNA vaccination by boosting with 
modified vaccinia virus Ankara. Nat Med 4:397-402. 
72. 
Zak DE, Andersen-Nissen E, Peterson ER, Sato A, Hamilton MK, Borgerding J, 
Krishnamurty AT, Chang JT, Adams DJ, Hensley TR, Salter AI, Morgan CA, Duerr AC, 
De Rosa SC, Aderem A, McElrath MJ. 2012. Merck Ad5/HIV induces broad innate 
immune activation that predicts CD8(+) T-cell responses but is attenuated by preexisting 
Ad5 immunity. Proc Natl Acad Sci U S A 109:E3503-12. 
73. 
Quinn KM, Da Costa A, Yamamoto A, Berry D, Lindsay RW, Darrah PA, Wang L, 
Cheng C, Kong WP, Gall JG, Nicosia A, Folgori A, Colloca S, Cortese R, Gostick E, 
Price DA, Gomez CE, Esteban M, Wyatt LS, Moss B, Morgan C, Roederer M, Bailer 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
Confidential
Page 128 of 143
 
 
RT, Nabel GJ, Koup RA, Seder RA. 2013. Comparative analysis of the magnitude, 
quality, phenotype, and protective capacity of simian immunodeficiency virus gag-
specific CD8+ T cells following human-, simian-, and chimpanzee-derived recombinant 
adenoviral vector immunization. J Immunol 190:2720-35. 
74. 
Dicks MD, Spencer AJ, Edwards NJ, Wadell G, Bojang K, Gilbert SC, Hill AV, 
Cottingham MG. 2012. A novel chimpanzee adenovirus vector with low human 
seroprevalence: improved systems for vector derivation and comparative 
immunogenicity. PLoS One 7:e40385. 
75. 
Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, Aley PK, Angus B, 
Baillie VL, Barnabas SL, Bhorat QE, Bibi S, Briner C, Cicconi P, Collins AM, Colin-
Jones R, Cutland CL, Darton TC, Dheda K, Duncan CJA, Emary KRW, Ewer KJ, Fairlie 
L, Faust SN, Feng S, Ferreira DM, Finn A, Goodman AL, Green CM, Green CA, Heath 
PT, Hill C, Hill H, Hirsch I, Hodgson SHC, Izu A, Jackson S, Jenkin D, Joe CCD, 
Kerridge S, Koen A, Kwatra G, Lazarus R, Lawrie AM, Lelliott A, Libri V, Lillie PJ, 
Mallory R, Mendes AVA, Milan EP, Minassian AM, et al. 2021. Safety and efficacy of 
the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of 
four randomised controlled trials in Brazil, South Africa, and the UK. Lancet 397:99-111. 
76. 
Ramasamy MN, Minassian AM, Ewer KJ, Flaxman AL, Folegatti PM, Owens DR, 
Voysey M, Aley PK, Angus B, Babbage G, Belij-Rammerstorfer S, Berry L, Bibi S, 
Bittaye M, Cathie K, Chappell H, Charlton S, Cicconi P, Clutterbuck EA, Colin-Jones R, 
Dold C, Emary KRW, Fedosyuk S, Fuskova M, Gbesemete D, Green C, Hallis B, Hou 
MM, Jenkin D, Joe CCD, Kelly EJ, Kerridge S, Lawrie AM, Lelliott A, Lwin MN, 
Makinson R, Marchevsky NG, Mujadidi Y, Munro APS, Pacurar M, Plested E, Rand J, 
Rawlinson T, Rhead S, Robinson H, Ritchie AJ, Ross-Russell AL, Saich S, Singh N, 
Smith CC, et al. 2021. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine 
administered in a prime-boost regimen in young and old adults (COV002): a single-blind, 
randomised, controlled, phase 2/3 trial. Lancet 396:1979-1993. 
77. 
Sadoff J, Le Gars M, Shukarev G, Heerwegh D, Truyers C, de Groot AM, Stoop J, Tete 
S, Van Damme W, Leroux-Roels I, Berghmans PJ, Kimmel M, Van Damme P, de Hoon 
J, Smith W, Stephenson KE, De Rosa SC, Cohen KW, McElrath MJ, Cormier E, Scheper 
G, Barouch DH, Hendriks J, Struyf F, Douoguih M, Van Hoof J, Schuitemaker H. 2021. 
Interim Results of a Phase 1-2a Trial of Ad26.COV2.S Covid-19 Vaccine. N Engl J Med 
doi:10.1056/NEJMoa2034201. 
78. 
Logunov DY, Dolzhikova IV, Shcheblyakov DV, Tukhvatulin AI, Zubkova OV, 
Dzharullaeva AS, Kovyrshina AV, Lubenets NL, Grousova DM, Erokhova AS, Botikov 
AG, Izhaeva FM, Popova O, Ozharovskaya TA, Esmagambetov IB, Favorskaya IA, 
Zrelkin DI, Voronina DV, Shcherbinin DN, Semikhin AS, Simakova YV, Tokarskaya 
EA, Egorova DA, Shmarov MM, Nikitenko NA, Gushchin VA, Smolyarchuk EA, 
Zyryanov SK, Borisevich SV, Naroditsky BS, Gintsburg AL, Gam C-VVTG. 2021. 
Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost 
COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in 
Russia. Lancet 397:671-681. 
79. 
Barouch DH, Kik SV, Weverling GJ, Dilan R, King SL, Maxfield LF, Clark S, Ng'ang'a 
D, Brandariz KL, Abbink P, Sinangil F, de Bruyn G, Gray GE, Roux S, Bekker LG, 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
Confidential
Page 129 of 143
 
 
Dilraj A, Kibuuka H, Robb ML, Michael NL, Anzala O, Amornkul PN, Gilmour J, Hural 
J, Buchbinder SP, Seaman MS, Dolin R, Baden LR, Carville A, Mansfield KG, Pau MG, 
Goudsmit J. 2011. International seroepidemiology of adenovirus serotypes 5, 26, 35, and 
48 in pediatric and adult populations. Vaccine 29:5203-9. 
80. 
McElrath MJ, De Rosa SC, Moodie Z, Dubey S, Kierstead L, Janes H, Defawe OD, 
Carter DK, Hural J, Akondy R, Buchbinder SP, Robertson MN, Mehrotra DV, Self SG, 
Corey L, Shiver JW, Casimiro DR, Step Study Protocol T. 2008. HIV-1 vaccine-induced 
immunity in the test-of-concept Step Study: a case-cohort analysis. Lancet 372:1894-
1905. 
81. 
Iampietro MJ, Larocca RA, Provine NM, Abbink P, Kang ZH, Bricault CA, Barouch DH. 
2018. Immunogenicity and Cross-Reactivity of Rhesus Adenoviral Vectors. J Virol 92. 
82. 
Penaloza-MacMaster P, Provine NM, Ra J, Borducchi EN, McNally A, Simmons NL, 
Iampietro MJ, Barouch DH. 2013. Alternative serotype adenovirus vaccine vectors elicit 
memory T cells with enhanced anamnestic capacity compared to Ad5 vectors. J Virol 
87:1373-84. 
83. 
Baden LR, Karita E, Mutua G, Bekker LG, Gray G, Page-Shipp L, Walsh SR, 
Nyombayire J, Anzala O, Roux S, Laher F, Innes C, Seaman MS, Cohen YZ, Peter L, 
Frahm N, McElrath MJ, Hayes P, Swann E, Grunenberg N, Grazia-Pau M, Weijtens M, 
Sadoff J, Dally L, Lombardo A, Gilmour J, Cox J, Dolin R, Fast P, Barouch DH, Laufer 
DS, Group BIHS. 2016. Assessment of the Safety and Immunogenicity of 2 Novel 
Vaccine Platforms for HIV-1 Prevention: A Randomized Trial. Ann Intern Med 164:313-
22. 
84. 
Scully M, Singh D, Lown R, Poles A, Solomon T, Levi M, Goldblatt D, Kotoucek P, 
Thomas W, Lester W. 2021. Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 
nCoV-19 Vaccination. N Engl J Med doi:10.1056/NEJMoa2105385. 
85. 
Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S. 2021. 
Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination. N Engl J Med 
doi:10.1056/NEJMoa2104840. 
86. 
Bourguignon A, Arnold DM, Warkentin TE, Smith JW, Pannu T, Shrum JM, Al 
Maqrashi ZAA, Shroff A, Lessard MC, Blais N, Kelton JG, Nazy I. 2021. Adjunct 
Immune Globulin for Vaccine-Induced Thrombotic Thrombocytopenia. N Engl J Med 
doi:10.1056/NEJMoa2107051. 
87. 
Kilpelainen A, Saubi N, Guitart N, Moyo N, Wee EG, Ravi K, Hanke T, Joseph J. 2019. 
Priming With Recombinant BCG Expressing Novel HIV-1 Conserved Mosaic 
Immunogens and Boosting With Recombinant ChAdOx1 Is Safe, Stable, and Elicits 
HIV-1-Specific T-Cell Responses in BALB/c Mice. Front Immunol 10:923. 
88. 
Sutter G, Moss B. 1992. Nonreplicating vaccinia vector efficiently expresses recombinant 
genes. Proc Natl Acad Sci U S A 89:10847-51. 
89. 
Drexler I, Heller K, Wahren B, Erfle V, Sutter G. 1998. Highly attenuated modified 
vaccinia virus Ankara replicates in baby hamster kidney cells, a potential host for virus 
propagation, but not in various human transformed and primary cells. J Gen Virol 
79:347-52. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
Confidential
Page 130 of 143
 
 
90. 
Antoine G, Scheiflinger F, Dorner F, Falkner FG. 1998. The complete genomic sequence 
of the modified vaccinia Ankara strain: comparison with other orthopoxviruses. Virology 
244:365-96. 
91. 
Rampling T, Ewer KJ, Bowyer G, Bliss CM, Edwards NJ, Wright D, Payne R, 
Venkatraman N, de Barra E, Snudden CM, Poulton ID, de Graaf H, Sukhtankar P, 
Roberts R, Ivinson K, Weltzin R, Rajkumar BY, Wille-Reece U, Lee C, Ockenhouse C, 
Sinden RE, Gerry S, Lawrie AM, Vekemans J, Morelle D, Lievens M, Ballou RW, 
Cooke GS, Faust SN, Gilbert S, Hill AV. 2016. Safety and High Level Efficacy of the 
Combination Malaria Vaccine Regimen of RTS,S/AS01B with ChAd-MVA Vectored 
Vaccines Expressing ME-TRAP. J Infect Dis doi:10.1093/infdis/jiw244. 
92. 
Afolabi MO, Tiono AB, Adetifa UJ, Yaro JB, Drammeh A, Nebie I, Bliss C, Hodgson 
SH, Anagnostou NA, Sanou GS, Jagne YJ, Ouedraogo O, Tamara C, Ouedraogo N, 
Ouedraogo M, Njie-Jobe J, Diarra A, Duncan CJ, Cortese R, Nicosia A, Roberts R, 
Viebig NK, Leroy O, Lawrie AM, Flanagan KL, Kampman B, Bejon P, Imoukhuede EB, 
Ewer KJ, Hill AV, Bojang K, Sirima SB. 2016. Safety and Immunogenicity of ChAd63 
and MVA ME-TRAP in West African Children and Infants. Mol Ther 
doi:10.1038/mt.2016.83. 
93. 
Ndiaye BP, Thienemann F, Ota M, Landry BS, Camara M, Dieye S, Dieye TN, Esmail 
H, Goliath R, Huygen K, January V, Ndiaye I, Oni T, Raine M, Romano M, Satti I, 
Sutton S, Thiam A, Wilkinson KA, Mboup S, Wilkinson RJ, McShane H, investigators 
MAt. 2015. Safety, immunogenicity, and efficacy of the candidate tuberculosis vaccine 
MVA85A in healthy adults infected with HIV-1: a randomised, placebo-controlled, phase 
2 trial. Lancet Respir Med 3:190-200. 
94. 
Mothe B, Climent N, Plana M, Rosas M, Jimenez JL, Munoz-Fernandez MA, Puertas 
MC, Carrillo J, Gonzalez N, Leon A, Pich J, Arnaiz JA, Gatell JM, Clotet B, Blanco J, 
Alcami J, Martinez-Picado J, Alvarez-Fernandez C, Sanchez-Palomino S, Guardo AC, 
Pena J, Benito JM, Rallon N, Gomez CE, Perdiguero B, Garcia-Arriaza J, Esteban M, 
Lopez Bernaldo de Quiros JC, Brander C, Garcia F, Group R-S. 2015. Safety and 
immunogenicity of a modified vaccinia Ankara-based HIV-1 vaccine (MVA-B) in HIV-
1-infected patients alone or in combination with a drug to reactivate latent HIV-1. J 
Antimicrob Chemother 70:1833-42. 
95. 
Hodgson SH, Choudhary P, Elias SC, Milne KH, Rampling TW, Biswas S, Poulton ID, 
Miura K, Douglas AD, Alanine DG, Illingworth JJ, de Cassan SC, Zhu D, Nicosia A, 
Long CA, Moyle S, Berrie E, Lawrie AM, Wu Y, Ellis RD, Hill AV, Draper SJ. 2014. 
Combining viral vectored and protein-in-adjuvant vaccines against the blood-stage 
malaria antigen AMA1: report on a phase 1a clinical trial. Mol Ther 22:2142-54. 
96. 
Hayton EJ, Rose A, Ibrahimsa U, Del Sorbo M, Capone S, Crook A, Black AP, Dorrell 
L, Hanke T. 2014. Safety and tolerability of conserved region vaccines vectored by 
plasmid DNA, simian adenovirus and modified vaccinia virus ankara administered to 
human immunodeficiency virus type 1-uninfected adults in a randomized, single-blind 
phase I trial. PLoS One 9:e101591. 
97. 
Antrobus RD, Berthoud TK, Mullarkey CE, Hoschler K, Coughlan L, Zambon M, Hill 
AV, Gilbert SC. 2014. Coadministration of seasonal influenza vaccine and MVA-

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
Confidential
Page 131 of 143
 
 
NP+M1 simultaneously achieves potent humoral and cell-mediated responses. Mol Ther 
22:233-8. 
98. 
Rowland R, Pathan AA, Satti I, Poulton ID, Matsumiya MM, Whittaker M, Minassian 
AM, O'Hara GA, Hamill M, Scott JT, Harris SA, Poyntz HC, Bateman C, Meyer J, 
Williams N, Gilbert SC, Lawrie AM, Hill AV, McShane H. 2013. Safety and 
immunogenicity of an FP9-vectored candidate tuberculosis vaccine (FP85A), alone and 
with candidate vaccine MVA85A in BCG-vaccinated healthy adults: a phase I clinical 
trial. Hum Vaccin Immunother 9:50-62. 
99. 
Dieye TN, Ndiaye BP, Dieng AB, Fall M, Brittain N, Vermaak S, Camara M, Diop-
Ndiaye H, Ngom-Gueye NF, Diaw PA, Toure-Kane C, Sow PS, Mboup S, McShane H. 
2013. Two doses of candidate TB vaccine MVA85A in antiretroviral therapy (ART) 
naive subjects gives comparable immunogenicity to one dose in ART+ subjects. PLoS 
One 8:e67177. 
100. 
Ratto-Kim S, Currier JR, Cox JH, Excler JL, Valencia-Micolta A, Thelian D, Lo V, 
Sayeed E, Polonis VR, Earl PL, Moss B, Robb ML, Michael NL, Kim JH, Marovich MA. 
2012. Heterologous prime-boost regimens using rAd35 and rMVA vectors elicit stronger 
cellular immune responses to HIV proteins than homologous regimens. PLoS One 
7:e45840. 
101. 
O'Hara GA, Duncan CJ, Ewer KJ, Collins KA, Elias SC, Halstead FD, Goodman AL, 
Edwards NJ, Reyes-Sandoval A, Bird P, Rowland R, Sheehy SH, Poulton ID, Hutchings 
C, Todryk S, Andrews L, Folgori A, Berrie E, Moyle S, Nicosia A, Colloca S, Cortese R, 
Siani L, Lawrie AM, Gilbert SC, Hill AV. 2012. Clinical assessment of a recombinant 
simian adenovirus ChAd63: a potent new vaccine vector. J Infect Dis 205:772-81. 
102. 
Antrobus RD, Lillie PJ, Berthoud TK, Spencer AJ, McLaren JE, Ladell K, Lambe T, 
Milicic A, Price DA, Hill AV, Gilbert SC. 2012. A T cell-inducing influenza vaccine for 
the elderly: safety and immunogenicity of MVA-NP+M1 in adults aged over 50 years. 
PLoS One 7:e48322. 
103. 
Sheehy SH, Duncan CJ, Elias SC, Collins KA, Ewer KJ, Spencer AJ, Williams AR, 
Halstead FD, Moretz SE, Miura K, Epp C, Dicks MD, Poulton ID, Lawrie AM, Berrie E, 
Moyle S, Long CA, Colloca S, Cortese R, Gilbert SC, Nicosia A, Hill AV, Draper SJ. 
2011. Phase Ia clinical evaluation of the Plasmodium falciparum blood-stage antigen 
MSP1 in ChAd63 and MVA vaccine vectors. Mol Ther 19:2269-76. 
104. 
Howles S, Guimaraes-Walker A, Yang H, Hancock G, di Gleria K, Tarragona-Fiol T, 
Hayes P, Gilmour J, Bridgeman A, Hanke T, McMichael A, Dorrell L. 2010. Vaccination 
with a modified vaccinia virus Ankara (MVA)-vectored HIV-1 immunogen induces 
modest vector-specific T cell responses in human subjects. Vaccine 28:7306-12. 
105. 
Draper SJ, Biswas S, Spencer AJ, Remarque EJ, Capone S, Naddeo M, Dicks MD, Faber 
BW, de Cassan SC, Folgori A, Nicosia A, Gilbert SC, Hill AV. 2010. Enhancing blood-
stage malaria subunit vaccine immunogenicity in rhesus macaques by combining 
adenovirus, poxvirus, and protein-in-adjuvant vaccines. J Immunol 185:7583-95. 
106. 
Guimaraes-Walker A, Mackie N, McCormack S, Hanke T, Schmidt C, Gilmour J, Barin 
B, McMichael A, Weber J, Legg K, Babiker A, Hayes P, Gotch F, Smith C, Dally L, 
Dorrell L, Cebere I, Kay R, Winstone N, Moore S, Goonetilleke N, Fast P, Group I-S. 
2008. Lessons from IAVI-006, a phase I clinical trial to evaluate the safety and 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Page 132 of 143
 
 
immunogenicity of the pTHr.HIVA DNA and MVA.HIVA vaccines in a prime-boost 
strategy to induce HIV-1 specific T-cell responses in healthy volunteers. Vaccine 
26:6671-7. 
107. 
Greenough TC, Cunningham CK, Muresan P, McManus M, Persaud D, Fenton T, Barker 
P, Gaur A, Panicali D, Sullivan JL, Luzuriaga K, Pediatric ACTGPT. 2008. Safety and 
immunogenicity of recombinant poxvirus HIV-1 vaccines in young adults on highly 
active antiretroviral therapy. Vaccine 26:6883-93. 
108. 
Harrop R, Drury N, Shingler W, Chikoti P, Redchenko I, Carroll MW, Kingsman SM, 
Naylor S, Melcher A, Nicholls J, Wassan H, Habib N, Anthoney A. 2007. Vaccination of 
colorectal cancer patients with modified vaccinia ankara encoding the tumor antigen 5T4 
(TroVax) given alongside chemotherapy induces potent immune responses. Clin Cancer 
Res 13:4487-94. 
109. 
Dorrell L, Williams P, Suttill A, Brown D, Roberts J, Conlon C, Hanke T, McMichael A. 
2007. Safety and tolerability of recombinant modified vaccinia virus Ankara expressing 
an HIV-1 gag/multiepitope immunogen (MVA.HIVA) in HIV-1-infected persons 
receiving combination antiretroviral therapy. Vaccine 25:3277-83. 
110. 
Ondondo BO, Yang H, Dong T, di Gleria K, Suttill A, Conlon C, Brown D, Williams P, 
Rowland-Jones SL, Hanke T, McMichael AJ, Dorrell L. 2006. Immunisation with 
recombinant modified vaccinia virus Ankara expressing HIV-1 gag in HIV-1-infected 
subjects stimulates broad functional CD4+ T cell responses. Eur J Immunol 36:2585-94. 
111. 
Dunachie SJ, Walther M, Epstein JE, Keating S, Berthoud T, Andrews L, Andersen RF, 
Bejon P, Goonetilleke N, Poulton I, Webster DP, Butcher G, Watkins K, Sinden RE, 
Levine GL, Richie TL, Schneider J, Kaslow D, Gilbert SC, Carucci DJ, Hill AV. 2006. A 
DNA prime-modified vaccinia virus ankara boost vaccine encoding thrombospondin-
related adhesion protein but not circumsporozoite protein partially protects healthy 
malaria-naive adults against Plasmodium falciparum sporozoite challenge. Infect Immun 
74:5933-42. 
112. 
Mwau M, Cebere I, Sutton J, Chikoti P, Winstone N, Wee EG, Beattie T, Chen YH, 
Dorrell L, McShane H, Schmidt C, Brooks M, Patel S, Roberts J, Conlon C, Rowland-
Jones SL, Bwayo JJ, McMichael AJ, Hanke T. 2004. A human immunodeficiency virus 1 
(HIV-1) clade A vaccine in clinical trials: stimulation of HIV-specific T-cell responses by 
DNA and recombinant modified vaccinia virus Ankara (MVA) vaccines in humans. J 
Gen Virol 85:911-9. 
113. 
McShane H, Pathan AA, Sander CR, Keating SM, Gilbert SC, Huygen K, Fletcher HA, 
Hill AV. 2004. Recombinant modified vaccinia virus Ankara expressing antigen 85A 
boosts BCG-primed and naturally acquired antimycobacterial immunity in humans. Nat 
Med 10:1240-4. 
114. 
Moorthy VS, McConkey S, Roberts M, Gothard P, Arulanantham N, Degano P, 
Schneider J, Hannan C, Roy M, Gilbert SC, Peto TE, Hill AV. 2003. Safety of DNA and 
modified vaccinia virus Ankara vaccines against liver-stage P. falciparum malaria in non-
immune volunteers. Vaccine 21:2004-11. 
115. 
McConkey SJ, Reece WH, Moorthy VS, Webster D, Dunachie S, Butcher G, Vuola JM, 
Blanchard TJ, Gothard P, Watkins K, Hannan CM, Everaere S, Brown K, Kester KE, 
Cummings J, Williams J, Heppner DG, Pathan A, Flanagan K, Arulanantham N, Roberts 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Page 133 of 143
 
 
MT, Roy M, Smith GL, Schneider J, Peto T, Sinden RE, Gilbert SC, Hill AV. 2003. 
Enhanced T-cell immunogenicity of plasmid DNA vaccines boosted by recombinant 
modified vaccinia virus Ankara in humans. Nat Med 9:729-35. 
116. 
Cosma A, Nagaraj R, Buhler S, Hinkula J, Busch DH, Sutter G, Goebel FD, Erfle V. 
2003. Therapeutic vaccination with MVA-HIV-1 nef elicits Nef-specific T-helper cell 
responses in chronically HIV-1 infected individuals. Vaccine 22:21-9. 
117. 
Stickl HA. 1974. Smallpox vaccination and its consequences: first experiences with the 
highly attenuated smallpox vaccine "MVA". Prev Med 3:97-101. 
118. 
Abdul-Jawad S, Ondondo B, van Hateren A, Gardner A, Elliott T, Korber B, Hanke T. 
2016. Increased Valency of Conserved-mosaic Vaccines Enhances the Breadth and Depth 
of Epitope Recognition. Mol Ther 24:375-84. 
119. 
Hanke T, McMichael AJ, Samuel RV, Powell LA, McLoughlin L, Crome SJ, Edlin A. 
2002. Lack of toxicity and persistence in the mouse associated with administration of 
candidate DNA- and modified vaccinia virus Ankara (MVA)-based HIV vaccines for 
Kenya. Vaccine 21:108-14. 
120. 
Hanke T, McMichael AJ, Dennis MJ, Sharpe SA, Powell LA, McLoughlin L, Crome SJ. 
2005. Biodistribution and persistence of an MVA-vectored candidate HIV vaccine in 
SIV-infected rhesus macaques and SCID mice. Vaccine 23:1507-14. 
121. 
Wilkie M, Satti I, Minhinnick A, Harris S, Riste M, Ramon RL, Sheehan S, Thomas ZM, 
Wright D, Stockdale L, Hamidi A, O'Shea MK, Dwivedi K, Behrens HM, Davenne T, 
Morton J, Vermaak S, Lawrie A, Moss P, McShane H. 2020. A phase I trial evaluating 
the safety and immunogenicity of a candidate tuberculosis vaccination regimen, 
ChAdOx1 85A prime - MVA85A boost in healthy UK adults. Vaccine 38:779-789. 
122. 
Mensah VA, Roetynck S, Kanteh EK, Bowyer G, Ndaw A, Oko F, Bliss CM, Jagne YJ, 
Cortese R, Nicosia A, Roberts R, D'Alessio F, Leroy O, Faye B, Kampmann B, Cisse B, 
Bojang K, Gerry S, Viebig NK, Lawrie AM, Clarke E, Imoukhuede EB, Ewer KJ, Hill 
AVS, Afolabi MO. 2017. Safety and Immunogenicity of Malaria Vectored Vaccines 
Given with Routine Expanded Program on Immunization Vaccines in Gambian Infants 
and Neonates: A Randomized Controlled Trial. Front Immunol 8:1551. 
123. 
Tapia MD, Sow SO, Lyke KE, Haidara FC, Diallo F, Doumbia M, Traore A, Coulibaly 
F, Kodio M, Onwuchekwa U, Sztein MB, Wahid R, Campbell JD, Kieny MP, Moorthy 
V, Imoukhuede EB, Rampling T, Roman F, De Ryck I, Bellamy AR, Dally L, Mbaya 
OT, Ploquin A, Zhou Y, Stanley DA, Bailer R, Koup RA, Roederer M, Ledgerwood J, 
Hill AV, Ballou WR, Sullivan N, Graham B, Levine MM. 2016. Use of ChAd3-EBO-Z 
Ebola virus vaccine in Malian and US adults, and boosting of Malian adults with MVA-
BN-Filo: a phase 1, single-blind, randomised trial, a phase 1b, open-label and double-
blind, dose-escalation trial, and a nested, randomised, double-blind, placebo-controlled 
trial. Lancet Infect Dis 16:31-42. 
124. 
Hodgson SH, Ewer KJ, Bliss CM, Edwards NJ, Rampling T, Anagnostou NA, de Barra 
E, Havelock T, Bowyer G, Poulton ID, de Cassan S, Longley R, Illingworth JJ, Douglas 
AD, Mange PB, Collins KA, Roberts R, Gerry S, Berrie E, Moyle S, Colloca S, Cortese 
R, Sinden RE, Gilbert SC, Bejon P, Lawrie AM, Nicosia A, Faust SN, Hill AV. 2015. 
Evaluation of the efficacy of ChAd63-MVA vectored vaccines expressing 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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circumsporozoite protein and ME-TRAP against controlled human malaria infection in 
malaria-naive individuals. J Infect Dis 211:1076-86. 
125. 
Swadling L, Capone S, Antrobus RD, Brown A, Richardson R, Newell EW, Halliday J, 
Kelly C, Bowen D, Fergusson J, Kurioka A, Ammendola V, Del Sorbo M, Grazioli F, 
Esposito ML, Siani L, Traboni C, Hill A, Colloca S, Davis M, Nicosia A, Cortese R, 
Folgori A, Klenerman P, Barnes E. 2014. A human vaccine strategy based on 
chimpanzee adenoviral and MVA vectors that primes, boosts, and sustains functional 
HCV-specific T cell memory. Sci Transl Med 6:261ra153. 
126. 
Ogwang C, Afolabi M, Kimani D, Jagne YJ, Sheehy SH, Bliss CM, Duncan CJ, Collins 
KA, Garcia Knight MA, Kimani E, Anagnostou NA, Berrie E, Moyle S, Gilbert SC, 
Spencer AJ, Soipei P, Mueller J, Okebe J, Colloca S, Cortese R, Viebig NK, Roberts R, 
Gantlett K, Lawrie AM, Nicosia A, Imoukhuede EB, Bejon P, Urban BC, Flanagan KL, 
Ewer KJ, Chilengi R, Hill AV, Bojang K. 2013. Safety and immunogenicity of 
heterologous prime-boost immunisation with Plasmodium falciparum malaria candidate 
vaccines, ChAd63 ME-TRAP and MVA ME-TRAP, in healthy Gambian and Kenyan 
adults. PLoS One 8:e57726. 
127. 
Tiono AB, Nebie I, Anagnostou N, Coulibaly AS, Bowyer G, Lam E, Bougouma EC, 
Ouedraogo A, Yaro JBB, Barry A, Roberts R, Rampling T, Bliss C, Hodgson S, Lawrie 
A, Ouedraogo A, Imoukhuede EB, Ewer KJ, Viebig NK, Diarra A, Leroy O, Bejon P, 
Hill AVS, Sirima SB. 2018. First field efficacy trial of the ChAd63 MVA ME-TRAP 
vectored malaria vaccine candidate in 5-17 months old infants and children. PLoS One 
13:e0208328. 
128. 
de Barra E, Hodgson SH, Ewer KJ, Bliss CM, Hennigan K, Collins A, Berrie E, Lawrie 
AM, Gilbert SC, Nicosia A, McConkey SJ, Hill AV. 2014. A phase Ia study to assess the 
safety and immunogenicity of new malaria vaccine candidates ChAd63 CS administered 
alone and with MVA CS. PLoS One 9:e115161. 
129. 
Bauza K, Malinauskas T, Pfander C, Anar B, Jones EY, Billker O, Hill AV, Reyes-
Sandoval A. 2014. Efficacy of a Plasmodium vivax malaria vaccine using ChAd63 and 
modified vaccinia Ankara expressing thrombospondin-related anonymous protein as 
assessed with transgenic Plasmodium berghei parasites. Infect Immun 82:1277-86. 
130. 
Sheehy SH, Duncan CJ, Elias SC, Biswas S, Collins KA, O'Hara GA, Halstead FD, Ewer 
KJ, Mahungu T, Spencer AJ, Miura K, Poulton ID, Dicks MD, Edwards NJ, Berrie E, 
Moyle S, Colloca S, Cortese R, Gantlett K, Long CA, Lawrie AM, Gilbert SC, Doherty 
T, Nicosia A, Hill AV, Draper SJ. 2012. Phase Ia clinical evaluation of the safety and 
immunogenicity of the Plasmodium falciparum blood-stage antigen AMA1 in ChAd63 
and MVA vaccine vectors. PLoS One 7:e31208. 
131. 
Schneider J, Gilbert SC, Hannan CM, Degano P, Prieur E, Sheu EG, Plebanski M, Hill 
AV. 1999. Induction of CD8+ T cells using heterologous prime-boost immunisation 
strategies. Immunol Rev 170:29-38. 
132. 
Xu Y, Trumble IM, Warren J, Clutton G, Abad-Fernandez M, Kirchnerr J, Adimora AA, 
Deeks S, Margolis D, Kuruc J, Gay C, Archin N, Mollan KR, Hudgens M, N G. 2019. 
HIV-specific T cell responses are highly stable on antiretroviral therapy. Molecular 
Therapy Methods and Clinical Development 
doi:https://doi.org/10.1016/j.omtm.2019.07.008. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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133. 
Berthoud TK, Hamill M, Lillie PJ, Hwenda L, Collins KA, Ewer KJ, Milicic A, Poyntz 
HC, Lambe T, Fletcher HA, Hill AV, Gilbert SC. 2011. Potent CD8+ T-cell 
immunogenicity in humans of a novel heterosubtypic influenza A vaccine, MVA-
NP+M1. Clin Infect Dis 52:1-7. 
134. 
Minassian AM, Rowland R, Beveridge NE, Poulton ID, Satti I, Harris S, Poyntz H, 
Hamill M, Griffiths K, Sander CR, Ambrozak DR, Price DA, Hill BJ, Casazza JP, Douek 
DC, Koup RA, Roederer M, Winston A, Ross J, Sherrard J, Rooney G, Williams N, 
Lawrie AM, Fletcher HA, Pathan AA, McShane H. 2011. A Phase I study evaluating the 
safety and immunogenicity of MVA85A, a candidate TB vaccine, in HIV-infected adults. 
BMJ Open 1:e000223. 
135. 
Sander CR, Pathan AA, Beveridge NE, Poulton I, Minassian A, Alder N, Van Wijgerden 
J, Hill AV, Gleeson FV, Davies RJ, Pasvol G, McShane H. 2009. Safety and 
immunogenicity of a new tuberculosis vaccine, MVA85A, in Mycobacterium 
tuberculosis-infected individuals. Am J Respir Crit Care Med 179:724-33. 
136. 
Folegatti PM, Ewer KJ, Aley PK, Angus B, Becker S, Belij-Rammerstorfer S, Bellamy 
D, Bibi S, Bittaye M, Clutterbuck EA, Dold C, Faust SN, Finn A, Flaxman AL, Hallis B, 
Heath P, Jenkin D, Lazarus R, Makinson R, Minassian AM, Pollock KM, Ramasamy M, 
Robinson H, Snape M, Tarrant R, Voysey M, Green C, Douglas AD, Hill AVS, Lambe 
T, Gilbert SC, Pollard AJ, Oxford CVTG. 2020. Safety and immunogenicity of the 
ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, 
single-blind, randomised controlled trial. Lancet 396:467-478. 
137. 
Ewer K, Rampling T, Venkatraman N, Bowyer G, Wright D, Lambe T, Imoukhuede EB, 
Payne R, Fehling SK, Strecker T, Biedenkopf N, Krahling V, Tully CM, Edwards NJ, 
Bentley EM, Samuel D, Labbe G, Jin J, Gibani M, Minhinnick A, Wilkie M, Poulton I, 
Lella N, Roberts R, Hartnell F, Bliss C, Sierra-Davidson K, Powlson J, Berrie E, Tedder 
R, Roman F, De Ryck I, Nicosia A, Sullivan NJ, Stanley DA, Mbaya OT, Ledgerwood 
JE, Schwartz RM, Siani L, Colloca S, Folgori A, Di Marco S, Cortese R, Wright E, 
Becker S, Graham BS, Koup RA, Levine MM, Volkmann A, Chaplin P, et al. 2016. A 
Monovalent Chimpanzee Adenovirus Ebola Vaccine Boosted with MVA. N Engl J Med 
374:1635-46. 
138. 
Cappuccini F, Stribbling S, Pollock E, Hill AV, Redchenko I. 2016. Immunogenicity and 
efficacy of the novel cancer vaccine based on simian adenovirus and MVA vectors alone 
and in combination with PD-1 mAb in a mouse model of prostate cancer. Cancer 
Immunol Immunother 65:701-13. 
139. 
Satti I, Meyer J, Harris SA, Manjaly Thomas ZR, Griffiths K, Antrobus RD, Rowland R, 
Ramon RL, Smith M, Sheehan S, Bettinson H, McShane H. 2014. Safety and 
immunogenicity of a candidate tuberculosis vaccine MVA85A delivered by aerosol in 
BCG-vaccinated healthy adults: a phase 1, double-blind, randomised controlled trial. 
Lancet Infect Dis 14:939-46. 
 
 
 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Appendix 1  
Rationale for Protocol Version 3.0 
The rationale for this amendment is to update C1-C62 risks section per C1 IB v4 and C62 IB v3, 
incorporated clarification memo #1 dated 27-Feb-2023, to clarify AE/SAE reporting, to remove 
contradictory language for allowable Mpox vaccine window, and to resolve discrepancies and 
provide clarifications. The table below outlines substantive and non-substantive changes to the 
protocol. Other minor typographical and/or editorial changes have been made. A redline version 
showing detailed changes to the protocol is available on request. 
Summary of Changes in IGHID 12107 Protocol Version 3.0 
Section 
Summary of changes and rationale 
Section 1.1 
Description of Sites Enrolling Participants 
Clarified Duke is also a study site. 
Section 1.1 
Section 10.5 
Description of Study Intervention 
Clarified vaccination that a maximum of two participants per week will initiate study 
treatment at Day 0. 
Section 1.1 
Section 10.5 
Participant Study Duration 
Corrected duration of participation to be approximately 36 weeks (9 months). 
Section 2.2.2, 
Section 6.1.1 
C1-C62 Manufacturer  
Updated the name of C1 and C62 manufacturer from Advent Srl to Advaxia 
Biologics Srl per Clarification Memo #1 dated February 17, 2023 
Section 2.3.1 
Known Potential Risks of C1 and C62 Vaccines 
Updated potential risks to include transient lymphopenia as reported in C1 IB v4 
dated 09-Dec-2022 and C62 IB v3 dated 09-Dec-2022  
Section 5.1, 
Section 5.2 
Inclusion and Exclusion Criteria 
Adjusted inclusion and exclusion timelines for IC #13 and #23 as well as EC #3, #5, 
#6, #8, #10, #12, #13, #14, #16, and #18.  Adjusted IC #26 to indicated Magnesium 
must be > LLN.  Clarified which investigational ART is allowed in EC #13.  
Section 6.5.2 
Prohibited Medications 
Removed conflicting information regarding allowable window for Mpox 
vaccination. Adjusted prohibited medication windows for vaccine to align with 
eligibility criteria. Clarified allowed investigational ART. 
Section 8.1.2, 
Appendix 2 
Visit windows 
Clarified visit windows for telephone call visits (D2, D5, D10, D18, D22, and D30) 
per Clarification Memo #1 dated February 17, 2023 
Section 8.1.3 
Medical History 
Clarified medical history to include significant medical history condition in noted in 
medical records. 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Section 
Summary of changes and rationale 
Section 8.1.5 
Clinical Assessments 
Clarified vital sign measurements on vaccination days.  Clarified post-vaccine 
assessment. 
Section 8.2.14 
Laboratory Evaluations  
Clarified Hepatitis C screening requirements. 
Section 8.3, 
Section 8.4, 
Section 9.1, 
Section 9.3, 
Section 9.4, 
Section 9.5 
Adverse Event Reporting  
Created Table 21 to summarize adverse event reporting requirements and timelines 
for Grade 3 or 4 AEs, hypersensitivity or allergic reactions, SAEs, and AESIs.  
Removed redundant reporting requirements consolidated in Table 21. Adjusted 
reporting timelines for UNC IRB and FDA in alignment with agency policies.   
Section 9.1.1 
Section 9.1.2 
Section 9.3.1 
Adverse Event Toxicity Management 
Clarified Grade 1 and Grade 2 toxicity management for events related and unrelated 
to study treatment. Harmonized Grade 3 and Grade 4 AE toxicity management for 
AEs in Section 9.1.2 and solicited AEs (local or systemic reactions) in Section 9.3.1. 
Added note to reference Table 21 (AESI reporting) for Grade 3 or greater injection 
site reactions. 
Section 8.4.1 
Relationship to Study Intervention 
Removed instruction to assess causality separately for each study product. 
Section 8.4.2 
Time Period and Frequency for Event Assessment and Follow-Up 
Clarified solicited AEs will be followed through 28 days following each dose of 
study product. Removed references to Day 196. 
Section 9.2.3 
Delayed Dose 
Added reference to Section 9.1.2 for additional instructions regarding delayed 
booster dose in the event of a prior Grade 3 or 4 AE. 
Section 11.4 
Table 22 
Adjusted table numbering after adding Table 21. 
 
 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Appendix 2 Assessment for Post C62 and C1C62 Vaccine Adverse Reactions 
I. 
Telephone Assessment Schedule  
 
Day 2 
Day 5 
Day 10 
Day 18 
Day 22 
Visit Window 
 
 ± 1 D 
 ± 1 D 
 ± 1 D 
 ± 1 D 
Review Symptom Check List for Post Vaccine Local and 
Systemic Adverse Reactions  
X 
 
 
 
 
Review Symptom Check List for Post vaccine for development 
of symptoms associated with clotting disorder  
X 
X 
X 
X 
X 
II. 
Telephone Assessment for Local and Systemic Reactions (Reference Participant 
Symptom Diary)  
1. 
Review Solicited AE assessment diary on the phone with the participant.   
a. Observation of solicited AEs?   
• Systemic solicited AEs include increased body temperature, malaise, fatigue, 
myalgia, arthralgia, headache, nausea, and feverishness.    
• Local solicited AEs include erythema, swelling, pain, pruritus, and warmth at 
infusion site.  
b. Observation of other signs/symptoms   
III. 
Telephone Assessment for Development of Symptoms Associated with Clotting 
Disorder  
1. 
Assess for the following signs and symptoms  
a. Shortness of breath 
b. Chest pain 
c. Blurred vision or other vision changes 
d. Swelling, pain or erythema in a limb 
e. Severe or persistent abdominal pain 
f. Nausea or vomiting 
g. Dizziness 
h. Mental status changes 
i. Seizure 
j. Severe or persistent headaches 
k. Easy bruising and/or bleeding 
l. Microhemorrhage beside the site of vaccination 
m. Change in gait; problem with walking, balance or coordination 
n. Weakness 
o. Facial weakness 
p. Numbness or tingling 
q. Difficulty swallowing or slurring of your speech 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Those vaccinated should be instructed to contact study staff immediately for clinical 
evaluation. If symptoms develop after clinical hours or on the weekend the participant 
should seek immediate medical attention if they develop any of the above.  
Appendix 3  
SARS-CoV-2 Pandemic Considerations 
Sites should follow local guidelines regarding management of participants during periods of 
SARS-CoV-2 activity (or other public health emergencies), and all applicable DAIDS 
guidelines. 
Participants diagnosed with or suspected of having SARS-CoV-2 infection  
Participants with suspected SARS-CoV-2 infection should be offered testing using locally 
available, FDA-approved or FDA-EUA assays. Participants who become infected with SARS-
CoV-2 may remain on study. Sites should follow local guidelines for management of participants 
in consultation with primary care providers, local specialists, and the protocol team. 
Screening and Enrollment 
Participants acquiring SARS-CoV-2 during the screening window may complete 
screening/enrollment, but no study visits should occur while the participant is deemed to be 
infectious using local guidelines. Screening and enrollment periods can be extended to allow for 
recovery. However, all entry criteria must be met as described in the protocol. The participant 
may be required to repeat screening labs and evaluations at a later time point, based on time of 
initial screening evaluations and recovery from illness, per site investigator discretion.  
Intervention Period (Day 0 through Day 35)  
Participants acquiring SARS-CoV-2 during study intervention period should not return for study 
visits until the participant is deemed to be no longer infectious. Participants should be followed 
using remote visits (e.g., telephone or video) at least weekly to follow the clinical course of 
disease and to monitor any ongoing AEs. No study treatment should be administered while the 
infection is thought to be ongoing. This may lead to missing the Day 28 vaccine, in this scenario 
the participant can receive the booster dose preferably within the 30 days after the Day 28 visit, 
but can be extended out 60 days, if needed. 
Immunogenicity Follow up Period (Day 42 through Day 196) 
Participants with suspected SARS-CoV-2 should not return for study visits until the participant is 
deemed no longer infectious. Participant will be asked to complete the post vaccine 
leukapheresis procedure when they are recovered from their illness per site investigator 
discretion. Participants should be followed using remote visits (e.g., telephone or video) at least 
weekly to follow the clinical course of disease and to monitor any ongoing AEs. 
SARS-CoV-2 vaccination 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Potential IGHID 12107 participants who are participating in a clinical trial with an acceptable 
experimental SARS-CoV-2 vaccine or who have been vaccinated with an acceptable SARS-
CoV-2 vaccine are able to screen after 14 days since receiving the final dose of vaccine. Receipt 
of licensed SARS-CoV-2 vaccine is encouraged. Participants are allowed to co-enroll in clinical 
trials of acceptable investigational SARS-CoV-2 agent per PI approval and provided that limits 
for blood collection volumes can be maintained and vaccination follows eligibility criteria in 
regards to timing of vaccination.  
Conduct of visits and assessments of study endpoints during periods of restricted travel or 
in-person visits 
If in-person visits are restricted at the CRS, or if the site investigator feels that in-person visits 
pose a risk to the participant that alters the overall risk-benefit ratio, then reasonable efforts 
should be made to conduct study assessments remotely. Sites should follow FDA guidance 
(https://www.fda.gov/media/136238/download or use the more recent FDA updates) for 
conducting assessments of study endpoints during a public health emergency. Sites can obtain 
study-required plasma HIV-1 levels and safety laboratories through alternative sites such as a 
commercial laboratory near the participant’s home. The decision to do the test at a commercial 
laboratory is made by the site based on the local situation. The site should take into account any 
change in blood volume required based on the laboratory selected.

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Page 141 of 143
 
 
Appendix 4  Neurology Testing 
 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ ChAdOx1.tHIVconsv1 boosted with 
M4+MVA.tHIVconsv3 (M3)  
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Appendix 5  Diagnosis and Management 
 
 

16.1.1 Protocol 
IGHID-12107 - The CM (HIV-CORE 008) Study Version 3.0 
ChAdOx1.HIVconsv62 (C62) boosted with MVA.tHIVconsv4 (M4) or C62+ 
ChAdOx1.tHIVconsv1 boosted with M4+MVA.tHIVconsv3 (M3)  
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Appendix 6  MedDRA Preferred Terms (PTs) for TTS 
I. 
MedDRA PTs for large vessel thrombosis and embolism in unusual locations  
Aortic embolus, aortic thrombosis, aseptic cavernous sinus thrombosis, brain stem 
embolism, brain stem thrombosis, carotid arterial embolus, carotid artery thrombosis, 
cavernous sinus thrombosis, cerebral artery thrombosis, cerebral venous sinus 
thrombosis, cerebral venous thrombosis, superior sagittal sinus thrombosis, transverse 
sinus thrombosis, mesenteric artery embolism, mesenteric artery thrombosis, mesenteric 
vein thrombosis, splenic artery thrombosis, splenic embolism, splenic thrombosis, 
thrombosis mesenteric vessel, visceral venous thrombosis, hepatic artery embolism, 
hepatic artery thrombosis, hepatic vein embolism, hepatic vein thrombosis, portal vein 
embolism, portal vein thrombosis, portosplenomesenteric venous thrombosis, splenic 
vein thrombosis, spontaneous heparin-induced thrombocytopenia syndrome, femoral 
artery embolism, iliac artery embolism, jugular vein embolism, jugular vein thrombosis, 
subclavian artery embolism, subclavian vein thrombosis, obstetrical pulmonary 
embolism, pulmonary artery thrombosis, pulmonary thrombosis, pulmonary venous 
thrombosis, renal artery thrombosis, renal embolism, renal vein embolism, renal vein 
thrombosis, brachiocephalic vein thrombosis, vena cava embolism, vena cava 
thrombosis, truncus coeliacus thrombosis  
II. 
MedDRA PTs for more common thrombotic events 
 Axillary vein thrombosis, deep vein thrombosis, pulmonary embolism  
III. 
MedDRA PTs for thrombocytopenia  
Autoimmune heparin-induced thrombocytopenia, Heparin-induced thrombocytopenia, 
Immune thrombocytopenia, Nonimmune heparin associated thrombocytopenia, 
Spontaneous heparin-induced thrombocytopenia syndrome, Thrombocytopenia, 
Thrombocytopenic purpura  
IV. 
Text string for  
“thrombocytopenia” or “low platelets” in symptom text 
 
 
 
 

Page 1 of 2 
 IGHID 12107 – THE CM (HIV-CORE 008) STUDY – PROTOCOL VERSION 3.0  
CLARIFICATION MEMO 
DATE:  
January 22, 2024  
SUBJECT:  
Clarification Memo #1 for IGHID-12107 Protocol Version 3.0 
This clarification memo (CM) does not result in a change in the protocol informed consent document. 
Each site should file a copy of this CM with the protocol for reference. The protocol clarification 
contained in this memo should be implemented immediately.  
This clarification memo further clarifies adverse events are the defined reactogenicity adverse events 
beginning within 7-days following vaccination.  In addition, it updates Appendix 6, MedDRA Preferred 
Terms (PTs) for Thrombosis with Thrombocytopenia Syndrome (TTS) events. These updates are 
inclusive of Coagulopathy PTs from CDC Vaccine Adverse Event Reporting System (VAERS) Standard 
Operating Procedures for COVID-19 (as of 02Feb2022) and Standardised MedDRA Query (SMQ) for 
embolic and thrombotic events.   
Text noted below with a strikethrough represents deletion; text appearing below in bold represents an 
addition. 
1. Section 4.1, Overall Design, page 46 
Safety will be assessed for the duration of the study. Solicited AEs will be recorded for 28 days 
after each dose of study intervention (through Day 57), and AEs, SAEs, MAAEs, and AESIs will 
be recorded through the EOS.  
2. Section 8.1.5.j, Solicited Adverse Events, page 71: 
Local and systemic predefined solicited AEs for reactogenicity assessment (Section 8.2.10) will 
be collected in a Participant Symptom Diary for 7 days following the administration of each dose 
of study product. In addition, assessments of solicited AEs will occur at study visits through 28 
days following administration of each dose of study product.  
3. Section 8.4.2, Time Period and Frequency for Event Assessment and Follow-Up, page 85: 
Solicited AEs will be assessed and recorded for 7 28 days following each dose of study product. 
4. Section 10.2, Endpoints, page 101:  
Secondary Safety Efficacy Endpoint(s):  
• 
Occurrence of any ≥ Grade 1 AE including signs/symptoms, lab toxicities, and/or 
clinical events, that is possibly or definitely related to study treatment any time from 
the first day of treatment (D0) through D196 (Week 28).  
5. Appendix 6, MedDRA Preferred Terms (PTs) for Thrombosis with Thrombocytopenia Syndrome 
(TTS) events, page 143:  
I. 
MedDRA PTs for large vessel thrombosis and embolism in unusual locations  
Aortic embolus, aortic thrombosis, aseptic cavernous sinus thrombosis, brain stem 
embolism, brain stem thrombosis, carotid arterial embolus, carotid artery thrombosis, 
cavernous sinus thrombosis, cerebral artery thrombosis, cerebral venous sinus 

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thrombosis, cerebral venous thrombosis, superior sagittal sinus thrombosis, transverse 
sinus thrombosis, mesenteric artery embolism, mesenteric artery thrombosis, mesenteric 
vein thrombosis, splenic artery thrombosis, splenic embolism, splenic thrombosis, 
thrombosis mesenteric vessel, visceral venous thrombosis, hepatic artery embolism, 
hepatic artery thrombosis, hepatic vein embolism, hepatic vein thrombosis, portal vein 
embolism, portal vein thrombosis, portosplenomesenteric venous thrombosis, splenic 
vein thrombosis, spontaneous heparin-induced thrombocytopenia syndrome, femoral 
artery embolism, iliac artery embolism, jugular vein embolism, jugular vein thrombosis, 
subclavian artery embolism, subclavian vein thrombosis, obstetrical pulmonary 
embolism, pulmonary artery thrombosis, pulmonary thrombosis, pulmonary venous 
thrombosis, renal artery thrombosis, renal embolism, renal vein embolism, renal vein 
thrombosis, brachiocephalic vein thrombosis, vena cava embolism, vena cava 
thrombosis, truncus coeliacus thrombosis, embolism venous, intracranial venous sinus 
thrombosis 
II. 
MedDRA PTs for more common thrombotic events 
Axillary vein thrombosis, deep vein thrombosis, disseminated intravascular 
coagulation, pulmonary embolism, thrombosis, venous thrombosis 
III. 
MedDRA PTs for thrombocytopenia  
Acquired amegakaryocytic thrombocytopenia, Amegakaryocytic thrombocytopenia, 
Autoimmune heparin-induced thrombocytopenia, Heparin-induced thrombocytopenia, 
Immune thrombocytopenia, Nonimmune heparin associated thrombocytopenia, Severe 
fever with thrombocytopenia syndrome, Spontaneous heparin-induced 
thrombocytopenia syndrome, Thrombocytopenia, Thrombocytopenic purpura, 
Thrombotic thrombocytopenic purpura 
IV. 
Text string for  
“thrombocytopenia” or “low platelets” in symptom text 
V. 
Reference additional PTs included in the Standardised MedDRA Query (SMQ) for 
Embolic and thrombotic events