A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of HIV-1 BG505 SOSIP.664 gp140 With TLR Agonist and/or Aalum Adjuvants and VRC HIV Env Trimer 4571 and 3M-052-AF With Alum in Healthy, HIV-uninfected Adults
Phase: PHASE1
Conditions: HIV Infections
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

PROTOCOL 
HVTN 137 
A phase 1 clinical trial to evaluate the safety and 
immunogenicity of HIV-1 BG505 SOSIP.664 gp140 with 
TLR agonist and/or Alum adjuvants and VRC HIV Env 
Trimer 4571 and 3M-052-AF with Alum in healthy, HIV-
uninfected adults 
DAIDS DOCUMENT ID 38559 
IND 019275 HELD BY DAIDS 
CLINICAL TRIAL SPONSORED BY 
Division of AIDS (DAIDS) 
National Institute of Allergy and Infectious Diseases (NIAID) 
National Institutes of Health (NIH) 
Department of Health and Human Services (DHHS) 
Bethesda, Maryland, USA 
STUDY PRODUCTS PROVIDED BY 
International AIDS Vaccine Initiative (IAVI) 
New York, New York, USA 
Access to Advanced Health Institute (AAHI) 
Seattle, Washington, USA 
Division of AIDS (DAIDS), National Institutes of Health 
Rockville, Maryland, USA 
The Dale and Betty Bumpers Vaccine Research Center (VRC) 
Bethesda, Maryland, USA 
September 26, 2022 
Final 
HVTN 137 
Version 5.0 

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Contents 
1 Ethical considerations ....................................................................................................5 
2 IRB/EC review considerations .......................................................................................7 
2.1 
Minimized risks to participants ......................................................................7 
2.2 
Reasonable risk/benefit balance .....................................................................7 
2.3 
Equitable participant selection .......................................................................8 
2.4 
Appropriate informed consent ........................................................................8 
2.5 
Adequate safety monitoring ...........................................................................8 
2.6 
Protect privacy/confidentiality .......................................................................8 
3 Overview ......................................................................................................................10 
3.1 
Protocol Team ..............................................................................................15 
4 Background ..................................................................................................................16 
4.1 
Rationale for trial concept ............................................................................16 
4.2 
Trial design rationale ....................................................................................26 
4.3 
Preclinical safety studies ..............................................................................31 
4.4 
Preclinical immunogenicity studies .............................................................42 
4.5 
Clinical studies .............................................................................................51 
4.6 
Potential risks of study products and administration ...................................57 
5 Objectives and endpoints .............................................................................................58 
5.1 
Objectives and endpoints for Part A ............................................................58 
5.2 
Objectives and endpoints for Part B .............................................................59 
5.3 
Objectives and endpoints for Part C .............................................................63 
6 Statistical considerations ..............................................................................................66 
6.1 
Accrual and sample size calculations ...........................................................66 
6.2 
Randomization .............................................................................................72 
6.3 
Blinding ........................................................................................................73 
6.4 
Statistical analyses ........................................................................................73 
7 Selection and withdrawal of participants .....................................................................82 
7.1 
Inclusion criteria ...........................................................................................82 
7.2 
Exclusion criteria ..........................................................................................85 
7.3 
Eligibility for optional procedures ...............................................................89 
7.4 
Participant departure from vaccination schedule or withdrawal ..................89 
8 Study product preparation and administration .............................................................92 
8.1 
Vaccine regimen ...........................................................................................92 
8.2 
Study product formulation ...........................................................................94 
8.3 
Preparation of study products .......................................................................95 
8.4 
Administration ............................................................................................103 
8.5 
Acquisition of study products ....................................................................103 
8.6 
Pharmacy records .......................................................................................104 
8.7 
Final disposition of study products ............................................................104 
9 Clinical procedures ....................................................................................................105 
9.1 
Informed consent ........................................................................................105 
9.2 
Pre-enrollment procedures .........................................................................107 
9.3 
Enrollment and vaccination visits ..............................................................109 

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9.4 
Follow-up visits ..........................................................................................110 
9.5 
Optional procedures ...................................................................................112 
9.6 
AESI contact for Part A .............................................................................116 
9.7 
HIV counseling and testing ........................................................................117 
9.8 
Contraception status ...................................................................................119 
9.9 
Urine testing ...............................................................................................119 
9.10 Assessments of reactogenicity ...................................................................119 
9.11 Visit windows and missed visits ................................................................121 
9.12 Early termination visit ................................................................................121 
9.13 Pregnancy ...................................................................................................122 
9.14 HIV infection during the study ...................................................................122 
10 Laboratory ..................................................................................................................123 
10.1 HVTN CRS laboratory procedures ............................................................123 
10.2 Total blood volume ....................................................................................123 
10.3 Primary immunogenicity timepoint ...........................................................123 
10.4 Endpoint assays: cellular ............................................................................124 
10.5 Endpoint assays: humoral ...........................................................................125 
10.6 Innate immunity and inflammation assays .................................................127 
10.7 Mucosal assays ...........................................................................................128 
10.8 Lab assay algorithm ...................................................................................128 
10.9 Exploratory studies .....................................................................................129 
10.10 Specimen storage and other use of specimens ...........................................129 
10.11 Biohazard containment ...............................................................................129 
11 Safety monitoring and safety review .........................................................................131 
11.1 Safety monitoring and oversight ................................................................131 
11.2 Safety reporting ..........................................................................................132 
11.3 Safety reviews ............................................................................................135 
11.4 Safety pause and prompt PSRT AE review................................................136 
11.5 Review of cumulative safety data ..............................................................137 
11.6 Study termination .......................................................................................138 
12 Protocol conduct ........................................................................................................139 
12.1 Social impacts ............................................................................................140 
12.2 Emergency communication with study participants ..................................140 
13 Version history ...........................................................................................................141 
14 Document references (other than literature citations) ................................................146 
15 Acronyms and abbreviations......................................................................................148 
16 Literature cited ...........................................................................................................153 
Appendix A Sample informed consent form for Part A .................................................163 
Appendix B Sample informed consent form for Part B .................................................183 
Appendix C Sample informed consent form for Part C .................................................212 
Appendix D Sample addendum to informed consent form for Part A with Optional Third 
Vaccination participants only .....................................................................234 

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Appendix E Approved birth control methods for persons assigned female sex at birth 
(for Part A sample informed consent form) ...............................................239 
Appendix F Approved birth control methods for persons assigned female sex at birth 
(for Part B and Part C sample informed consent form) ..............................241 
Appendix G Sample consent form for use of samples and information in other studies 243 
Appendix H Tables of procedures (for sample informed consent form) ........................248 
Appendix I Optional procedure images for Part B Sample informed consent form .....252 
Appendix J Laboratory procedures for Part A ...............................................................254 
Appendix K Laboratory procedures for Part A with Optional Second Boost ................255 
Appendix L Laboratory procedures for Part B with leukapheresis and lymph node FNA
 256 
Appendix M Laboratory procedures for Part B with leukapheresis (no lymph node FNA)
 258 
Appendix N Laboratory procedures for Part B with lymph node FNA (no leukapheresis)
 260 
Appendix O Laboratory procedures for Part B (no leukapheresis and no lymph node 
FNA) ...........................................................................................................262 
Appendix P Laboratory procedures for Part B (no optional procedures) and Part C .....264 
Appendix Q Procedures at HVTN CRS for Part A .........................................................265 
Appendix R Procedures at HVTN CRS for Part A with Optional Second Boost ..........267 
Appendix S Procedures at HVTN CRS for Part B (with lymph node FNA) .................269 
Appendix T Procedures at HVTN CRS for Part B (no lymph node FNA) and Part C ..271 
Appendix U HVTN low risk guidelines for the US ........................................................273 
Appendix V Adverse events of special interest ..............................................................277 
Appendix W Visit Windows ............................................................................................278 
Appendix X Protocol Signature Page .............................................................................281 
 

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1 
Ethical considerations 
Multiple candidate HIV vaccines will need to be studied simultaneously in 
different populations around the world before a successful HIV preventive 
vaccine is found. It is critical that universally accepted ethical guidelines are 
followed at all sites involved in the conduct of these clinical trials. The HIV 
Vaccine Trials Network (HVTN) has addressed ethical concerns in the following 
ways: 
• HVTN trials are designed and conducted to enhance the knowledge base 
necessary to find a preventive vaccine, using methods that are scientifically 
rigorous and valid, and in accordance with International Council for 
Harmonisation of Technical Requirements for Pharmaceuticals for Human 
Use (ICH) and/or other Good Clinical Practice (GCP) guidelines. 
• HVTN scientists and operational staff incorporate the philosophies underlying 
major codes (1-3), declarations, and other guidance documents relevant to 
human subjects research into the design and conduct of HIV vaccine clinical 
trials. 
• HVTN scientists and operational staff are committed to substantive 
community input—into the planning, conduct, and follow-up of its research—
to help ensure that locally appropriate cultural and linguistic needs of study 
populations are met. Community Advisory Boards (CAB) are required by 
DAIDS and supported at all HVTN research sites to ensure community input.  
• HVTN clinical trial staff counsel study participants routinely on how to 
reduce HIV risk. Participants who become HIV-infected during the trial are 
provided counseling on notifying their partners and about HIV infection 
according to local guidelines. Staff members will also counsel them about 
reducing their risk of transmitting HIV to others. 
• Participants who become HIV-infected during the trial are referred to medical 
practitioners to manage their HIV infection and to identify potential clinical 
trials they may want to join. If a program for antiretroviral therapy (ART) 
provision is not available at a site and ART is needed, a privately established 
fund will be used to pay for access to treatment to the fullest extent possible. 
• The HVTN provides training so that all participating sites similarly ensure fair 
participant selection, protect the privacy of research participants, and obtain 
meaningful informed consent. During the study, participants will have their 
wellbeing monitored, and to the fullest extent possible, their privacy 
protected. Participants may withdraw from the study at any time. 
• Prior to implementation, HVTN trials are rigorously reviewed by scientists 
who are not involved in the conduct of the trials under consideration. 

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• HVTN trials are reviewed by local and national regulatory bodies and are 
conducted in compliance with all applicable national and local regulations. 
• The HVTN designs its research to minimize risk and maximize benefit to both 
study participants and their local communities. For example, HVTN protocols 
provide enhancement of participants’ knowledge of HIV and HIV prevention, 
as well as counseling, guidance, and assistance with any social impacts that 
may result from research participation. HVTN protocols also include careful 
medical review of each research participant’s health conditions and reactions 
to study products while in the study. 
• HVTN research aims to benefit local communities by directly addressing the 
health and HIV prevention needs of those communities and by strengthening 
the capacity of the communities through training, support, shared knowledge, 
and equipment. Researchers involved in HVTN trials are able to conduct other 
critical research in their local research settings. 
• The HVTN values the role of in-country Institutional Review Boards (IRBs), 
Ethics Committees (ECs), and other Regulatory Entities (REs) as custodians 
responsible for ensuring the ethical conduct of research in each setting. 

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2 
IRB/EC review considerations 
US Food and Drug Administration (FDA) and other US federal regulations 
require IRBs/ECs/REs to ensure that certain requirements are satisfied on initial 
and continuing review of research (Title 45, Code of Federal Regulations (CFR), 
Part 46.111(a) 1-7; 21 CFR 56.111(a) 1-7). The following section highlights how 
this protocol addresses each of these research requirements. Each HVTN 
Investigator welcomes IRB/EC/RE questions or concerns regarding these research 
requirements. 
2.1 
Minimized risks to participants 
45 CFR 46.111 (a) 1 and 21 CFR 56.111 (a) 1: Risks to subjects are 
minimized. 
This protocol minimizes risks to participants by (a) correctly and promptly 
informing participants about risks so that they can join in partnership with the 
researcher in recognizing and reporting harms; (b) respecting local/national blood 
draw limits; (c) performing direct observation of participants postvaccination and 
collecting information regarding side effects for several days postvaccination; (d) 
having staff properly trained in administering study procedures that may cause 
physical harm or psychological distress, such as blood draws, vaccinations, HIV 
testing and counseling and HIV risk reduction counseling; (e) providing HIV risk 
reduction counseling and checking on contraception use (for persons assigned 
female at birth); and (f) providing safety monitoring. 
2.2 
Reasonable risk/benefit balance 
45 CFR 46.111(a) 2 and 21 CFR 56.111(a) 2: Risks to subjects are 
reasonable in relation to anticipated benefits, if any, to subjects, and 
the importance of the knowledge that may reasonably be expected to 
result. 
In all public health research, the risk-benefit ratio may be difficult to assess 
because the benefits to a healthy participant are not as apparent as they would be 
in treatment protocols, where a study participant may be ill and may have 
exhausted all conventional treatment options. However, this protocol is designed 
to minimize the risks to participants while maximizing the potential value of the 
knowledge it is designed to generate. 

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2.3 
Equitable participant selection  
45 CFR 46.111 (a) 3 and 21 CFR 56.111 (a) 3: Subject selection is 
equitable 
This protocol has specific inclusion and exclusion criteria for investigators to 
follow in admitting participants into the protocol. Participants are selected 
because of these criteria and not because of positions of vulnerability or privilege. 
Investigators are required to maintain screening and enrollment logs to document 
volunteers who screened into and out of the protocol and for what reasons. 
2.4 
Appropriate informed consent 
45 CFR 46.111 (a) 4 and 5 and 21 CFR 56.111 (a) 4 and 5: Informed 
consent is sought from each prospective subject or the subject’s 
legally authorized representative as required by 45 CFR 46.116 and 
21 CFR Part 50; informed consent is appropriately documented as 
required by 45 CFR 46.117 and 21 CFR 50.27 
The protocol specifies that informed consent must be obtained before any study 
procedures are initiated and assessed throughout the trial (see Section 9.1). Each 
site is provided training in informed consent by the HVTN as part of its entering 
the HVTN. The HVTN requires a signed consent document for documentation, in 
addition to chart notes or a consent checklist. 
2.5 
Adequate safety monitoring 
45 CFR 46.111 (a) 6 and 21 CFR 56.111 (a) 6: There is adequate 
provision for monitoring the data collected to ensure the safety of 
subjects. 
This protocol has extensive safety monitoring in place (see Section 11). Safety is 
monitored daily by HVTN Core and routinely by the HVTN 137 Protocol Safety 
Review Team (PSRT). In addition, the HVTN Safety Monitoring Board (SMB) 
periodically reviews study data. 
2.6 
Protect privacy/confidentiality 
45 CFR 46.111 (a) 7 and 21 CFR 56.111 (a) 7: There are adequate 
provisions to protect the privacy of subjects and maintain the 
confidentiality of data. 
Privacy refers to an individual’s right to be free from unauthorized or 
unreasonable intrusion into his/her private life and the right to control access to 
individually identifiable information about him/her. The term “privacy” concerns 
research participants or potential research participants as individuals whereas the 

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term “confidentiality” is used to refer to the treatment of information about those 
individuals. This protocol respects the privacy of participants by informing them 
about who will have access to their personal information and study data (see 
Appendix A, Appendix B and Appendix C). The privacy of participants is 
protected by assigning unique identifiers in place of the participant’s name on 
study data and specimens. In the United States, research participants in HVTN 
protocols are protected by a Certificate of Confidentiality from the US NIH, 
which can prevent disclosure of study participation even when that information is 
requested by subpoena. Participants are told of the use and limits of the certificate 
in the study consent form. In addition, each staff member at each study site in this 
protocol signs an Agreement on Confidentiality and Use of Data and Specimens 
with the HVTN. In some cases, a comparable confidentiality agreement process 
may be acceptable. Each study site participating in the protocol is required to have 
a standard operating procedure on how the staff members will protect the 
confidentiality of study participants. 

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3 
Overview 
Title  
A phase 1 clinical trial to evaluate the safety and immunogenicity of HIV-1 
BG505 SOSIP.664 gp140 with TLR agonist and/or Alum adjuvants and VRC 
HIV Env Trimer 4571 and 3M-052-AF with Alum in healthy, HIV-uninfected 
adults 
Primary objective(s) 
• To evaluate the safety and tolerability of intramuscular (IM) administration of 
BG505 SOSIP.664 gp140 with the following adjuvants: cytidine 
phosphoguanosine (CpG) 1018 + Alum, 3M-052-AF + Alum, GLA-LSQ, or 
Alum alone 
• To evaluate and compare the neutralizing antibody (nAb) response induced by 
BG505 SOSIP.664 gp140 formulated in different adjuvants (CpG 1018 + 
Alum, 3M-052-AF + Alum, GLA-LSQ, or Alum alone) 
• To evaluate the safety and tolerability of Trimer 4571 formulated in 3M-052-
AF + Alum 
• To evaluate the neutralizing antibody response induced by Trimer 4571 
formulated in 3M-052-AF + Alum 
Study products and routes of administration 
• BG505 SOSIP.664 gp140: A stable, soluble cleaved trimeric HIV envelope 
(Env) gp140 glycoprotein based on the HIV-1 subtype A strain BG505 
envelope sequence. To be administered as 100 mcg dose admixed with 
different adjuvants as 0.5 mL IM injection in the deltoid muscle. 
• Trimer 4571 (VRC-HIVRG096-00-VP) (labeled as HIV-1 Trimer 4571 
Vaccine): Consists of an HIV-1 envelope (Env) trimer variant derived from 
the clade A HIV-1 strain BG505. To be administered IM as 100-mcg dose 
admixed with 5 mcg of 3M-052-AF and 500 mcg of Alum. 
• CpG 1018 adjuvant (labeled as CpG 1018 Drug Product): A cytosine 
phosphoguanosine oligodeoxynucleotide (CpG-ODN) designated 1018 
containing a short unmethylated immunostimulatory DNA sequence (CpG), a 
toll-like receptor (TLR) 9 agonist. To be administered IM as 300 mcg dose 
admixed with BG505 SOSIP.664 gp140 and 500 mcg of Alum. 
• 3M-052-AF adjuvant (labeled as AP 60-702): An aqueous formulation (AF) 
of the small molecule imidazoquinoline immune response modifier (IRM) 
3M-052; TLR7/8 agonist. To be administered IM as 1 mcg or 5 mcg admixed 
with BG505 SOSIP.664 gp140 and 500 mcg of Alum in Part A and at the 

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highest tolerated dose from Part A admixed with BG505 SOSIP.664 gp140 
and 500 mcg of Alum in Part B. To be administered IM as 3 mcg with BG505 
SOSIP.664 gp140 and 500 mcg of Alum (Group 7) or 5 mcg with Trimer 
4571 and 500 mcg of Alum (Group 8) in Part C 
• GLA-LSQ adjuvant (labeled as AP 10-602): A liposomal formulation of the 
synthetic TLR4 ligand glucopyranosyl lipid A (GLA) with the saponin 
Quillaja saponaria fraction 21 (QS-21). To be administered IM as 5 mcg 
GLA and 2 mcg QS-21 admixed with BG505 SOSIP.664 gp140. 
• Alum adjuvant (labeled as Aluminum Hydroxide Suspension): Aluminum 
hydroxide to be administered IM as 500 mcg (Aluminum content) admixed 
with the BG505 SOSIP.664 gp140 and Trimer 4571 (and adjuvants) as shown.  
• Placebo: Tris-NaCl  

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Table 3-1 Schema 
 
N 
(V:P) 
Protein Dose 
Adjuvant dose 
Injection schedule in months (days) 
Part A 3M-052-AF + Alum dose escalation 
 
 
 
 
M0 (D0) 
M2 (D56) 
M6 (168) 
Optional 2nd Boost* 
Group 
1 
5:1 
100 mcg 
1 mcg 3M-052-
AF + 500 mcg 
Alum 
BG505 SOSIP.664 
gp140 + (3M-052-AF 
+ Alum) 
BG505 SOSIP.664 
gp140 + (3M-052-AF 
+ Alum) 
BG505 SOSIP.664 
gp140 + (3M-052-AF + 
Alum) 
Group 
2 
10:1 
100 mcg 
5 mcg 3M-052-
AF + 500 mcg 
Alum 
BG505 SOSIP.664 
gp140 + (3M-052-AF 
+ Alum) 
BG505 SOSIP.664 
gp140 + (3M-052-AF 
+ Alum) 
BG505 SOSIP.664 
gp140 + (3M-052-AF + 
Alum) 
Part B Adjuvant comparison 
 
 
 
 
M0 (D0) 
M2 (D56) 
M6 (D168) 
Group 
3 
20:2 
100 mcg 
300 mcg CpG 
1018 + 500 mcg 
Alum 
BG505 SOSIP.664 
gp140 + (CpG 1018 
+ Alum) 
BG505 SOSIP.664 
gp140 + (CpG 1018 + 
Alum) 
BG505 SOSIP.664 
gp140 + (CpG 1018 + 
Alum) 
Group 
4 
20:2 
100 mcg 
5 mcg 3M-052-
AF + 
500 mcg Alum 
BG505 SOSIP.664 
gp140 + (3M-052-AF 
+ Alum) 
BG505 SOSIP.664 
gp140 + (3M-052-AF 
+ Alum) 
BG505 SOSIP.664 
gp140 + (3M-052-AF + 
Alum) 
Group 
5 
20:2 
100 mcg 
GLA-LSQ 
(5 mcg GLA + 
2 mcg QS-21) 
BG505 SOSIP.664 
gp140 + GLA-LSQ 
BG505 SOSIP.664 
gp140 + GLA-LSQ 
BG505 SOSIP.664 
gp140 + GLA-LSQ 
Group 
6 
20:2 
100 mcg 
500 mcg Alum 
BG505 SOSIP.664 
gp140 + Alum 
BG505 SOSIP.664 
gp140 + Alum 
BG505 SOSIP.664 
gp140 + Alum 
Part C 3M052-AF + Alum Optimization for Elicitation of Neutralizing Activity with Trimers 
Group 
7** 
10:1 
100 mcg 
3 mcg 3M-052-
AF + 500 mcg 
Alum 
BG505 SOSIP.664 
gp140 + (3M-052-AF 
+ Alum) 
BG505 SOSIP.664 
gp140 + (3M-052-AF 
+ Alum) 
BG505 SOSIP.664 
gp140 + (3M-052-AF + 
Alum) 
Group 
8*** 
10:1 
100 mcg 
5 mcg 3M-052-
AF +500 mcg 
Alum 
Trimer 4571 + (3M-
052-AF + Alum) 
Trimer 4571 + (3M-
052-AF + Alum) 
Trimer 4571 + (3M-
052-AF + Alum) 
Total 
127: 115 vaccine recipients / 12 placebo recipients 
* Participants consenting to an optional second boost vaccination will undergo procedures as 
shown in the Part A with Optional Second Boost - specific clinical and laboratory procedure tables 
which are included in Appendix K and Appendix R. 
** Enrollment in Part C will be stepwise by Group (Group 7 will fully enroll before Group 8 
begins enrollment) 
*** Enrollment into Group 8 will be restricted to 1 participant per day for the first 5 participants, 
and enrollment will then pause after the first 5 participants are enrolled in Group 8. Details are 
described in Section 11.3.3.  
Participants 
127 healthy, HIV-1–uninfected volunteers aged 18 through 50 years (inclusive); 
115 vaccine recipients, 12 placebo recipients. 
Design 
Multicenter, randomized, controlled, double-blind trial 

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Duration per participant 
Part A: 8 months of scheduled clinic visits (main study) plus an adverse event of 
special interest (AESI) health contact at month 14 
Part A Optional Second Boost: additional 12 months of scheduled clinic visits 
(main study) after the third vaccination. 
Part B: 18 months of scheduled clinic visits (main study) 
Part C: 18 months of scheduled clinic visits (main study) 
Estimated total study duration 
41 months (includes enrollment, planned safety holds, and follow-up). 
Investigational New Drug (IND) sponsor 
DAIDS, NIAID, NIH, DHHS (Bethesda, Maryland, USA) 
Study product providers 
• BG505 SOSIP.664 gp140: International AIDS Vaccine Initiative (IAVI) (New 
York, New York, USA) 
• Trimer 4571 (BG505 DS-SOSIP.664 gp140 Env): The Dale and Betty 
Bumpers Vaccine Research Center (VRC) (Bethesda, Maryland, USA) 
• CpG 1018 (CpG 1018 Drug Product): Division of AIDS (DAIDS), NIAID, 
NIH (Rockville, Maryland, USA) 
• 3M-052-AF (AP 60-702): Access to Advanced Health Institute (AAHI) 
(Seattle, Washington, USA) 
• GLA-LSQ (AP 10-602): DAIDS, NIAID, NIH (Rockville, Maryland, USA) 
• Alum (Aluminum Hydroxide Suspension): DAIDS, NIAID, NIH (Rockville, 
Maryland, USA) 
• Tris-NaCl Diluent: IAVI (New York, New York, USA) 
Core operations 
HVTN Vaccine Leadership Group/Core Operations Center, Fred Hutchinson 
Cancer Research Center (Fred Hutch) (Seattle, Washington, USA) 

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Statistical and data management center (SDMC) 
Statistical Center for HIV/AIDS Research and Prevention (SCHARP), Fred Hutch 
(Seattle, Washington, USA) 
HVTN Laboratory Center (LC) 
HIV diagnostic laboratory 
University of Washington Virology Specialty Laboratory (UW-VSL) (Seattle, 
Washington, USA) 
Endpoint laboratories 
• Duke University Medical Center (Durham, North Carolina, USA) 
• Fred Hutchinson Cancer Research Center/University of Washington (Seattle, 
Washington, USA) 
• Cape Town HVTN Immunology Laboratory (CHIL) (Cape Town, South 
Africa)  
Study sites 
HVTN Clinical Research Sites (HVTN CRSs) in the US to be specified in the Site 
Announcement Memo 
Safety monitoring 
HVTN 137 PSRT; HVTN Safety Monitoring Board (SMB) 
 
 

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3.1 
Protocol Team 
Protocol leadership 
 
Chair 
M. Juliana McElrath 
Seattle Vaccine Trials 
Unit 
206-667-6704 
jmcelrat@fredhutch.org 
Statistician 
Holly Janes 
SCHARP, Fred Hutch 
206-667-6353 
hjanes@fredhutch.org 
Co-chair 
Nadine Rouphael 
Emory University 
404-712-1435 
nroupha@emory.edu  
Medical officer 
Chris Duplessis 
DAIDS, NIAID  
240-292-0676 
chris.duplessis@nih.gov 
Protocol Team 
leader 
Will Hahn 
HVTN Core, Fred Hutch 
206-667-3431 
whahn@fredhutch.org 
Laboratory lead 
Mingchao Shen 
HVTN Laboratory Center 
206-667-5360 
mshen@fredhutch.org 
Other contributors to the original protocol 
Core medical 
monitor 
Will Hahn 
HVTN Core, Fred 
Hutch 
DAIDS protocol 
pharmacists 
Kelly Colsh 
DAIDS, NIAID 
240-669-5721 
Study product 
developer 
representatives 
Tom Hassell 
IAVI 
Robert Coffman 
Dynavax 
Michael Eller 
DAIDS, NIAID  
Zachary Sagawa 
AAHI 
Lucio Gama 
VRC, NIAID 
Statistical research 
associate 
Lorel Schmitzberger 
SCHARP, Fred Hutch 
 
Clinical safety 
specialist 
Maija Anderson 
Nadia McCloskey 
HVTN Core, Fred Hutch 
 
Clinical trials 
manager 
Julie Hunt 
HVTN Core, Fred Hutch 
 
Manager, Clinical 
data management 
Kristine Donaty 
SCHARP, Fred Hutch 
Laboratory 
Center 
representative 
Jen Hanke 
HVTN Laboratory 
Program, Fred Hutch 
Clinical data manager 
Nate Holm 
SCHARP, Fred Hutch 
Regulatory 
affairs associate 
Liz Briesemeister 
HVTN Core, Fred 
Hutch 
SDMC Associate 
director of lab science 
April Randhawa 
SCHARP, Fred Hutch 
Clinic 
coordinators 
Renata Dennis 
Emory CRS 
DAIDS Product Lead 
Michael Pensiero 
DAIDS, NIAID 
 
David Berger 
Seattle CRS 
Protocol development 
managers 
Rufi Dalvi 
Kajari Mondal 
HVTN Core, Fred Hutch 
Community 
Advisory Board 
(CAB) members 
Ward Rushton 
Vanderbilt University  
Community 
engagement unit 
representatives 
Rafael Gonzalez 
HVTN Core, Fred Hutch 
 
Andrew Braun 
Seattle Vaccine Trials 
Unit  
Community 
educator/recruiter 
Keith Richardson 
Vanderbilt University 

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4 
Background 
4.1 
Rationale for trial concept 
An estimated 1.8 million people with new HIV-1 infections were reported 
worldwide in 2017 (4). Based on models predicting the future rate of decline in 
new infections, the HIV epidemic is unlikely to end by sustaining current 
treatment and prevention approaches alone (5). The development of a safe, highly 
effective HIV vaccine remains the utmost priority to induce long-lived immunity 
against HIV-1 infection. Such a vaccine implemented globally, alone or in 
combination with novel prevention strategies such as monoclonal antibodies 
(mAbs) for immunoprophylaxis or pre-exposure prophylaxis with antiretrovirals, 
holds the greatest promise to halt the HIV epidemic.  
To confer protection, an efficacious HIV vaccine, like most licensed viral 
vaccines, is thought to require the induction of antibodies (Ab) that can recognize 
circulating strains of HIV upon encounter and prevent infection. One of the major 
goals in new HIV immunogen development is to activate B cells whose receptors 
can recognize and bind to antigens resembling functional components on the 
envelope glycoprotein spike on the virus particle, and thereby produce 
neutralizing antibodies (nAbs) that prevent HIV entry and infection of a 
susceptible CD4-expressing host target cell.  
This phase 1 HVTN protocol is a landmark study. First, it will test a new vaccine 
design, BG505 SOSIP.664 gp140, the first clinically produced, stabilized soluble 
Env trimer exposing multiple HIV-1 broadly neutralizing antibody (bnAb) 
epitopes (6, 7). The soluble native-like trimer design is a recent advance in the 
HIV vaccine field, and it is envisioned that the trimer platform will have wide 
applicability in tailoring immunogens as components of a neutralizing antibody-
based HIV vaccine regimen. 
Second, this protocol will evaluate BG505 SOSIP.664 gp140 separately combined 
with four different adjuvant formulations that activate different innate immune 
pathways; a separate placebo group will receive Tris-buffered saline. Three 
adjuvants are newly developed in this decade (GLA-LSQ, 3M-052-AF, and CpG 
1018) and the fourth is the licensed Alum adjuvant (Alhydrogel) as an active 
control. The study aims to identify at least one novel trimer-adjuvant formulation 
that induces more potent, durable neutralizing antibodies to the tier 2 BG505 
subtype A viral strain than the trimer-Alum formulation. This study provides a 
unique opportunity to compare a single common antigen, the first-in-class stable 
Env SOSIP trimer, with four clinical-grade adjuvants available in humans. The in-
depth analyses of safety and immunological effects may lead to identification of a 
more suitable adjuvant than Alum for Env immunogens in future studies, as well 
as a platform for novel adjuvant discovery in first in human studies. For example, 
building on information obtained in Part A of this protocol, we will evaluate a 
stabilized Env SOSIP trimer (Trimer 4571) in combination with 3M-052-AF to 
see if neutralization activity in human sera can be improved by combining a 

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stabilized trimer with a promising adjuvant. Trimer 4571 has two amino acid 
differences with BG505 SOSIP.664, designed to mimic the vulnerable prefusion 
state. By fixing the trimeric protein into this configuration, in theory this should 
allow for more visibility to the immune system and greater degree of 
neutralization. This theory will be directly tested in Part C. In addition, Part C will 
also test whether an intermediate dose (3 mcg) of the 3M-052 AF plus Alum leads 
to equivalent neutralization to the high dose (5 mcg, evaluated in Parts A and B) 
when combined with the original BG505 SOSIP.664 and establish the tolerability 
of this dose The intended purpose of this arm is to test whether an intermediate 
dose of this promising adjuvant can drive similar immune responses and therefore 
will be important for clinical development of this adjuvant. 
4.1.1 
BG505 SOSIP.664 gp140: a native-like soluble Env trimer 
Because of the remarkable sequence and antigenic diversity of HIV-1 Env 
worldwide, vaccine-induced antibodies will likely need to neutralize a high 
percentage of circulating strains and with high potency to provide protection. 
Such broadly neutralizing antibodies (bnAbs) emerge in > 15% of persons within 
two years of HIV-1 infection, indicating that humans are capable of making these 
functional Abs (8-13). Nevertheless, no preventive vaccine candidate and regimen 
has elicited human bnAbs after three decades of evaluation. The failures can be 
explained in large part by two reasons, discussed below.  
First, the Env immunogens tested thus far in clinical trials, while often highly 
immunogenic in the induction of Abs to immunodominant epitopes, fail to 
adequately display the neutralizing epitopes in the relevant conformation of the 
functional Env spike and therefore, with rare exceptions, only induce neutralizing 
antibodies to easily neutralized tier 1 HIV-1 strains, a panel primarily composed 
of lab-adapted strains (14, 15). Thus, one of the greatest challenges in HIV 
vaccine development has been to design Env immunogens that resemble the 
native Env trimeric structure of the virion-associated spike, affording B cells 
access to conformationally correct neutralizing epitopes, and to feasibly 
manufacture the trimer in sufficient amounts with long-term stability for clinical 
testing. Over the past decade, John Moore and colleagues described and improved 
a cleaved SOSIP trimer design platform to successfully produce a stable 
recombinant Env gp140 trimer that structurally mimics the native HIV-1 Env 
spike (16-20). The prototype, BG505 SOSIP.664 gp140, is the first of this class 
now manufactured for clinical use and will be evaluated in this phase 1 HVTN 
protocol. The gp140 sequence is modified from a tier 2 HIV-1 subtype A, CCR5-
dependent, transmitted founder virus isolated from a 6-week-old Kenyan infant 
infected at birth (21, 22). 
Second, analysis of the molecular and structural properties of bnAbs reveal 
unusual features and complex maturation pathways, including high levels of 
somatic mutation in the variable domains, long heavy chain complementarity 
determining regions, and autoreactivity with host antigens. The bnAbs induced in 
natural infection only occur in a fraction of people after the initial autologous nAb 
response, and this is driven by progressive exposure to HIV-1 variation within the 
epitopic regions. Thus, it is unlikely that a single Env immunogen, including the 

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BG505 SOSIP.664 gp140 trimer alone with near native Env virion structure, will 
be able to induce bnAbs in uninfected persons and within the time frame of an 
immunization schedule typical for licensed protein-based viral vaccines. Instead, 
a sequential vaccine approach will likely be needed to activate the relevant naïve 
precursor B cells and steer the appropriate affinity maturation of memory B cells 
to produce bnAbs. Nevertheless, we expect that a stable trimer such as BG505 
SOSIP.664 gp140 may induce nAbs in some proportion (up to 50%) of vaccine 
recipients to the autologous HIV-1 BG505 subtype A tier 2 strain, based on 
reports from animal studies summarized below. The study will determine if nAbs 
to other tier 2 viruses emerge in HVTN 137 vaccine recipients, but this will likely 
be a variable effect and we expect a low response rate and heterologous tier 2 nAb 
titers. Nevertheless, this will be an important benchmark for the vaccine field and 
can guide strategies for future Env immunogen designs. 
The interactions of the BG505 SOSIP.664 gp140 trimer with bnAbs have been 
extensively characterized and have contributed a wealth of insight into improved 
designs of Env immunogens as well as the identification of potent bnAbs as mAbs 
for HIV immune prophylaxis and possibly treatment (23). Since its construction, 
several other trimers have been successfully engineered and are being evaluated 
in animal models now and as clinical germline-targeting immunogens and boosts 
for lineage and epitope structure-based designs in the near future. While the 
soluble cleaved SOSIP.664 design platform is the current lead strategy for 
stabilized cleaved trimer immunogens, others include the native flexibly-linked 
(NFL) and uncleaved prefusion optimized (UFO) platforms. It is anticipated that 
the native-like soluble Env trimers will be important designs in the prime-boost 
sequential bnAb pathway regimens, and they will offer the advantage of 
presenting more than one bnAb epitope region. 
The BG505 SOSIP.664 gp140 trimer has now been evaluated as an immunogen in 
a variety of animal models, including wild-type and bnAb unmutated common 
ancestor (UCA) knock-in mice, guinea pigs, rats, rabbits, rhesus macaques, and 
cows. One key rationale for this study will be to define the immunogenicity of 
this trimer in humans in comparison to the various animal species. The preclinical 
studies supporting this protocol’s IND (see Section 4.4) were designed to use 
appropriate trimer-adjuvant formulations, dose levels, and schedule as planned in 
this study, while other reported studies have used primarily research grade BG505 
SOSIP.664 gp140 combined with adjuvants that were frequently not available for 
clinical use. Despite potential differences in experimental design of these animal 
studies from the planned clinical trial, these comparative data will have utility in 
defining the suitability of each animal model in guiding antibody-inducing 
vaccine development in humans. Importantly, additional stabilizing approaches to 
ensure a closed, prefusion form and minimize presentation of the fully open, CD4 
receptor-bound form have been undertaken since the manufacturing of the BG505 
SOSIP.664 product that will be tested here. These approaches are aimed at 
reducing the induction of tier 1 nAbs directed at the Env V3 immunodominant 
and non-neutralizing CD4 binding site (CD4bs) epitopes. Despite the reduction of 
responses to these potentially less desirable antibodies, no increases in Ab breadth 
or autologous neutralization were observed in mice or rabbits (24) following 
immunization with these modified trimers. 

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The recent review by Sanders and Moore (23) nicely summarizes many of the key 
animal studies using BG505 SOSIP.664 as an immunogen, and a few other recent 
studies in rhesus macaques and cows are presented in Table 4-1. 
Table 4-1 Assessment of antibody responses in rabbits, nonhuman primates, and cows 
following BG505 SOSIP gp140 immunization 
• 
Mapping neutralization epitopes recognized by BG505 autologous nAbs: defined by mapping 
autologous neutralizing Ab specificities in rabbits and rhesus macaques previously immunized with the 
BG505 SOSIP.664 gp140. Those observed were epitopes in 1) a glycan hole at either residue 241 or 289 
in gp120, 2) an area at residue 465 near the junction of the gp120 V5 loop and beta 24 strand and 
influenced by amino acid changes in the structurally nearby C3 region (the C3/465 epitope, and 3) in the 
V1 region of gp120 (25). 
• 
Induction of autologous tier 2 nAbs: nine of twelve rhesus macaques developed autologous tier 2 
nAbs after BG505 SOSIP.v5.2 with adjuvant (ISCOMATRIX or R848 (a TLR7/8 agonist) and 
monophosphoryl lipid A (MPL) (a TLR4 agonist) encapsulated in Poly(lactic-co-glycolic acid) (PLGA) 
immunization. The best correlate of tier 2 nAb induction was lymph node germinal center B cell 
magnitude and T follicular helper (Tfh) properties of Env-specific CD4+ T cells (26). 
• 
Protection against SHIVBG505 challenge: 78 rhesus macaques were immunized three times with 
BG505 SOSIP.664 gp140. 12 animals with either low or high titers received a fourth immunization and 
subsequently were repeatedly challenged with homologous SHIVBG505 intrarectally. Animals with 
high-titers of autologous nAbs were protected (no infection or lowered peak viremia) until the titers 
waned. An autologous serum ID50 nAb titer of ~1:500 was consistent with >90% protection from the 
median challenge dose (27). 
• 
Immune response kinetics: Rhesus macaques receiving bilateral, adjuvanted, subcutaneous (SC) 
immunization with BG505 SOSIP.664 gp140 generated tier 2 nAbs after two immunizations 8 weeks 
apart, and these were further enhanced by a third immunization with BG505 SOSIP.664 gp140. 
Neutralizing Abs were strongly associated with germinal center reactions, as assessed by lymph node B 
and T cells obtained by fine needle aspiration (28). 
• 
bnAb induction by BG505 SOSIP.664 vaccination in cows: Four cows immunized with a single 
injection of BG505 SOSIP.664 rapidly generated broad, potent antibodies. One cow more extensively 
analyzed for neutralization against a 117 cross-clade HIV-1 panel developed 20% breadth within 42 
days, and this increased to 96% breadth at 381 days. A mAb isolated from this cow neutralized 72% of 
isolates and was found to have an ultra-long heavy chain complementarity-determining region 3 
(HCDR3) (60 amino acids) (29). 
4.1.2 
Trimer 4571 (BG505 DS-SOSIP.664 gp140): A Stabilized Soluble 
Trimer 
The prototype, BG505 SOSIP.664 gp140, is the first of the stable trimer class 
manufactured for clinical use. The HIV envelope is dynamic, however, and can 
have multiple conformations. Since HIV can assume multiple conformations, it is 
not known which conformation is optimal to target for inducing tier 2 neutralizing 
antibodies. The rationale for engineering the two cysteine residue changes into 
Trimer 4571 was to fix the antigen into the mature, pre-fusion closed form (a 
“vulnerable” state) (Figure 4-1). This “DS” form of the BG505 SOSIP.664 
demonstrates substantial binding to canonical broadly neutralizing antibodies and 
virtually no binding to poorly neutralizing epitopes in preclinical models (30).  

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Rationale for Trimer 4571 
In proof-of-concept preclinical studies in guinea pigs, Trimer 4571 adjuvanted 
with Alum-induced autologous neutralizing antibodies to BG505.W6M.C2 after 
the second administration, which increased after the third administration. Rhesus 
macaques immunized via IM injection with research-grade Trimer 4571 produced 
neutralizing antibodies to BG505.W6M.C2.T332N (see the Investigator’s 
Brochure [IB] for more detail on these BG505 variants). 
4.1.3 
Adjuvants 
Since HIV preventive vaccine clinical trials began in 1987, more than a dozen 
unique adjuvants have been evaluated with HIV-1 Env protein or peptide 
immunogens (31-35). Alum and MF59 have been the most frequently used in 
formulation with subunit Env immunogens, but others have been evaluated in 
phase 1 trials, including emulsions, saponins, surfactants, particles, and TLR4 
agonists. Among these are QS-21, monophosphoryl lipid A (MPL), muramyl 
dipeptide (MDP), muramyl tripeptide phosphatidylethanolamine (MTP-PE), 
liposome-encapsulated lipid A, Montanide ISA-51, AS02A, AS01B, AS01E, and 
more recently glucopyranosyl lipid A (GLA). One adjuvant, Montanide ISA-51, 
was highly reactogenic at doses delivered (32, 36). Newer formulations elicited 
mild-to-moderate increased antibody and T cell responses (eg, QS-21, AS01B, 
and liposome-encapsulated lipid A) (37), and these components are now in use in 
a number of new vaccine formulations for malaria, HIV, and other viral 
pathogens. Unfortunately, specimens needed for retrospective analysis were not 
archived from these trials and, until recently, the immunologic tools to explore at 
Figure 4-1 Structure of Trimer 4571 Trimer 4571 has two specific mutations introducing two 
cysteine residues at positions 201 and 433 A number of candidates were screened and this trimer 
was determined to have two desirable properties: 1) it was conformationally stable and 2) it was not 
“triggered” by binding to CD4 which can lead to exposure of non-neutralizing epitopes. 

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the molecular level patterns of innate and adaptive vaccine/adjuvant–induced 
immune responses were unavailable.  
The development of new generation adjuvants beyond Aluminum and emulsion 
formulations, together with a deeper understanding of the mechanistic role of 
adjuvant formulations in stimulating innate immunity, offer opportunities to 
improve candidate vaccine designs intended to prevent HIV infection. In addition, 
renewed interest in novel adjuvants for use in clinical HIV subunit vaccines has 
emerged with the findings from the RV144 trial (38-42) that more potent and 
durable antibodies with distinct effector functions may be important to elicit. In 
addition, the potential utility of improved adjuvants is well recognized for use 
with Env immunogens designed to induce immune responses along the pathway 
to bnAbs. Thus, we seek to combine a novel new class of HIV Env immunogen 
with three novel adjuvant formulations signaling through specific TLRs, either 
TLR4 (GLA-LSQ), TLR7/8 (3M-052-AF), or TLR9 (CpG 1018), all of which 
show promise in altering the potency and quality of antibody responses in 
preclinical studies. 
Several recent reviews highlight the role of adjuvants in modern vaccines, present 
their mechanisms of action when known, and attest to the need to develop more 
clinically effective adjuvant/immunogen combinations for HIV and other disease 
targets (35, 43-47). Novel adjuvants have been shown to increase the magnitude 
and breadth of vaccine-induced antibodies in animal models (48-52) and, less 
frequently, in humans (53). Nevertheless, while the past several years have seen 
much progress in understanding immunologic effects of adjuvants and their 
underlying signaling mechanisms in in vitro and animal models, only a few 
studies have been performed in humans, particularly head-to-head adjuvant 
comparisons, in HIV vaccine clinical trials (54).  
Molecular immunostimulants and carrier systems comprise the two main adjuvant 
categories (55). Most immunostimulants act as ligands for pattern recognition 
receptors. These include toll-like receptors, nucleotide-binding oligomerization 
domain (NOD)-like receptors, helicases and C-type lectin receptors. Current 
novel adjuvants primarily act as agonists targeting TLR3, 4, 7/8 and 9. These 
adjuvants can stimulate, increase or regulate immune responses to the antigen, 
which could be critical for poorly immunogenic antigens such as HIV-1 envelope 
bnAb epitopes. Desirable adjuvant properties may include increasing the breadth 
of immunity, enhancing responses in persons with advanced age or immune 
impairments, extending the durability of vaccines in newborns or the elderly, 
reducing the need for repeated booster immunizations, sparing antigen dose, and 
targeting specific types of immune responses. 
Development of new adjuvants for clinical use has been challenging, and because 
of safety concerns a limited number have advanced to licensure. In some cases, 
enhanced adjuvant potency has been accompanied by increased reactogenicity 
and systemic toxicity. This may be due to irritant effects at the site of injection or 
release of proinflammatory mediators and vasoactive substances (56, 57), and 
infrequently to the breakdown of self-tolerance, possibly leading to autoimmune 
disorders (58). Rappouli et al described vaccine adjuvant development as “one of 

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the slowest processes in the history of medicine” (59). This highlights the need to 
develop standardized predictive models to assess safety, including adverse events 
(AE), pre-existing genetic variations in innate immunity and the application of 
systems approaches to define early biomarkers of adjuvant activity and safety 
signals, such as genomics, transcriptomics, proteomics and metabolomics. This 
study offers a unique opportunity to systematically assess the safety of multiple 
adjuvants with one vaccine antigen and contribute a potential expanded safety 
marker panel. While discordant adjuvant effects may be seen when formulated 
with different antigens, a safety marker panel that can be used in future studies of 
novel HIV and non-HIV vaccine adjuvants could be beneficial in preventing 
infections of major public health importance. 
4.1.4 
Recent preclinical investigations with HIV vaccine-adjuvant and 
delivery formulations 
One challenge in understanding adjuvant effects in humans relates to species 
differences in innate cell receptor expression and tissue distribution, and the 
regulation of innate signaling responses, which may limit translation of preclinical 
experimental findings to clinical applications. TLR expression on antigen 
presenting cells (APCs) varies between mouse and human. In inbred mice, 
functional TLR8 is not expressed on APCs, whereas in humans, myeloid dendritic 
cells (mDCs) express both TLR4 and TLR8. Human plasmacytoid DCs (pDCs) 
and B cells express intracellular TLR7 and TLR9, which recognize viral and 
bacterial nucleic acids and mediate the production of type I interferons (IFNs). 
However, in mice, TLR7 is primarily expressed by CD8- mDCs (43) and TLR9 in 
CD8- mDCs and in B cells (60). Less is known about how responses to TLR 
ligand stimulation compare between rhesus macaques and humans. In vitro 
stimulation studies (61) indicate that the response pattern of human and rhesus 
macaque pDCs and B cells to TRL7/8 and TLR9 is comparable, despite some 
differences in surface phenotype of responding cells. A comprehensive evaluation 
of rhesus macaque innate responses in blood and draining lymph node (LN) 
following TLR agonist intradermal injection highlights the distinct signatures of 
early innate responses both locally and systemically, and provides a major step 
toward addressing species differences in recognizing TLR agonists now being 
used in non-human primate vaccine models and advanced to clinical studies (62). 
These insights into species differences in innate responses can influence the 
selection of suitable animal models for preclinical immunogenicity and toxicity 
studies in developing candidates for clinical testing. 
Francica and Seder performed a longitudinal analysis of adjuvant effects and HIV 
Env-specific B cell receptor (BCR) responses in rhesus macaques following Env 
protein vaccination with eight different adjuvants (63). The immunogens were 
HIV subtype C Env gp140 (Novartis) alone or formulated with Alum or MF59 
with or without agonists of TLR4 or 7, or with poly IC:LC or immune stimulating 
complexes (ISCOMs). Increased anti-Env binding titers and neutralization titers 
to tier 1A viruses were observed among the adjuvanted groups in contrast to the 
un-adjuvanted group after four immunizations; notably the Alum/TLR7, MF59 
and ANE/TLR4 recipients produced the highest mean IgG endpoint titers. 
Moreover, the MF59, poly IC:LC and ISCOM formulations elicited marked 

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increases in Env-specific memory B cells after two or four immunizations, 
although these contracted by 12 weeks after the fourth immunization. Various 
adjuvant formulations did not modulate changes in overall somatic hypermutation 
levels and HCDR3 length, properties consistent with but not sufficient for 
development of bnAbs. This investigation provides an important framework for 
assessing B cell and antibody responses with HIV vaccines that can be applied in 
preclinical and clinical models. 
An additional study by Francica and colleagues (64) assessed eight adjuvants 
combined with an Env gp140 immunogen to examine and compare innate 
transcriptional effects with the potency and quality of Env-specific immune 
responses in rhesus macaques. Among the adjuvant groups assessed, the 
Alum/TLR7 and poly IC:LC adjuvants were the most potent in assays 
characterizing both Ab and cellular responses. This hierarchy of potency was 
sustained throughout the longitudinal follow up. Of note, antiviral interferon gene 
signatures during innate timepoints post vaccination correlated with Fc-receptor 
binding across all adjuvant groups. The study also described the impact of adding 
a TLR7 agonist to Alum, finding that the TLR7 agonist suppressed expression of 
inflammatory genes commonly seen with Alum alone, and the combination 
enhanced upregulation of antiviral and interferon genes; the overall effect of the 
Alum/TLR combination was to boost Env binding Ab titers 3-10-fold compared 
to Alum alone. 
Franchini and collaborators (65-67) conducted extensive investigations in a rhesus 
macaque simian immunodeficiency virus (SIV) vaccine challenge model to 
elucidate and validate correlates of protection associated with the mildly 
efficacious RV144 Thai trial regimen that used a recombinant canarypox vector 
(ALVAC)-SIV and gp120 formulated either in Alum or MF59. Vaccine efficacy 
against SIVmac251 intrarectal challenge was associated with Alum-induced, but 
not with MF59-induced, Env-dependent mucosal innate lymphoid cells producing 
interleukin (IL)-17, gp120 V2-specific mucosal IgG, and activation of the Ras 
pathway (65). Follow-up studies have pointed to the potential importance of 
mucosal anti-V2 antibodies at the site of virus challenge (67) and the ability of 
vaccine-induced antibodies to inhibit infectivity of virus that it binds and captures 
(66). An additional study from the Franchini and Sekaly laboratories (68) 
evaluated various priming vectors (ALVAC, DNA, Ad26) with SIV inserts 
followed by pathogenic SIV challenge. They used a systems biology approach to 
determine innate and adaptive responses associated with protection. The authors 
found that the activation of hypoxia and the inflammasome in CD14+16- 
monocytes, CD4+ Th2 cells with gut-homing markers and anti-V2 Abs correlated 
with reduced risk of SIV acquisition. Larger confirmatory studies are in progress 
to understand the impact of these adjuvants and vectors on SIV protection, 
particularly at mucosal sites, which may inform future human trials with similar 
regimens. In addition, it will be important to assess some of these effects with the 
adjuvant responses in this protocol. 
Examination of early events in vaccine antigen-adjuvant priming in animal 
models are lending insight into new methods to induce desired immunity (26, 69-
71). Irvine and colleagues reported heightened antibody responses by sustained 

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delivery of HIV antigens through either repeated injections or osmotic pumps 
over 1-2 weeks (71). Exponentially increasing dosing was superior to a single full 
dose priming; findings were consistent with antigen retention in draining lymph 
nodes and expanded germinal center B and T follicular helper (Tfh) cell 
responses. Thus, regulating the kinetics of antigen and adjuvant delivery may 
stimulate increased vaccine potency. Monitoring germinal center reactivities in 
this protocol potentially would be useful in understanding the qualitative effects 
of various adjuvants and the potential for inducing tier 2 HIV nAbs. 
Havenar-Daughton and colleagues have employed repeated direct probing of 
germinal center responses by fine needle lymph node aspirates in nonhuman 
primate (NHP) studies and found that induction of neutralizing antibodies against 
tier 2 autologous HIV strains best correlated with germinal center B cell 
magnitude and Env-specific CD4+ Tfh cells (26). Furthermore, based on murine, 
NHP and human data, Havenar-Daughton and Crotty (70) found that significantly 
higher levels of plasma CXCL13 were associated with heightened germinal center 
reactivity, attesting to the potential use of CXCL13 as a biomarker in blood to 
follow germinal center activities promoting functional antibody responses and 
persistence. Similar sampling strategies are under evaluation in licensed vaccine 
and early phase human HIV vaccine studies and are planned in this protocol (72).  
Taken together, these animal studies support the further study of novel adjuvanted 
vaccines and their potential for advanced evaluation in clinical trials. Clearly new 
HIV vaccine-adjuvant formulations are needed to induce Abs with greater 
potency and persistence. Probing the dynamic and molecular effects of complex 
adjuvant formulations with novel HIV Env immunogens is critical for advancing 
candidate adjuvanted vaccine regimens that induce desired immune response 
profiles. 
4.1.5 
Clinical studies 
We anticipate that the native-like soluble Env trimers will be important designs in 
the sequential bnAb pathway regimens, particularly as more native-like Envs may 
be required as booster immunogens, and they will offer the advantage of 
presenting more than one bnAb epitope region. Additional designs will include 
stabilized Env trimers expressed as DNA and in viral vectors (73). Two clinical 
trials with stabilized soluble trimers will be underway when this protocol begins, 
IAVI W001 evaluating the same BG505 SOSIP.664 gp140 vaccine as in this 
protocol but formulated with AS01B, and a NIH Vaccine Research Center (VRC) 
phase 1 study with HIVRGP096-00-VP with Alum, a DS-SOSIP trimer.  
IAVI W001 (ClinicalTrials.gov Identifier: NCT03699241) is a randomized 
double-blinded, placebo-controlled, dose-escalation phase 1 clinical trial 
evaluating safety and immunogenicity of recombinant HIV BG505 SOSIP.664 
gp140 vaccine formulated with AS01B (GlaxoSmithKline [GSK]) administered 
IM in HIV-uninfected study participants. This is the first in human study of 
BG505 SOSIP.664. The protocol was activated in December 2018 and the first 
vaccination was administered in March 2019. The study will enroll 36 U.S. 
participants (30 vaccine recipients/6 placebo recipients) in Seattle and Boston, 

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evaluating three dose levels (30, 100, and 300 mcg) of BG505 SOSIP.664 gp140. 
Later in 2019, 24 study participants (20 vaccine recipients/4 placebo recipients) 
are scheduled to be enrolled in Nairobi, Kenya, and to receive either 30 or 100 
mcg of BG505 SOSIP.664 gp140. As of August 9, 2019, 6 participants have been 
enrolled in Group 1 (30 mcg dose). To date there have been no immune mediated 
diseases, no deaths, no pregnancies, no incident HIV infections, and no Grade 3 
or higher hematology, chemistry, or urine laboratory values. No volunteers have 
been discontinued from the trial. This trial is completely enrolled and near 
completion. 
The NIH VRC has manufactured Trimer 4571, a CHO-cell line derived DS-
SOSIP.664 trimer design, and its ligand-free crystal structure reveals a soluble 
stabilized prefusion-closed Env trimer (30, 74). This new HIV vaccine, 
designated HIVRGP096-00-VP with Alum, is being evaluated for safety and 
immunogenicity in 25 healthy adults in a first in human phase 1 trial 
(ClinicalTrials.gov Identifier: NCT03783130) that began in March 2019. The 
clinical trial evaluated two doses of the trimer, 100 and 500 mcg, each delivered 
either IM or subcutaneous (SC).  
For HIV vaccines, MF59, a squalene-based oil-in-water emulsion, has been 
formulated with several HIV-1 envelope proteins for extensive clinical testing and 
is presently in phase 2b efficacy evaluation (HVTN 702) in South Africa as part 
of an ALVAC/HIV vector prime and adjuvanted bivalent gp120 boost regimen. In 
addition to AS03 and AS04, the Adjuvant System family (GSK) (75, 76) includes 
two adjuvants containing monophosphoryl lipid A (MPL) and Quillaja saponaria 
fraction 21 (QS-21), AS01 and AS02, both of which have been evaluated in phase 
1 HIV vaccine studies (33, 77, 78). AS01 has been formulated with various new 
Env immunogens for clinical testing, including the eOD-GT8 Env immunogen 
(IAVI G001) and BG505 SOSIP.664 gp140 in the IAVI W001 trial described 
above. Table 4-2 summarizes novel adjuvant formulations in HIV vaccine clinical 
trials. 

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Table 4-2 Adjuvant formulations in HIV vaccine clinical trials 
Adjuvant 
Vaccine 
Study 
MF-59 (Novartis/Seqirus) 
ALVAC-HIV (vCP2438) and 
bivalent subtype C gp120/MF59 
Pivotal phase 2b/3 trial (HVTN 
702), prime-boost regimen in 
South Africa 
HIV-DNA and bivalent gp120 
(all subtype C) 
Phase 1/2a trial (HVTN 107 and 
HVTN 108), 2 adjuvant arms 
ALVAC-HIV (vCP2438 and 
bivalent subtype C gp120/MF59) 
2-adjuvant–arm study (in planning) 
AS01B (GSK): Liposome-
based QS-21 + 
monophosphoryl lipid A 
HIV-DNA and bivalent 
up120/AS01B (all subtype C) 
Phase 1/2a trial (HVTN 108), 2 
adjuvant arms 
eOD GT8 60-mer nanoparticle 
Germline targeting Env 
immunogen (IAVI G001) 
BG505 SOSIP.664 gp140 
Well-ordered native-like soluble 
Env trimer (IAVI W001) 
ALVAC-HIV (vCP2438) and 
bivalent subtype C gp120/AS01B 
2-adjuvant–arm study (HVTN 120) 
GLA-SE AAHI): 
glucopyranosyl lipid A in 
stable emulsion 
Polyvalent gp120 
Phase 1 trial (HVTN 124) 
CH505 gp120 
Phase 1 trial, B-cell lineage 
(HVTN 115)  
4.2 
Trial design rationale 
4.2.1 
Dose (amount and number) 
Part A: BG505 SOSIP.664 gp140 admixed with adjuvants will be administered 
two times.  
• BG505 SOSIP.664 gp140: 100 mcg 
• 3M-052-AF adjuvant: 1 mcg and 5 mcg 
• Alum adjuvant: 500 mcg (Aluminum content)  
Part A optional second boost: a third administration of BG505 SOSIP.664 gp140 
admixed with 3M-052-AF and Alum (see below for rationale). 
• BG505 SOSIP.664 gp140: 100 mcg 
• 3M-052-AF adjuvant: 1 mcg and 5 mcg 
• Alum adjuvant: 500 mcg (Aluminum content)  
HVTN studies have tested HIV Env antigen doses ranging from 20 to 600 mcg. 
The effects of adjuvants may be less pronounced at high antigen doses, based on 
data from HVTN 041 (79) and animal studies. Therefore, 100 mcg is chosen as an 

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intermediate dose that may be sufficient to generate immune responses and induce 
potential detectable distinguishing features among different adjuvant groups. 
3M-052 has been tested in patients with cancer. This will be the first-in-human 
study in which 3M-052 is used as a vaccine adjuvant. Based on the preclinical and 
clinical data, we will test 1 and 5 mcg of 3M-052 in aqueous formulation 
(3M-052-AF) to ensure that the adjuvant is safe.  
Alum has been used safely as an adjuvant in licensed vaccines up to 850 mcg per 
dose. The dose of 500 mcg is sufficient for adsorption of 3M-052-AF and BG505 
SOSIP.664.  
Part B: BG505 SOSIP.664 gp140 admixed with adjuvants will be administered 
three times. 
• BG505 SOSIP.664 gp140: 100 mcg dose 
• 3M-052-AF adjuvant: 5 mcg dose  
• CpG 1018 adjuvant: 300 mcg dose 
• GLA-LSQ adjuvant: 5 mcg GLA and 2 mcg QS-21 
• Alum adjuvant: 500 mcg (Aluminum content)  
In the licensed HEPLISAV-B hepatitis B vaccine, 3 mg dose of CpG 1018 is 
used. The dose of 300 mcg will be used in this study, based on formulation data 
with Alum and BG505 SOSIP.664. 
The same dose of GLA-LSQ was used in a TB vaccine study and the safety data 
were acceptable (ClinicalTrials.gov Identifier: NCT02508376).  
Part C: BG505 SOSIP.664 gp140 admixed with adjuvant (Group 7) and Trimer 
4571 admixed with adjuvant (Group 8) will be administered 3 times on the same 
schedule as Part B. 
The 100-mcg dose of Trimer 4571 was found to elicit trimer-specific binding 
antibodies in participants in VRC018 and was well tolerated. We selected the 100 
mcg dose of Trimer 4571 to permit direct comparisons with the participants who 
were given the 100 mcg dose of the BG505 SOSIP.664 gp140 trimer in Parts A 
and B. 
• BG505 SOSIP.664 gp140: 100-mcg dose 
• Trimer 4571: 100 mcg-dose 
• 3M-052-AF adjuvant: 3- and 5-mcg dose 
• Alum adjuvant: 500 mcg (Aluminum content)  

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4.2.2 
Schedule 
The schedule of vaccinations in Part A is 0 and 2 months. An optional third 
vaccination – Part A optional second boost – will be administered to participants 
who received two vaccinations at 0 and 2 months in Part A and consent to one 
additional (third) immunization with the same dose of protein and adjuvant.  
The schedule of vaccinations in Part B and Part C is 0, 2, and 6 months. This 
second schedule and a similar schedule 0, 1, 6 months are commonly used for 
subunit recombinant vaccines. This is the same schedule as licensed HPV 
vaccines Gardasil and Gardasil 9. Hepatitis B vaccines Engerix-B and 
Recombivax HB use 0, 1, 6 month schedule. In addition, recent studies from the 
Crotty laboratory showed that immune responses in lymph nodes escalate over 3 
weeks after immunization in rhesus macaques (26), suggesting that the second 
dose may better activate desirable immune responses if it is given at a later 
timepoint such as month 2 rather than month 1. 
Rationale for Optional Third Dose to Participants in Part A: 
There are two major justifications for offering all participants who received two 
doses in Part A the opportunity to receive a third dose of the same products they 
have already received, which is also one of the same three dose regimens included 
in Part B. 
First, disruptions from the ongoing COVID-19 pandemic allowed for an 
unanticipated opportunity to take a preliminary look at the immunologic response 
in participants in Part A. These data are now available and look extremely 
promising. Serum from 1 out of 5 participants in the low dose adjuvant group and 
3 out of 10 participants in the high dose adjuvant group neutralized 
BG505/T332N, albeit with low titers (see Figure 4-2 below). This is the first 
example of vaccine elicited autologous tier 2 neutralization in humans. The 
internal controls strongly suggest that the neutralizing effect is specific to HIV 
and not an artifact of the pseudovirus assay because no neutralizing activity 
against the MLV control virus was detected in the assays with MLV. A major 
question for HIV vaccinology is whether these neutralization titers can be boosted 
with a third dose. To test whether this low-tier neutralization could be improved, 
the protocol was modified to allow participants in Part A an optional third boost. 
Indeed, 3/5 participants in the 5-mcg dose group had high autologous tier-2 
neutralization. The 1-mcg dose group had 1 participant (out of 3) with low-level 
neutralization, suggesting that the dose of adjuvant may matter. 
Second, delays associated with the ongoing COVID-19 pandemic have altered the 
timelines of anticipated studies such that it is important to understand the role of 
additional vaccinations with products containing 3M-052 AF. Waiting until Part 
B is fully enrolled and data is available will take substantially more time (~18 
months) as compared to offering participants an additional boost in Part A. The 
additional boost dose was added to Part A due to a need to evaluate the 3M-052-
AF for planned future studies.  

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Rationale for Adding Part C: Optimization of 3M-052-AF 
A third dose of BG505 SOSIP.664 and 3M-052-AF + Alum was offered to 
participants in Part A (see above). Data from participants who provided additional 
informed consent are now available and are presented in Figure 4-2. 
 
Figure 4-2 Response rate and ID50 neutralizing antibody titers against the autologous tier 2 
virus BG505/T332N 2 weeks post second and third vaccination in HVTN 137 Part A. 
The high neutralization (with maximum ID50 titers of ~8,000) seen in some of the 
participants in Part A is the first time such high titers have been observed 
following vaccination in humans (to our knowledge). 
The protocol team therefore desires to build on these exciting results with a goal 
of optimizing the 3M-052 AF + Alum for advancement of this product. 
Using the same schedule, we propose to determine whether a 3-mcg dose of 3M-
052 AF + Alum is sufficient to drive tier 2 autologous neutralization with less 
systemic reactogenicity than observed with the 5-mcg dose.  
Additionally, we propose to test whether the VRC trimer 4571 adjuvanted with 
3M-052 AF leads to the development of tier 2 (both autologous and heterologous) 
neutralizing antibodies. The VRC 4571 trimer is a stabilized BG505 trimer 
designed to better elicit nAbs. The VRC trimer 4571 was formulated in Alum in a 
recent VRC phase 1 trial, but no autologous nAbs were elicited. This trial used 
Alum as an adjuvant. To test whether there is a conceptual issue with trimer 
design or, alternatively, whether the adjuvant is a critical mediator for 
neutralization, we proposed to add an arm testing whether VRC 4571 leads to 

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neutralization of the autologous and other tier 2 viruses. This is a critical question 
for the field because it will determine whether the conceptual framework (that 
alterations in the stabilization of a trimer will lead to improved neutralization) is 
accurate. 
4.2.3 
Choice of control 
Tris-NaCl Diluent will be administered as a placebo control. 
4.2.4 
Rationale for mucosal specimens and sample collection by 
leukapheresis, lymph node aspiration, bone marrow aspiration 
4.2.4.1 
Mucosal specimens 
Env antibody IgG and IgA titers will be examined in rectal and vaginal tissues 
and secretions. These studies will determine the amount of antibodies available 
post 3rd immunization at mucosal sites of potential HIV exposure and the 
antibody levels that can be achieved with use of different adjuvants. 
4.2.4.2 
Leukapheresis 
Blood mononuclear cells will be collected by leukapheresis to increase cell yield 
after the 2nd immunization in consenting participants. This will provide sufficient 
cell numbers to analyze the B cell receptor sequence repertoire, including 
detection of signatures associated with broad neutralizing antibodies, as well as B 
cell function and specificities. Similarly, the additional cell yields will permit 
comprehensive T cell analyses, including T cell receptor repertoire, function, and 
epitope specificities. 
4.2.4.3 
Lymph node fine needle aspiration (FNA) 
Draining axillary lymph node cells will be examined for germinal center 
reactivities after vaccination and the influence of various adjuvants on germinal 
center B cell, CD4+ T follicular cell, and myeloid cell functions. We will also 
direct efforts to find germinal cell reactivity biomarkers in peripheral blood for 
future studies that can be used to potentially predict Env-specific broad 
neutralizing activities. 
4.2.4.4 
Bone marrow aspiration 
Long-lived plasma cells resident in bone marrow will be examined to determine 
adjuvant effects on durability of antibody responses. Additional immune cells in 
the marrow will be characterized that potentially support these effects in the bone 
marrow microenvironment.  

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4.3 
Preclinical safety studies 
Several preclinical studies have been performed to assess the potential toxicity of 
the vaccine-adjuvant formulations that will be evaluated in this clinical trial. The 
design of these studies is outlined in Table 4-3.

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Table 4-3 Summary of preclinical safety studies 
Study 
number 
Product 
Dose (mcg*) 
Type of 
study 
Animal 
N** 
Dose 
groups 
Route 
Schedule 
Covance 
8394847 
BG505 SOSIP.664 g140  
3M-052-AF + Alum 
CpG 1018 + Alum 
GLA-LSQ (GLA+QS-21)  
50 
0.5+250 and 
2.5+250 
150+250 
2.5+1.0 
Toxicity 
Rat 
15m, 15f per 
dose group 
5 
IM 
0, 3, 6, 9 
weeks 
12-728 
HEPLISAV-B  
(HBsAg+CpG 1018) 
 
20+3000 and 4+600 
Toxicity 
Rat 
15m, 15f per 
dose group 
2 
IM 
0, 2, 4, 6 
weeks 
2416-001 
ID93 
GLA-LSQ (GLA+QS-21) 
0 or 20 
0 or 20+40 
Toxicity 
Rabbit 
10m, 10f per 
dose group 
4 
IM 
0, 2, 4, 6 
weeks 
11943 
H5 VLP 
3M-052-SE 
20 
0, 2, 10 
Toxicity 
Rat 
15m, 15f per 
dose group 
4 
IM 
0, 3, 6, 9 
weeks 
NA 
3M-052 
0, 1.25, 3.75, or 6.25 
mg/kg 
Toxicity 
Mouse 
10-16m,  
10-16f per 
dose group 
4 
SC 
0, 1, 2, 3 
weeks 
NA 
3M-052 
0, 1.25, 2.5, or 5.0 
mg/kg 
Toxicity 
Cynomolgus 
monkeys 
5m, 5f per 
dose group 
4 
SC 
0, 1, 2, 3 
weeks 
* Except where noted. 
** m = male; f = female 
 
 

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4.3.1 
IND-enabling, GLP repeat dose toxicity study of BG505 SOSIP.664 
gp140 with adjuvants GLA-LSQ, CpG 1018+Alum, 3M-052-AF+Alum 
in rats (Covance study 8394847) 
The objective of this IND-enabling study was to evaluate the safety and 
tolerability of BG505 SOSIP.664 gp140 + adjuvants in rats. The study was 
conducted in rats because two adjuvants (3M-052-AF and CpG 1018) were 
deemed unlikely to enhance the immune response to the antigen in rabbits. We 
have demonstrated an active immune response in rats in a pilot study following 
immunization with the various adjuvanted investigational vaccines that would be 
evaluated in the current study. Likewise, rats historically have been used in safety 
evaluation studies and are recommended by appropriate regulatory agencies. 
The animals were dosed by IM injection in week 0, 3, 6, and 9. Ten animals per 
sex per group were assigned to the main study. Five animals per sex per group 
were in the 4-week dose-free recovery period. To make a direct comparison of the 
toxicity of each investigational vaccine, the dosing interval and recovery periods 
were identical across all adjuvanted vaccines evaluated. This also facilitated 
management of study logistics and interpretation of the study data. Repetition of 
dosing once every three weeks ensured that the animals had sufficient time in 
between doses to recover from any potential toxic effects. 
The mixing proportion of the various experimental vaccines were identical to that 
proposed in the clinical trial in terms of concentration of BG505 SOSIP.664 
gp140 and adjuvant levels used. However, the dose volume in the nonclinical 
study was limited to the maximum tolerated volume for IM injections in rats of 
0.25 mL, whereas the clinical dose volume is 0.5 mL. 
In a pre-IND technical consultation, the FDA concurred with the study design and 
proposed in-life activities (see Table 4-4). 
Table 4-4 Covance 8394847 group designations and dose levels in rats 
 
 
No. of Animals 
Dose Level (mcg) 
Group 
Test article(s) 
Male 
Female 
BG505 
SOSIP.664 
gp140 
Alum 
3M-052 
CpG 
GLA/ 
QS-21 
1 
Control 
15 
15 
0 
0 
0 
0 
0 
2 
BG505 SOSIP.664 
gp140 + Alum + 
Low 3M-052 
15 
15 
50 
250 
0.5 
0 
0 
3 
BG505 SOSIP.664 
gp140 + Alum + 
High 3M-052 
15 
15 
50 
250 
2.5 
0 
0 
4 
BG505 SOSIP.664 
gp140 + Alum + 
CpG 1018 
15 
15 
50 
250 
0 
150 
0 
5 
BG505 SOSIP.664 
gp140 + GLA-LSQ 
15 
15 
50 
0 
0 
0 
2.5 GLA/ 
1.0 QS-21 

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Assessment of toxicity was based on mortality, clinical observations, body 
weights, food consumption, dermal irritation scoring, body temperature, 
ophthalmic observations, and clinical and anatomic pathology. Blood samples 
were collected for antibody, α-acid glycoprotein, and α-2-macroglobulin (acute 
phase markers) analyses. 
No test article or adjuvant-related mortality; clinical observations (other than 
dermal irritation findings at the dose site); or effects on body weight, food 
consumption, body temperature, ophthalmic observations, or organ weight 
parameters were observed during the dosing or recovery phase. 
Dermal irritation, included erythema (barely perceptible to well-defined) and 
edema (barely perceptible to slight), were typically observed only after the second 
dose and were observed between 1 and 72 hours postdose. Erythema and edema 
were considered study product related since controls were largely unaffected. In 
general, no adjuvant combination caused a markedly higher incidence or severity 
of dermal irritation. The pattern of dermal irritation was generally consistent with 
injection site irritation findings noted microscopically, with the clinical pathology 
changes, and with the acute phase markers response identified in the study. No 
abnormal dermal observations were noted during the recovery phase. 
During the dosing phase, all dose groups administered BG505 SOSIP.664 gp140 
had minimal test article-related hematology, coagulation, and/or clinical 
chemistry changes at 72 hours post dose after the first and last dose that were 
consistent with injection site inflammation and/or the immune response elicited 
by the test articles. These changes included minimally higher fibrinogen and/or 
globulin concentrations, neutrophil count, and/or red blood cell distribution width; 
minimally lower albumin concentration, reticulocyte count, and/or 
albumin:globulin ratio; and/or minimally prolonged prothrombin time. 
Acute phase marker proteins were evaluated 24 and 72 hours after the first and 
last dose and at terminal sacrifice. Minimal to moderately higher levels of both 
acute phase proteins were identified in all groups administered the adjuvanted 
vaccine. 
Collectively, these clinical pathology changes were generally most pronounced 72 
hours after the last vaccination during the dosing phase and in animals 
administered adjuvants containing Alum (Groups 2, 3, and 4). A dose response 
was generally evident in animals administered ≥ 0.5 mcg 3M-052-AF (Groups 2 
and 3).  
During the recovery phase, these test article-related clinical pathology changes 
fully reversed, except for minimally lower reticulocyte count and albumin 
concentration in males administered the adjuvants containing 2.5 mcg 3M-052-
AF or 150 mcg CpG 1018, which partially reversed. 
Very few gross necropsy findings were identified. One female rat from the GLA-
LSQ group had discoloration of the last injection site that correlated 

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microscopically with mononuclear cell inflammation. Macroscopic finding of 
thickening observed at the last injection site in two female rats from the high dose 
3M-052-AF group lacked confirmatory microscopic correlates; its etiology 
remains unresolved. No vaccine induced macroscopic findings were identified at 
recovery necropsy. 
At terminal sacrifice, test article-related microscopic findings were observed in 
both vaccination sites (right and left thigh musculature) and the left quadriceps 
muscle, stifle joint and sciatic nerve. Histologically it was characterized by mixed 
cell inflammation, mononuclear cell inflammation, and/or mononuclear cell 
infiltrates. 
Mixed cell inflammation, an acute physiological response was limited to tissues in 
the left hindlimb, the site of the last vaccination and often extended into the left 
quadriceps muscle and stifle joint. The mixed inflammation was characterized by 
infiltrates of neutrophils, macrophages, and lymphocytes and foci of necrosis 
containing cellular debris, edema, and/or hemorrhage. This finding was observed 
in all vaccinated group; however, with higher incidence and severity in Groups 2, 
3, and 4, compared with Groups 5; therefore, mixed cell inflammation appeared to 
be exacerbated by Alum administration.  
Mononuclear cell inflammation, characterized by infiltrates of lymphocytes and 
histiocytes (often vacuolated and forming clusters) with occasional fibroplasia, 
was noted at both injection sites, which often extended into the quadriceps 
muscle, stifle joint, and/or sciatic nerve (epineurium). Mononuclear cell 
inflammation was considered a more chronic reaction to the test article. This 
finding was noted in all BG505 SOSIP.664 gp140 treated groups without a clear 
relationship with any tested adjuvant and was considered related to BG505 
SOSIP.664 gp140. No GLA-LSQ–related mononuclear cell inflammation was 
noted in the right thigh of Group 5 animals, which was consistent with a more 
rapid resolution of inflammation than groups administered test articles containing 
Alum. 
At the recovery sacrifice, test article-related microscopic findings were limited to 
mononuclear cell inflammation and infiltrates and generally occurred at a lower 
incidence and severity (compared with the terminal sacrifice), consistent with 
partial recovery. Group 5 animals had the lowest incidence of test article-related 
microscopic findings during the recovery phase. 
In conclusion, administration of BG505 SOSIP.664 gp140 with various 
combinations of adjuvants was well tolerated when administered by intramuscular 
injection to rats once every 3 weeks for 10 weeks (four total doses). 
Seroconversion was observed in all groups administered the adjuvanted BG505 
SOSIP.664 gp140. Local dermal reactivity to the administered vaccine was 
characterized by reversible dose site edema and erythema of minimal severity. 
Clinical pathology changes were of minimal severity, consistent with injection 
site inflammation and/or the immune response elicited by the test articles, and 

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HVTN137_v5.0_Final_26Sep22 / Page 36 of 281 
generally most pronounced 72 hours after the last vaccination and in animals 
administered adjuvants containing Alum. Microscopically, vaccination site 
inflammation (mixed and mononuclear cell) was observed in all test article-
treated groups; however, mixed cell inflammation appeared to be most severe in 
animals administered test articles adjuvanted with Alum, while mononuclear cell 
inflammation (and infiltrates) was without a clear relationship with any tested 
adjuvant and was considered related to BG505 SOSIP.664 gp140. Partial recovery 
of test article-related microscopic findings was noted at the recovery sacrifice. 
As part of the nonclinical repeat dose toxicity study, an immunogenicity 
assessment of serum samples was done by a binding antibody multiplex assay 
(BAMA). The antibody assay was conducted in compliance with Good Clinical 
Laboratory Practice (GCLP). Rat samples were tested for IgG antibodies to 
BG505 SOSIP.664 gp140 prevaccination, 72 hours after the last vaccination and 
towards the end of the four-week dose free recovery phase. Prevaccination 
samples were used for baseline assessment.  
At both the post vaccination collection interval, a 100% seroconversion response 
rate was evident in Groups 2 through 5 vaccinated with adjuvanted 
BG505 SOSIP.664 gp140. None of the control animals administered saline 
showed positive results post vaccination. On both days, the magnitude of the 
immune response to BG505 SOSIP.664 gp140 was significantly higher in Groups 
2, 3, and 4 in comparison to Group 5 as shown in Table 4-5. 
Table 4-5 Geometric mean titer of MFI-background-blank dilution at 1:5000 and 95% 
confidence intervals  
 
Geometric Mean Titer (MFI) 
Timepoint 
Parameter 
BG505 
SOSIP.664 + 250 
mcg Alum + 
0.5 mcg 3M052 
(Group 2) 
BG505 
SOSIP.664 + 
250 mcg Alum 
+ 
2.5 mcg 3M052 
(Group 3) 
BG505 
SOSIP.664 + 
250 mcg Alum 
+ 
150 mcg CpG 
(Group 4) 
BG505 
SOSIP.664 + 2.5 
mcg GLA/ 1 mcg 
QS-21 
(Group 5) 
72 hours after 
last 
vaccination 
Mean 
13,003 
14,490 
15,324 
1955 
Range 
12,057-16,519 
13,437-18,392 
14,227-18,846 
1869-3404 
End of dose 
free recovery 
phase 
Mean 
16,238 
18,486 
17,348 
3140 
Range 
14,055-19,847 
16,706-20,971 
15,281-20,532 
2259-7479 
4.3.2 
GLP repeat dose toxicity study of hepatitis B vaccine HEPLISAV-B in 
rats (study 12-728)  
Dynavax’s licensed hepatitis B vaccine HEPLISAV-B consists of a hepatitis B 
antigen and CpG 1018 adjuvant. Dynavax has completed a series of toxicity 
studies, including CpG 1018 single-dose toxicity studies in rabbits and baboons, 
CpG 1018 repeat-dose toxicity studies in mice, rats, and cynomolgus monkeys, 

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CpG 1018 genotoxicity studies, CpG 1018 + hepatitis B surface antigen (HBsAg) 
reproductive and developmental toxicity study, and repeat-dose toxicity studies of 
CpG 1018 + HBsAg in mice and rats. The objective of rat repeat dose study #12-
728 was to evaluate the toxicity of 2 dose levels: 3000 mcg CpG 1018 + 20 mcg 
HBsAg/dose and 600 mcg CpG 1018 + 4 mcg HBsAg/dose when administered by 
IM injection to Sprague-Dawley rats once every 2 weeks over a 6-week period 
(total of 4 doses). The studies all demonstrated acceptable safety profile of CpG 
1018 and CpG 1018 + HBsAg. 
4.3.3 
GLP repeat dose toxicity study of TB vaccine ID93 with adjuvant 
GLA-LSQ in rabbits (study 2416-001) 
The objective of this study by AAHI was to evaluate the potential toxicity of the 
TB vaccine ID93 ± GLA-LSQ adjuvant in male and female New Zealand White 
rabbits following repeated IM administrations, and to evaluate the reversibility of 
effects after a four-week recovery period. 
Eighty rabbits were administered control article or test article for four bi-weekly 
doses, as described in Table 4-6. Half of the animals of each sex from each dose 
group were euthanized for terminal postmortem examinations approximately 48 
hours after the final dose. The remaining animals from each dose group were 
retained and observed for a postdosing recovery period of four weeks following 
the final dose, followed by euthanasia and postmortem examination. 
Table 4-6 Treatment Groups for Rabbit Toxicity Study #2416-001 
Group 
Treatment 
ID93 
Dose 
(mcg) 
GLA 
Dose 
(mcg) 
QS-21 
Dose 
(mcg) 
Injection 
Volume 
(mL) 
Injection 
Route 
Terminal 
Animal #s 
Recovery 
Animal #s 
M 
F 
M 
F 
1 
Control (0.9% saline) 
- 
- 
- 
0.75 
IM 
5 
5 
5 
5 
2 
GLA-LSQ 
- 
20 
40 
0.75 
IM 
5 
5 
5 
5 
3 
ID93 
20 
- 
- 
0.75 
IM 
5 
5 
5 
5 
4 
ID93 + GLA-LSQ 
20 
20 
40 
0.75 
IM 
5 
5 
5 
5 
All study rabbits survived to the scheduled necropsies. No treatment-related 
clinical findings or injection site reactogenicity were observed. No treatment-
related or toxicologically significant effects were observed for body weights, 
body weight changes, food consumption, body temperatures, ophthalmology, 
serum protein electrophoresis, and organ weights. 
Alterations in various clinical pathology parameters were noted throughout the 
study and were likely attributed to treatment with the GLA-LSQ adjuvant 
component of the vaccine (with or without ID93); however, these findings were 
reversible and no longer observed near the end of the recovery period suggesting 
that these adjuvant-related findings may be of minimal toxicological significance, 
and none of these findings resulted in any limiting toxicity. 

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No test article-related gross findings were noted at the terminal and recovery 
necropsies. There were test article-related microscopic findings in the left sciatic 
nerve perineurium (mixed cell infiltrates), left administration site (serocellular 
crust; mixed cell infiltrates in the subcutaneous tissue and skeletal muscle), right 
administration site (mixed cell infiltrates in the subcutaneous tissue and skeletal 
muscle), and testes (multinucleated giant cells) on Study Day 45 in groups 
receiving GLA-LSQ, ID93, and/or ID93 + GLA-LSQ. At the end of the 28-day 
recovery period (on Study Day 71), most of these microscopic findings were no 
longer present or were generally decreased. Additional findings (previously not 
seen on Study Day 45) were noted in the lungs (mixed cell infiltrates), mandibular 
lymph nodes (erythrophagocytosis), stomach (mononuclear cell infiltrates), and 
testes (multinucleated giant cells) in groups receiving GLA-LSQ, ID93, and/or 
ID93 + GLA-LSQ; these additional findings were limited to a single gender and 
were generally seen in only one treatment group. 
Repeated administration of the ID93 + GLA-LSQ vaccine, or its components, by 
IM injection was well-tolerated as there were no treatment-related and/or 
toxicologically-significant findings noted throughout the study for most of the 
endpoints evaluated except for clinical pathology and microscopic pathology. The 
increases in globulin, fibrinogen, blood cells (WBCs, heterophils, and 
monocytes), and microscopic findings of mixed or mononuclear cell infiltrates are 
consistent with the administration of immunogenic substances (ie, the ID93 
antigen and the GLA-LSQ adjuvant). As most of these findings were reversible 
and no longer seen near or at the end of the 28-day recovery period (on Study Day 
71) and/or were limited to a single gender, these findings are considered to be of 
less toxicological significance than if these findings persisted until the end of the 
recovery period and/or were seen in both sexes. 
Administration of the ID93 + GLA-LSQ vaccine or the ID93 antigen component 
alone produced appropriate IgG titers following repeated administration. 
Immunogenicity analyses also demonstrated that total IgG titers were 
approximately 10 times higher in rabbits receiving ID93 + GLA-LSQ compared 
to total IgG titers in rabbits receiving ID93 alone. 
4.3.4 
GLP repeat dose toxicity study of flu vaccine H5-VLP + 3M-052-SE 
adjuvant in rats (study 11943) 
This study in rats was based on the intent to use 3M-052-SE adjuvant with flu 
antigen as a flu vaccine by AAHI. The repeat dose toxicity study in Sprague 
Dawley rats was sponsored by AAHI where the toxicity of 3M-052-SE (SE – 
Stable Emulsion) was evaluated in combination with an influenza hemagglutinin 
antigen. The highest dose of 3M-052 in the study is four times as high as the high 
dose in our toxicity study (Covance study 8394847). AAHI’s IND 17789 for the 
indication of pre-exposure prophylaxis against influenza received a safe to 
proceed notification on November 29, 2017. 

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The objective of the study was to evaluate the toxicity of influenza H5 virus like 
particle (H5-VLP) antigen adjuvanted with 3M-052-SE, an oil-in-water emulsion 
formulation. A single dose of the H5-VLP antigen at 20 mcg was evaluated in 
combination with 0, 2, or 10 mcg of 3M-052-SE. Rats were dosed three times 21 
days apart. Ten rats/sex/group were allocated to the main study group and were 
necropsied on Day 45. Five rats/sex/group that were dosed identically were 
assigned to a 4-week dose free recovery period and were necropsied on Day 71. 
The majority of rats exhibited slight erythema at the injection site starting on Day 
1-2 post dose that persisted up to 6 days. Decreased body weight was noted in the 
adjuvanted vaccine groups after 24 hours after all three doses with a partial 
recovery after each occurrence. Decreased food consumption was observed and 
closely mirrored the body weight changes. Body weight and food consumption 
changes were not apparent in the recovery phase. A minimal increase of body 
temperature was observed at 24 hours post dose in the adjuvanted vaccine groups. 
In a majority of animals, the average increase in body temperature was < 1°C. 
The absolute WBC and neutrophil counts were increased while the platelets count 
was decreased in the two adjuvanted vaccine groups consequent to the 
inflammatory response at the injection site. These changes resolved by the end of 
the recovery period. Coagulation parameter changes attributed to the adjuvanted 
vaccine included increased activated partial thromboplastin time (APTT) and 
fibrinogen levels that resolved by the end of the recovery period in male rats. 
Clinical chemistry changes included increases in serum globulin and total protein 
levels and decreases in albumin/globulin (A/G) ratio which are consistent with an 
immune response to an antigen. Increased alanine aminotransferase (ALT) and 
aspartate aminotransferase (AST) levels correlated with vacuolation in the liver 
and was considered to be of minimal toxicological significance. C-reactive 
protein (CRP) was increased in the two adjuvanted vaccine groups and was 
consistent with an acute phase response following vaccination.  
At Day 45, the adjuvanted vaccine groups had antigen-specific IgG titers that 
were 10 times higher that the group receiving the antigen alone. On a log10 scale 
the mean total IgG titer in the antigen alone and the antigen adjuvanted groups 
were 5 and 6 respectively. An increase in spleen weight was identified in both 
sexes and correlated with increased myelopoiesis. Microscopic changes were 
noted in the adjuvanted vaccine groups. The injection site showed inflammatory 
cell infiltration, degeneration/necrosis and hemorrhage. An increased myeloid to 
erythroid ratio was noted in the bone marrow and was interpreted as a secondary 
response to the inflammation at the injection site. The incidence and severity of 
liver vacuolation was increased in the 10 mcg adjuvanted vaccine group female 
animals. Single cell necrosis was identified in the pancreas of animals 
administered high doses of the adjuvant in combination with the vaccine. 
Degeneration of the white matter of the spinal cord was seen in one female 
administered 10 mcg of 3M-052-SE. With the exception of the mononuclear 
inflammatory cell infiltration at the injection site, all other microscopic changes 
resolved by the end of the recovery phase. None of the toxicological findings 
were considered significant with the exception of injection site findings. 

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4.3.5 
GLP repeat dose toxicity study of 3M-052 in sesame oil formulation 
for cancer treatment in mice  
This study was preparatory to testing 3M-052 for use in intratumoral therapy by 
3M. The mouse was chosen as the rodent species because the antitumor efficacy 
of 3M-052 was demonstrated in mouse models. 3M-052 in a sesame oil/ethanol 
formulation was administered to mice SC once weekly over a 22-day period (4 
total doses) at doses of 0, 1.25, 3.75, and 6.25 mg/kg body weight. (The dose 
tested was significantly higher than the dose planned in the current BG505 
SOSIP.664 gp140 + Adjuvants study.) In comparison, the 3M-052 dose in the 
IND-enabling rat study (Covance 8394847) is in the range of 0.008 mg/kg body 
weight, more than 100-fold lower than the low dose in the mice study.  
Dose sites were rotated weekly among left and right dorsoscapular and 
dorsolumbar sites. Necropsies were performed the day following the last dose. 
Additional animals were included in the 0 and 6.25 mg/kg dose groups to assess 
reversibility of treatment effects; these animals were necropsied 15 days after the 
last dose. 
Effects at the injection site were observed in mice following SC administration. 
Scabbing occurred at a similar incidence in all groups, as did the microscopic 
finding of granulomatous inflammation. Microscopic findings of epithelial 
hyperplasia, necrosis, exudate, and ulceration occurred exclusively or at much 
greater incidence in the 3M-052–treated mouse groups versus the control group. 
One female in the 6.25 mg/kg group was found dead 15 days after the last dose. 
For 2 to 3 days prior to death, this animal exhibited a swollen abdomen and 
yellow ventral staining. Autolysis precluded histologic examination and the cause 
of death was not determined. This death was considered to be potentially test 
article-related, with test article-related effects possibly persisting or evolving in 
the recovery period. 
Statistically significant test article-related changes occurred in serum protein, 
RBC, and WBC parameters in all 3M-052–treated male groups. Changes in these 
parameters were consistent with 3M-052 pharmacologic activity, were within or 
very close to historic control ranges, and were not considered adverse. 
Test article-related effects on organ weights at the end of treatment included 
higher liver and spleen weights or weight ratios in all 3M-052–treated male and 
female groups. The increased spleen weights correlated to microscopic findings of 
extramedullary hematopoiesis (EMH) and mild lymphoid hyperplasia. Both EMH 
and lymphoid hyperplasia were consistent with the pharmacologic effects of 
3M-052. The degree of EMH and lymphoid hyperplasia were not considered 
adverse. There were no histologic correlates to the liver weight changes. 
At necropsy at the end of treatment, grossly enlarged lymph nodes were noted in 
all 3M-052–treated male and female groups. The lymphoid hypercellularity was 
consistent with 3M-052 pharmacologic activity and was not considered adverse.  

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There were no 3M-052–related changes in body weights, food consumption, 
ophthalmology, or coagulation parameters either at the end of treatment or at the 
end of the 14-day recovery period. 
Many of the toxicities reported in this repeat dose study might not be relevant 
from a clinical perspective since the 3M-052 in this study will be given much 
lower dose levels (1 or 5 mcg total dose; maximum approximately 0.000025 to 
0.000125mg/kg for a 40 kg participant or ~1/10,000 the lowest dose administered 
in this mouse study) and at greater intervals. 
4.3.6 
GLP repeat dose toxicity study of 3M-052 in sesame oil formulation 
for cancer treatment in cynomolgus monkeys  
This study was preparatory to testing 3M-052 for use in intratumoral therapy by 
3M. 3M-052 in a sesame oil/ethanol formulation was administered to cynomolgus 
monkeys (5/sex/group) by SC route once weekly over a 22-day period (4 total 
doses) at doses of 0, 1.25, 2.5, and 5.0 mg/kg body weight. The doses tested were 
significantly higher than the dose planned in the current BG505 SOSIP.664 gp140 
+ Adjuvants study. In comparison, the 3M-052 dose in the IND-enabling rat study 
(Covance 8394847) is in the range of 0.008 mg/kg body weight, more than 100-
fold lower than the low dose (1.25 mg/kg) in the cynomolgus monkey study.  
There were no deaths during the study. Compared with the control group, 
inappetence was noted more frequently in the 3M-052 groups and was noted in 
the recovery phase as well as the treatment phase. During the recovery period, all 
3M-052–treated groups gained weight. Body temperatures measured 1 day post 
dose were statistically significantly increased in all 3M-052 male groups (but not 
in females), and in most individual animals the temperatures exceeded laboratory 
historical control values. Body temperatures were within normal range when 
measured during the recovery period. 
In cynomolgus monkeys, clinical signs of swelling and sores, and microscopic 
findings of ulceration occurred at greater incidence and/or severity at the injection 
sites of the 3M-052–treated groups versus the control group. The control and 3M-
052 groups showed similar incidence of adipose tissue necrosis, ulceration, and 
(at recovery) dermal scar tissue formation. Clinical signs of discharge, and 
microscopic findings of inflammatory cells at the injection site, occurred 
exclusively in the 3M-052–treated cynomolgus monkey groups. The discharge 
was usually described as purulent and persisted into the recovery phase. The 
inflammatory cell population changed over time, being primarily neutrophils at 
the end of dosing and predominantly lymphocytes at the end of the recovery 
period. These findings were considered adverse. 
Test article-related hematology changes occurred in all 3M-052 groups. These 
changes were frequently statistically significant and/or outside of laboratory 
historic control values. Generally, the severity of effects was similar in the mid 

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and high doses, which in turn were slightly more severe than the low dose effects. 
None of the hematology changes were considered adverse. 
Serum protein changes occurred in all 3M-052 groups. These changes were 
frequently statistically significant and/or outside of laboratory historic control 
values. Generally, the severity of effects was similar in the mid and high doses, 
which in turn were slightly more severe than the low dose effects. The changes in 
serum proteins were not considered adverse. 
Changes in serum chemistry parameters were observed only in the 3M-052 male 
groups. At the end of the recovery period, all of these parameters were 
comparable to the vehicle control. Based on reversibility of the findings, these 
changes were not considered adverse. 
At necropsy at the end of treatment, there were multiple organ changes in all 3M-
052 treated male and female groups, manifested as changes in organ weights 
and/or histology. None of the inflammatory/mononuclear infiltrates were 
considered to cause injury or functional impairment. Thymus changes were 
considered to be related to an indirect, stress-related effect of 3M-052. At the 
recovery necropsy, the histologic changes appeared to be resolving. 
4.3.7 
Preclinical Toxicology Studies of Trimer 4571 
Preclinical toxicology studies of Trimer 4571 formulated with Alum were 
conducted in New Zealand White Rabbits (VRC-HIVRGP096-00-VP). No 
treatment-related or toxicologically significant clinical findings were determined. 
For full details, please consult the investigator’s brochure. These data have been 
reinforced by clinical data from clinical studies (please see Section 4.5.5 below).    
4.4 
Preclinical immunogenicity studies  
Various preclinical immunogenicity studies have been performed evaluating the 
BG505 SOSIP.664 with various adjuvant formulations, as summarized in Table 
4-7. 

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Table 4-7 Summary of preclinical immunogenicity studies 
Study number 
Product 
Animal 
N 
Dose 
groups 
Route 
Schedule 
Assay 
CAVD 708 
(Covance 
0066-18) 
BG505 SOSIP.664 
gp140, 3M-052-Alum, 
CpG 1018, GLA-LSQ, 
VRCplex, Alum 
Guinea 
pig 
6 females 
per group 
9 
IM 
0, 8, 20 
weeks 
Neutralizing 
Ab, binding Ab 
CAVD 724 
(Covance 
0102-18) 
BG505 SOSIP.664 
gp140, 3M-052-AF, CpG 
1018, GLA-LSQ, Alum 
Rat 
2 females, 
2 males 
per group 
4 
IM 
0, 2, 4 
weeks 
Binding Ab, 
neutralizing Ab 
CAVD 749 
(Covance 
0147-18) 
BG505 SOSIP.664 
gp140, 3M-052-AF, CpG 
1018, GLA-LSQ, GLA-
SE, LMQ, Alum 
Rabbit 
5 females 
per group 
7 
IM 
0, 8, 20 
weeks 
Neutralizing 
Ab, binding Ab 
CAVD 641 
(by Bali 
Pulendran 
Lab) 
BG505 SOSIP.664 
gp140, 3M-052-Alum, 
GLA-LSQ, 
Rhesus 
macaques 
14 males 
per group 
3 
SC, IM 
0, 8, 24 
weeks 
Neutralizing 
Ab, binding Ab 
4.4.1 
Immunogenicity of BG505 SOSIP.664 gp140 + adjuvants in guinea 
pigs (CAVD 708) 
The objective of the guinea pig study, CAVD 708, was to assess the 
immunogenicity of BG505 SOSIP.664 gp140 + adjuvants, measured by 
neutralizing antibody and binding antibody responses. The adjuvants used in the 
study were based on the proposed clinical trial plan. Guinea pigs have been shown 
to develop neutralizing antibody responses against the tier 2 autologous virus after 
immunization with BG505 SOSIP.664 gp140 + Poly IC adjuvant (80), and after 
immunization with glycan modified BG505 SOSIP.664 gp140 with Adjuplex 
adjuvant (81). Guinea pigs are also known to respond to TLR4, 7/8, and 9 
agonists. Adjuvant doses were selected based on recommendations of the 
adjuvant providers. Some variations of formulation and/or doses were tested to 
identify the optimal conditions. The groups, adjuvants, and doses are shown in 
Table 4-8. Note that 3M-052-Alum was prepared by mixing 3M-052-AF with 
Alum and vialed. VRCplex is the same adjuvant as Adjuplex. 

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Table 4-8 CAVD 708 guinea pig groups, antigen + adjuvants, and doses 
Group 
(N=6) 
Antigen / Adjuvant Assignment 
Antigen 
Dose 
Adjuvant dose 
1 
BG505 SOSIP.664 gp140 / Alum 
30 mcg 
500 mcg 
2 
BG505 SOSIP.664 gp140 / GLA-LSQ 
30 mcg 
5 mcg GLA, 2 mcg QS-21 
3 
BG505 SOSIP.664 gp140 / 3M-052-Alum, low dose 
30 mcg 
2 mcg 3M-052, 100 mcg Alum 
4 
BG505 SOSIP.664 gp140 / 3M-052-Alum, high dose 
30 mcg 
5 mcg 3M-052, 500 mcg Alum 
5 
BG505 SOSIP.664 gp140 / CpG 1018 
30 mcg 
100 mcg 
6 
BG505 SOSIP.664 gp140 / CpG 1018 / Alum, mixing 1 
30 mcg 
CpG 100 mcg, Alum 500 mcg 
(CpG mix with Alum first) 
7 
BG505 SOSIP.664 gp140 / CpG 1018 / Alum, mixing 2 
30 mcg 
CpG 100 mcg, Alum 500 mcg 
(Antigen will mix with Alum first) 
8 
BG505 SOSIP.664 gp140 / VRCplex 
30 mcg 
80 mcL 
9 
BG505 SOSIP.664 gp140 only 
30 mcg 
None 
Guinea pigs were immunized at weeks 0, 8, and 20. Injection volume was 500 
mcl total, with 250 mcl at each injection site (in the left and right rear quadriceps 
muscle). Antibody responses were measured at weeks 10, 22, 28, 36, and 40. 
Neutralization antibody titers to autologous BG505.T332N and selected tier 2 
HIV-1 strains were measured by the Comprehensive Antibody Vaccine Immune 
Monitoring Consortium (CAVIMC)/Montefiori lab. Binding antibody binding 
titers to the homologous antigen were measured by the CAVIMC/Tomaras Lab. 
The results showed that BG505 SOSIP.664 gp140 + adjuvants were immunogenic 
in guinea pigs.  
Autologous and heterologous serum neutralizing antibodies to tier 2 HIV-1 strains 
were detected in guinea pig serum at various titers, and in general the magnitude 
of responses depended on the adjuvant groups. High nAb responses against the 
tier 1A virus MW965.26 (a neutralization sensitive virus) was elicited in all of the 
adjuvant groups, while the response was remarkably lower in the no-adjuvant 
group 9. The responses reached peak at week 22, 2 weeks after the 3rd dose, and 
decreased somewhat over the next 18 weeks until study termination at week 40 
(see Figure 4-3). 

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Figure 4-3 ID50 neutralizing antibody titers against the tier 1A virus MW965.26 after 
administration of BG505 SOSIP.664 gp140 with various adjuvants 
The detection of nAbs recognizing the autologous tier 2 virus BG505 T332N is 
the main endpoint for this study. At the peak timepoint (week 22), the nAb titers 
were the highest in 3M052-Alum and VRCplex groups (ID50 500-1000), lower in 
the CpG 1018/Alum and Alum groups (ID50 100-600), and lowest in the GLA-
LSQ, CpG 1018, and no-adjuvant groups (ID50 below 100). The titers in general 
decreased over time after week 22 or 28; however, the pattern of kinetics varied 
across different adjuvant groups (see Figure 4-4). Group 1 and 4 titers fell at week 
28 and rose again at week 36. Peak response was at week 28 for Group 7 and 8. 
 
Figure 4-4 Neutralizing antibody responses against the autologous tier 2 virus BG505.T332N 
after administration of BG505 SOSIP.664 gp140 with various adjuvants 

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Neutralizing antibody responses to heterologous subtype C viruses 25710 and 
CE1176 were also elicited in selected adjuvant groups, with ID50 near or below 
100 (lower than that to BG505 T332N) (see Figure 4-5 for responses to tier 2 
HIV-1 CE1176). 
 
Figure 4-5 Neutralizing antibody responses against the heterologous tier 2 virus CE1176 
after administration of BG505 SOSIP.664 gp140 with various adjuvants. For group definitions, 
see Table 4-8. 
Binding antibody responses to the autologous antigen varied across adjuvant 
groups. It was the highest in 3M-052-Alum, lower in CpG 1018/Alum and Alum 
groups, and lowest in GLA-LSQ and no-adjuvant groups (Figure 4-6). The 
responses were pronounced after 2 doses at week 10, reached peak after 3 doses at 
week 22, and declined slowly over time. Assays for binding antibody responses 
from week 28, 36, and 40 timepoints are in progress.  
 
Figure 4-6 Binding antibody responses to BG505 SOSIP.664 gp140 administered with 
various adjuvants 
G ro u p  1
G ro u p  2
G ro u p  3
G ro u p  4
G ro u p  5
G ro u p  6
G ro u p  7
G ro u p  8
G ro u p  9
1 0
1 0 0
1 0 0 0
C E 1 1 7 6 _ W k 2 2
ID 5 0  in  T Z M -b l

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4.4.2 
Immunogenicity of BG505 SOSIP.664 gp140 + Adjuvants in rats 
The objective of this study, CAVD 724, was to evaluate the immunogenicity 
(antibody responses) of BG505 SOSIP.664 gp140 + adjuvants in rats. The 
purpose of the study is to ensure that rats are a suitable model for the toxicity 
study. The study groups are shown in Table 4-9. 
Table 4-9 CAVD 724 groups, antigen + adjuvants, and doses 
Group 
N 
Antigen +  
Adjuvant  
Antigen 
Dose 
Adjuvant dose 
1 
4 
BG505 SOSIP.664 gp140 
only 
50 mcg 
None 
2 
4 
BG505 SOSIP.664 gp140 +  
(3M-052-AF + Alum) 
50 mcg 
5 mcg 3M-052-AF, 250 mcg Alum 
3 
4 
BG505 SOSIP.664 gp140 +  
(CpG 1018 + Alum) 
50 mcg 
1500 mcg CpG 1018, 250 mcg 
Alum 
4 
4 
BG505 SOSIP.664 gp140 +  
GLA-LSQ 
50 mcg 
2.5 mcg GLA, 1 mcg QS-21 
Animals were immunized in week 0, 2, and 4. Injection volume was 250 mcl 
total, with 250 mcl in the left or right rear quadriceps muscle alternatively. BG505 
SOSOP.664 gp140-specific binding antibody titers were measured on day 43. The 
results indicated that BG505 SOSOP.664 gp140 were immunogenic in rats, and 
the magnitude of the binding antibody responses varied depending on the 
adjuvants (Figure 4-7). Little neutralizing antibody response to the autologous tier 
2 virus BG505 T332N was observed but the binding antibody results assured us 
that rat is the appropriate model for toxicity study. 
 
Figure 4-7 Binding antibody responses to BG505 SOSIP.664 gp140 adjuvanted with Alum 
(Group 1), 3M-052+Alum (Group 2), CpG 1018+Alum (Group 3), or GLA-LSQ (Group 4) in 
rats. For group definitions, see Table 4-9 above. 
4.4.3 
Immunogenicity of BG505 SOSIP.664 gp140 + Adjuvants in rabbits 
The objective of this study, CAVD 749, is to assess the immunogenicity of 
BG505 SOSIP.664 gp140 + adjuvants in rabbits measured by neutralizing 
antibody and binding antibody responses. Immune responses to BG505 

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SOSIP.664 gp140 with ISCOMATRIX adjuvant in rabbits were robust and have 
been reported extensively in the literature. However, it was considered that rabbits 
may not respond to adjuvants that are TLR7/8 or TLR9 agonists (3M-052 and 
CpG 1018). This study will bridge past studies and will also compare several 
additional TLR4 agonists (Table 4-10). 
Table 4-10 CAVD 749 groups, antigen + adjuvants, doses, and dosing schedule 
Group 
N 
Antigen + 
Adjuvant 
Antigen 
Dose 
Adjuvant dose 
Dosing schedule 
in weeks 
1 
5 
BG505 SOSIP.664 gp140 
only 
30 mcg 
None 
0, 8, and 20 
2 
5 
BG505 SOSIP.664 gp140 + 
Alum 
30 mcg 
500 mcg 
0, 8, and 20 
3 
5 
BG505 SOSIP.664 gp140 + 
GLA-LSQ 
30 mcg 
25 mcg GLA, 
10 mcg QS-21 
0, 8, and 20 
4 
5 
BG505 SOSIP.664 gp140 + 
(3M-052-AF + Alum) 
30 mcg 
5 mcg 3M-052-AF,  
Alum 500 mcg  
0, 8, and 20 
5 
5 
BG505 SOSIP.664 gp140 + 
(CpG 1018 + Alum) 
30 mcg 
CpG 1018 300 mcg,  
Alum 500 mcg 
0, 8, and 20 
6 
5 
BG505 SOSIP.664 gp140 + 
LMQ 
30 mcg 
10 mcg 3D-MPL,  
25 mcg QS-21 
0, 8, and 20 
7 
5 
BG505 SOSIP.664 gp140 + 
GLA-SE 
30 mcg 
25 mcg GLA,  
2% squalene 
0, 8, and 20 
Animals were immunized in week 0, 8, and 20. Injection route was IM. Injection 
volume was 500 mcl total, with 250 mcl at each injection site (in the left and right 
rear quadriceps muscle). At week 10, some of the animals across all groups 
developed neutralizing antibody responses against the tier 1A virus MW965.26 
and the autologous tier 2 virus BG505 T332N (Figure 4-8). 
 
Figure 4-8 Neutralizing antibody responses to BG505 SOSIP.664 gp140 with or without 
adjuvants in rabbits at week 10 
At week 22, most of animals in all groups developed neutralizing antibody 
responses against the tier 1A virus MW965.26 and the autologous tier 2 virus 
BG505 T332N (Figure 4-9). 

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Figure 4-9 Neutralizing antibody responses to BG505 SOSIP.664 gp140 with or without 
adjuvants in rabbits at week 22 
Binding antibody responses at week 22 were robust across all groups (Figure 
4-10). 
 
 
Figure 4-10 Binding antibody responses to BG505 SOSIP.664 gp140 with or without 
adjuvants in rabbits at week 22. The samples were tested at 1:800 dilution. 
4.4.4 
Immunogenicity of BG505 SOSIP.664 gp140 + 3M-052-Alum in rhesus 
macaques 
The objective of this study, CAVD 641, was to assess the immunogenicity of 
BG505 SOSIP.664 gp140 with 3M-052-Alum adjuvant by SC or IM routes, in 
comparison to GLA-LSQ adjuvant, in rhesus macaques. The study was conducted 
by Bali Pulendran’s lab at Emory University. 3M-052-Alum was prepared by 
mixing 3M-052-AF with Alum and vialed. 
The groups are specified in Table 4-11. At each immunization, two sites (left and 
right leg quadriceps) were injected, 30 mcg of 3M-052-Alum at each site for a 
total dose of 60 mcg. Animals were immunized at weeks 0, 8, and 24.  

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Table 4-11 CAVD 641 antigen + adjuvant, routes, doses, and dosing schedule 
Group 
N 
Antigen +  
Adjuvant 
Antigen 
Dose 
Adjuvant dose 
Dosing 
schedule in 
weeks 
1 
3 
BG505 SOSIP.664 gp140 + 
3M-052-Alum, SC 
100 mcg 60 mcg 3M-052 
0, 8, 24 
2 
3 
BG505 SOSIP.664 gp140 + 
3M-052-Alum, IM 
100 mcg 60 mcg 3M-052 
0, 8, 24 
3 
3 
BG505 SOSIP.664 gp140 + 
GLA-LSQ, IM 
100 mcg 12.5 mcg GLA 
5 mcg QS-21 
0, 8, 24 
Robust autologous tier 2 neutralizing antibody responses were observed. The 
responses persist for at least 4 months post vaccination (Figure 4-11). There was 
limited breadth of tier 2 HIV neutralizing antibodies. 
After the second immunization, SC immunization appears to induce a slightly 
higher autologous tier 2 response than IM immunization. This trend disappeared 
following the third immunization.  
 
Figure 4-11 Neutralizing antibody responses to BG505 SOSIP.664 gp140 adjuvanted with 
3M-052-Alum or GLA-LSQ 
Robust and persistent GC and Tfh responses were observed in the draining LN. 
Long lived bone marrow plasma cell responses were also observed. 
4.4.5 
Immunogenicity of Trimer 4571  
In the VRC018 trial, Trimer-4571–specific antibody titers in serum samples were 
measured by Electrochemiluminescence (ECLIA) using a Meso Scale Discovery 
(MSD) platform at baseline and at 2 weeks after the third product administration. 
Both the 100-mcg (n = 3) and 500-mcg (n = 5) IM and SC doses elicited Trimer-
4571–specific antibodies, with geometric mean AUCs 8- fold and 40-fold over 
background, respectively. No tier-2 neutralizing activity was observed.  
In pre-clinical studies, Trimer 4571 adjuvanted with Alum elicited autologous 
tier-2 neutralizing antibodies in guinea pigs (50 mcg of Trimer 4571) and rhesus 

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macaques (100 mcg of Trimer 4571). For full details, please see the Investigator’s 
Brochure. 
4.5 
Clinical studies 
4.5.1 
Clinical studies of HEPLISAV-B 
HEPLISAV is a hepatitis B virus vaccine comprised of recombinant, yeast cell-
derived hepatitis B surface antigen (HBsAg) and CpG 1018. HEPLISAV is a 
sterile liquid dosage form that is administered as an IM injection. The CpG 1018 
in HEPLISAV is a synthetic 22-mer phosphorothioate oligodeoxynucleotide (PS 
ODN) containing an immunostimulatory sequence that is an agonist for Toll-like 
receptor 9. The desired biological activity of CpG 1018 is to enhance the 
generation of antibodies to HBsAg by mimicking the immunostimulatory activity 
of single-stranded viral and bacterial DNA. HEPLISAV is administered as a 
single dose of 0.5 mL, containing 20 mcg HBsAg and 3000 mcg CpG 1018. 
Cumulatively, 10,049 subjects (10,038 subjects 18 years of age and older and 11 
subjects below 18 years old) and 386 adult subjects with chronic kidney disease 
18 years of age and older have received HEPLISAV in clinical trials. Before it 
was approved by the FDA, that vaccine was tested in more than 9500 people. 
HEPLISAV appeared to be well tolerated in clinical trials in healthy adults. The 
reactogenicity profile of HEPLISAV is similar to Engerix-B (a non-adjuvanted 
HBV vaccine) in time course and severity. Compared with Engerix-B, 
HEPLISAV caused more local reactions and fewer systemic reactions. Common 
adverse events (AEs) determined by investigators to be related to HEPLISAV 
included injection site erythema, headache, nasopharyngitis, myalgia, fatigue, 
diarrhea, nausea, injection site swelling, back pain, injection site hematoma, 
injection site pain, pain in extremity, dizziness, oropharyngeal pain, 
postprocedural hematoma, arthralgia, injection site pruritus, and increased white 
blood cell count. SAEs, autoimmune adverse events, and deaths have been 
infrequent in the HEPLISAV clinical program. One SAE of Wegener’s 
granulomatosis (also called granulomatosis with polyangiitis [GPA]) has been 
reported in a recipient of HEPLISAV; this event was considered by the 
investigator as possibly related to trial vaccine (82). In one randomized, observer-
blind, active-controlled, multicenter study in the United States in which 5587 
participants received at least 1 dose of HEPLISAV-B and 2781 participants 
received at least 1 dose of Engerix-B, acute myocardial infarction (AMI) was 
reported in 0.25% (n = 14) of HEPLISAV-B recipients and 0.04% (n = 1) of 
Engerix-B recipients. Additional evidence, including information on temporal 
relationship and baseline risk factors, does not support a causal relationship 
between HEPLISAV-B administration and AMI. No deaths have been considered 
by the investigator to be related to HEPLISAV.  
For more information, see the Investigator’s Brochure (IB). 

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4.5.2 
Clinical studies of ID93 + GLA-LSQ 
A phase 1, randomized, double blind clinical trial evaluated the safety, 
tolerability, and immunogenicity of the vaccine candidates ID93 + AP10-602 
(GLA-LSQ) and ID93 + GLA-SE administered IM in in 70 healthy adults 18-49 
years of age (ClinicalTrials.gov Identifier: NCT02508376). 
The four treatment groups are outlined in Table 4-12. General safety was 
evaluated for 28 days following each injection at days 1, 29, and 57. Subjects 
were monitored for approximately 422 days (one year following the third study 
injection), including safety laboratory analyses done just prior to and 7 days 
following each study injection. Blood samples were obtained for immunological 
assays (Luminex, intracellular cytokine staining at Days 1 and 71, and antibody 
analysis at Days 1 and 85). 
Table 4-12 Protocol DMID 12-0109 treatment groups 
Cohort 
N 
Treatment Assignment 
Route 
Volume 
Injection Schedule 
1 
20 
10 mcg ID93 + 5 mcg AP10-602* 
IM 
0.5 mL 
Days 1, 29, and 57 
2 
20 
10 mcg ID93 + 10 mcg AP10-602 
1 mL 
3 
20 
10 mcg ID93 + 5 mcg GLA-SE 
0.5 mL 
4 
10 
10 mcg ID93 
0.5 mL 
* AP10-602 is GLA-LSQ. 
All participants have completed the study. All treatment regimens were safe and 
well tolerated. There were no Grade 4 adverse events and no related SAEs, 
AESIs, or deaths. No participants withdrew or discontinued vaccination due to 
adverse reactions. The most common local reactions were mild to moderate 
injection site pain, tenderness, warmth, and pruritus. The most common systemic 
reactions were mild to moderate headache, fatigue, and myalgia. No significant 
safety issues have been noted. 
4.5.3 
Clinical studies of 3M-052 
3M-052 (MEDI9197) has been evaluated in a clinical study using a sesame oil 
formulation to evaluate its effects following intratumoral injection 
(ClinicalTrials.gov Identifier NCT02556463). In this study, 52 cancer patients 
with metastatic or locally advanced solid tumors received 3M-052 dissolved in 
sesame oil intratumorally at doses of 55, 37, 12, and 5 mcg alone, in combination 
with the anti-PD-L1 antibody durvAlumab delivered IV, or with durvAlumab plus 
radiation therapy. Two dose-limiting-toxicities were observed in this study: Grade 
3 cytokine release syndrome at 37 mcg and Grade 4 cytokine release syndrome at 
55 mcg. The most common (≥ 15%) drug related adverse events (AEs) were 
pyrexia, fatigue, decreased lymphocyte count, chills, nausea, arthralgia, and 
injection site pain (83). Based on this safety record, the 37 mcg dose of 3M-052 
was defined as the maximum tolerated dose for this study. 

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One patient with Stage IV recurrent anal squamous cell carcinoma died following 
a second round of intrahepatic tumoral injection of 12mcg 3M-052 plus IV 
durvAlumab. Two weeks prior, per-protocol liver biopsy performed demonstrated 
necrotic metastatic lesions. This death could not be attributed to a specific cause 
(autopsy and post-mortem CT scan were not performed). However, the study 
investigator considered the event to be related to 3M-052 and the study procedure. 
Medimmune, the trial sponsor, informed the FDA that this event was potentially 
related to hemorrhagic shock due to a ruptured liver metastasis. The FDA 
required protocol alterations prohibiting injection of deep-seated lesions before 
allowing continuation of the clinical trial. 
HVTN 300 (NCT04915768): This study is a first-in-human, unblinded trial 
testing a 300 mcg dose of a CH505 TF chTrimer (a stabilized, chimeric SOSIP 
Env trimer) in combination with a 5 mcg 3M-052-AF + 500 mcg Alum delivered 
via split injection into both the right and left deltoids. The planned schedule is 5 
total vaccinations at months zero, two, four, eight, and twelve.  
As of September 7, 2022, the study is ongoing and all 13 participants have 
received the first vaccination, 10 participants have received the second 
vaccination, 9 participants have received the third vaccination, 9 participants have 
received the fourth vaccination, and 6 participants have received the fifth 
vaccination. Five participants have discontinued further vaccinations, 1 due to a 
panic attack after the first injection (this participant had a history of panic attacks 
before being part of the study), 3 due to reactogenicity events and 1 was lost to 
follow-up. Out of these 5, 2 terminated from the study early (panic attack and lost 
to follow-up) and 3 have remained in the study for follow-up. 
All participants experienced at least some local reactogenicity during the trial, 
mostly mild to moderate. One (1) participant experienced severe pain/tenderness 
in both the right and left injection sites 3 days following the fourth vaccination, 
though it lasted only one day. 
All participants reported some systemic reactogenicity during the course of the 
trial to date, mostly mild to moderate. For example, 11 of 13 participants 
experienced systemic reactogenicity after the first dose. Five (5) participants 
reported Grade 3 (severe) systemic reactogenicity during the trial through 
September 7, 2022. One (1) of these 5 participants received a subsequent 
vaccination without any Grade 3 reactogenicity, one (1) experienced an additional 
repeat Grade 3 systemic reactogenicity symptom, one (1) has not yet received a 
subsequent vaccination, and two (2) declined to receive additional vaccinations 
after their first Grade 3 systemic reactogenicity event. All Grade 3 events resolved 
within the 7-day reactogenicity period; the longest duration for severe 
reactogenicity was 2 days.  
There have been no related SAEs, AESIs, or deaths as of September 7, 2022. 

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4.5.4 
Clinical studies of the proposed product combination 
No previous clinical studies of BG505 SOSIP.664 gp140 with any of the 
proposed adjuvants (GLA-LSQ, CpG 1018 + Alum, 3M-052-AF + Alum, or 
Alum) have been performed. 
HVTN 137 (NCT04177355): HVTN 137 Part A is a first-in-human, double-
blinded, dose-escalation study testing the combination of 100-mcg BG505 
SOSIP.664 gp140 with 3M-052-AF at 2 doses, including 1 mcg (Group 1) and 5 
mcg (Group 2), both combined with 500-mcg Alum. The study is ongoing and 
remains blinded to within-group treatment assignment. As of October 18, 2021, 
both the 1-mcg 3M-052-AF group (6 participants total; 5 receiving 
protein/adjuvant, 1 receiving placebo) and the 5-mcg 3M-052-AF group (11 
participants total; 10 receiving protein/adjuvant, 1 receiving placebo) completed 
enrollment. Part A of the initial protocol specified that participants in Groups 1 
and 2 would receive 2 total doses, 1 at month zero and the other at month two. 
Five out of 6 participants received 2 doses of the 1-mcg dose (1 participant 
discontinued for reasons unrelated to vaccination) and 10 out of 11 participants 
received 2 doses of the 5-mcg dose. One participant in the 5-mcg dose group 
(Group 2) decided to discontinue vaccination due to Grade-3 induration/erythema 
first noted on Day 8 postvaccination. The maximum size of both the induration 
and erythema was measured at 17 x 17 cm on Day 8 (Grade 3). The erythema 
resolved over 3 days and the induration subsided to less than 5 cm on Day 11 
(Grade 1). The induration was measured at 2 x 2 cm on Day 14 but did not 
completely resolve until 41 days post injection. At no point was the 
pain/tenderness greater than mild, and the participant continued to work. It is 
unknown at present whether this participant received placebo or study product. 
Another participant in Group 2 experienced 2 days of Grade-3 induration and 
erythema from Days 6-7 postvaccination that resolved completely by Day 8. In 
consultation with the Protocol Safety Review Team, the participant did receive 
the second dose, which was uneventful. In addition, 4 participants reported Grade-
3 systemic reactogenicity events. 
The protocol was amended and participants in Groups 1 and 2 were given the 
option to receive a third dose for 3 total doses. Nine (out of 17) participants 
elected to receive a third dose. There were no unsolicited Grade-3 or -4 AEs and 
no related SAEs, AESIs, or deaths in either group after this third dose. Both local 
and systemic reactogenicity were similar between all 3 doses in participants who 
received 3 doses in Part A.  
HVTN 137 Part B is evaluating the safety and immunogenicity of 100-mcg 
BG505 SOSIP.664 gp140 in combination with 3 TLR agonists, including 5-mcg 
3M-052 AF + 500-mcg Alum, and Alum alone. Enrollment is now complete and 
88 participants have been enrolled. Of these 88 participants, 20 have been 
randomized to the 3M-052-AF + Alum group. All 88 participants have received at 
least two doses and, as of June 7th, 81 have received the third dose. Given that the 

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trial remains blinded across the 4 treatment arms, interpretation of the blinded 
safety data from HVTN 137 Part B is not possible, but there have been no related 
SAEs, AESIs, deaths, or unplanned study pauses. No additional grade 3 local 
reactogenicity events have been observed. 
Overall, BG505 SOSIP.664 with 3M-052-AF + Alum was generally well 
tolerated, with no unsolicited Grade-3 or -4 AEs; no related SAEs, AESIs, or 
deaths; and no unplanned study pauses. Other than the persistent erythema in one 
of the HVTN 137 Part A Group 2 participants described above, all reactogenicity 
symptoms resolved within 14 days and generally within 7 days. For more detailed 
information, please see the IB. 
HVTN 300 (NCT04915768): Refer to Section 4.5.3 for more information. 
4.5.5 
Clinical studies of Trimer 4571 
A summary of the clinical studies for Trimer 4571 with Alum is shown in Table 
4-13.  
VRC-018: Data on the safety and immunogenicity of Trimer 4571 + Alum from 
VRC 018 are available. As of August 2021, final data from this study are 
available. No related SAEs, related grade 4 AEs, or related MAAEs were reported 
or other unexpected reactions, and no study pause criteria were met at any time. 
The immunologic assays and analysis for this study are ongoing.  
NIAID- 19-I-0069: As of January 5, 2022, enrollment in the study is ongoing, 
with 12 participants receiving Trimer 4571 with Alum adjuvant. The dose was 
administered as a boost and was generally well tolerated. No SAEs were reported, 
and no adverse events resulted in study product discontinuation, including no 
SUSARs. 
For additional information, see the Investigator’s Brochure (IB). 

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Table 4-13 Clinical studies for Trimer 4571 with Alum 
Study 
ClinicalTrials.gov 
NCT # / Study 
Status 
Participant 
HIV status 
Number 
receiving 
Trimer 
4571 + 
Alum 
Route /  
Dose 
Schedule 
Safety data 
(ClinicalTrials.gov) 
VRC 018 
NCT03783130 / 
Completed 
Negative 
16 
IM or SC at 100- 
or 500-mcg 
Trimer and 500-
mcg Alum 
0, 2, 5 
months 
No serious adverse 
events 
NIAID 19-I-
0069 
NCT03878121 / 
Enrolling 
Negative 
Max 100 
IM at 500-mcg 
Trimer with 500-
mcg Alum 
Boost post 
adenovirus 
vector prime 
As of Jan 5, 2022, 12 
participants have 
received study product. 
No SAEs, no SUSARs 
PI: M 
Choudhary, 
Univ of 
Pittsburg 
NCT04985760 / 
Enrolling 
Positive 
24 
IM at 100- or 
500-mcg Trimer 
and 500-mcg 
Alum 
0, 2, 5 
months 
As of Jan 1, 2022, 5 
participants have 
received Trimer 4571. 
No related SAES, no 
SUSARs 

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4.6 
Potential risks of study products and administration 
Table 4-14 Summary of potential risks of study products and administration 
Common 
• 
Mild to moderate injection site pain, tenderness, erythema, or 
swelling/induration/edema 
• 
Malaise/fatigue, myalgia, or headache in the first few days following 
injection 
• 
A vaccine-induced positive HIV antibody test result 
Less common 
• 
Severe injection site pain or tenderness 
• 
Fever, chills, flu-like syndrome, arthralgia, rash, nausea, or dizziness in the 
first few days following injection  
• 
Vasovagal reaction/lightheadedness/dizziness related to the injection 
procedure 
• 
Transient changes in clinical laboratory values 
• 
Injection site hematoma, bruising/ecchymosis, other transient lesions, 
itching, or bleeding related to the injection procedure 
Uncommon or rare 
• 
Severe localized injection site reaction, such as sterile abscess or secondary 
bacterial infection  
• 
Allergic reaction, including rash, urticaria, angioedema, bronchospasm, or 
anaphylaxis 
• 
Muscle damage at the injection site 
Theoretical risks 
• 
Autoimmune disease  
• 
Effects on a participant’s response to an approved HIV vaccine 
administered in the future 
• 
Effects on susceptibility to HIV, if the participant is exposed to HIV  
• 
Effects on the course of HIV infection/disease, if the participant is infected 
with HIV 
• 
Effects on the fetus and on pregnancy 

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5 
Objectives and endpoints 
5.1 
Objectives and endpoints for Part A 
5.1.1 
Primary objectives and endpoints for Part A 
Primary objective 1:  
To evaluate the safety and tolerability of intramuscular (IM) administration of 
BG505 SOSIP.664 gp140 with 3M-052-AF + Alum 
Primary endpoint 1:  
Signs and symptoms of local and systemic reactogenicity, laboratory measures of 
safety, adverse events (AEs), expedited AEs (EAEs), and AEs of special interest 
(AESIs)  
5.1.2 
Secondary objectives and endpoints for Part A 
Secondary objective 1:  
To evaluate and compare immune responses elicited by BG505 SOSIP.664 gp140 
with each 3M-052-AF +Alum dose regimen 
Secondary endpoints 1:  
Response rate and magnitude of serum antibody neutralization of autologous 
(HIV-1 BG505.664) and other heterologous tier 2 HIV-1 strains as measured by 
the TZM-bl assay 2 weeks after the second and after the optional third 
vaccination, if available 
Response rate and magnitude of serum IgG binding antibodies to BG505 
SOSIP.664 gp140 as measured by BAMA 2 weeks after the second and after the 
optional third vaccination, if available 
Response rate and magnitude of IgG+ B cells binding to BG505 SOSIP.664 
gp140 tetramers as measured by multiparameter flow cytometry 2 weeks after the 
second and after the optional third vaccination, if available 
Percent HIV Env-specific CD4+ T cells in blood as measured by multiparameter 
flow cytometry 2 weeks after the second and after the optional third vaccination, 
if available 

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5.1.3 
Exploratory objectives for Part A 
Exploratory objective 1: 
To further evaluate immunogenicity of each vaccine regimen, additional 
immunogenicity assays may be performed in a subset of participants, including on 
samples from other timepoints, based on the HVTN Laboratory Assay Algorithm 
Exploratory objective 2: 
To conduct analyses related to furthering the understanding of HIV, immunology, 
vaccines, adjuvant effects, and clinical trial conduct 
5.2 
Objectives and endpoints for Part B 
5.2.1 
Primary objectives and endpoints for Part B 
Primary objective 1:  
To evaluate the safety and tolerability of intramuscular (IM) administration of 
BG505 SOSIP.664 gp140 with the following adjuvants: CpG 1018 + Alum, 3M-
052-AF + Alum, GLA-LSQ, or Alum alone 
Primary endpoint 1:  
Signs and symptoms of local and systemic reactogenicity, laboratory measures of 
safety, adverse events (AEs), expedited AEs, and AEs of special interest (AESIs)  
Primary objective 2:  
To evaluate and compare the neutralizing antibody response induced by BG505 
SOSIP.664 gp140 with different adjuvants (CpG 1018 + Alum, 3M-052-AF + 
Alum, GLA-LSQ, or Alum alone) 
Primary endpoint 2:  
Response rate and magnitude of serum antibody neutralization of autologous 
(HIV-1 BG505) and other heterologous tier 2 HIV-1 strains as measured by TZM-
bl assay 2 weeks after the second and third vaccinations 
5.2.2 
Secondary objectives and endpoints for Part B 
Secondary objective 1: 
To evaluate and compare the durability of neutralizing antibody responses elicited 
by BG505 SOSIP.664 gp140 with various adjuvants (CpG 1018 + Alum, 3M-
052-AF + Alum, GLA-LSQ, or Alum) 

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Secondary endpoint 1: 
Response rate and magnitude of serum antibody neutralization of autologous 
(HIV-1 BG505) and other heterologous tier 2 HIV-1 strains as measured by TZM-
bl assay 6 and 12 months post third vaccination 
Secondary objective 2: 
To evaluate and compare the peak and durability of serum binding antibody 
responses elicited by BG505 SOSIP.664 gp140 HIV-1 Env protein with various 
adjuvants (CpG 1018 + Alum, 3M-052-AF + Alum, GLA-LSQ, or Alum) 
Secondary endpoints 2: 
Response rate, magnitude, and breadth of IgG binding antibody responses to HIV 
BG505 SOSIP.664 gp140, and HIV-1 gp120 and gp140 variant strains (to 
determine off-target non-neutralizing Abs) as measured by BAMA 2 weeks after 
the second vaccination and 2 weeks, 6 months, and 12 months after the third 
vaccination 
Secondary objective 3: 
To evaluate and compare the peak and durability of BG505 SOSIP.664 gp140-
specific B cells elicited by BG505 SOSIP.664 gp140 with various adjuvants (CpG 
1018 + Alum, 3M-052-AF + Alum, GLA-LSQ, or Alum) 
Secondary endpoint 3: 
Response rate and magnitude of memory IgG+ B cells binding to BG505 
SOSIP.664 gp140 tetramers as measured by multiparameter flow cytometry 2 
weeks after the second vaccination and 2 weeks, 6 months, and 12 months after 
the third vaccination 
Response rate and magnitude of BG505 SOSIP.664 gp140-specific plasmablasts 
as measured by multiparameter flow cytometry 1 week after the second and third 
vaccinations 
Secondary objective 4: 
To evaluate Env-specific CD4+ T-helper subpopulations, phenotypes and 
functions elicited by BG505 SOSIP.664 gp140 with various adjuvants (CpG 1018 
+ Alum, 3M-052-AF + Alum, GLA-LSQ, or Alum) 
Secondary endpoint 4: 
Percent HIV Env-specific cytokine-expressing CD4+ T cells in blood by 
intracellular cytokine staining (ICS) multiparameter flow cytometry and 

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polyfunctional subset analysis 2 weeks after the second vaccination and 2 weeks, 
6 months, and 12 months after the third vaccination 
Secondary objective 5: 
To evaluate innate immune responses and baseline predictors, compare the innate 
immune responses elicited by BG505 SOSIP.664 gp140 with various adjuvants 
(CpG 1018 + Alum, 3M-052-AF + Alum, GLA-LSQ, or Alum) after the first 
vaccination, and correlate with adaptive immune responses 
Secondary endpoints 5: 
Alterations in blood leukocyte populations during the innate response (day 1, 3 
and 7) relative to prevaccine levels (day 0) 
Alterations in RNAseq expression of leukocyte and/or immune cells (lymphocyte 
populations, natural killer (NK) cells, dendritic cell (DC) subsets, monocytes 
subsets, and granulocytes) (days 1, 3, and 7) relative to prevaccine levels (day 0) 
Alterations of concentrations of immune cytokines and chemokines in serum 
samples postvaccination (days 1, 3, 7) relative to prevaccine levels (day 0) 
Secondary objective 6: 
To characterize systemic inflammatory markers among participants with moderate 
to severe reactogenicity after any vaccination  
Secondary endpoint 6 
Blood cell subpopulation dynamics by multiparameter flow cytometry, gene 
expression alterations by RNAseq/transcripts and soluble cytokine/inflammatory 
mediator alterations comparing day of last vaccination and day of visit for 
moderate to severe reactogenicity 
5.2.3 
Exploratory objectives for Part B 
Exploratory objective 1: 
To further characterize antibody responses (eg, IgA/IgG subclass binding, epitope 
mapping, Ab avidity, infected cell binding, linear peptide array) 
Exploratory objective 2: 
To characterize Fc-mediated antibody functions (eg, fragment crystallizable 
receptor [FcR] array, antibody-dependent cellular phagocytosis [ADCP], 
antibody-dependent neutrophil phagocytosis [ADNP], antibody-dependent 
cellular cytotoxicity [ADCC], and/or complement binding/deposition) 

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Exploratory objective 3: 
To further characterize neutralizing antibody responses using diagnostic mutants 
of HIV-1 Env pseudotyped viruses in the TZM-bl assay  
Exploratory objective 4: 
To analyze the B cell repertoire including somatic hypermutation, affinity 
maturation, CDRH3 length, and other signatures of bnAb class epitopes 
Exploratory objective 5: 
To apply systems biology approaches (eg, RNAseq, LC-MS) to examine 
transcriptomic, and metabolomic and/or proteomic profiles of innate and adaptive 
immune responses 
Exploratory objective 6: 
To characterize Env-specific B and CD4+ T cells (including Tfh/pTfh) and 
antigen receptor sequences using samples such as PBMC, lymph node fine needle 
aspirates, bone marrow aspirates, or leukapheresis 
Exploratory objective 7: 
To assess polyclonal serum Ab (Fab) binding to Env epitopes using electron 
microscopic imaging  
Exploratory objective 8: 
To measure Env-specific antibody levels in mucosal secretions and tissues using a 
quantitative immunoassay and/or immunohistochemistry (IHC) 
Exploratory objective 9: 
To identify the regions and epitopes of the BG505 SOSIP.664 gp140 protein 
targeted by CD4+ T cells in response to vaccination 
Exploratory objective 10: 
To further evaluate immunogenicity of each vaccine regimen, additional 
immunogenicity assays may be performed in a subset of participants, including on 
samples from other timepoints, based on the HVTN Laboratory Assay Algorithm 
Exploratory objective 11: 
To conduct analyses related to furthering the understanding of HIV, immunology, 
vaccines, adjuvant effects, and clinical trial conduct 

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5.3 
Objectives and endpoints for Part C 
5.3.1 
Primary objectives and endpoints for Part C 
Primary objective 1: 
To evaluate the safety and tolerability of IM administration of Trimer 4571 
(BG505 SOSIP.664 DS gp140) with 3M-052-AF + Alum. 
Primary endpoint 1: 
Signs and symptoms of local and systemic reactogenicity and laboratory measures 
of safety, AEs, expedited AEs, and AESIs. 
Primary objective 2: 
To evaluate the neutralizing antibody response induced by Trimer 4571 (BG505 
SOSIP.664 DS gp140) with 3M-052-AF + Alum. 
Primary endpoint 2: 
Response rate and magnitude of serum antibody neutralization of autologous 
(HIV-1 BG505) and other heterologous tier-2 HIV-1 strains, as measured by 
TZM-bl assay 2 weeks after the second and third vaccinations. 
5.3.2 
Secondary objectives and endpoints for Part C 
Secondary objective 1: 
To test whether a 3-mcg dose of 3M-052-AF + Alum is sufficient to generate 
autologous serum antibody neutralization (HIV-1 BG505) and other heterologous 
tier-2 HIV-1 strains, as measured by TZM-bl assay 2 weeks after the second and 
third vaccinations. 
Secondary endpoint 1: 
Response rate and magnitude of serum antibody neutralization of autologous 
(HIV-1 BG505) and other heterologous tier-2 HIV-1 strains, as measured by 
TZM-bl assay 2 weeks after the second and third vaccinations, comparing the 5-
mcg dose of the 3M-052-AF + Alum with the 3-mcg dose of 3M-052-AF + Alum. 
Secondary objective 2: 
To evaluate and compare the peak and durability of serum binding antibody 
responses elicited by BG505 SOSIP.664 gp140 adjuvanted with 3 mcg of 3M-
052-AF+Alum, and by Trimer 4571 adjuvanted with 5 mcg of 3M-052-AF+Alum 
with Part B groups 

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Secondary endpoints 2: 
Response rate, magnitude, and breadth of IgG binding antibody responses to HIV 
BG505 SOSIP.664 gp140, Trimer 4571, and HIV-1 gp120 and gp140 variant 
strains (to determine off-target non-neutralizing Abs) as measured by BAMA 2 
weeks after the second vaccination and 2 weeks, 6 months, and 12 months after 
the third vaccination 
Secondary objective 3: 
To evaluate and compare the peak and durability of BG505 SOSIP.664 gp140-
specific B cells elicited by BG505 SOSIP.664 gp140 adjuvanted with 3 mcg of 
3M-052-AF+Alum, and by Trimer 4571 adjuvanted with 5 mcg of 3M-052-
AF+Alum with Part B groups 
Secondary endpoint 3: 
Response rate and magnitude of memory IgG+ B cells binding to BG505 
SOSIP.664 gp140 tetramers as measured by multiparameter flow cytometry 2 
weeks after the second vaccination and 2 weeks, 6 months, and 12 months after 
the third vaccination 
Response rate and magnitude of BG505 SOSIP.664 gp140 antigen-specific 
plasmablasts as measured by multiparameter flow cytometry 1 week after the 
second and third vaccinations 
Secondary objective 4: 
To evaluate Env-specific CD4+ T-helper subpopulations, phenotypes and 
functions elicited by BG505 SOSIP.664 gp140 adjuvanted with 3 mcg of 3M-
052-AF+Alum, and by Trimer 4571 adjuvanted with 5 mcg of 3M-052-AF+Alum 
Secondary endpoint 4: 
Percent HIV Env-specific cytokine-expressing CD4+ T cells in blood by 
intracellular cytokine staining (ICS) multiparameter flow cytometry and 
polyfunctional subset analysis 2 weeks after the second vaccination and 2 weeks, 
6 months, and 12 months after the third vaccination 
Secondary objective 5: 
To evaluate innate immune responses and baseline predictors, compare the innate 
immune responses elicited by BG505 SOSIP.664 gp140 adjuvanted with 3 mcg of 
3M-052-AF+Alum, and by Trimer 4571 adjuvanted with 5 mcg of 3M-052-
AF+Alum after the first vaccination, and correlate with adaptive immune 
responses 

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Secondary endpoints 5: 
Alterations in blood leukocyte populations during the innate response (day 1, 3 
and 7) relative to prevaccine levels (day 0) 
Alterations in RNAseq expression of leukocyte and/or immune cells (lymphocyte 
populations, natural killer (NK) cells, dendritic cell (DC) subsets, monocytes 
subsets, and granulocytes) (days 1, 3, and 7) relative to prevaccine levels (day 0) 
Alterations of concentrations of immune cytokines and chemokines in serum 
samples postvaccination (days 1, 3, 7) relative to prevaccine levels (day 0) 
Secondary objective 6: 
To characterize systemic inflammatory markers among participants with moderate 
to severe reactogenicity after any vaccination  
Secondary endpoint 6 
Blood cell subpopulation dynamics by multiparameter flow cytometry, gene 
expression alterations by RNAseq/transcripts and soluble cytokine/inflammatory 
mediator alterations comparing day of last vaccination and day of visit for 
moderate to severe reactogenicity 
5.3.3 
Exploratory objectives for Part C 
Exploratory objective 1: 
To further evaluate immunogenicity of each vaccine regimen, additional 
immunogenicity assays may be performed in a subset of participants, including on 
samples from other timepoints, based on the HVTN Laboratory Assay Algorithm 
Exploratory objective 2: 
To conduct analyses related to furthering the understanding of HIV, immunology, 
vaccines, adjuvant effects, and clinical trial conduct 

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6 
Statistical considerations 
6.1 
Accrual and sample size calculations 
Recruitment will target enrolling 127 healthy, HIV-uninfected adult participants; 
115 vaccinees and 12 placebo recipients. 
Part A is a dose-escalation study; two doses of the 3M-052-AF adjuvant will be 
studied in 17 participants (5 vaccinees and 1 placebo in the low-dose group; 10 
vaccinees and 1 placebo in the higher dose group). Enrollment to the higher dose 
group will be triggered when safety in the lower dose group is deemed acceptable. 
Part B is the adjuvant comparison study; 88 participants will be randomized to 
one of four groups, with 20 participants randomized to vaccine and 2 to placebo 
within each group. Section 11.3.2 of the protocol describes the criteria for 
advancing to Part B based on the Part A data. Part C augments Part B with data on 
a “medium” dose of the 3M-052 adjuvant (3 mcg as compared to 5 mcg studied in 
Part B) and with data on a next-generation BG505 trimer (Trimer 4571 versus 
BG505 SOSIP.664 studied in Part B). The sample-size rationale is described 
separately for Parts A, B, and C. 
Since enrollment is concurrent with receiving the first study vaccination, all 
participants will provide some safety data. However, for immunogenicity 
analyses, it is possible that data may be missing for various reasons, such as 
participants terminating from the study early, problems in shipping specimens, 
low cell viability of processed PBMCs or high assay background. 
Immunogenicity data from 17 phase 1 and 2 phase 2a HVTN vaccine trials, which 
began enrolling after June 2005 (data as of September 2014), indicate that 10% is 
a reasonable estimate for the rate of missing data at Month 2.5 and 6.5, and 15% 
is a reasonable estimate at Month 18. For this reason, the sample size calculations 
in Section 6.1.3 account for 10% and 15% of enrolled participants having missing 
data for the primary immunogenicity and durability endpoints, respectively.  
6.1.1 
Sample size calculations for safety (Part A) 
The purpose of Part A is to select the 3M-052-AF adjuvant dose, by identifying 
potential safety concerns associated with product administration. The ability of 
the study to detect SAEs (see Section 11.2.3) can be expressed by the true event 
rate above which at least 1 SAE would likely be observed and the true event rate 
below which no events would likely be observed. Specifically, for the low-dose 
vaccine arm (n = 5), there is a 90% chance of observing at least 1 event if the true 
rate of such an event is 37% or more; and there is at least a 90% chance of 
observing no events if the true rate is 1% or less. For the high-dose vaccine arm (n 
= 10), there is at least a 90% chance of observing at least 1 event if the true rate of 
such an event is 21% or more; and there is a 90% chance of observing no events if 
the true rate is 1% or less. For the two vaccine arms combined (n = 15), there is at 
least a 90% chance of observing at least 1 event if the true rate of such an event is 

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14.3% or more; there is a 90% chance of observing no events if the true rate is 
0.5% or less. As a reference, in HVTN vaccine trials from April 2008 through 
March 2018, about 1.74% of participants who received placebos experienced an 
SAE. 
Binomial probabilities of observing 0, 1 or more, and 2 or more events among 
arms of size 5 and 10 are presented in Table 6-1 for a range of possible true 
adverse event rates. These calculations provide a more complete picture of the 
sensitivity of the Part A study design to identify potential safety problems with 
the 3M-052-AF–adjuvanted vaccine. 
Table 6-1 Probability of observing 0 events, 1 or more events, and 2 or more events, among 
arms of size 5 and 10, for different true event rates 
True event rate (%) 
Pr(0/5) 
Pr(1+/5) 
Pr(2+/5) 
Pr(0/10) 
Pr(1+/10) 
Pr(2+/10) 
1 
95.1 
4.9 
0.1 
90.4 
9.6 
0.4 
4 
81.5 
18.5 
1.5 
66.5 
33.5 
5.8 
10 
59 
41 
8.1 
34.9 
65.1 
26.4 
20 
32.8 
67.2 
26.3 
10.7 
89.3 
62.4 
30 
16.8 
83.2 
47.2 
2.8 
97.2 
85.1 
40 
7.8 
92.2 
66.3 
0.6 
99.4 
95.4 
6.1.2 
Sample size calculations for safety (Part B) 
The goal of the safety evaluation for Part B of this study is to identify safety 
concerns associated with administration of one or more vaccine regimens. 
Specifically, for each vaccine arm of Part B (n = 20), there is a 90% chance of 
observing at least 1 event if the true rate of such an event is 11% or more; and 
there is a 90% chance of observing no events if the true rate is 0.5% or less. For 
the four vaccine arms combined (n = 80), there is a 90% chance of observing at 
least 1 event if the true rate of such an event is 2.9% or more; and there is a 90% 
chance of observing no events if the true rate is 0.1% or less.  
Binomial probabilities of observing 0, 1 or more, and 2 or more events among 
arms of size 20 and 80 are presented in Table 6-2 for a range of possible true 
adverse event rates. These calculations provide a more complete picture of the 
sensitivity of the Part B study design to identify potential safety problems with the 
four vaccine regimens. 

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Table 6-2 Probability of observing 0 events, 1 or more events, and 2 or more events, among 
arms of size 20 and 80, for different true event rates 
True event rate (%) 
Pr(0/20) 
Pr(1+/20) 
Pr(2+/20) 
Pr(0/80) 
Pr(1+/80) 
Pr(2+/80) 
1 
81.8 
18.2 
1.7 
44.8 
5.2 
19.1 
4 
44.2 
55.8 
19.0 
3.8 
96.2 
83.5 
10 
12.2 
87.8 
60.8 
0 
100 
99.8 
20 
1.2 
98.8 
93.1 
0 
100 
100 
30 
0.1 
99.9 
99.2 
0 
100 
100 
An alternative way of describing the statistical properties of the study design is in 
terms of the 95% confidence interval for the true rate of an adverse event based 
on the observed data. Table 6-3 shows the 2-sided 95% confidence intervals for 
the probability of an event based on a particular observed rate. Calculations are 
done using the score test method (84). If none of the 80 participants receiving a 
vaccine regimen experience a safety event, the 95% 2-sided upper confidence 
bound for the true rate of such events in the total vaccinated population is 4.6%. 
For each individual vaccine arm (n = 20), the 2-sided upper confidence bound for 
this rate is 16.1%. 
Table 6-3 Two-sided 95% confidence intervals based on observing a particular rate of safety 
endpoints for arms of size n1 and n2 
Observed event rate 
95% Confidence interval (%) 
0/20 
(0%, 16.1%) 
1/20 
(0.9%, 23.6%) 
2/20 
(2.8%, 30.1%) 
 
 
0/80 
(0%, 4.6%) 
1/80 
(0.2%, 6.7%) 
2/80 
(0.7%, 8.7%) 
6.1.3 
Sample size calculations for immunogenicity (Part B) 
Immunogenicity sample size calculations allow for a 10% rate of missing 
immunogenicity data at Month 2.5 and 6.5 (n = 18 for analysis) and 15% rate of 
missing immunogenicity data at Months 12 and 18 (n = 17 for analysis).  
The first goal is to evaluate immune response rates based on data from the 
primary TZM-bl neutralizing antibody assay among vaccinees. The precision with 
which the true response rate can be estimated from the observed data depends on 
the true underlying response rate and the sample size. Two-sided 95% confidence 
intervals for the response rate based on observing a particular rate of responses in 
the vaccinees is shown in Table 6-4. Calculations are done using the score test 
method (84).  

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Table 6-4 Two-sided 95% confidence intervals for the true response rate based on observing 
a particular rate of responses in the vaccinees (n = 18) 
No. of responses 
Observed response rate (%) 
95% Confidence interval 
4/18 
22.2 
(9.0, 45.2) 
6/18 
33.3 
(16.3, 56.3) 
8/18 
44.4 
(24.6, 66.3) 
10/18 
55.6 
(33.7, 75.4) 
12/18 
66.7 
(43.7, 83.7) 
14/18 
77.8 
(54.8, 91.0) 
15/18 
83.3 
(60.8, 94.2) 
16/18 
88.9 
(67.2, 96.9) 
17/18 
94.4 
(74.2, 99.0) 
As shown in Table 6-5, there is limited power for a formal comparison of 
immunogenicity response rates between vaccine arms of size n = 20. For either 
80% or 90% power, the sizes of differences that the trial is powered to detect are 
large. These calculations use a Fisher’s exact 2-sided test with a Type I error rate 
of 0.05. However, the study is adequately powered to detect the differences seen 
in the CAVD 641 study in rhesus macaques led by Bali Pulendran. Rates of 
autologous tier 2 neutralizing antibody responses at week 26 (the peak timepoint) 
were compared between arms with Alum-3M-052 or GLA-LSQ adjuvant, both 
with BG505-SOSIP protein. The large difference in response rates—50% vs. 
100%—could be detected with 97% power. 
Table 6-5 Power for comparison of response rates between 2 arms (n1 = 18, n2 = 18) 
True response rate Arm 1 
(%) 
Minimum true response rate in Arm 2 in order to detect a 
difference 
80% power 
90% power 
10 
58 
65 
20 
71 
77 
30 
81 
87 
40 
89 
94 
50 
95 
99 
Power for comparing the magnitude of immune responses between pairs of arms 
with different adjuvants is first calculated using binding antibody data from the 
aforementioned HEPLISAV study. Engerix, an HBV vaccine formulated with 
Alum, was compared to HEPLISAV, the same HBV vaccine formulated with 
CpG 1018. With n = 18 vaccinees per arm, the current study has 100% power to 
detect the difference in geometric mean immune response seen in the HEPLISAV 
study at Week 28 (the peak timepoint) (79.7 mIU/mL vs. 206.1 mIU/mL), 
assuming based on the HEPLISAV study that the group with higher geometric 
mean has a smaller standard deviation (51.38 mIU/mL vs. 6.04 mIU/mL), using a 
0.025-level one-sided Wilcoxon rank sum test. In addition, power is also 100% 
for detecting the difference seen between adjuvants at Week 52 (the durability 
timepoint), based on the HEPLISAV data (geometric means 19.0 vs. 131.0 
mIU/mL and standard deviations 34.57 vs. 6.92 mIU/mL).  

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In addition, “generic” power calculations inform the power of the study to 
compare immune response magnitudes between arms. These presume a 
continuous immune response, transformed to a 1-standard deviation scale, and a 
mean shift in scaled immune response between arms. Table 6-6 shows the power 
for comparing immune responses between pairs of arms with different adjuvants, 
separately at Months 2.5 and 6.5 (n = 18 per arm) and Months 12 or 18 (durability 
= 17 per arm) timepoints. Observe that the study is powered to detect moderate 
1-standard deviation differences in immune responses between adjuvants at the 
early timepoints and 1.1-standard-deviation differences at the durability 
timepoints.  
Table 6-6 Power for comparing the magnitude of a generic immune response between arms. 
Immune responses are compared using 0.025-level one-sided Wilcoxon rank sum tests. 
Continuous immune responses are assumed to follow a normal distribution, transformed to a 1-
standard deviation scale, with a mean of zero in one arm and the same standard deviation in the 
two arms. To allow for missing immunogenicity data, analyses include 17 or 18 subjects in each 
arm. Power is based on 1000 simulations. 
Mean difference between arms 
(in standard-deviation units) 
Power, n = 18 per arm 
Power, n = 17 per arm 
0.8 SD 
63% 
61% 
0.9 SD 
71% 
69% 
1.0 SD 
81% 
78% 
1.1 SD 
85% 
85% 
1.2 SD 
92% 
90% 
1.3 SD 
97% 
95% 
In addition, we assessed the ability of the study to rank and select the adjuvant 
with the highest immune response at a given timepoint. Table 6-7 shows the 
probability of correctly selecting the adjuvant with the highest mean immune 
response at Month 6.5, as a function of the mean in the arm with next-lowest 
mean immune response. Calculations again assume that immune responses have 
been transformed to the 1-standard deviation scale. The results show that the 
study is sufficiently sized to correctly rank adjuvant arms, assuming the top two 
arms have a mean difference of at least 0.5 standard-deviations.  
Table 6-7 Probability of correct ranking. Probability of correctly selecting the adjuvant with the 
highest mean immune response at Month 6.5, based on a generic standard-deviation-scaled 
continuous immune response. Probability is shown as a function of the mean immune response in 
the next-best arm. To allow for missing immunogenicity data, analyses include 18 subjects in each 
arm. Calculations assume all arms below the best have a mean immune response equal to that of 
the next-best arm and thus the results are conservative. 
Mean difference, best – next-best 
Probability of correct ranking 
0.1 SD 
0.38 
0.2 SD 
0.52 
0.3 SD 
0.65 
0.4 SD 
0.75 
0.5 SD 
0.82 
0.6 SD 
0.92 

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6.1.4 
Sample size calculations for safety (Part C) 
The goal of the safety evaluation for Part C of this study is to identify safety 
concerns associated with administration of 1 or more vaccine regimens studied in 
Part C. Specifically, for each vaccine arm of Part C (n = 10), there is a 90% 
chance of observing at least 1 event if the true rate of such an event is 20.6% or 
more and there is a 90% chance of observing no events if the true rate is 1% or 
less. 
Binomial probabilities of observing 0 events, 1 or more events, and 2 or more 
events among arms of size 10 are presented in Table 6-8 for a range of possible 
true adverse event rates. These calculations provide a more complete picture of 
the sensitivity of the Part C study design to identify potential safety problems with 
the two vaccine regimens. 
Table 6-8 Probability of observing 0 events, 1 or more events, and 2 or more events among 
arms of size 10 for different true event rates 
True event rate (%) 
Pr (0/10) 
Pr (1+/10) 
Pr (2+/10) 
1 
90.4 
9.6 
0.4 
4 
66.5 
33.5 
5.8 
10 
34.9 
65.1 
26.4 
20 
10.7 
89.3 
62.4 
30 
2.8 
97.2 
85.1 
An alternative way of describing the statistical properties of the study design is in 
terms of the 95% confidence interval (CI) for the true rate of an adverse event 
based on the observed data. Table 6-9 shows the 2-sided 95% CIs for the 
probability of an event based on a particular observed rate. Calculations are done 
using the score test method (84). If none of the 10 participants receiving a vaccine 
regimen experience a safety event, the 95% 2-sided upper confidence bound for 
the true rate of such events in the total vaccinated population is 27.8%. 
Table 6-9 Two-sided 95% confidence intervals based on observing a particular rate of safety 
endpoints for arms of size n1 and n2 
Observed event rate 
95% Confidence interval (%) 
0/10 
(0%, 27.8%) 
1/10 
(1.8%, 40.4%) 
2/10 
(5.7%, 51%) 
6.1.5 
Sample size calculations for immunogenicity (Part C) 
Immunogenicity sample-size calculations allow for a 10% rate of missing 
immunogenicity data at Month 2.5 and 6.5 (n = 9 for analysis). 

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The first goal is to evaluate immune response rates based on data from the 
primary TZM-bl neutralizing antibody assay among vaccinees. The precision with 
which the true response rate can be estimated from the observed data depends on 
the true underlying response rate and the sample size. Two-sided 95% CIs for the 
response rate based on observing a particular rate of responses in the vaccinees is 
shown in Table 6-10. Calculations are done using the score test method (84). 
Table 6-10 Two-sided 95% confidence intervals for the true response rate based on 
observing a particular rate of responses in the vaccinees (n = 9) 
No. of responses 
Observed response rate (%) 
95% Confidence interval 
1/9 
11.1 
(2.0, 43.5) 
2/9 
22.2 
(6.3, 54.7) 
3/9 
33.3 
(12.1, 64.6) 
4/9 
44.4 
(18.9, 73.3) 
5/9 
55.6 
(26.7, 81.1) 
6/9 
66.7 
(35.4, 87.9) 
7/9 
77.8 
(45.3, 93.7) 
8/9 
88.9 
(56.5, 98.0) 
9/9 
100.0 
(70.1, 100.0) 
As shown in Table 6-11and Table 6-12, there is limited power for a formal 
comparison of immunogenicity response rates between Parts B and C based on 
vaccine arms of size n = 10 (Parts A and C) and n = 20 (Part B). For either 80% or 
90% power, the sizes of differences that the trial is powered to detect are large. 
Table 6-11 Power for comparison of response rates between 2 arms (n1 = 9, n2 = 9) 
True response rate Arm 1 
(%) 
Minimum true response rate in Arm 2 in order to detect a 
difference 
80% power 
90% power 
10 
83 
91 
20 
92 
99 
30 
99 
N/A 
Table 6-12 Power for comparison of response rates between 2 arms (n1 = 9, n2 = 18) 
True response rate Arm 1 
(%) 
Minimum true response rate in Arm 2 in order to detect a 
difference 
80% power 
90% power 
10 
72 
90 
20 
83 
90 
30 
91 
96 
40 
92 
100 
6.2 
Randomization  
A participant’s randomization assignment will be computer generated and 
provided to the HVTN CRS pharmacist through a Web-based randomization 

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system. For Part A, B and C, participants within each dose group will be 
randomized to vaccine or placebo assignment. For Part C, Group 7 will be 
enrolled before Group 8. There will be no randomization for Groups 1 and 2 as 
they will be enrolled sequentially for dose escalation. At each institution, the 
pharmacist with primary responsibility for dispensing study products is charged 
with maintaining security of the treatment assignments (except in emergency 
situations as specified in the HVTN Manual of Operations [MOP]). 
6.3 
Blinding 
Participants and site staff (except for site pharmacists) will be blinded as to 
treatment arm assignments (ie, vaccine vs placebo) throughout the trial. In 
addition, in Part B, participants and site staff (except for site pharmacists) will be 
blinded to participant group assignments as well. Study product assignments are 
accessible to those HVTN CRS pharmacists, DAIDS protocol pharmacists and 
contract monitors, and SDMC staff who are required to know this information in 
order to ensure proper trial conduct. Any discussion of study product assignment 
between pharmacy staff and any other HVTN CRS staff is prohibited. The HVTN 
SMB members also are unblinded to treatment assignment in order to conduct 
review of trial safety.  
When a participant leaves the trial prior to study completion, the participant will 
be told he or she must wait until all participants are unblinded to learn his or her 
treatment assignment.  
In some cases, the CRS, PSRT, or study sponsor may believe unblinding of the 
site Principal Investigator (PI) and participant would be appropriate to facilitate 
the clinical management of an AE or SAE. The HVTN Unblinding MOP specifies 
procedures for emergency unblinding, and for early unblinding for medical 
reasons. 
6.4 
Statistical analyses 
This section describes the final study analyses, unblinded as to treatment arm 
assignment. All data from enrolled participants will be analyzed according to the 
initial randomization assignment regardless of how many vaccinations they 
received. In the rare instance that a participant receives the wrong treatment at a 
specific vaccination time, the Statistical Analysis Plan (SAP) will address how to 
analyze the participant’s safety data. Analyses are modified intent-to-treat in that 
individuals who are randomized but not enrolled do not contribute data and hence 
are excluded. Because of blinding and the brief length of time between 
randomization and enrollment—typically no more than 4 working days—very 
few such individuals are expected. 

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Analyses for primary endpoints will be performed using SAS and R. All other 
descriptive and inferential statistical analyses will be performed using SAS, 
StatXact, or R statistical software. 
No formal multiple comparison adjustments will be employed for multiple safety 
endpoints, multiple primary immunogenicity endpoints, or secondary endpoints. 
However, multiplicity adjustments will be made for certain immunogenicity 
assays, as discussed below, when the assay endpoint is viewed as a collection of 
hypotheses (eg, testing multiple peptide pools to determine a positive response). 
6.4.1 
Analysis variables 
The analysis variables consist of baseline participant characteristics, safety, and 
immunogenicity for primary- and secondary-objective analyses. 
6.4.2 
Baseline comparability 
Treatment arms will be compared for baseline participant characteristics using 
descriptive statistics. 
6.4.3 
Safety/tolerability analysis 
Since enrollment is concurrent with receiving the first vaccination, all participants 
will have received at least 1 vaccination and therefore will provide some safety 
data. 
6.4.3.1 
Reactogenicity 
The number and percentage of participants experiencing each type of 
reactogenicity sign or symptom will be tabulated by severity and treatment arm 
and the percentages displayed graphically by arm. For a given sign or symptom, 
each participant’s reactogenicity will be counted once under the maximum 
severity for all injection visits. In addition, to the individual types of events, the 
maximum severity of local pain or tenderness, induration or erythema, and of 
systemic symptoms will be calculated. Kruskal-Wallis tests will be used to test for 
differences in severity between arms. 
6.4.3.2 
AEs and SAEs 
AEs will be summarized using Medical Dictionary for Regulatory Activities 
(MedDRA) System Organ Class and preferred terms. Tables will show by 
treatment arm the number and percentage of participants experiencing an AE 
within a System Organ Class or within preferred term category by severity or by 
relationship to study product. For the calculations in these tables, a participant 
with multiple AEs within a category will be counted once under the maximum 
severity or the strongest recorded causal relationship to study product. Formal 
statistical testing comparing arms is not planned since interpretation of the 
magnitude of differences must rely heavily upon clinical judgment. 

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A listing of SAEs reported to the DAIDS Regulatory Support Center (RSC) 
Safety Office will provide details of the events including severity, relationship to 
study product, time between onset and last vaccination, and number of 
vaccinations received.  
6.4.3.3 
Local laboratory values  
Box plots of local laboratory values will be generated for baseline values and for 
values measured during the course of the study by treatment arm and visit. Each 
box plot will show the first quartile, the median, and the third quartile. Outliers 
(values outside the box plot) will also be plotted. If appropriate, horizontal lines 
representing boundaries for abnormal values will be plotted. 
For each local laboratory measure, summary statistics will be presented by 
treatment arm and timepoint, as well as changes from baseline for postenrollment 
values. In addition, the number (percentage) of participants with local laboratory 
values recorded as meeting Grade 1 AE criteria or above as specified in the 
Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse 
Events (see Section 11.2.2) will be tabulated by treatment arm for each 
postvaccination timepoint. Reportable clinical laboratory abnormalities without an 
associated clinical diagnosis will also be included in the tabulation of AEs 
described above. 
6.4.3.4 
Reasons for vaccination discontinuation and early study termination 
The number and percentage of participants who discontinue vaccination and who 
terminate the study early will be tabulated by reason and treatment arm. 
6.4.4 
Immunogenicity analysis 
6.4.4.1 
General approach 
For the statistical analysis of immunogenicity endpoints, data from enrolled 
participants will be used according to the initial randomization assignment 
regardless of how many injections they received. Additional analyses may be 
performed, limited to participants who received all scheduled injections per 
protocol. Assay results that are unreliable, from specimens collected outside of 
the visit window, or from HIV-infected participants postinfection are excluded. 
Since the exact date of HIV infection is unknown, any assay data from blood 
draws 4 weeks prior to an infected participant’s last seronegative sample and 
thereafter may be excluded. If an HIV-infected participant does not have a 
seronegative sample postenrollment, then all data from that participant may be 
excluded from the analysis. 
Data from placebo arms will be pooled across groups (n = 8 for analysis in Part 
B). For analyses of immunogenicity after the second vaccination, data on the 3M-
052-AF from Part A (with the MTD of the 3M-052-AF) and Part B will be 

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pooled. Otherwise, analyses of immunogenicity will be performed separately for 
Part A and Part B participants. 
Discrete categorical assay endpoints (eg, response rates) will be analyzed by 
tabulating the frequency of positive response for each assay by antigen and 
treatment arm at each timepoint for which an assessment is performed. Crude 
response rates will be presented with their corresponding 95% confidence interval 
estimates calculated using the score test method (84). Because of the small 
numbers of control participants in each group, no adjustment will be made to the 
vaccine arm estimates for the false positive rates (FPRs) in the control arms. 
Barnard or Fisher’s exact tests, as specified in the SAP, will be used to compare 
the response rates of any 2 vaccine arms, with a significant difference declared if 
the 2-sided p-value is ≤ 0.05. In general Barnard’s is preferred since under most 
circumstances it is more powerful than Fisher’s (85).  
For quantitative assay data (eg, percentage of positive cells from ICS assay), 
graphical and tabular summaries of the distributions by antigen, treatment arm, 
and timepoint will be made. For all primary and secondary immunogenicity 
endpoints, box plots and plots of estimated reverse cumulative distribution curves 
will be used for graphical display of all of the study arms. Typically, the results 
will be shown for each vaccine arm and for the pooled placebo group.  
The difference between arms at a specific timepoint will be tested with a 
nonparametric Wilcoxon rank sum test if the data are not normally distributed and 
with a 2-sample t-test if the data appear to be normally distributed. Individual 
tests comparing the 6 pairs of vaccine arms will be performed unless prespecified. 
If rank-based tests are used, then the tests will be inverted to construct Hodges-
Lehmann point estimates and 2-sided (1-0.05/6) × 100% confidence intervals 
(CIs) about the differences in location centers of the 6 pair-wise comparisons of 
vaccine arms. If actual-value tests are used then the Dunnett’s procedure will be 
used to construct simultaneous confidence intervals about the pairs of mean 
differences for the many-to-one comparisons (86) when multiple vaccine arms are 
each compared with the pooled placebo group. Given that all pair-wise 
comparisons between the multiple vaccine arms are of interest, the Tukey 
procedure (87) will be used. An appropriate data transformation (eg, log10 
transformation) may be applied to better satisfy assumptions of symmetry and 
homoscedasticity (constant variance). Significance of the differences between 
pairs will be evaluated using two procedures, first based on whether the 
simultaneous 95% CIs exclude zero and secondly based on whether the nominal 
(unadjusted) 95% CIs exclude zero.  
Some immunologic assays have underlying continuous or count-type readout that 
are dichotomized into responder/nonresponder categories (eg, intracellular 
cytokine staining). If treatment arm differences for these assays are best 
summarized by a mixture model, then either Lachenbruch’s test statistic (88) or 
an alternative two-part test (89) (as defined in the SAP) will be used to evaluate 
the composite null hypothesis of equal response rates in the 2 arms and equal 

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response distributions. Lachenbruch’s test statistic equals the square of a binomial 
Z-statistic for comparing the response rates plus the square of a Wilcoxon statistic 
for comparing the response distributions in the subgroup of responders. A 
permutation procedure is used to obtain a 2-sided p-value. For estimation, 
differences in response rates between arms will be estimated using the methods 
described above, and in the subgroup of positive responders, differences in 
location parameters between arms will be estimated using the methods described 
above.  
More sophisticated analyses employing repeated measures methodology (for 
example, linear mixed models or marginal mean models fit by generalized 
estimating equations) will be utilized to incorporate immune responses over 
several timepoints and to test for differences over time and differences in 
trajectories across treatment arms. For example, repeated measures analyses will 
be conducted to evaluate trajectories in innate immune responses over Days 1, 3, 
7 relative to responses measured at Day 0. However, inference from such analyses 
would be limited by the small sample size of this study. All statistical tests will be 
2-sided and will be considered statistically significant if p  0.05. 
Based upon previous HVTN trials, missing 10% of immunogenicity results for a 
specific assay is common due to study participants terminating from the study 
early, problems in shipping specimens, or low cell viability of processed PBMCs. 
To achieve unbiased statistical estimation and inferences with standard methods 
applied in a complete-case manner (only including participants with observed data 
in the analysis), missing data need to be missing completely at random (MCAR). 
Following the most commonly used definition, MCAR assumes that the 
probability of an observation being missing does not depend on any participant 
characteristics (observed or unobserved). When missing data are minimal 
(specifically if no more than 20% of participants are missing any values), then 
standard complete-case methods will be used, because violations of the MCAR 
assumption will have little impact on the estimates and hypothesis tests.  
If a substantial amount of immunogenicity data are missing for an endpoint (at 
least 1 value missing from more than 20% of participants), then using the methods 
that require the MCAR assumption may give misleading results. In this situation, 
analyses of the immunogenicity endpoints at a specific timepoint will be 
performed using parametric generalized linear models fit by maximum likelihood. 
These methods provide unbiased estimation and inferences under the parametric 
modeling assumptions and the assumption that the missing data are missing at 
random (MAR). MAR assumes that the probability of an observation being 
missing may depend upon the observed responses and upon observed covariates, 
but not upon any unobserved factors. Generalized linear models for response rates 
will use a binomial error distribution and for quantitative endpoints, a normal 
error distribution. For evaluating repeated immunogenicity measurements over 
time, linear mixed effects models will be used. If the immunological outcomes are 
left- and/or right- censored, then the linear mixed effects models of Hughes (90) 
will be used, because they accommodate the censoring. In addition, secondary 

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analyses of repeated immunogenicity measurements may be done using weighted 
generalized estimating equation (GEE) (91) methods, which are valid under 
MAR. All of the models described above in this paragraph will include as 
covariates all available baseline predictors of the missing outcomes.  
Some immunogenicity endpoints are only measured in subset of participants. For 
example, fine needle lymph node aspirates, bone marrow aspirates, and 
leukapheresis will be performed only on participants consenting to these optional 
procedures, and immunogenicity endpoints based on these samples will only exist 
for those participants. For such endpoints, exploratory analyses will be conducted 
to assess the correlation of participant characteristics measured in (nearly) all 
participants with the resource-intensive endpoints. For example, if the same assay 
is performed on blood and fine needle lymph node aspirate samples, then a 
scatterplot and Spearman rank correlation coefficient (r) will be used to assess the 
correlation of responses. If at least moderate correlations exist (eg, r ≥ 0.3), then 
the semiparametric efficient analysis method of Rotnitzky and Robins (92) will be 
used (described in Gilbert, Sato et al. for application to vaccine studies (93)) to 
estimate the mean of the resource-intensive endpoint for each group and to 
compare means between groups. 
6.4.4.2 
Multivariate display of immunogenicity endpoints 
Data visualization techniques may be used to explore the relationship among 
immunogenicity readouts across assays, and across readouts for assays that 
produce high dimensional data. The set of readouts may be based on one of the 
primary endpoints (eg, neutralizing Abs), on the set of primary endpoints, or on 
immunogenicity endpoints that also include secondary or exploratory endpoints. 
To understand the relationship between pairs of readouts, scatter plots may be 
used when the number of readouts is small or for a larger number of readouts, a 
heatmap showing the degree of correlation between any two pairs. Principal 
component analysis (PCA) and associated ‘biplots’ of the scores and loadings are 
particularly useful to understand associations between readouts, especially when 
readouts are correlated (94). PCA is a method to reduce the dimensionality of the 
number of readouts to a smaller set of values (principal components) that are 
normalized linear combinations of the readouts in such a way that the first 
principal component accounts for the most variability in the data and subsequent 
components, while maximizing variability, are uncorrelated with each other. A 
‘biplot’ displays the first and second principal component scores and principal 
component loadings. The x-axis is the value from the first principal component 
and the y-axis is the second principal component, where each axis label includes 
the percentage of variation in the total set of readouts captured by the principal 
component. The top axis is the first principal component loadings and the right 
axis is the second principal component loadings. An arrow is drawn for each 
immunogenicity readout (eg, Env-specific CD4+ T cell polyfunctionality score) 
from the origin to the point defined by its first two principal component loadings. 
The length of the arrow represents the amount of total variation of the set of 
readouts captured by the given readout. The direction of an arrow conveys the 
extent to which the variation of a readout is in the direction of the first or second 

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principal component. The angle between two arrows conveys information about 
the correlation of the two readouts, with a zero degree angle denoting perfect 
correlation and a 90 degree angle denoting no correlation. Each arrow on the 
biplot is labeled by the immunogenicity readout it represents. A biplot is 
annotated with key meta-information such as the treatment arm (most common 
application) or a demographic category. Depending on the application, K-means 
clustering and hierarchical clustering may also be applied for multivariate 
graphical display of immunogenicity readouts.  
6.4.4.3 
Primary analyses of neutralization data 
The primary measure of antibody neutralization is the response to the vaccine-
matched BG505.T332N isolate. As well, responses to a single highly 
neutralization-sensitive tier 1 virus (MW965.26) will be assessed. The mean 
magnitude of the response to the vaccine-matched isolate will be estimated for 
each arm and compared to the pooled placebo group. As well, the ratio of the 
response to the vaccine-matched antigen, relative to that to the neutralization-
sensitive isolate, will be estimated for each arm.  
If a tier 2 panel of viral isolates is used to assess the breadth of neutralizing 
antibody responses, the area-under-the-magnitude-breadth curve (AUC-MB) to a 
global panel of viral isolates (14) will be computed for each participant with 
evaluable neutralization data, as described in (95). 95% CIs about the four 
differences in mean AUC-MB for each vaccine regimen versus the pooled 
placebo groups (vaccine – placebo), will be calculated.  
6.4.4.4 
Analysis of CD4+ T cell responses as measured by the ICS assay  
The analysis of CD4+ T cell response rates as measured by the ICS assay will be 
evaluated and compared as described under the general approach. For each T cell 
subset, the positivity call for each peptide pool will include a multiple comparison 
adjustment for the number of peptide pools used in the assay. In general, the 
Mixture Models for Single-cell Assays (MIMOSA) statistical framework (96) 
and/or the Fisher’s exact test-based positivity criteria will be used. Details of the 
positivity criteria will be discussed in the SAP. The magnitude of marginal 
response will be analyzed as described for quantitative data in the general 
approach section. For each T-cell subset, graphs will be used to display the 
background-subtracted magnitudes for each participant by protein, treatment arm 
and timepoint. When 3 or more cytokines are being measured by the ICS assay, 
the polyfunctionality of ICS responses may also be analyzed as an exploratory 
endpoint. Besides descriptive plots of the magnitude of polyfunctional responses, 
the COMPASS (Combinatorial Polyfunctionality analysis of Antigen-Specific T-
cell Subsets) statistical framework (97) may also be used to perform joint 
modelling of multiple T-cell subsets of different cytokine combinations. For 
example, the functionality score (FS) and the polyfunctionality score (PFS) may 
be used to summarize the multi-parameter ICS responses.  

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6.4.4.5 
Analysis of epitope mapping data 
The minimal set of optimal length epitopes that can explain the observed T cells 
responses to a set of individually tested overlapping 15-mer peptides may be 
obtained to assess the breadth and depth of the T cell responses based on the 
epitope mapping data. When human leukocyte antigen (HLA) data are also 
available, computational HLA:peptide binding predictors (eg, NetMHCpan) may 
be used to more accurately identify each participant’s T cell epitopes. 
The set of epitopes may also be used to assess “coverage” of a representative set 
of circulating viruses by each participant’s set of T-cell responses. The coverage 
provided by each epitope is defined by the fraction of viruses that match the 
sequence of the mapped epitope. The coverage provided by a participant’s set of 
epitopes is defined by the fraction of viruses covered by at least one of the 
participant’s epitopes.  
6.4.4.6 
Analysis of multiplexed immunoassay data 
When a small panel of analytes (eg, ≤ 5) is being assessed in a multiplexed 
immunoassay, the analysis of response rates and response magnitudes will be 
evaluated and compared as described under the general approach. Details for 
calculating a positive response and response magnitude will be provided in the 
SAP. When a larger panel is being assessed, 3 approaches may be considered to 
evaluate the magnitude and breadth of these responses. First, Magnitude–Breadth 
(M-B) curves maybe employed to display individual- and group-level response 
breadth as a function of magnitude. Applied to tier 2 virus neutralizing antibody 
data, response breadth is defined as the number of isolates with magnitude above 
a positivity threshold. Two choices are to compare the M-B curves among vaccine 
arms, as follows: a non-parametric Wilcoxon rank sum test on the subject-specific 
AUC-MB or a Kolmogorov-Smirnov type test on the 2 group-average M-B 
curves. Simulations can be used to obtain 2-sided p-values for the latter test. 
Second, a weighted-average score-like variable may be constructed to account for 
the correlations between analytes as an integrate magnitude of responses to 
multiple analytes. Similar group comparison methods described in the first 
approach may be adopted. Third, machine-learning approaches such as super-
learning (98) will be employed which achieve the goal of reducing the 
dimensionality of the assay readouts and simultaneously identifying individual 
responses and groups of responses that differ between treatment groups or over 
time. Details of either approach will be described in the SAP.  
6.4.5 
Analyses and data sharing prior to end of scheduled follow-up visits 
Any analyses conducted prior to the end of the scheduled follow-up visits should 
not compromise the integrity of the trial in terms of participant retention or safety 
or immunogenicity endpoint assessments. In particular, early unblinded analyses 
by treatment assignment require careful consideration and should be made 
available on a need to know basis in accordance with Sections 6.4.5.1 and 6.4.5.2. 
Interim blinded safety and immunogenicity data should not be shared outside of 

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the SMB, HVTN 137 PSRT, the protocol team leadership, the HVTN Executive 
Management Team, the study product developer, and the study sponsor and/or its 
designee(s) for their regulatory reporting unless approved by the protocol 
leadership and the HVTN leadership. 
6.4.5.1 
Safety analyses 
During the course of the trial, unblinded analyses of safety data will be prepared 
approximately every 4 months during the main study, as defined in Section 3, for 
review by the SMB. Ad hoc safety reports may also be prepared for SMB review 
at the request of the HVTN 137 PSRT. Refer to the process described in the 
HVTN Unblinding MOP for any requests for unblinded safety data prior to the 
end of the scheduled follow-up visits. 
6.4.5.2 
Immunogenicity analyses 
An unblinded statistical analysis by treatment assignment of a primary 
immunogenicity endpoint may be performed when all participants have 
completed the corresponding primary immunogenicity visit and data are available 
for analysis from at least 80% of these participants. Similarly, an unblinded 
statistical analysis by treatment assignment of a secondary or exploratory 
immunogenicity endpoint may be performed when all participants have 
completed the corresponding immunogenicity visit and data are available for 
analysis from at least 80% of these participants. However, such analyses for a 
secondary or exploratory immunogenicity endpoint will only take place after the 
primary immunogenicity endpoint (neutralizing antibody response) reaches the 
aforementioned threshold. The Laboratory Center will review the analysis report 
prior to distribution to the protocol chairs, DAIDS, study product developer, and 
other key HVTN members and investigators. Reports for distribution or 
presentation should use PubIDs and not participant ID (PTIDs) for individual 
responses. Distribution of reports will be limited to those with a need to know for 
the purpose of informing future trial-related decisions. The HVTN leadership 
must approve any other requests for HVTN immunogenicity analyses prior to the 
end of the scheduled follow-up visits. 
 
 

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7 
Selection and withdrawal of participants 
Participants will be healthy, HIV-uninfected (seronegative) adults who 
comprehend the purpose of the study and have provided written informed consent. 
Volunteers will be recruited and screened; those determined to be eligible, based 
on the inclusion and exclusion criteria, will be enrolled in the study. Final 
eligibility determination will depend on information available at the time of 
enrollment, including results of screening laboratory tests, medical history, 
physical examinations, and answers to self-administered and/or interview 
questions.  
Investigators should always use good clinical judgment in considering a 
volunteer’s overall fitness for trial participation. Some volunteers may not be 
appropriate for enrollment even if they meet all inclusion/exclusion criteria. 
Medical, psychiatric, occupational, or other conditions may make evaluation of 
safety and/or immunogenicity difficult, and some volunteers may be poor 
candidates for retention. 
Determination of eligibility, taking into account all inclusion and exclusion 
criteria, must be made within 56 days prior to enrollment unless otherwise noted 
in Sections 7.1 and 7.2. 
7.1 
Inclusion criteria 
General and Demographic Criteria 
1. Age of 18 through 50 years, inclusive 
2. Access to a participating HVTN CRS and willingness to be followed for the 
planned duration of the study 
3. Ability and willingness to provide informed consent 
4. Assessment of understanding: volunteer demonstrates understanding of this; 
completes a questionnaire prior to first vaccination with verbal demonstration of 
understanding of all questionnaire items answered incorrectly 
5. Agrees not to enroll in another study of an investigational research agent until 
after the final study contact. 
6. Good general health as shown by medical history, physical exam, and screening 
laboratory tests 
HIV-Related Criteria: 
7. Willingness to receive HIV test results 

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8. Willingness to discuss HIV infection risks and amenable to HIV risk reduction 
counseling 
9. Assessed as low risk for HIV acquisition per low-risk guidelines (see Appendix 
U) and agrees to avoid behavior associated with high risk of HIV exposure 
through the final study visit. Low risk may include persons stably taking PrEP as 
prescribed for 6 months or longer (see Appendix U). 
Laboratory Inclusion Values 
Hemogram/Complete blood count (CBC) 
10. Hemoglobin  
• ≥ 11.0 g/dL for volunteers who were assigned female sex at birth  
• ≥ 13.0 g/dL for volunteers who were assigned male sex at birth and 
transgender males who have been on hormone therapy for more than 6 
consecutive months 
• ≥ 12.0 g/dL for transgender females who have been on hormone therapy for 
more than 6 consecutive months 
• For transgender volunteers who have been on hormone therapy for less than 6 
consecutive months, determine hemoglobin eligibility based on the sex 
assigned at birth. 
11. White blood cell count = 2,500 to 12,000 cells/mm3 with normal differential, or 
differential approved by Investigator of Record (IoR) or designee as not clinically 
significant 
12. Total lymphocyte count ≥ 650 cells/mm3 with normal differential, or differential 
approved by IoR or designee as not clinically significant 
13. Remaining differential either within institutional normal range or with IoR or 
designee approval 
14. Platelets = 125,000 to 550,000 cells/mm3 
Chemistry 
15. Alanine aminotransferase (ALT) < 1.25 times the institutional upper limit of 
normal  
16. Creatinine < 1.1 times the institutional upper limit of normal 

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Virology 
17. Negative HIV-1 and -2 blood test: US volunteers must have a negative FDA-
approved enzyme immunoassay (EIA) or chemiluminescent microparticle 
immunoassay (CMIA). 
18. Negative hepatitis B surface antigen (HBsAg)  
19. Negative anti-hepatitis C virus antibodies (anti-HCV), or negative HCV 
polymerase chain reaction (PCR) if the anti-HCV is positive 
Urine 
20. Normal urine: 
• Negative or trace urine protein, and 
• Negative or trace urine hemoglobin (If trace hemoglobin is present on 
dipstick, a microscopic urinalysis with red blood cells levels within 
institutional normal range,) 
Reproductive Status 
21. Volunteers who were assigned female sex at birth: negative serum or urine beta 
human chorionic gonadotropin (β-HCG) pregnancy test at screening (ie, prior to 
randomization) and prior to study product administration. For any optional study 
procedure, pregnancy testing should be performed as per Section 9.5. Persons 
who are NOT of reproductive potential due to having undergone hysterectomy or 
bilateral oophorectomy (verified by medical records), are not required to undergo 
pregnancy testing. 
22. Reproductive status: A volunteer who was assigned female sex at birth: 
• Must agree to use effective contraception for sexual activity that could lead to 
pregnancy from at least 21 days prior to enrollment until 6 months after the 
final study vaccination. Effective contraception is defined as using the 
following methods: 
▪ Condoms (male or female) with or without a spermicide, 
▪ Diaphragm or cervical cap with spermicide, 
▪ Intrauterine device (IUD), 
▪ Hormonal contraception,  
▪ Tubal ligation, or 
▪ Any other contraceptive method approved by the HVTN 137 PSRT 

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▪ Successful vasectomy in any partner assigned male sex at birth 
(considered successful if a volunteer reports that a male partner has [1] 
documentation of azoospermia by microscopy, or [2] a vasectomy more 
than 2 years ago with no resultant pregnancy despite sexual activity 
postvasectomy); 
• Or not be of reproductive potential, such as having reached menopause (no 
menses for 1 year) or having undergone hysterectomy or bilateral 
oophorectomy; 
• Or be sexually abstinent. 
23. Volunteers who were assigned female sex at birth must also agree not to seek 
pregnancy through alternative methods, such as artificial insemination or in 
vitro fertilization until 6 months after the last vaccination. 
7.2 
Exclusion criteria 
General 
1. Blood products received within 120 days before first vaccination  
2. Investigational research agents received within 30 days before first vaccination 
3. Body mass index (BMI) ≥ 40; or BMI ≥ 35 with 2 or more of the following: age 
> 45, systolic blood pressure > 140 mm Hg, diastolic blood pressure > 90 mm Hg, 
current smoker, known hyperlipidemia  
4. Intent to participate in another study of an investigational research agent or 
any other study that requires non-HVTN HIV antibody testing during the planned 
duration of the HVTN 137 study  
5. Pregnant or breastfeeding 
6. Active duty and reserve US military personnel 
Vaccines and other Injections 
7. HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have 
received control/placebo in an HIV vaccine trial, the HVTN 137 PSRT will 
determine eligibility on a case-by-case basis. 
8. Previous receipt of monoclonal antibodies (mAbs), whether licensed or 
investigational; the HVTN 137 PSRT will determine eligibility on a case-by-case 
basis 

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9. Non-HIV experimental vaccine(s) received within the last 1 year in a prior 
vaccine trial. Exceptions may be made by the HVTN 137 PSRT for vaccines that 
have subsequently undergone licensure or Emergency Use Authorization by the 
FDA or, if outside the United States, equivalent authorization by the national 
regulatory authority. For volunteers who have received control/placebo in an 
experimental vaccine trial, the HVTN 137 PSRT will determine eligibility on a 
case-by-case basis. For volunteers who have received an experimental vaccine(s) 
greater than 1 year ago, eligibility for enrollment will be determined by the 
HVTN 137 PSRT on a case-by-case basis. 
10. Live attenuated vaccines received within 30 days before first vaccination or 
scheduled within 30 days after injection (eg, measles, mumps, and rubella 
[MMR]; oral polio vaccine [OPV]; varicella; yellow fever; live attenuated 
influenza vaccine) 
11. ACAM2000 vaccine for monkeypox received within 30 days prior to enrollment 
(note that enrollment of a participant coincides with receipt of study product) or 
scheduled within 30 days after injection.   
▪ ACAM2000 vaccine >30 days prior with a vaccination scab still present 
12. Any vaccines that are not live attenuated vaccines and were received within 14 
days prior to first vaccination or scheduled for 14 days after injection (eg, tetanus, 
pneumococcal, hepatitis virus A or B); replication incompetent vaccines such as 
the Jynneos monkeypox vaccine are not considered to be live vaccines 
13. Previous receipt of HEPLISAV, Shingrix, or RTS,S/AS01B/Mosquirix 
vaccine received within 30 days prior to first vaccination or scheduled for 30 days 
after injection.  
14. Allergy treatment with antigen injections within 30 days before first 
vaccination or that are scheduled within 14 days after first vaccination  
Immune System  
15. Immunosuppressive medications received within 168 days before first 
vaccination (Not exclusionary: [1] corticosteroid nasal spray; [2] inhaled 
corticosteroids; [3] topical corticosteroids for mild, uncomplicated dermatologic 
condition; or [4] a single course of oral/parenteral prednisone or equivalent at 
doses < 60 mg/day and length of therapy < 11 days with completion at least 30 
days prior to enrollment) 
16. Serious adverse reactions to vaccines or to vaccine components, including 
history of anaphylaxis and related symptoms such as hives, respiratory difficulty, 
angioedema, and/or abdominal pain. (Not excluded from participation: a 
volunteer who had a non-anaphylactic adverse reaction to pertussis vaccine as a 
child.)  

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17. Immunoglobulin received within 60 days before first vaccination (for mAb see 
criterion 8 above) 
18. Autoimmune disease, current or history  
19. AESIs: Volunteers who currently have, or have a history of, any condition that 
could be considered an AESI for the product(s) administered in this protocol 
(representative examples are listed in Appendix V) 
20. Immunodeficiency 
Clinically significant medical conditions  
21. Clinically significant medical condition, physical examination findings, 
clinically significant abnormal laboratory results, or past medical history with 
clinically significant implications for current health. A clinically significant 
condition or process includes but is not limited to: 
• A process that would affect the immune response, 
• A process that would require medication that affects the immune response, 
• Any contraindication to repeated injections or blood draws, 
• A condition that requires active medical intervention or monitoring to avert 
grave danger to the volunteer’s health or well-being during the study period, 
• A condition or process for which signs or symptoms could be confused with 
reactions to vaccine, or 
• Any condition specifically listed among the exclusion criteria below. 
22. Any medical, psychiatric, occupational, or other condition that, in the 
judgment of the investigator, would interfere with, or serve as a contraindication 
to, protocol adherence, assessment of safety or reactogenicity, or a volunteer’s 
ability to give informed consent 
23. Psychiatric condition that precludes compliance with the protocol. 
Specifically excluded are persons with psychoses within the past 3 years, ongoing 
risk for suicide, or history of suicide attempt or gesture within the past 3 years. 
24. Current anti-tuberculosis (TB) prophylaxis or therapy 

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25. Asthma other than mild, well-controlled asthma (Symptoms of asthma severity as 
defined in the most recent National Asthma Education and Prevention Program 
(NAEPP) Expert Panel report) 
 
Exclude a volunteer who: 
• Uses a short-acting rescue inhaler (typically a beta 2 agonist) daily, or 
• Uses moderate/high dose inhaled corticosteroids, or 
• In the past year has either of the following: 
▪ Greater than 1 exacerbation of symptoms treated with oral/parenteral 
corticosteroids; 
▪ Needed emergency care, urgent care, hospitalization, or intubation for 
asthma 
26. Diabetes mellitus type 1 or type 2 (Not exclusionary: type 2 cases controlled with 
diet alone or a history of isolated gestational diabetes.) 
27. Thyroidectomy, or thyroid disease requiring medication during the last 12 
months 
28. Hypertension: 
• If a person has been found to have elevated blood pressure or hypertension 
during screening or previously, exclude for blood pressure that is not well 
controlled. Well-controlled blood pressure is defined in this protocol as 
consistently < 140 mm Hg systolic and ≤ 90 mm Hg diastolic, with or without 
medication, with only isolated, brief instances of higher readings, which must 
be ≤ 150 mm Hg systolic and ≤ 100 mm Hg diastolic. For these volunteers, 
blood pressure must be ≤ 140 mm Hg systolic and ≤ 90 mm Hg diastolic at 
enrollment. 
• If a person has NOT been found to have elevated blood pressure or 
hypertension during screening or previously, exclude for systolic blood 
pressure ≥ 150 mm Hg at enrollment or diastolic blood pressure ≥ 100 mm Hg 
at enrollment. 
29. Bleeding disorder (eg, factor deficiency, coagulopathy, or platelet disorder 
requiring special precautions) 
30. Malignancy (Not excluded from participation: Volunteer who has had 
malignancy excised surgically and who, in the investigator’s estimation, has a 
reasonable assurance of sustained cure, or who is unlikely to experience 
recurrence of malignancy during the period of the study) 

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31. Seizure disorder: History of seizure(s) within past three years. Also exclude if 
volunteer has used medications in order to prevent or treat seizure(s) at any time 
within the past 3 years. 
32. Asplenia: any condition resulting in the absence of a functional spleen 
33. History of generalized urticaria, angioedema, or anaphylaxis. (Not 
exclusionary: angioedema or anaphylaxis to a known trigger with at least 5 years 
since last reaction to demonstrate satisfactory avoidance of trigger.) 
7.3 
Eligibility for optional procedures 
Eligibility requirements for optional procedures are listed in Section 9.5. 
7.4 
Participant departure from vaccination schedule or withdrawal 
This section concerns an individual participant’s departure from the study product 
administration schedule. Pause rules for the trial are described in Section 11.4. 
7.4.1 
Delaying vaccinations for a participant 
Under certain circumstances, a participant’s scheduled vaccination will be 
delayed. The factors to be considered in such a decision include but are not 
limited to the following: 
• Within 45 days prior to any study injection  
▪ Receipt of blood products or immunoglobulin 
• Within 30 days prior to any study injection 
▪ Receipt of live attenuated vaccines  
▪ Receipt of allergy treatment with antigen injections 
▪ Receipt of ACAM2000 vaccine for monkeypox   
▪ After administration of ACAM2000 vaccine, a minimum of 30 days is 
required before administration of study vaccination if vaccination scab 
no longer present,  
▪ If a vaccination scab still present 30 days after receiving ACAM2000, 
delay study vaccination until the scab is no longer present; 
• Within 14 days prior to any study injection 
▪ Receipt of any vaccines that are not live attenuated vaccines (eg, 
pneumococcal); replication incompetent vaccines such as the Jynneos 
monkeypox vaccine are not considered to be live vaccines  

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• Prevaccination abnormal vital signs or clinical symptoms that may mask 
assessment of vaccine reaction. 
Vaccinations should not be administered outside the visit window period (see 
Appendix W). 
In order to avoid vaccination delays and missed vaccinations, participants who 
plan to receive licensed vaccines or allergy treatments should be counseled to 
schedule receipt of these substances, when possible, outside the intervals 
indicated above. The effects of these substances on safety and immunogenicity 
assessments and their interactions with study vaccines are unknown. Therefore, if 
circumstances allow, these substances should also be avoided in the interval 
between a study vaccination and completion of the 2 or 3-week postvaccination 
follow-up visit. 
7.4.2 
Participant departure from vaccination schedule 
Every effort should be made to follow the vaccination schedule per the protocol. 
If a participant misses a vaccination and the visit window period for the 
vaccination has passed, that vaccination cannot be given. The participant should 
be asked to continue study visits. The participant should resume the vaccination 
schedule with the next vaccination unless there are circumstances that require 
further delay or permanent discontinuation of vaccination (see Sections 7.4.1 and 
7.4.3).  
7.4.3 
Discontinuing vaccination for a participant 
Under certain circumstances, an individual participant’s vaccinations will be 
permanently discontinued. Specific events that will result in stopping a 
participant’s vaccination schedule include: 
• Co-enrollment in a study with an investigational research agent (rare 
exceptions allowing for the continuation of vaccinations may be granted with 
the unanimous consent of the HVTN 137 PSRT) 
• Clinically significant condition (ie, a condition that affects the immune system 
or for which continued vaccinations and/or blood draws may pose additional 
risk), including but not limited to the following: 
▪ Pregnancy (regardless of outcome) Vaccinations will be stopped while a 
participant is pregnant. If the participant is no longer pregnant and can be 
vaccinated within an appropriate visit window, vaccinations may resume 
▪ HIV infection 
▪ Any grade 4 local or systemic reactogenicity symptom, lab abnormality, or 
AE that is subsequently considered to be related to vaccination 

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▪ Any grade 3 lab abnormality that is subsequently considered to be related 
to vaccination  
▪ Other grade 3 clinical AE that is subsequently considered to be related to 
vaccination with the exception of fever, and subjective local and systemic 
symptoms. For grade 3 injection site erythema and/or induration, upon 
review, the PSRT may allow continuation of vaccination 
▪ SAE that is subsequently considered to be related to vaccination 
▪ Clinically significant type 1 hypersensitivity reaction associated with 
study vaccination. Consultation with the HVTN 137 PSRT is required 
prior to subsequent vaccinations following any type 1 hypersensitivity 
reaction associated with study vaccination 
• Investigator determination in consultation with Protocol Team leadership (eg, 
for repeated nonadherence to study staff instructions) 
Participants discontinuing study product for reasons other than HIV infection 
should be counseled on the importance of continuing with the study and strongly 
encouraged to participate in follow-up visits and protocol-related procedures per 
the protocol for the remainder of the trial, unless medically contraindicated (see 
HVTN 137 Study Specific Procedures (SSP)). 
Participants diagnosed with HIV infection during the study should be encouraged 
to participate in follow-up visits as indicated in Section 9.14. 
7.4.4 
Participant termination from the study 
Under certain circumstances, an individual participant may be terminated from 
participation in this study. Specific events that will result in early termination 
include: 
• Participant refuses further participation, 
• Participant relocates and remote follow-up or transfer to another HVTN CRS 
is not possible, 
• HVTN CRS determines that the participant is lost to follow-up,  
• Investigator decides, in consultation with Protocol Team leadership, to 
terminate participation (eg, if participant exhibits inappropriate behavior 
toward clinic staff), or 
• Any condition where termination from the study is required by applicable 
regulations. 

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8 
Study product preparation and administration 
CRS pharmacists should consult the Pharmacy Guidelines and Instructions for 
DAIDS Clinical Trials Networks for standard pharmacy operations. The protocol 
schema is shown in Table 3-1. See the Investigator’s Brochure (IB) for further 
information about study products. 
8.1 
Vaccine regimen 
The schedule of vaccination is shown in Section 3 and additional information is 
given below. 
Part A: 
Vaccination at month 6 for Group 1 and Group 2 of Part A is optional. 
Group 1 
Treatment 1 (T1): BG505 SOSIP.664 gp140, 100 mcg, admixed with 3M-052-
AF, 1 mcg, and Aluminum Hydroxide Suspension (Alum), 500 mcg, to be 
administered as one 0.5 mL dose intramuscularly (IM) at months 0, 2, and 6 
(optional).  
Or 
Placebo 1 (P1): Placebo (Tris-NaCl Buffer) to be administered as one 0.5 mL 
dose IM at months 0, 2, and 6 (optional). 
Group 2 
Treatment 2 (T2): BG505 SOSIP.664 gp140, 100 mcg, admixed with 3M-052-
AF, 5 mcg, and Alum, 500 mcg, to be administered as one 0.5 mL dose IM at 
months 0, 2, and 6 (optional).  
Or 
Placebo 2 (P2): Placebo (Tris-NaCl Buffer) to be administered as one 0.5 mL 
dose IM at months 0, 2, and 6 (optional). 
Part B: 
Group 3 
Treatment 3 (T3): BG505 SOSIP.664 gp140, 100 mcg, admixed with CpG 1018, 
300 mcg, and Alum, 500 mcg, to be administered as one 0.5 mL dose IM at 
months 0, 2, and 6. 

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Or 
Placebo 3 (P3): Placebo (Tris-NaCl Buffer) to be administered as one 0.5 mL 
dose IM at months 0, 2, and 6. 
Group 4 
Treatment 4 (T4): BG505 SOSIP.664 gp140, 100 mcg, admixed with 3M-052-
AF, 5 mcg (highest tolerated dose from Part A), and Alum, 500 mcg, to be 
administered as one 0.5 mL dose IM at months 0, 2, and 6. 
Or 
Placebo 4 (P4): Placebo (Tris-NaCl Buffer) to be administered as one 0.5 mL 
dose IM at months 0, 2, and 6. 
Group 5 
Treatment 5 (T5): BG505 SOSIP.664 gp140, 100 mcg, admixed with GLA-LSQ 
(GLA 5 mcg, and QS-21 2 mcg) to be administered as one 0.5 mL dose IM at 
months 0, 2, and 6. 
Or 
Placebo 5 (P5): Placebo (Tris-NaCl Buffer) to be administered as one 0.5 mL 
dose IM at months 0, 2, and 6. 
Group 6 
Treatment 6 (T6): BG505 SOSIP.664 gp140, 100 mcg, admixed with Alum, 500 
mcg, to be administered as one 0.5 mL dose IM at months 0, 2, and 6. 
Or 
Placebo 6 (P6): Placebo (Tris-NaCl Buffer) to be administered as one 0.5 mL 
dose IM at months 0, 2, and 6. 
Part C: 
Group 7 
Treatment 7 (T7): BG505 SOSIP.664 gp140, 100 mcg admixed with 3M-052-AF, 
3 mcg and Alum, 500 mcg to be administered as one 0.5-mL dose intramuscularly 
(IM) at months 0, 2, and 6.  
Or 

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Placebo 7 (P7): Placebo (Tris-NaCl Buffer) to be administered as one 0.5 mL 
dose IM at months 0, 2, and 6. 
Group 8 
Treatment 8 (T8): Trimer 4571, 100 mcg admixed with 3M-052-AF, 5 mcg and 
Alum, 500 mcg to be administered as one 0.4-mL dose IM at months 0, 2, and 6. 
Or 
Placebo 8 (P8): Placebo (Tris-NaCl Buffer) to be administered as one 0.4 mL 
dose IM at months 0, 2, and 6. 
8.2 
Study product formulation 
8.2.1 
BG505 SOSIP.664 gp140  
BG505 SOSIP.664 gp140 will be provided in 2 mL Type 1 glass vials with a 
rubber stopper and flip-off Aluminum seal. Each vial contains a fill volume of 0.6 
± 0.05 mL at a concentration of 2 mg/mL. BG505 SOSIP.664 gp140 is a clear to 
opalescent, colorless to slightly yellow liquid, without any visible particles. The 
product is stored at ≤ -65° C. The study product is described in further detail in 
the Investigator’s Brochure (IB). 
8.2.2 
HIV-1 Trimer 4571 (VRC-HIVRGP096-00-VP) 
Trimer 4571 will be provided as 3-mL glass vials with a 1.2 mL ± 0.1 mL fill 
volume at a concentration of 500 mcg/mL. Each vial contains a sterile, aqueous, 
buffered solution that is clear and colorless. Some small white or translucent 
particles may be present. Store Trimer 4571 frozen at -35ºC to -15ºC. 
Vials should not be refrozen after thaw. Thawed vials can be stored at 2ºC to 8ºC 
for up to 48 hours or at 15ºC to 27ºC for up to 24 hours. Vials are intended for 
single use only and do not contain a preservative. A single vial may not be used 
for multiple dose preparations. The study product is described in further detail in 
the IB. 
8.2.3 
Tris-NaCl buffer (TBS) (Diluent for BG505 SOSIP.664 gp140 and 
Placebo) 
Tris-NaCl buffer will be provided in 2 mL Type 1 glass vials with 13 mm rubber 
stoppers and 13 mm 6-Bridge, Flip-Off, Matte Top seals. Each vial contains a fill 
volume of 1.1 ± 0.1 mL. Tris-NaCl buffer is a clear to opalescent, colorless to 
slightly yellow liquid, without any visible particulates. The product is stored at 2-
8° C. The study product is described in further detail in the IB.  
 

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8.2.4 
3M-052-AF (Labeled as AP 60-702) 
3M-052-AF will be provided in 2 mL Type 1 glass vials with a rubber stopper and 
flip-off Aluminum seal. Each vial contains a fill volume of 0.4 mL at a 
concentration of 50 mcg/mL. 3M-052-AF is a clear to slightly hazy, colorless 
liquid. The product is stored at 2-8° C. Do not freeze. The study product is 
described in further detail in the IB. 
8.2.5 
CpG 1018 (Labeled as CpG 1018 Drug Product) 
CpG 1018 will be provided in 2 mL Type 1 glass vials. Each vial contains a fill 
volume of 0.7 mL at a concentration of 6 mg/mL. CpG 1018 is a colorless, clear 
liquid, free of visible particles. The product is stored at 2-8° C. The study product 
is described in further detail in the IB. 
8.2.6 
GLA-LSQ (Labeled as AP 10-602) 
Glucopyranosyl Lipid A (GLA) is formulated in a liposomal composition with 
QS-21 to generate the adjuvant GLA-LSQ. GLA-LSQ will be provided in 2 mL 
Type I glass vials with stoppers and flip-off Aluminum seals. Each vial contains a 
fill volume of 0.4 mL at a concentration of 20 mcg/mL GLA and 8 mcg/mL QS-
21. GLA-LSQ is a hazy, water-white, semi-transparent liquid. The product is 
stored at 2-8° C. Do not freeze. The study product is described in further detail in 
the IB. 
8.2.7 
Aluminum Hydroxide Suspension (Alum) 
The Aluminum Hydroxide Suspension consists of Alhydrogel® 2% (Brenntag 
Biosector, Frederikssund, Denmark) and will be provided in 3 mL Type 1 glass vials. 
Each vial contains 0.7 mL fill volume at a concentration of 5 mg/mL Aluminum. 
Alum appears as an opaque, white gelatinous precipitate in aqueous suspension. The 
product is stored refrigerated at 2-8° C. Do not freeze. The study product is described 
in further detail in the IB. 
8.3 
Preparation of study products 
Pharmacists must follow appropriate aseptic technique and sterile preparation 
procedures/guidance as outlined in USP <797> [medium risk], utilizing a 
pharmacy biosafety cabinet/isolator or better. Local regulations and site 
institutional policies and procedures for use of personal protective equipment, 
such as gloves, gowns, masks, and safety glasses, must be followed. Pharmacists 
should follow the requirements of their country, their institution, and their 
pharmacy regulatory authority regarding these procedures. 
Any unused portion of study product will not be used for another participant. 
Empty vials, unused portion of entered vials, or unused prepared study product 

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should be discarded in a biohazard container and disposed of in accordance with 
institutional or pharmacy policy. 
PART A: 
8.3.1 
BG505 SOSIP.664 gp140, 100 mcg, admixed with 3M-052-AF, 1 mcg, 
and Alum, 500 mcg (Group 1) 
For all preparation steps, use a 1 mL Luer-Lok syringe with 0.01 mL graduations 
and a 22-27 gauge Luer-Lok needle.  
1. Remove one vial of 3M-052-AF, one vial of TBS and one vial of Alum from 
the refrigerator. Resuspend Alum by inverting the vial for 30-60 seconds.  
2. Remove one vial of BG505 SOSIP.664 gp140 from the freezer. Thaw BG505 
SOSIP.664 gp140vial by holding in gloved hand. Once thawed, maintain the 
vial in upright position and gently swirl or tap the vial to mix the contents. Do 
not invert the vial.  
Preparation of Adjuvants: 
3. Remove one vial of Water for injection (WFI) from storage. 
4. Withdraw 0.6 mL WFI and inject it into 3M-052-AF vial. Mix by gently 
swirling and inverting the vial about 5 times. Do not shake vigorously.  
5. Withdraw 0.1 mL of the mixed preparation and inject it into an empty sterile 
vial (mixing vial).  
6. Withdraw 0.2 mL of Alum and inject into the mixing vial. Mix by gently 
swirling and inverting the vial about 5 times. Do not shake vigorously. Allow 
formulation to incubate at room temperature for 30 minutes. 
7. Withdraw 0.6 mL TBS and inject into the mixing vial. Mix by gently swirling 
and inverting the vial about 5 times. Do not shake vigorously. 
Preparation of BG505 SOSIP.664 gp140: 
8. Withdraw 0.1 mL BG505 SOSIP.664 gp140 and add it to the mixing vial. Mix 
by gently swirling and inverting the vial about 5 times. Do not shake 
vigorously. 

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Preparation of the Admixed Vaccine: 
9. Withdraw 0.5 mL of the mixed preparation for study participant 
administration. Prior to administration, gently invert the syringe to resuspend 
admixed product.  
10. The admixed product is stable for 4 hours at room temperature.  
8.3.2 
BG505 SOSIP.664, gp140 100 mcg, admixed with 3M-052-AF, 5 mcg, 
and Alum, 500 mcg (Group 2) 
For all preparation steps, use a 1 mL Luer-Lok syringe with 0.01 mL graduations 
and a 22-27 gauge Luer-Lok needle.  
1. Remove one vial of 3M-052-AF, one vial of TBS, and one vial of Alum from 
the refrigerator. Resuspend Alum by inverting the vial for 30-60 seconds.  
2. Remove one vial of BG505 SOSIP.664 gp140 from the freezer. Thaw BG505 
SOSIP.664 gp140 vial by holding in gloved hand. Once thawed, maintain the 
vial in upright position and gently swirl or tap the vial to mix the contents. Do 
not invert the vial.  
Preparation of Adjuvants: 
3. Withdraw 0.2 mL of 3M-052-AF and inject it into an empty sterile vial 
(mixing vial).  
4. Withdraw 0.2 mL of Alum and inject into the mixing vial. Mix by gently 
swirling and inverting the vial about 5 times. Do not shake vigorously. Allow 
formulation to incubate at room temperature for 30 minutes. 
5. Withdraw 0.5 mL TBS and inject into the mixing vial. Mix by gently swirling 
and inverting the vial about 5 times. Do not shake vigorously. 
Preparation of BG505 SOSIP.664 gp140: 
6. Withdraw 0.1 mL BG505 SOSIP.664 gp140 and add it to the mixing vial. Mix 
by gently swirling and inverting the vial about 5 times. Do not shake 
vigorously. 
Preparation of the Admixed Vaccine: 
7. Withdraw 0.5 mL of the mixed preparation for study participant 
administration. Prior to administration, gently invert the syringe to resuspend 
admixed product.  
8. The admixed product is stable for 4 hours at room temperature.  

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PART B: 
8.3.3 
BG505 SOSIP.664 gp140, 100 mcg, admixed with CpG 1018, 300 mcg, 
and Alum, 500 mcg (Group 3) 
For all preparation steps, use a 1 mL Luer-Lok syringe with 0.01 mL graduations 
and a 22-27 gauge Luer-Lok needle.  
1. Remove one vial of CpG 1018, one vial of TBS, and one vial of Alum from 
the refrigerator. Resuspend Alum by inverting the vial for 30-60 seconds.  
2. Remove one vial of BG505 SOSIP.664 gp140 from the freezer. Thaw BG505 
SOSIP.664 gp140 vial by holding in gloved hand. Once thawed, maintain the 
vial in upright position and gently swirl or tap the vial to mix the contents. Do 
not invert the vial.  
Preparation of Adjuvants: 
3. Withdraw 0.1 mL of CpG 1018 and inject it into an empty sterile vial (mixing 
vial).  
4. Withdraw 0.2 mL of Alum and inject into the mixing vial. Mix by gently 
swirling and inverting the vial about 5 times. Do not shake vigorously. Allow 
formulation to incubate at room temperature for 30 minutes. 
5. Withdraw 0.6 mL TBS and inject into the mixing vial. Mix by gently swirling 
and inverting the vial about 5 times. Do not shake vigorously. 
Preparation of BG505 SOSIP.664 gp140: 
6. Withdraw 0.1 mL BG505 SOSIP.664 gp140 and add it to the mixing vial. Mix 
by gently swirling and inverting the vial about 5 times. Do not shake 
vigorously. 
Preparation of the Admixed Vaccine: 
7. Withdraw 0.5 mL of the mixed preparation for study participant 
administration. Prior to administration, gently invert the syringe to resuspend 
admixed product.  
8. The admixed product is stable for 4 hours at room temperature.  
8.3.4 
BG505 SOSIP.664 gp140, 100 mcg, admixed with 3M-052-AF, 5 mcg, 
and Alum, 500 mcg (Group 4) 
The highest tolerated dose of 3M-052-AF, 5 mcg, will be used in preparation of 
study product for administration to Group 4 participants. Follow preparation 
instructions in Section 8.3.2. 

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8.3.5 
BG505 SOSIP.664 gp140, 100 mcg, admixed with GLA-LSQ, (GLA 5 
mcg and QS-21 2 mcg) (Group 5) 
For all preparation steps, use a 1 mL Luer-Lok syringe with 0.01 mL graduations 
and a 22-27 gauge Luer-Lok needle.  
1. Remove one vial of GLA-LSQ and one vial of TBS from the refrigerator.  
2. Remove one vial of BG505 SOSIP.664 gp140 from the freezer. Thaw BG505 
SOSIP.664 gp140 vial by holding in gloved hand. Once thawed, maintain the 
vial in upright position and gently swirl or tap the vial to mix the contents. Do 
not invert the vial.  
Preparation of BG505 SOSIP.664 gp140: 
3. Withdraw 0.8 mL of TBS and inject it into an empty sterile vial (mixing vial).  
4. Withdraw 0.2 mL BG505 SOSIP.664 gp140 and add it to the mixing vial. Mix 
by gently swirling and inverting the vial about 5 times. Do not shake 
vigorously. 
Preparation of the Admixed Vaccine: 
5. Withdraw 0.4 mL of the mixed preparation and add to GLA-LSQ vial. Mix by 
gently swirling and inverting the vial about 5 times. Do not shake vigorously. 
6. Withdraw 0.5 mL of the mixed preparation for study participant 
administration. To maintain study blind, wait 30 minutes prior to study product 
delivery to clinic staff. Prior to administration, gently invert the syringe to 
resuspend admixed product.  
7. The admixed product is stable for 4 hours at room temperature.  
8.3.6 
BG505 SOSIP.664 gp140, 100 mcg, admixed with Alum, 500 mcg 
(Group 6) 
For all preparation steps, use a 1 mL Luer-Lok syringe with 0.01 mL graduations 
and a 22-27 gauge Luer-Lok needle.  
1. Remove one vial of TBS and one vial of Alum from the refrigerator. 
Resuspend Alum by inverting the vial for 30-60 seconds.  
2. Remove one vial of BG505 SOSIP.664 gp140 from the freezer. Thaw BG505 
SOSIP.664 gp140 vial by holding in gloved hand. Once thawed, maintain the 
vial in upright position and gently swirl or tap the vial to mix the contents. Do 
not invert the vial.  

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Preparation of the Admixed Vaccine: 
3. Withdraw 0.2 mL of Alum and inject into an empty sterile vial (mixing vial). 
4. Withdraw 0.7 mL TBS and inject into the mixing vial. Mix by gently swirling 
and inverting the vial about 5 times. Do not shake vigorously. 
5. Withdraw 0.1 mL BG505 SOSIP.664 gp140 and add it to the mixing vial. Mix 
by gently swirling and inverting the vial about 5 times. Do not shake 
vigorously. 
6. Withdraw 0.5 mL of the mixed preparation for study participant 
administration. To maintain study blind, wait 30 minutes prior to study product 
delivery to clinic staff. Prior to administration, gently invert the syringe to 
resuspend admixed product.  
7. The admixed product is stable for 4 hours at room temperature.  
PART C: 
8.3.7 
BG505 SOSIP.664 gp140, 100 mcg admixed with 3M-052-AF, 3 mcg 
and Alum, 500 mcg (Group 7) 
For all preparation steps, use a 1-mL Luer-Lok syringe with 0.01-mL graduations 
and a 22-27 gauge Luer-Lok needle. 
1 
Remove one vial of 3M-052-AF, one vial of TBS, and one vial of Alum from 
the refrigerator. Resuspend Alum by inverting the vial for 30-60 seconds. 
2 
Remove one vial of BG505 SOSIP.664 gp140 from the freezer. Thaw BG505 
SOSIP.664 gp140 vial by holding in gloved hand. Once thawed, maintain the 
vial in upright position and gently swirl or tap the vial to mix the contents. Do 
not invert the vial. 
Preparation of Adjuvants: 
3 
Withdraw 0.12 mL of 3M-052-AF and inject it into an empty sterile vial 
(mixing vial). 
4 
Withdraw 0.2 mL of Alum and inject into the mixing vial. Mix by gently 
swirling and inverting the vial about 5 times. Do not shake vigorously. Allow 
formulation to incubate at room temperature for 30 minutes. 
5 
Withdraw 0.58 mL of TBS and inject into the mixing vial. Mix by gently 
swirling and inverting the vial about 5 times. Do not shake vigorously. 

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Preparation of BG505 SOSIP.664 gp140: 
6 
Withdraw 0.1 mL of BG505 SOSIP.664 gp140 and add it to the mixing vial. 
Mix by gently swirling and inverting the vial about 5 times. Do not shake 
vigorously. 
Preparation of the Admixed Vaccine: 
7 
Withdraw 0.5 mL of the mixed preparation for study participant 
administration. Prior to administration, gently invert the syringe to resuspend 
admixed product. 
8 
The admixed product is stable for 4 hours at room temperature. 
8.3.8 
Trimer 4571, 100 mcg admixed with 3M-052-AF, 5 mcg and Alum, 500 
mcg (Group 8) 
For all preparation steps, use a 1-mL Luer-Lok syringe with 0.01-mL graduations 
and an 18-25 gauge Luer-Lok needle. 
Preparation of Adjuvants: 
1. Remove one vial of Alum from the refrigerator and equilibrate at ambient 
temperature (15°C to 27°C) for a minimum of 15 minutes. 
2. Remove one vial of 3M-052-AF from the refrigerator and equilibrate at 
ambient temperature (15°C to 27°C) for a minimum of 15 minutes. 
3. Mix the vial of 3M-052-AF gently by inverting 5 times. Withdraw 0.2 mL of 
3M-052-AF and inject it into an empty sterile vial (mixing vial). 
4. Mix the vial of Alum by gently inverting 5 times.  
5. Withdraw 0.2 mL of Alum and inject into the mixing vial. 
6. Mix and wait for 30 minutes. During this time, proceed to Step 7. 
Preparation of Trimer 4571: 
7. During the incubation period of the mixing vial, thaw one vial of Trimer 4571 
at ambient temperature (15ºC to 27ºC) for a minimum of 30 minutes. Vial 
should NOT be moved directly from the freezer to the refrigerator to thaw. 
8. Swirl the thawed, equilibrated Trimer 4571 vial for about 30 seconds with 
sufficient force to mix the solution, yet avoid foaming. Do NOT shake the 
vial. If some white to translucent particles are observed, the vial may still be 
used. 

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9. Withdraw 0.4 mL of Trimer 4571 and add it to the mixing vial. The final 
volume in the mixing vial will be 0.8 mL. 
Preparation of the Admixed Vaccine: 
10. Invert mixing vial gently 5 times to mix. Withdraw 0.4 mL of the mixed 
preparation for study participant administration. Immediately prior to 
administration, gently invert the syringe 10 times to mix.  
11. The admixed product may be stored for up to 8 hours at 2°C to 8°C and/or up 
to 4 hours at ambient temperature (15°C to 27°C), including dose 
administration time. 
8.3.9 
Placebo (Tris-NaCl buffer) (Placebo 1-8) 
1. Remove one vial of TBS from the refrigerator.  
2. For Groups 1-7, use a 1 mL Luer-Lok syringe and a 22-27 gauge needle to 
withdraw 0.5 mL of TBS for study participant administration. For Group 8, 
use a 1 mL Luer-Lok syringe and an 18-25 gauge needle to withdraw 0.4 mL 
of TBS for study participant administration. To maintain study blind, wait 30 
minutes prior to study product delivery to clinic staff.  
3. For Groups 1-7, the placebo is stable for 4 hours at room temperature. For 
Group 8, the placebo is stable for up to 8 hours at 2°C to 8°C and/or up to 4 
hours at ambient temperature (15°C to 27°C), including dose administration 
time.  
8.3.10 
Labeling of Study Product 
Label the study product as follows and apply an overlay/tape to each syringe to 
ensure blinding is maintained:  
• Participant identifier(s) 
• Study Product Name in blinded manner, for example: 
o Protein (BG505 SOSIP.664 gp140 or Trimer 4571) + Adjuvant(s) or 
Placebo 
• Final volume (mL) 
• Route (IM) 
• Beyond use date and time 
• Any additional information required by jurisdiction 

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8.4 
Administration 
All injections are to be given IM in the deltoid, using standard IM injection 
technique.  
When preparing a dose in a syringe and administering the dose, consideration 
should be given to the volume of solution in the needle before and after the dose 
is administered. Particularly, if the needle used to withdraw the product is 
replaced prior to vaccine administration, consideration should be given to 
conserving the full dose of product. The pharmacy and clinic staff members are 
encouraged to work together to administer the dose specified in the protocol.  
Any administrator of study product will be blinded to the individual participant's 
treatment assignment. 
8.5 
Acquisition of study products 
BG505 SOSIP.664 gp140 and Tris-NaCl buffer were manufactured by Ajinomoto 
Althea, Inc (San Diego, CA, USA) and will be provided by the International 
AIDS Vaccine Initiative (IAVI, New York, NY, USA). 
Trimer 4571 was manufactured by Leidos Biomed (Vaccine Research Center, 
Frederick, MD, USA) and will be provided by DAIDS, NIAID, NIH (Rockville, 
MD, USA). 
Alum was manufactured by Leidos Biomed (Vaccine Research Center, Frederick, 
MD, USA) and will be provided by DAIDS, NIAID, NIH (Rockville, MD, USA). 
3M-052-AF (labeled as AP 60-702) is manufactured and provided by Access to 
Advanced Health Institute (AAHI, Seattle, WA, USA). 
GLA-LSQ (labeled as AP 10-602) was manufactured by the Access to Advanced 
Health Institute (AAHI) (AAHI, Seattle, WA, USA) and will be provided by 
DAIDS, NIAID, NIH (Rockville, MD, USA) 
CpG 1018 (labeled as CpG 1018 Drug Product) was manufactured by Aji Bio-
Pharma (Ajinomoto Althea, Inc., San Diego, CA, USA) and will be provided by 
DAIDS, NIAID, NIH (Rockville, MD, USA).  
Once an HVTN CRS is protocol registered, the pharmacist can obtain study 
products from the NIAID Clinical Research Products Management Center 
(CRPMC) by following the ordering procedures outlined in Pharmacy Guidelines 
and Instructions for DAIDS Clinical Trials Networks. 

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8.6 
Pharmacy records 
The HVTN CRS pharmacist is required to maintain complete records of all study 
products. The pharmacist of record is responsible for maintaining randomization 
codes and randomization confirmation notices for each participant in a secure 
manner. 
8.7 
Final disposition of study products 
For US clinical research sites, all unused study products must be returned to the 
CRPMC after the study is completed or terminated unless otherwise instructed by 
the study sponsor. For non-US clinical research sites, all unused study products 
must be destroyed after the study is completed or terminated unless otherwise 
instructed by the study sponsor. The procedures are included in the Pharmacy 
Guidelines and Instructions for DAIDS Clinical Trials Networks. 

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9 
Clinical procedures 
The schedules of clinical procedures are shown in Appendix Q, Appendix R 
Appendix S, and Appendix T. 
9.1 
Informed consent 
Informed consent is the process of working with participants so that they fully 
understand what will and may happen to them while participating in a research 
study. The HVTN informed consent form documents that a participant (1) has 
been informed about the potential risks, benefits, and alternatives to participation, 
and (2) is willing to participate in an HVTN study. Informed consent 
encompasses all written or verbal study information HVTN CRS staff provide to 
the participant, before and during the trial. HVTN CRS staff will obtain informed 
consent of participants according to HVTN policies and procedures. 
The informed consent process continues throughout the study. Key study concepts 
should be reviewed periodically with the participant and the review should be 
documented. At each study visit, HVTN CRS staff should consider reviewing the 
procedures and requirements for that visit and for the remaining visits. 
Additionally, if any new information is learned that might affect the participants’ 
decisions to stay in the trial, this information will be shared with trial participants. 
If necessary, participants will be asked to sign revised informed consent forms. 
An HVTN CRS may employ recruitment efforts prior to the participant 
consenting. For example, some HVTN CRSs use a telephone script to prescreen 
people before they come to the clinic for a full screening visit. Participants must 
sign a screening or protocol-specific consent before any procedures are performed 
to determine eligibility. HVTN CRSs must submit recruitment and prescreening 
materials to their IRB/EC and any applicable Regulatory Entity (RE) for human 
subjects protection review and approval. 
Note: As defined in the DAIDS Protocol Registration Manual, an RE is “Any 
entity/body that has the power to regulate which includes authorities that review 
submitted clinical data and those that conduct inspections. These are sometimes 
referred to as competent authorities. These are entities/bodies whose 
approval/authorization/acknowledgment of a clinical trial is required for 
conducting a clinical trial. Any organization whose approval is required prior to a 
CRS’s participation in DAIDS funded and/or Sponsored Clinical Trial. Includes 
but not limited to approvals from state/national health systems and administrative 
bodies, drug agencies etc.” CRSs are responsible for knowing the requirements of 
their applicable REs. 

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9.1.1 
Screening consent form 
Without a general screening consent, screening for a specific study cannot take 
place until the site receives protocol registration from the DAIDS RSC Protocol 
Registration Office. 
Some HVTN CRSs have approval from their IRB/EC and any applicable RE to 
use a general screening consent form that allows screening for an unspecified HIV 
vaccine trial. In this way, HVTN CRS staff can continually screen potential 
participants and, when needed, proceed quickly to obtain protocol-specific 
enrollment consent. Sites conducting general screening or prescreening approved 
by their IRB/EC and any applicable RE may use the results from this screening to 
determine eligibility for this protocol, provided the tests are conducted within the 
time periods specified in the eligibility criteria. 
9.1.2 
Protocol-specific consent forms 
The protocol-specific consent forms describe the study products to be used and all 
aspects of protocol participation, including screening and enrollment procedures. 
Sample protocol-specific consent forms for Parts A, B, and C of the main study 
are located in Appendix A, Appendix B, and Appendix C. A separate sample 
consent form for other uses of specimens is located in Appendix G. An addendum 
consent form for participation in the Part A Optional Second Boost is located in 
Appendix D (Sample addendum to informed consent form for Part A with 
Optional Third Vaccination participants only). 
Each HVTN CRS is responsible for developing a protocol-specific consent 
form(s) for local use, based on the sample protocol-specific consent forms in 
Appendix A, Appendix B, Appendix C, Appendix D and Appendix G. The 
consent form(s) must be developed in accordance with requirements of the 
following: 
• CRS’s IRB/EC and any applicable REs, 
• CRS’s institution, and 
• Elements of informed consent as described in Title 45, CFR Part 46 and Title 
21 CFR, Part 50, and in ICH E6, Good Clinical Practice: Consolidated 
Guidance 4.8. 
Study sites are strongly encouraged to have their local CABs review their sites-
specific consent forms. This review should include, but should not be limited to, 
issues of cultural competence, local language considerations, and the level of 
understandability. 
The sample informed consent forms include instructions for developing specific 
content. 

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Regarding protocol registration, sites should follow procedures outlined in the 
current version of the DAIDS Protocol Registration Manual. 
9.1.3 
Assessment of Understanding 
Study staff are responsible for ensuring that participants fully understand the 
study before enrolling them. This process involves reviewing the informed 
consent form with the participant, allowing time for the participant to reflect on 
the procedures and issues presented, and answering all questions completely. 
An Assessment of Understanding is used to document the participant’s 
understanding of key concepts in this HIV vaccine trial. The participant must 
complete the Assessment of Understanding before enrollment. Staff may provide 
assistance in reading and understanding the questions and responses, if necessary. 
Participants must verbalize understanding of all questions answered incorrectly. 
This process and the participant’s understanding of the key concepts should be 
recorded in source documentation at the site. 
IRB/EC and any applicable RE may require that a participant has signed either a 
screening or protocol-specific consent document prior to administering the 
Assessment of Understanding. The consent process (including the use of the 
Assessment of Understanding) should be explained thoroughly to the IRB/EC and 
any applicable RE, whose recommendations should be followed.  
9.2 
Pre-enrollment procedures 
Screening may occur over the course of several contacts/visits, up to and 
including before vaccination on day 0. All inclusion and exclusion criteria must 
be assessed within 56 days before enrollment, unless otherwise specified in the 
eligibility criteria (or below in this section). 
After the appropriate informed consent has been obtained and before enrollment, 
the following procedures are performed: 
• Medical history, documented in the case history record 
• Assessment of whether the volunteer is at low risk for HIV infection (see 
Appendix U) 
• Complete physical examination, including height, weight, vital signs, and 
clinical assessments of head, ears, eyes, nose, and throat; neck; lymph nodes; 
heart; chest; abdomen; extremities; neurological function; skin (and pelvic 
and/or rectal exam for volunteers agreeing to provide mucosal samples) 
• Assessment of concomitant medications the volunteer is taking, including 
prescription and nonprescription drugs, vitamins, topical products, 

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alternative/complementary medicines (eg, herbal and health food 
supplements), recreational drugs, vaccinations, and allergy shots 
• Laboratory tests, including: 
▪ Screening HIV test 
▪ HBsAg 
▪ Anti-HCV Abs 
▪ CBC with differential and platelets 
▪ Chemistry panel (ALT, creatinine) 
▪ Urine dipstick 
▪ Urine or serum pregnancy test (volunteers who were assigned female sex 
at birth); Persons who are NOT of reproductive potential due to having 
undergone total hysterectomy or bilateral oophorectomy (verified by 
medical records), are not required to undergo pregnancy testing. 
• Administration of behavioral risk assessment (BRA) questionnaire 
• Obtaining of volunteer demographics in compliance with the NIH Policy on 
Reporting Race and Ethnicity Data: Subjects in Clinical Research, Aug. 8, 
2001 (available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-01-
053.html) 
• Counseling on HIV testing and risk reduction, performed in compliance with 
the US Centers for Disease Control and Prevention (CDC)’s current 
guidelines or other local guidelines for HIV counseling, testing, and referral as 
described in Section 9.7 
• Discussion of pregnancy prevention. A pregnant or breastfeeding person may 
not be enrolled in this trial. Specific criteria and assessment of contraception 
and pregnancy status are described in study inclusion criteria. Discussion of 
pregnancy prevention includes advising a participant who was assigned 
female sex at birth and who reports no current sexual activity that could lead 
to that participant becoming pregnant to have a plan to begin adequate birth 
control. This plan would be put to use if, during the study, the participant 
becomes sexually active in a way that could lead to that participant becoming 
pregnant. 
• Assessment of volunteer eligibility for optional procedures  
9.2.1 
Use of screening results from another HVTN study 
If a participant screens for an HVTN study at the same HVTN CRS but then does 
not join that study, screening results from that effort may be applied to the 
screening for this protocol, as long as the screening was done under participant 

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consent, the participant has signed a consent form to begin screening for this 
study, and the tests were conducted within the time periods specified in the 
eligibility criteria (see Sections 7.1 and 7.2). 
9.3 
Enrollment and vaccination visits 
Once a volunteer has consented to trial participation and is found to meet all 
eligibility criteria (see Sections 7.1 and 7.2), the HVTN CRS requests the 
randomization assignment via a Web-based randomization system. Enrollment is 
simultaneous with first vaccination. In general, the time interval between 
randomization and enrollment should not exceed 4 working days. However, 
circumstances may require a participant’s enrollment visit to be changed. This 
may exceed the 4-day randomization time limit. 
At all vaccination visits, the following procedures are performed before 
vaccination: 
• Abbreviated physical examination, including weight, vital signs, and a 
symptom-directed evaluation by history and/or appropriate physical exam 
based on participant self-reported symptoms or complaints; 
• Assessment of baseline reactogenicity parameters; 
• Assessment of concomitant medications (as described in Section 9.2); 
• Assessment of any new or unresolved AEs/intercurrent illnesses; and 
• Urine or serum pregnancy test (for participants who were assigned female sex 
at birth). Persons who are NOT of reproductive potential due to having 
undergone hysterectomy or bilateral oophorectomy (verified by medical 
records), are not required to undergo pregnancy testing. For pregnant 
participants, see Section 9.13. 
Following completion of all procedures in the preceding list, and if results 
indicate that vaccination may proceed, vaccination is prepared and administered 
(see Sections 8.3 and 8.4).  
Immediately following vaccination, the participant remains in the clinic for 
observation. An initial reactogenicity assessment is made at a target of 30 minutes 
after injection, with an acceptable range of 25-60 minutes. Before leaving the 
clinic, the participant is given the Participant Diary and is instructed on how to 
complete it. The site will make arrangements to be in contact with the participant 
during the reactogenicity period (as described in Section 9.10). 
The following procedures will be performed at all vaccination visits. These 
procedures may be performed prior to or following vaccination: 

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• Risk reduction counseling (as described in Section 9.7); 
• Contraception status assessment (as described in Section 9.2 and 9.8). During 
follow-up in persons who are confirmed pregnant, contraception status 
assessment is not required; and 
• Assessment of new or unresolved social impacts (site staff will ask participant 
about the status of any unresolved social impacts and if s/he has experienced 
any new social impacts as a result of the trial participation). 
Additional procedures and clinical laboratory tests will be performed at 
vaccination visits as specified in Appendix J, Appendix K, Appendix L, 
Appendix M, Appendix N, Appendix O, Appendix P, Appendix Q, Appendix R, 
Appendix S, and Appendix T: 
• Specimen collection (including optional rectal and/or vaginal secretion and/or 
biopsy samples) 
• Pelvic and/or rectal exam (as appropriate) for volunteers agreeing to provide 
optional mucosal samples 
• Gonorrhea and chlamydia (for participants providing any biopsy samples) 
• Trichomonas vaginalis (for participants providing cervicovaginal secretion 
and/or vaginal biopsy, only when clinically indicated) 
• Bacterial vaginosis (for participants providing cervicovaginal secretion and/or 
vaginal biopsy samples, only when clinically indicated) 
• Yeast (for participants providing cervicovaginal secretion and/or vaginal 
biopsy samples, only when clinically indicated) 
9.4 
Follow-up visits 
The following procedures are performed at all scheduled follow-up visits: 
• Risk reduction counseling (as described in Section 9.7); 
• Contraception status assessment (as described in Section 9.2 and 9.8). During 
follow-up in persons who are confirmed pregnant, contraception status 
assessment is not required; and 
• Assessment of new or unresolved social impacts (site staff will ask participant 
about the status of any unresolved social impacts and if s/he has experienced 
any new social impacts as a result of the trial participation); 

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• Assessment of new or continuing concomitant medications (as described in 
Section 9.2);  
• Assessment of new or unresolved AEs/intercurrent illnesses; and  
• Specimen collection. 
Additional procedures will be performed at scheduled follow-up visits as 
specified in Appendix Q, Appendix R, Appendix S and Appendix T: 
• Administration of the social impact assessment questionnaire (types of 
impacts assessed involve personal relationships, health insurance, life 
insurance, educational or employment opportunities, housing, immigration, or 
travel); 
• Administration of a questionnaire that asks the participant about any HIV 
testing he or she may have received outside of the study. Participants will also 
be asked whether they believe they received the active vaccine or the control; 
• HIV infection assessment including pretest counseling and HIV testing. A 
subsequent follow-up contact is conducted to provide post-test counseling and 
to report results to participant; 
• Abbreviated physical examination including weight, vital signs, and a 
symptom-directed evaluation by history and/or appropriate physical exam 
based on participant self-reported symptoms or complaints; 
• Complete physical examination, including weight, vital signs, and clinical 
assessments of head, ears, eyes, nose, and throat; neck; lymph nodes; heart; 
chest; abdomen; extremities; neurological function; and skin; 
• Pelvic and/or rectal exam (as appropriate) for volunteers agreeing to provide 
optional mucosal samples 
Clinical laboratory tests will be performed at scheduled follow-up visits as 
specified in, Appendix J, Appendix K, Appendix L, Appendix M, Appendix N, 
Appendix O, and Appendix P, including: 
• CBC with differential 
• Chemistry panel (see Section 9.2) 
• Urine dipstick (urinalysis if appropriate; see Section 9.9) 
• Gonorrhea and chlamydia (for participants providing biopsy samples) 

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• Trichomonas vaginalis (for participants providing cervicovaginal secretion 
and/or vaginal biopsy samples, only when clinically indicated) 
• Bacterial vaginosis (for participants providing cervicovaginal secretions 
and/or vaginal biopsy samples, only when clinically indicated) 
• Yeast (for participants providing cervicovaginal secretions and/or vaginal 
biopsy samples, only when clinically indicated) 
• Urine or serum pregnancy test (for participants who were assigned female sex 
at birth). Persons who are NOT of reproductive potential due to having 
undergone hysterectomy or bilateral oophorectomy (verified by medical 
records), are not required to undergo pregnancy testing. During follow-up in 
persons who are confirmed pregnant, pregnancy testing is not required, unless 
clinically indicated. 
Additional optional procedures may be performed at scheduled follow-up visits 
as specified in Appendix K, Appendix L, Appendix M, Appendix N, and 
Appendix O. These procedures may not be performed at all sites. At sites where 
the procedures are performed, eligible participants have the option of participating 
in none, any, or all available procedures. 
• Collection of rectal and/or cervicovaginal secretion and/or biopsy samples 
• Leukapheresis 
• Lymph node (LN) fine needle aspiration (FNA) 
• Bone marrow aspiration 
9.5 
Optional procedures 
Mucosal secretion and biopsy samples, leukapheresis samples, lymph node fine 
needle aspirates, and bone marrow aspirates will be collected at timepoints 
indicated in Appendix K, Appendix M, Appendix N, and Appendix O from study 
participants who agree (see Appendix B) and who are eligible for these 
procedures. Participants assigned female sex at birth may provide cervicovaginal 
secretions and/or vaginal biopsies.  
Rectal and vaginal samples 
Small (~2-4 mm) tissue biopsies are obtained from the vagina using a speculum 
and from the rectum by anoscopy by experienced clinicians. At the timepoints 
specified in Appendix K, Appendix L, Appendix M, Appendix N, and Appendix 
O, the following are collected: 5 biopsies per mucosal compartment (rectal and 
vaginal), one cervicovaginal secretion sample, and one rectal secretion sample; 

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however, fewer samples may be taken based on the judgment of the clinician 
performing the procedure.  
Eligibility for rectal and vaginal sampling: 
• Participants who can become pregnant must have a negative pregnancy test on 
the same day prior to any rectal mucosal sampling (secretions or biopsies) or 
vaginal biopsy sampling. For cervicovaginal secretion sampling, a pregnancy 
test must be done on the same day but can be performed prior to or after 
sampling. 
• Cervicovaginal secretion or vaginal biopsy sampling will not be performed (or 
may be deferred to a later date within the visit window) if a participant has an 
active ulcerative genital lesion, is known to have an active genital tract 
infection (GTI) at the scheduled timepoint, or has any condition noted during 
pelvic exam via speculum or in medical history that in the opinion of the 
clinician represents a contraindication to mucosal sampling (eg, bacterial 
vaginosis).  
• Participants will be instructed to refrain from vaginal sex and to avoid using 
anything in or around their vagina, including tampons, spermicide, lubricants, 
or medications (eg, topical yeast treatments) for 2 days prior to cervicovaginal 
secretion or vaginal biopsy sampling. Cervicovaginal sampling may be 
deferred to a later date within the visit window if a participant is known to 
have not followed these instructions. 
• Cervicovaginal secretion or vaginal biopsy sampling will be deferred to a later 
date if a participant is menstruating. 
• Rectal secretion or biopsy sampling will not be performed (or may be deferred 
to a later date within the visit window) if a participant has an anorectal 
condition, such as an active infection or inflammation of the colorectal area 
(eg, an HSV-2 outbreak or inflamed hemorrhoids or colitis/diarrhea), internal 
hemorrhoids, or any other condition noted during screening rectal exam via 
anoscope or in medical history that in the opinion of the clinician represents a 
contraindication to rectal secretion or biopsy sampling.  
• Participants will be instructed to refrain from receptive anal intercourse and to 
avoid inserting anything into their anus (including cleaning products, 
lubricant, enemas, or douches (including water) for 2 days prior to rectal 
secretion or biopsy sampling. Rectal sampling may be deferred to a later date 
within the visit window if a participant is known to have not followed these 
instructions. 

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Additional considerations for biopsies: 
• Participants must not have taken antithrombotic medications (except 
acetylsalicylic acid [ASA] and non-steroidal anti-inflammatory drug 
[NSAIDs]) for 5 days prior to the procedure. If a participant is taking these 
medications for medical reasons, biopsies should not be collected and these 
medications should not be interrupted.  
• Participant should not currently be taking anticoagulants. For participants with 
recent anticoagulant use, a CRS clinician must consult with the HVTN 137 
PSRT for approval prior to collecting any tissue biopsies.  
• Participants should not have receptive anal sex and/or insert any foreign 
object or substance into the rectum for 5 days after rectal biopsy samples have 
been collected.  
• Participants should not have receptive vaginal sex and/or insert any foreign 
object or substance into the vagina for 7 days after vaginal biopsy samples 
have been collected. 
Leukapheresis: 
Collection of PBMC via leukapheresis will be performed in accordance with the 
standard practices of the participating apheresis center. Typically, in this 
procedure, approximately 12 liters of blood will be processed over about 3 to 4 
hours using peripheral veins for venous access. The blood will be anti-coagulated 
in accordance with standard practice of the apheresis center.  
Post-procedural safety assessments will be performed in accordance with the 
standard practices of the participating apheresis center. Additionally, the 
participant will be advised to contact the study site if they experience any adverse 
events following the procedure. 
Eligibility for leukapheresis: 
• Prior to leukapheresis, participant must meet all apheresis center requirements 
for this procedure. 
• Participants who can become pregnant must have a negative pregnancy test 
within 48 hours prior to the procedure. 
Bone marrow aspiration:  
Collection of bone marrow will be performed in accordance with the standard 
practices of the participating provider and/or facility. Using a sterile needle and 
sterile technique, up to 20 cc of marrow will be aspirated following a single 
puncture of the skin and periosteum at the posterior iliac crest. The entire 

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aspiration procedure will take approximately 15 minutes, with the entire visit 
taking approximately 45 minutes.  
Post-procedural safety assessments will be performed in accordance with the 
standard practices of the participating provider and/or facility. The CRS will 
contact the participant approximately 7 days after the procedure for a post-
procedure safety check (see HVTN 137 SSP). The participant will be advised to 
contact the study site if they experience pain or numbness for greater than 48 
hours following the procedure or fever or other evidence of infection 
(inflammation and/or pus) at the aspiration site. In general, a participant who 
reports any post-procedure reaction greater than mild is seen by a clinician within 
48 hours, unless the reaction is improving and/or has completely resolved. 
Eligibility for bone marrow aspiration: 
• Participant may not be currently taking warfarin, oral antithrombin 
equivalents (including, but not limited to, apixiban, rivaroxiban, dabigatran), 
enoxaparin injections, or other medications that would increase the risk of 
bleeding as assessed by the clinician performing the procedure. 
• No evidence of localized infection directly superior to aspiration site 
• No history of allergy to local anesthesia (eg, Novocaine, Lidocaine) 
• No other contraindication to procedure as assessed by the clinician performing 
the procedure 
• Participants who can become pregnant must have a negative pregnancy test 
within 48 hours prior to the procedure. 
Lymph node FNA: 
Tissue sampling of an axillary lymph node will be carried out percutaneously by 
fine needle aspiration (FNA). This procedure will be performed in accordance 
with the standard practices of the participating provider and/or facility. The 
procedure involves tissue retrieval with a needle via a small skin incision under 
sonographic guidance. Approximately 2-4 passes will be made to retrieve 
cytologic material. 
Post-procedural safety assessments will be performed in accordance with the 
standard practices of the participating provider and/or facility. The participant will 
be advised to contact the study site if they experience severe pain, fever or other 
evidence of infection (inflammation and/or pus) at the aspiration site, or arm 
numbness or weakness. 

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Eligibility for lymph node FNA: 
• Participant may not be currently taking warfarin, oral antithrombin 
equivalents (including, but not limited to, apixiban, rivaroxiban, dabigatran), 
enoxaparin injections, or other medications that would increase the risk of 
bleeding as assessed by the clinician performing the procedure. 
• No evidence of localized infection directly superior to aspiration site 
• No history of allergy to local anesthesia (eg, Novocaine, Lidocaine) 
• No other contraindication to procedure as assessed by the clinician performing 
the procedure 
• Participants who can become pregnant must have a negative pregnancy test 
within 48 hours prior to the procedure. 
9.6 
AESI contact for Part A 
CRS staff will contact Part A study participants 14 months after enrollment to 
collect the information listed below; Part A Optional Second Boost participants 
will provide this information at a visit 12 months after the third vaccination (see 
Appendix J). Clinic visits will only be required if HIV confirmatory testing is 
necessary (see Section 9.7.1); however, a clinic visit may be arranged for other 
reasons (eg, AESI assessment and referral). 
• Confirmation of vital status; if deceased, attempt to learn cause and date of 
death; 
• If participant is alive, record the following events: 
▪ New AEs related to study product(s); 
▪ Medically attended adverse events (MAAE), defined as any adverse 
events leading to an unscheduled visit to a healthcare professional (see 
HVTN 137 SSP); 
▪ SAEs; 
▪ AEs of special interest (AESI, see Section 11.2.2). A sample list of AESI 
is provided in Appendix V. AESI are reported regardless of relationship to 
study product(s); 
▪ New diagnosis of HIV infection; and 
▪ Pregnancies and outcomes, including congenital anomalies/birth defects. 
All such events will be recorded. 

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9.6.1 
Interim contacts 
CRSs may report safety information obtained at a contact other than the AESI 
contact. These contacts are reported as interim visits. 
9.7 
HIV counseling and testing 
HIV counseling will be performed in compliance with the CDC’s guidelines or 
other local guidelines for HIV counseling and referral. HIV testing will be 
performed in accordance with the current HVTN HIV testing algorithm following 
enrollment. 
Participants will be counseled routinely during the trial on the avoidance of HIV 
infection and on the potential negative social impacts of testing antibody positive 
due to the vaccine. They will also be counseled on the risks of HIV antibody 
testing outside of the HVTN CRSs and will be discouraged from doing so during 
study participation and/or during any period of vaccine-induced positive serology. 
Study staff will take particular care to inform study participants of the likelihood 
of routine HIV testing being offered or performed outside the study CRS at 
emergency rooms, clinics, and medical offices. Such testing has become more 
likely due to the CDC’s revised guidelines for HIV counseling and testing, as well 
as policy changes in many countries to make HIV testing more frequent and 
routine. CRS staff should inform participants of their right to opt out of HIV 
testing outside the study site. CRS staff should inform study participants if local 
and/or state policies and regulations permit medical providers to perform HIV 
testing without first informing patients. If this is the case, then CRS staff should 
advise study participants that they may decline testing preemptively. CRS staff 
should also inform participants if positive results must be reported to local public 
health authorities. CRS staff should also inform participants of the need to 
maintain study blinding by getting HIV testing only at the study CRS. CRS staff 
should provide participants with CRS contact information and should encourage 
participants to ask medical providers to contact the CRS. The CRS can verify that 
the participant is in an HIV vaccine clinical trial and should only be tested at the 
study CRS. 
Potential participants identified as being HIV-infected during screening are not 
enrolled. Potential and enrolled participants identified as being HIV-infected will 
be referred for medical treatment, counseling, and management of the HIV 
infection. Participants who are found to be HIV-infected after enrollment will not 
receive any additional study product but will continue to be followed in the study 
for safety assessments. These individuals may also be referred to appropriate 
ongoing clinical trials or observational studies. 

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9.7.1 
Distinguishing intercurrent HIV infection from vaccine-induced 
positive serology 
The study product may elicit an antibody response to HIV proteins. Therefore, 
vaccine-induced positive serology may occur in this study. Several precautionary 
measures will be taken to distinguish intercurrent HIV infection from vaccine-
induced positive serology. These precautionary measures include: 
• Participants will have physical examinations at visits specified in Appendix Q, 
Appendix R, and Appendix T. Signs or symptoms of an acute HIV infection 
syndrome, an intercurrent illness consistent with HIV-1 infection, or probable 
HIV exposure would prompt a diagnostic workup per the HVTN algorithm for 
Recent Exposure/Acute Infection Testing to determine HIV infection. 
• HIV testing will be performed at multiple timepoints throughout the study 
(see Appendix J, Appendix K, Appendix L, Appendix M, Appendix N, 
Appendix O, and Appendix P). The Laboratory Program (or approved 
diagnostic laboratory) will follow the HVTN HIV testing algorithm (see 
HVTN 137 Study Specific Procedures (SSP)), which is able to distinguish 
vaccine-induced antibody responses from actual HIV infections. 
• All participants can receive HIV-1 diagnostic testing from the site following 
their last scheduled visit until they are told that they did not receive an HIV 
vaccine or that they do not have vaccine-induced seropositivity. 
• All participants who received vaccine product and who have vaccine-induced 
positive or indeterminate HIV-1 serology (as measured by the standard anti-
HIV antibody screening tests) at or after the study is unblinded will be offered 
poststudy HIV-1 diagnostic testing (per the HVTN poststudy HIV-1 testing 
algorithm) periodically and free of charge as medically/socially indicated 
(approximately every 6 months) unless or until HIV Ab testing is no longer 
the standard test in clinical settings. 
9.7.2 
VISP registry  
Experimental HIV vaccines may induce antibody production to HIV antigens, 
producing reactive results on commercially available HIV test kits. This is called 
“vaccine-induced seropositivity” (VISP) (see Section 9.7.2). In order to provide 
poststudy HIV testing to distinguish between VISP and HIV infection, and to 
mitigate potential social harms resulting from VISP in HIV vaccine recipients 
who are not infected with HIV, the HVTN has created a VISP registry. Following 
study unblinding, the registry will allow trained staff to verify that an individual 
has received an HIV vaccine, and therefore has the potential for VISP. 
Information in the VISP registry will not be used for research. Rather, the registry 
exists to support provision of poststudy testing and counseling services to HIV 
vaccine recipients. The registry contains the names of all study participants, 
unless they request that their names be removed. 

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9.8 
Contraception status 
Contraception status is assessed and documented at every scheduled clinic visit 
for a participant who was assigned female sex at birth and who is sexually active 
in a way that could cause that participant to become pregnant. Prior to enrollment 
and throughout the study, staff will ask participants to verbally confirm their use 
of adequate contraceptive methods. A participant who was assigned female sex at 
birth and is sexually active in a way that could cause that participant to become 
pregnant should be reminded at all scheduled clinic visits of the importance of 
using contraception and should be referred to specific counseling, information, 
and advice as needed. (Specific contraception requirements are listed in Section 
7.1). This reminder should be documented in the participant’s study record. 
Self-reported infertility—including having reached menopause (no menses for 1 
year) or having undergone hysterectomy, bilateral oophorectomy, or tubal 
ligation—must be documented in the participant’s study record. 
9.9 
Urine testing 
Dipstick testing may be performed in the clinic or the lab, as long as the required 
elements (protein and hemoglobin) are tested. The examination is performed on 
urine obtained by clean catch. 
If the screening dipstick is transiently abnormal due to non-urinary bleeding (eg, 
menstruation) or infection, document this issue in the participant’s source 
documentation. For infection, provide appropriate treatment and/or referral and 
document this in the participant's chart. Following resolution, repeat the dipstick 
and, if within the eligibility limits specified in the protocol, the participant may be 
enrolled. 
Follow-up visit dipstick testing should be deferred if a participant is experiencing 
non-urinary bleeding (eg, menstruation), but should be performed as soon as 
possible. If a follow-up visit dipstick is abnormal due to a participant’s non-
urinary bleeding (eg, menstruation), document in the comment section of the case 
report form (CRF) and repeat the dipstick once the participant is no longer 
experiencing non-urinary bleeding. A micro-urinalysis is not required. If a follow-
up visit dipstick or micro-urinalysis is abnormal due to infection, provide 
appropriate treatment and/or referral and document this in the participant's source 
documentation. See the Urine Testing MOP for further details. 
9.10 
Assessments of reactogenicity 
For all participants, baseline assessments are performed before and reactogenicity 
assessments are performed after each vaccination. All reactogenicity symptoms 
are followed until resolution and graded according to the Division of AIDS Table 

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for Grading the Severity of Adult and Pediatric Adverse Events, Corrected 
Version 2.1, July 2017, except as noted in Section 11.2.2. 
The reactogenicity assessment period is 7 full days for Part A and Part B and 14 
full days for Part C following each vaccination per the assessment schedule 
shown in Table 9-1. Participants are instructed to record symptoms using a 
Participant Diary. Contacts between the participant and the site staff should take 
place at least once between 1-3 days postvaccination. In general, a participant 
who self-reports any postvaccination reaction greater than mild is seen by a 
clinician within 48 hours after onset, unless the reaction is improving and/or has 
completely resolved. Clinic staff will follow new or unresolved reactogenicity 
symptoms present at day 7 (Parts A & B) or day 14 (Part C) to resolution. 
Reactogenicity events are reported using CRFs that correspond to the time of 
assessment in Table 9-1. Reactogenicity assessments include assessments of 
systemic and local symptoms, and vaccine-related lesions. Events not listed on a 
CRF, or with an onset after the reactogenicity assessment period (day of 
vaccination and 7 full days after for Part A and Part B and 14 full days after for 
Part C), or those meeting SAE/adverse events requiring expedited reporting 
according to DAIDS criteria, are recorded on an adverse event log form. 
Table 9-1 Schedule of reactogenicity assessments 
Day 
Time 
Performed by 
0a 
Baseline: before vaccination 
HVTN CRS clinician 
 
Early: 25-60 minutes after vaccination 
HVTN CRS clinician 
 
Between early assessment and 11:59pm 
day 0 
HVTN CRS clinician or 
participant 
1-7b 
Between 12:00am and 11:59pm on the 
respective day 
HVTN CRS clinician or 
participant 
1-14c 
Between 12:00am and 11:59pm on the 
respective day 
HVTN CRS clinician or 
participant 
a Day of vaccination 
b New or unresolved reactogenicity symptoms present on day 7 are followed until resolution for Parts A 
and B 
c New or unresolved reactogenicity symptoms present on day 14 are followed until resolution for Part C 
9.10.1 
Assessment of systemic and local symptoms 
Systemic symptoms include increased body temperature, malaise and/or fatigue, 
myalgia, headache, chills, arthralgia, and nausea. Local symptoms include pain 
and/or tenderness at the injection site. The daily maximum severity reached for 
each symptom during the assessment period is reported.  
Body temperature is measured by oral or infrared thermometry. All temperatures 
must be measured by non-axillary thermometry. This includes temperatures taken 
in the clinic, as well as temperatures taken by participants during the 
reactogenicity period. 

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Temperature is reported in degrees Celsius. If temperature is measured in 
Fahrenheit, the conversion to Celsius should be documented in the participant’s 
chart note. A measurement is taken once daily during the assessment period and 
should be repeated if participant is feeling feverish. 
Participants with evidence of moderate to severe reactogenicity may be asked to 
come to the clinic for additional assessment and/or blood sampling. 
9.10.2 
Assessment of injection site 
Typical injection site reactions are erythema/redness and induration/swelling. The 
maximum diameter for all injection site reactions is recorded. 
All injection site reactions are monitored until resolution. Reactions with 
diameters greater than 5 cm are followed daily; otherwise, the frequency of 
follow-up is based on clinician judgment. See HVTN 137 SSP for detail. 
9.11 
Visit windows and missed visits 
Visit windows are included in  Appendix W. The procedures for documenting 
missed visits and out of window visits are described in the HVTN 137 SSP. If the 
missed visit is one that required safety assessments or local safety labs, HVTN 
CRS staff should attempt to bring the participant in for an interim visit as soon as 
possible. 
Procedures performed at an interim visit are usually toxicity/safety assessments 
(including local safety labs) and HIV testing. Except for HIV testing, these 
procedures are performed only if they were required at the missed visit or if 
clinically indicated. HIV testing may be performed as deemed appropriate by the 
study staff. Blood samples for immunogenicity assays are not typically collected 
at interim visits. Detail will be provided in the HVTN 137 SSP. 
If a missed visit required vaccination, please refer to Section 7.4.2 and Section 
7.4.3 for resolution. 
9.12 
Early termination visit 
In the event of early participant termination, site staff should consider if the 
following assessments are appropriate: a final physical examination, clinical 
laboratory tests (including urine dipstick, CBC with differential, and chemistry 
panel), pregnancy testing (note: for persons who are confirmed pregnant, 
pregnancy testing is not required, unless clinically indicated), social impact 
assessment, and HIV test. For participants who have a confirmed diagnosis of 
HIV infection, see Section 9.14. 

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9.13 
Pregnancy 
If a participant becomes pregnant during the course of the study, no more 
injections of study product will be given. During pregnancy, no more STI testing, 
mucosal collections or additional optional collections will be conducted. 
Remaining visits and study procedures should be completed unless medically 
contraindicated or applicable regulations require termination from the study. 
During follow-up in persons who are confirmed pregnant, pregnancy testing is not 
required, unless clinically indicated. If the participant terminates from the study 
prior to the pregnancy outcome, the site should make every effort to keep in touch 
with the participant in order to ascertain the pregnancy outcome. Pregnancies and 
pregnancy outcomes will be reported as described in the HVTN 137 SSP section 
on Pregnancy Management and Reporting. If the participant is no longer 
pregnant, refer to Section 7.4.3. 
If the participant is no longer pregnant (as defined by two consecutive negative 
tests) or breast-feeding and study product administration and mucosal and 
additional optional collections can be performed within an appropriate visit 
window, these may resume with unanimous consent of the HVTN 137 PSRT. 
9.14 
HIV infection during the study 
If a participant becomes HIV-infected during the course of the study, no 
additional study product will be administered. Participants will be encouraged to 
continue scheduled study visits for up to 12 weeks following their last study 
product administration. Follow-up duration for participants diagnosed with HIV 
infection may be adjusted in consultation with the CRS investigator and the 
HVTN 137 PSRT (eg, to avoid interference with participant initiation of HIV 
treatment). At postinfection follow-up visits, only specimens required for 
protocol-specified safety laboratory tests, urinalysis, and pregnancy tests will be 
collected (note: for persons who are confirmed pregnant, pregnancy testing is not 
required, unless clinically indicated); in addition, some clinic procedures may be 
modified or discontinued (see Appendix Q, Appendix R, and Appendix T). 

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10 
Laboratory 
10.1 
HVTN CRS laboratory procedures 
The HVTN 137 Site Lab Instructions and SSP provide further guidelines for 
operational issues concerning the clinical and processing laboratories. These 
documents include guidelines for general specimen collection, special 
considerations for phlebotomy, specimen labeling, whole blood processing, HIV 
screening/diagnostic testing, and general screening and safety testing. 
Tube types for blood collection are specified in Appendix J, Appendix K, 
Appendix L, Appendix M, Appendix N, Appendix O, and Appendix P. For tests 
performed locally, the local lab may assign appropriate tube types. 
In specific situations, the blood collection tubes may be redirected to another 
laboratory or may require study-specific processing techniques. In these cases, 
laboratory special instructions will be posted on the protocol-specific section of 
the HVTN website. 
Of note, all assays described below are performed as research assays to evaluate 
the ability of the vaccine to induce immune responses in the context of the 
participants’ genetic background and are not approved for use in medical care. 
Results from these assays are not made available to participants or medical 
professionals to guide treatment decisions. 
10.2 
Total blood volume 
Required blood volumes per visit are shown in Appendix J, Appendix K, 
Appendix L, Appendix M, Appendix N, Appendix O, and Appendix P. Not 
shown is any additional blood volume that would be required if a safety lab needs 
to be repeated, or if a serum pregnancy test needs to be performed. The additional 
blood volume would likely be minimal. The total blood volume drawn for each 
participant will not exceed 500 mL in any 56-day (8-week) period. 
The preferred laboratory specimen tube types for research samples are shown in 
Appendix J, Appendix K, Appendix L, Appendix M, Appendix N, Appendix O, 
and Appendix P. Alternate tube types may be used under certain circumstances 
(eg, ACD tube shortages) upon approval of the HVTN Laboratory Center. Refer 
to the HVTN 137 Specimen Collection SSP for more information. 
10.3 
Primary immunogenicity timepoint 
The primary immunogenicity timepoints in this study occur 2 weeks after the last 
vaccination for groups receiving 2 vaccinations and 1 and 2 weeks after the 
second and third vaccinations for the groups receiving 3 vaccinations. For the 

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group receiving 3 vaccinations, primary timepoints for innate immunity and 
inflammation assays are baseline, and days 1, 3, and 7 post first vaccination. 
Endpoint assays for humoral and cellular responses are performed on specimens 
collected from participants at the primary immunogenicity timepoint and may be 
performed on samples collected at baseline. Depending on the initial results, 
assays for humoral, cellular, innate immunity, and inflammatory responses may 
be performed on samples collected from participants at other timepoints; the 
schedules are shown in Appendix J, Appendix K, Appendix L, Appendix M, 
Appendix N, Appendix O, and Appendix P. 
10.4 
Endpoint assays: cellular 
10.4.1 
Intracellular cytokine staining (ICS) assay 
Flow cytometry will be used to examine vaccine-specific CD4+ T-cell responses 
following stimulation of PBMCs with synthetic HIV peptides that span the HIV-1 
envelope protein. ICS parameters will include cytokines such as interferon 
gamma (IFN-γ), interleukin (IL)-2, and TNF-α, and may include other cytokines 
(such as cytokines relevant to Th2 and Th17 responses) to identify T cells of 
specific functionality. Data will be reported as percentages of CD4+ T cells 
responding to a specific peptide pool. Additional cell surface markers, cytokines, 
or functional markers may also be analyzed. 
10.4.2 
CD4+ T follicular helper cells (Tfh/pTfh)  
Multicolor flow cytometry may be used to identify, phenotype and isolate 
circulating CD3+ T cells in the peripheral blood (PBMC) and LN FNAs. 
Peripheral Tfh may be characterized based on expression of lineage markers 
including CXCR5, PD-1, and ICOS on CD4+ T cells. Functionality of Tfh cells 
might be tested by in vitro stimulation of cells with synthetic HIV peptides that 
span the HIV-1 envelope protein to identify, enumerate and immunophenotype 
antigen-specific Tfh cells.  
10.4.3 
Env-specific B cell and plasmablast phenotyping 
HIV-1 Env-specific B cells and plasmablasts induced by vaccination will be 
identified and characterized using fluorescently-labeled recombinant Env proteins 
(including BG505 SOSIP.664) in combination with a flow cytometry antibody 
panel. In particular, Env-reactive B cells and plasmablasts will be enumerated and 
may be further characterized for expression of memory, activation, inhibitory or 
other markers of interest.  
10.4.4 
BCR repertoire analysis 
Single or bulk populations of memory B cells and plasmablasts may be sorted for 
BCR sequencing and gene expression analysis. Env-specific B cells may instead 

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be expanded for detection of and functional testing of secreted antibodies by 
enzyme-linked immunosorbent assay (ELISA) or microneutralization assays, and 
BCR sequencing. The resulting VH and VL genes may be cloned into an IgG 
backbone for antibody expression and characterization of the binding, epitope-
specificity, and neutralization. 
10.4.5 
Epitope Mapping 
Epitope mapping will be performed using either the ICS or IFN-γ ELISpot assays. 
PBMCs will be stimulated with synthetic peptides that span the BG505 
SOSIP.664 gp140. Epitope mapping will be performed using BG505 SOSIP.664 
gp140 15-mer peptides overlapping by 11 aa. Once positive responders are 
identified using peptide pools, the specific responses will be mapped to the single 
15 amino acid peptides. 
10.5 
Endpoint assays: humoral 
10.5.1 
Binding antibody multiplex assay (BAMA) 
HIV-1–specific total binding IgG antibodies will be assessed on serum samples 
from study participants taken at the primary immunogenicity timepoints and 
baseline. In addition, HIV-1–specific total binding IgA antibodies and binding to 
IgG subclasses (IgG1, IgG2, IgG3, and IgG4) may also be assessed. Specimens 
from other timepoints may also be assayed based on the results of the initial 
assay. 
10.5.2 
Antibody avidity  
Antibody avidity may be measured using BAMA with the addition of a 
dissociation step to calculate the antibody avidity index (BAMA-AI). Biolayer 
Interferometry (BLI) and/or Surface Plasmon Resonance (SPR) technologies may 
also be used to define antibody avidity. 
10.5.3 
Antibody-dependent cellular cytotoxicity assay (ADCC)  
ADCC activity may be assessed using serum samples from study participants 
taken at the primary immunogenicity timepoints. Specimens from the baseline 
and other timepoints may also be analyzed at the discretion of the HVTN 
Laboratory Center, which may be contingent on the results of the primary 
immunogenicity timepoints. For the Luciferase-based cytotoxicity assay, 
participant sera are incubated with infectious molecular clone (IMC)-infected 
cells and percent killing is measured through the use of Viviren luminescence. 
10.5.4 
Antibody-dependent cellular phagocytosis (ADCP)  
To assess the ability of vaccine-elicited antibodies to engage cellular FcR for 
potential antiviral function, ADCP may be measured using serum samples from 

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study participants taken at baseline and at a primary immunogenicity timepoint. 
ADCP is measured by assessing the ability of vaccine elicited antibodies to 
mediate monocyte phagocytosis of HIV-1 antigen coated fluorescent beads by 
flow cytometry (99, 100). An array of antigens or viruses in addition to specimens 
from other timepoints may also be analyzed at the discretion of the HVTN 
Laboratory Center, which may be contingent on the results of the primary 
immunogenicity timepoint. 
10.5.5 
Antibody-dependent neutrophil phagocytosis (ADNP) 
To assess the ability of vaccine-elicited antibodies to engage cellular FcR for 
potential antiviral function, ADNP may be measured using serum samples from 
study participants at a primary immunogenicity timepoint and compared to 
placebo controls. ADNP is measured by assessing the ability of vaccine elicited 
antibodies to mediate neutrophil cell line phagocytosis of HIV-1 antigen coated 
fluorescent beads by flow cytometry (101). An array of antigens or viruses in 
addition to specimens from other timepoints may also be analyzed at the 
discretion of the HVTN Laboratory Center, which may be contingent on the 
results of the primary immunogenicity timepoint. 
10.5.6 
Complement assays 
The capacity of antibodies to bind complement will be assessed either through a 
direct binding assay or a complement deposition assay (102, 103). The 
complement deposition assay is a cell-based method. The binding assay is a bead-
based multiplexed method that measures engagement of antigen specific antibody 
with complement.  
10.5.7 
Infected cells antibody binding assay (ICABA) 
The capacity of vaccine elicited antibodies to recognize epitopes exposed on the 
surface of infected cells may be assessed using serum samples from study 
participants taken at baseline and the primary immunogenicity timepoint. 
Specimens from other timepoints may also be analyzed at the discretion of the 
HVTN Laboratory Center contingent upon the results of the primary 
immunogenicity timepoint. This assay measures the capacity of vaccine elicited 
antibodies to recognize HIV envelope on the surface of infected cells (ie, the first 
step in mediating antibody Fc effector function) with a readout by flow 
cytometry. 
10.5.8 
Fc receptor binding 
The ability of vaccine elicited antibodies to bind to cellular Fc receptors enables 
characterization of the antibody Fc profile that results in antiviral function (ie, 
includes subclass and glycans). HIV-specific antibody binding to FcγR proteins 
will be assessed by the FcR BAMA. The FCR BAMA is a modification of the 
binding assay where fluorescently labeled FcR proteins are utilized as the 
detection reagent for serum antibodies bound to HIV proteins on microspheres. 

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The readout may include the magnitude and/or avidity for an array of Fc receptors 
involved in mediating antiviral activity. 
10.5.9 
Peptide microarray 
Linear epitope specificities of purified serum IgG will be examined by peptide 
microarray using an Env peptide library, which contains 15-mer peptides that 
overlap by 12 amino acids and cover consensus Env strains (gp160) and vaccine 
strains (gp120). 
10.5.10 
Neutralizing antibody assay 
HIV-1–specific nAb assays will be performed on serum samples from study 
participants taken at the primary immunogenicity timepoint(s). Specimens from 
the baseline and other timepoints may also be analyzed at the discretion of the 
HVTN Laboratory Center, which may be contingent on the results of the primary 
immunogenicity timepoints. The TZM-bl assay will test neutralization of the 
vaccine strain (BG505.T332N) and a single highly neutralization-sensitive tier 1 
virus (MW965.26). The global panel and/or subtype-specific panels may be used 
to assess heterologous tier 2 neutralization (14, 15). 
10.5.11 
Polyclonal serum Ab (Fab) binding 
A comprehensive probe of polyclonal antibody responses will be performed on 
sera. Single particle electron microscopy will be conducted on IgGs that have 
been isolated and digested into Fabs and made into complexes with immunogens. 
This technique will be applied to reveal the epitopes that are targeted after 
immunization with stabilized, prefusion conformation HIV-1 envelope 
glycoprotein BG505 SOSIP gp140 in the presence of different adjuvants. If 
neutralization breadth is detected, then complexes will also be made with SOSIP 
trimers with corresponding sequences to map the cross-reactive antibody 
responses. 
10.6 
Innate immunity and inflammation assays 
10.6.1 
Soluble factors in serum or plasma 
Multiplex cytokine detection assays (such as meso-scale discovery [MSD]) or 
ELISA may be used to measure soluble cytokines, chemokines, and other 
immunomodulatory factors in the serum or plasma. Analytes may include IFN-γ, 
IL-6, TNF- α, IL-10, IFN-γ inducible protein 10 (IP-10), and/or monocyte 
chemoattractant protein 1 (MCP-1). Other analytes may also be included. 
10.6.2 
Enumeration and phenotyping of cell populations 
Phenotyping of DCs, monocytes, NK cells, B cells, T cells, or other leukocytes 
for lineage, maturation, and activation markers may be performed on fresh or 

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cryopreserved PBMC. Trucount tubes with whole blood will be used when 
possible for direct enumeration of major leukocyte populations in the blood, 
including DC, by flow cytometry. Data will be reported as cell concentrations per 
microliter of blood and/or as percentage of live cells. 
10.6.3 
Gene expression 
Bulk PBMC or whole blood will be cryopreserved in an RNA protection reagent. 
RNA may be isolated and used for analysis by RNA sequencing and/or real-time 
PCR. Signatures of gene expression changes will be analyzed over time after 
vaccination. 
10.6.4 
Metabolomic profiles 
Metabolomics profiling in response to study product may be performed on serum 
during innate responses. Liquid chromatography–mass spectrometry (LC-MS) 
analysis will be performed and mass spectral data will be collected using reversed 
phase chromatography with both positive and negative electrospray ionization. 
Metabolite confirmation will be performed with tandem MS-MS experiments 
with additional mass spectrometers. To identify vaccine-derived metabolites, the 
vaccine will be analyzed with the same metabolomics protocol as for serum. 
10.6.5 
Proteomics 
Proteomics profiling in response to study product may be performed on serum or 
plasma to identify and quantify peptides in human subjects. The proteomics 
method uses a modified higher-energy collisional dissociation (HCD) Liquid 
Chromatography-Tandem Mass Spectrometry (LC-MS/MS) method. Quantitation 
of proteins will be performed using summed peptide intensities given by 
MaxQuant. 
10.7 
Mucosal assays 
Env-specific antibodies in mucosal samples will be assessed using quantitative 
immunoassays and/or IHC. For immunoassays using mucosal secretions and/or 
tissue samples, antibody levels may be normalized relative to total protein and/or 
total IgG. Hemoglobin measurements may be used to perform quality control of 
mucosal secretions. For IHC using mucosal tissue samples, the distribution of 
Env-specific antibodies will be described qualitatively or semi-quantitatively 
relative to the mucosal epithelium, stroma and/or lamina propria. 
10.8 
Lab assay algorithm 
The Lab Assay Algorithm lists assays to characterize cellular, humoral, and innate 
immune responses as well as host genetics that may be conducted to determine 
endpoints in HVTN vaccine trials. The type of assay(s) employed will be 

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dependent on the response obtained by the primary immunogenicity assays at 
relevant timepoints. Please note that the Lab Assay Algorithm will be updated 
periodically to include new assays. 
10.9 
Exploratory studies 
Samples may be used for other testing and research related to furthering the 
understanding of HIV immunology or vaccines. In addition, cryopreserved 
samples may be used to perform additional assays to support standardization and 
validation of existing or newly developed methods.  
10.10 
Specimen storage and other use of specimens  
The HVTN stores specimens from all study participants indefinitely, unless a 
participant requests that specimens be destroyed or if required by IRB/EC, or RE.  
Other use of specimens is defined as studies not covered by the protocol or the 
informed consent form for the main study (see Appendix A, Appendix B and 
Appendix C).  
This research may relate to HIV, vaccines, the immune system, and other 
diseases. This could include genetic testing and, potentially, genome-wide studies. 
This research is done only to the extent authorized in each study site’s informed 
consent form, or as otherwise authorized under applicable law. Other research on 
specimens (“other use”) will occur only after review and approval by the HVTN, 
the IRB/EC of the researcher requesting the specimens, and the CRS’s 
IRBs/ECs/REs if required.  
As part of consenting for the study, participants document their initial decision to 
allow or not allow their specimens to be used in other research, and they may 
change their decision at any time. The participant’s initial decision about other 
use of their specimens, and any later change to that decision, is recorded by their 
CRS in a Web-based tool that documents their current decisions for other use of 
their specimens. The HVTN will only allow other research to be done on 
specimens from participants who allow such use.  
CRSs must notify HVTN Regulatory Affairs if institutional or local governmental 
requirements pose a conflict with or impose restrictions on specimen storage or 
other use of specimens. 
10.11 
Biohazard containment 
As the transmission of HIV and other blood-borne pathogens can occur through 
contact with contaminated needles, blood, and blood products, appropriate 
precautions will be employed by all personnel in the drawing of blood and 

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shipping and handling of all specimens for this study, as currently recommended 
by the CDC and the NIH or other applicable agencies. 
All dangerous goods materials, including Biological Substances, Category A or 
Category B, must be transported according to instructions detailed in the 
International Air Transport Association Dangerous Goods Regulations. 

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11 
Safety monitoring and safety review 
11.1 
Safety monitoring and oversight 
11.1.1 
HVTN 137 PSRT 
The HVTN 137 PSRT is composed of the following members: 
• DAIDS medical officer representative 
• Protocol chair and cochair 
• Protocol Team leader 
• Core medical monitor 
• Clinical safety specialist 
The clinician members of HVTN 137 PSRT are responsible for decisions related 
to participant safety. 
The Protocol Team clinic coordinator, clinical data manager, vaccine developer 
representative, clinical trial manager, and others may also be included in HVTN 
137 PSRT meetings. 
11.1.2 
HVTN SMB 
The SMB is a multidisciplinary group consisting of biostatisticians, clinicians, 
and experts in HIV vaccine research that, collectively, has experience in the 
conduct and monitoring of vaccine trials. Members of the SMB are not directly 
affiliated with the protocols under review. 
The SMB reviews safety data, unblinded as to treatment arm, approximately 
every 4 months. The reviews consist of evaluation of cumulative reactogenicity 
events, AE, laboratory safety data, and individual reports of adverse events 
requiring expedited reporting to DAIDS. The SMB conducts additional special 
reviews at the request of the HVTN 137 PSRT. 
Study sites will receive SMB summary minutes and are responsible for 
forwarding them to their IRB/EC and any applicable RE. 
11.1.3 
SDMC roles and responsibilities in safety monitoring  
The roles and responsibilities of the SDMC in relation to safety monitoring 
include: 

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• Maintaining a central database management system for HVTN clinical data; 
• Providing reports of clinical data to appropriate groups such as the HVTN 137 
PSRT and HVTN SMB (see Section 11.1.2); 
11.1.4 
HVTN Core roles and responsibilities in safety monitoring 
• Daily monitoring of clinical data for events that meet the safety pause and 
HVTN 137 PSRT AE review criteria (see Section 11.4); 
• Notifying HVTN CRSs and other groups when safety pauses or planned holds 
are instituted and lifted (see Section 11.4); 
• Querying HVTN CRSs for additional information regarding reported clinical 
data; and 
• Providing support to the HVTN 137 PSRT. 
11.2 
Safety reporting 
11.2.1 
Submission of safety forms to SDMC 
Site staff must submit all safety forms (eg, reactogenicity, adverse experience, 
urinalysis, local lab results, and concomitant medications) before the end of the 
next business day, excluding federal or bank holidays. The forms should not be 
held in anticipation of additional information at a later date. If additional 
information is received at a later date, the forms should be updated and 
resubmitted before the end of the next business day after receiving the new 
information. For the case of a longer site holiday closure, site staff must submit 
the data by the end of the 5th day (local time) after receiving the information even 
if this day is a holiday. 
For example: If the site becomes aware of an AE on Thursday (Day 0), the site 
must submit the data by the end of the next business day, on Friday. If there is a 
longer site holiday closure, then this AE must be reported no later than the end of 
the fifth day, Monday (Day 4). If Monday is a holiday as well, all safety forms 
still need to be submitted by the end of Monday (Day 4). 
11.2.2 
AE reporting 
An AE is any untoward medical occurrence in a clinical investigation participant 
administered a study product/procedure(s) and which does not necessarily have a 
causal relationship with this treatment. An AE can therefore be any unfavorable 
and unintended sign (including an abnormal laboratory finding), symptom, or 
disease temporally associated with the use of an investigational study 
product/procedure(s), whether or not related to the investigational study 
product/procedure(s). All AEs are graded according to the Division of AIDS 

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(DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, 
Corrected Version 2.1, July 2017, available on the RSC website at 
https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-
tables, except: 
• Unintentional Weight Loss is required to be reported as an AE only if it is 
considered to be potentially deleterious to the participant’s health (see HVTN 
137 Study Specific Procedures); 
• Injection Site Erythema or Redness and Injection Site Induration or Swelling 
will not consider surface area and interference with usual social and functional 
activities such that: 
▪ Grade 1 is: 2.5 to < 5 cm in diameter; 
▪ Grade 2 is: ≥ 5 to < 10 cm in diameter; 
▪ Grade 3 is: ≥ 10 cm in diameter OR Ulceration OR Secondary infection 
OR Phlebitis OR Sterile abscess OR Drainage; 
▪ Grade 4 is: Potentially life-threatening consequences (eg, abscess, 
exfoliative dermatitis, necrosis involving dermis or deeper tissue); 
• Creatinine is required to be reported as an AE only if it is gradable per the 
increase from local lab ULN parameter. Do not grade elevated creatinine 
based on the change from the baseline parameter. 
All AEs are reported to the SDMC on the appropriate CRF. Clinic staff should 
evaluate every AE to determine if (1) the AE meets the requirements for 
expedited reporting to DAIDS (see Section 11.2.3) and (2) if the AE meets the 
criteria for a safety pause/prompt AE review (see Section 11.4). 
During the main study period (see Section 3), all AEs are reported to the SDMC 
on the appropriate CRF. Clinic staff should evaluate every AE to determine if (1) 
the AE meets the requirements for expedited reporting to DAIDS (see Section 
11.2.3), (2) if the AE meets the criteria for a safety pause/prompt AE review (see 
Section 11.4), (3) if the AE is a medically attended adverse event (MAAE), and 
(4) if the AE is a potential immune-mediated disease that may be listed as an 
AESI. A sample list of AESI is provided in Appendix V. 
After the main study period in Part A, report the subset of AEs bulleted in Section 
9.6 until the AESI health contact (see Section 3) is complete. 
Sites are expected to notify HVTN clinical safety staff of any serious safety 
concern requiring their attention (Table 11-1). Telephone numbers and email 
addresses are found on the protocol home page on the HVTN Members’ site 
(https://members.hvtn.org/protocols/hvtn137). Concerns requiring immediate 
attention should be communicated by calling the clinical safety phone. 

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In the case of email notification, clinical safety staff will reply within one 
business day. Serious events that meet pause rule criteria will be addressed 
immediately (as outlined in Table 11-1). If email service is not available, the CRS 
should notify clinical safety staff of the event by telephone, and then submit 
CRFs.  
In addition, site investigators are required to submit AE information in accordance 
with IRB/EC and any applicable RE requirements. 
11.2.3 
Expedited reporting of adverse events to DAIDS 
Requirements, definitions and methods for expedited reporting of AEs are 
outlined in Version 2.0 (January 2010) of the Manual for Expedited Reporting of 
Adverse Events to DAIDS (DAIDS EAE Manual), which is available on the RSC 
website at https://rsc.niaid.nih.gov/clinical-research-sites/manual-expedited-
reporting-adverse-events-daids. The SAE Reporting Category will be used for this 
study. 
The internet-based DAIDS Adverse Experience Reporting System (DAERS) must 
be used for expedited AE (EAE) reporting to DAIDS. In the event of system 
outages or technical difficulties, expedited AE reports may be submitted via the 
DAIDS EAE Form. This form is available on the DAIDS RSC website at 
https://rsc.niaid.nih.gov/clinical-research-sites/paper-eae-reporting. 
For questions about DAERS, please contact CRMSsupport@niaid.nih.gov or 
from within the DAERS application itself. 
For questions about EAE reporting, please contact the DAIDS RSC Safety Office 
at (DAIDSRSCSafetyOffice@tech-res.com). 
The study products for which expedited reporting are required are:  
• BG505 SOSIP.664 gp140 
• Trimer 4571 
• CpG 1018 
• 3M-052-AF 
• GLA-LSQ 
• Alum adjuvant 
• Tris-NaCl Diluent 
• In addition to the expedited Reporting Category identified above, other AEs 
that must be reported in an expedited manner are all autoimmune diseases. 

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Throughout the duration of the study, the SAE Reporting Category will be used. 
After a Part A participant has completed the month 14 AESI health contact and is 
off study, sites must report SUSARs as defined in Version 2.0 of the DAIDS EAE 
Manual if the study site staff becomes aware of the events on a passive basis (eg, 
from publicly available information). 
For Part B and C participants, after completion of scheduled study visits, only 
SUSARs must be reported to DAIDS, if the study staff become aware of the 
events. 
The NIAID/DAIDS will report all unexpected SAEs related to the study products 
observed in this clinical trial to the FDA in accordance with 21 CFR 312.32 (IND 
Safety Reports). However, because safety is a primary study endpoint, the study 
sponsor Medical Officer will not routinely be unblinded to study treatment 
assignment when there is an assessment of relatedness of the SAE with the study 
product(s); and the safety report will be sent to the FDA based on the blinded 
attribution assessment. 
In some cases, the PSRT or CRS may believe unblinding of the site PI and 
participant would be appropriate to facilitate the clinical management of an AE or 
SAE. The HVTN MOP specifies procedures for emergency unblinding, and for 
early unblinding for medical reasons. 
11.3 
Safety reviews 
11.3.1 
Initial safety evaluation and dose escalation 
Enrollment in Group 1 across all participating HVTN CRSs will be restricted to a 
maximum of 1 participant per day until 6 participants have been enrolled. The 
HVTN 137 PSRT will review cumulative safety data available on all participants 
in Group 1 up to and including the 2-week visit after the first vaccination to 
determine whether dose escalation (ie, enrollment in Group 2) may begin. The 
HVTN 137 PSRT may consult with the HVTN SMB on an ad hoc basis for these 
evaluations. 
Enrollment in Group 2 across all participating HVTN CRSs will be restricted to a 
maximum of 1 participant per day until 5 participants have been enrolled. The 
HVTN 137 PSRT will review the cumulative safety data including at minimum 
local and systemic reactogenicity data reported for the first 72 hours 
postvaccination on each of these 5 participants and will determine whether it is 
safe to proceed with full enrollment in that group. 
11.3.2 
Safety evaluation for moving from Part A to Part B 
In addition to monitoring participant safety throughout the study period, the 
HVTN 137 PSRT will review all cumulative safety data available from groups 1 

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and 2 up to and including the 2-week visit after the second vaccination. Based on 
the assessment of these safety data, the HVTN 137 PSRT will make a decision 
regarding the appropriateness of moving to part B as well as regarding the 
recommended (maximum safe) dose of 3M-052-AF to be used in part B. The 
HVTN SMB may perform an additional unblinded review of this safety data to 
make the final determination based on safety for proceeding to part B. 
11.3.3 
Safety evaluation for Group 8 
Enrollment in Group 8 across all participating HVTN CRSs will be restricted to a 
maximum of 1 participant per day until 5 participants have been enrolled. 
Enrollment will then be held. The HVTN 137 PSRT will review cumulative 
safety data available on all participants in Group 8 up to and including the 2-week 
visit after the first vaccination to determine whether it is safe to proceed with full 
enrollment in that group. 
11.4 
Safety pause and prompt PSRT AE review 
When a trial is placed on safety pause, all enrollment and vaccination with the 
product related to the event that triggered the pause will be held until further 
notice. The AEs that will lead to a safety pause or prompt HVTN 137 PSRT AE 
review are summarized in Table 11-1. Vaccinations may be suspended for safety 
concerns other than those described in the table, or before pause rules are met, if, 
in the judgment of the HVTN 137 PSRT, participant safety may be threatened. 
Criteria for an individual participant’s departure from the schedule of vaccinations 
are listed in Section 7.4.2. 
Table 11-1 AE notification and safety pause/AE review rules 
Event and relationship to 
study products/procedures 
Severity 
HVTN CRS actiona 
HVTN Core action 
SAE, related 
Grade 5 or 
Grade 4 
Phone immediately, 
email and submit forms 
immediately 
Immediate pause 
SAE, not related 
Grade 5 
Phone immediately, 
email and submit forms 
immediately 
Immediate PSRT notification 
SAE, related 
Grade 3, 2, 
or 1 
Email and submit forms 
immediately 
Immediate PSRT notification 
and prompt PSRT AE review 
to consider pause 
AEb, related 
Grade 4 or 
3 
Email and submit forms 
immediately 
Immediate PSRT notification 
and prompt PSRT AE review 
to consider pause 
a Phone numbers and email addresses are found on the Protocol home page on the HVTN Members’ site 
(https://members.hvtn.org/protocols/hvtn137). 
b Does not include the following Grade 3 subjective reactogenicity symptoms: injection site pain, tenderness, 
fatigue/malaise, myalgia, arthralgia, chills, headache, nausea (unless IV rehydration required). 
For all safety pauses, HVTN Core notifies the HVTN 137 PSRT, HVTN 
Regulatory Affairs, DAIDS Pharmaceutical Affairs Branch (PAB), DAIDS 

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Regulatory Affairs Branch (RAB), DAIDS Safety and Pharmacovigilance Team 
(SPT), and participating HVTN CRSs. When an immediate safety pause is 
triggered, HVTN Core notifies the SMB. 
Once a trial is paused, the HVTN 137 PSRT reviews safety data and decides 
whether the pause can be lifted or permanent discontinuation of vaccination is 
appropriate, consulting the SMB if necessary. HVTN Core notifies the 
participating HVTN CRSs, HVTN Regulatory Affairs, DAIDS PAB, DAIDS 
RAB, and DAIDS SPT of the decision regarding resumption or discontinuation of 
study vaccinations. Based on the HVTN 137 PSRT assessment, DAIDS RAB 
notifies the FDA as needed. 
If an immediate HVTN 137 PSRT notification or prompt HVTN 137 PSRT AE 
review is triggered, HVTN Core notifies the HVTN 137 PSRT as soon as possible 
during working hours (local time)—or, if the information was received during off 
hours, by the morning of the next workday. If a prompt HVTN 137 PSRT AE 
review cannot be completed within 72 hours of notification (excluding weekends 
and US federal holidays), an automatic safety pause occurs. 
The HVTN requires that each CRS submit to its IRB/EC and any applicable RE 
protocol-related safety information (such as IND safety reports, notification of 
vaccine holds due to the pause rules, unanticipated problems involving risks to 
participants or others, and notification of other unplanned safety pauses). CRSs 
must also follow all applicable RE reporting requirements. 
In addition, all other AEs are reviewed routinely by the HVTN 137 PSRT (see 
Section 11.5.2). 
11.5 
Review of cumulative safety data 
Routine safety review occurs at the start of enrollment and then throughout the 
study. 
Reviews proceed from a standardized set of protocol-specific safety data reports. 
These reports are produced by the SDMC and include queries to the HVTN CRSs. 
Events are tracked by internal reports until resolution. 
11.5.1 
Daily review 
Blinded daily safety reviews are routinely conducted by HVTN Core for events 
requiring expedited reporting to DAIDS, and events that meet safety pause criteria 
or prompt HVTN 137 PSRT AE review criteria. 
11.5.2 
Weekly review 
During the injection phase of the trial, the HVTN 137 PSRT reviews clinical 
safety reports on a weekly basis and conducts calls to review the data as 

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appropriate. After the injections and the final 2-week safety visits are completed, 
less frequent reporting and safety reviews may be conducted at the discretion of 
the HVTN 137 PSRT. HVTN Core reviews reports of clinical and laboratory 
AEs. Events identified during the review that are considered questionable, 
inconsistent, or unexplained are referred to the HVTN CRS clinic coordinator for 
verification. 
11.5.3 
AESI health contact quarterly review 
After the main study period, a monitoring team reviews safety reports quarterly 
during the annual health contacts period. This monitoring team comprises a 
DAIDS Medical Officer, Core medical monitor, and an HVTN clinical safety 
staff member. 
11.6 
Study termination 
This study may be terminated early by the determination of the HVTN 137 PSRT, 
the US FDA, NIH, Office for Human Research Protections (OHRP), or study 
product developer(s). In addition, the conduct of this study at an individual HVTN 
CRS may be terminated by the determination of the IRB/EC and any applicable 
RE. 

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12 
Protocol conduct 
This protocol and all actions and activities connected with it will be conducted in 
compliance with the principles of GCP (ICHe6), and according to DAIDS and 
HVTN policies and procedures as specified in the HVTN Manual of Operations, 
DAIDS Clinical Research Policies and Standard Procedures Documents including 
procedures for the following: 
• Protocol registration, activation, and implementation; 
• Informed consent, screening, and enrollment; 
• Study participant reimbursement; 
• Clinical and safety assessments; 
• Safety monitoring and reporting; 
• Data collection, documentation, transfer, and storage; 
• Participant confidentiality; 
• Study follow-up and close-out; 
• Unblinding of staff and participants; 
• Quality control; 
• Protocol monitoring (on-site or remote) and compliance; 
• Advocacy and assistance to participants regarding negative social impacts 
associated with the vaccine trial; 
• Risk reduction counseling; 
• Specimen collection, processing, and analysis; 
• Exploratory and ancillary studies and sub-studies, and 
• Destruction of specimens. 
Any policies or procedures that vary from DAIDS and HVTN standards or require 
additional instructions (eg, instructions for randomization specific to this study) 
will be described in the HVTN 137 Study Specific Procedures. 

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12.1 
Social impacts 
Participants in this study risk experiencing discrimination or other personal 
problems, resulting from the study participation itself or from the development of 
VISP. The HVTN CRS is obliged to provide advocacy for and assistance to 
participants regarding these negative social impacts associated with the vaccine 
trial. If HVTN CRS staff have questions regarding ways to assist a participant 
dealing with a social impact, a designated NIAID or HVTN Core representative 
can be contacted. 
Social harms are tabulated by the SDMC and are subjected to descriptive analysis. 
The goal is to reduce their incidence and enhance the ability of study staff to 
mitigate them when possible. 
Summary tables of social impact events will be generated weekly, and made 
available for review by the protocol chairs, protocol team leader, and the 
designated NIAID representative. 
12.2 
Emergency communication with study participants 
As in all clinical research, this study may generate a need to reach participants 
quickly to avoid imminent harm, or to report study findings that may otherwise 
concern their health or welfare. 
When such communication is needed, the CRS will request that its IRB/EC and 
any applicable RE expedite review of the message. If this review cannot be 
completed in a timeframe consistent with the urgency of the required 
communication, the site can contact the participant without IRB/EC approval if 
such communication is necessary to avoid imminent harm to the study participant. 
The CRS must notify the IRB/EC and any applicable RE of the matter as soon as 
possible. 

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13 
Version history 
The Protocol Team may modify the original version of the protocol. 
Modifications are made to HVTN protocols via clarification memos, letters of 
amendment, or full protocol amendments. 
The version history of, and modifications to, Protocol HVTN 137 are described 
below. 
Protocol history and modifications 
Date: September 26, 2022 
Protocol version: Version 5.0 
Protocol modification: Full Protocol Amendment 4 
Item 1 Revised throughout the protocol: Title to reflect changes in study design 
Item 2 Added in Title page; Section 3, Overview; Section 4, Background; Section 5, 
Objectives and endpoints; Section 6, Statistical considerations; Section 8, 
Study product preparation and administration; Section 11, Safety 
monitoring and safety review; a new Appendix C, Sample informed consent 
form for Part C; Appendix F, Approved birth control methods for persons 
assigned female sex at birth (for Part B and Part C sample informed consent 
form); Appendix H, Tables of procedures (for sample informed consent 
form); Appendix P, Laboratory procedure for Part B (no optional 
procedures) and Part C; Appendix T, Procedures at HVTN CRS for Part B 
(no lymph node FNA) and Part C; and Appendix W, Visit Windows: 
Information for new Part C justifying recruitment of additional participants 
in order to optimize neutralizing antibody titers observed in Part A 
Item 3 Updated Section 3.1, Protocol Team 
Item 4 Updated Section 4.1.5, Clinical studies: Title of Table 4-2 
Item 5 Updated Section 4.5.3, Clinical studies of 3M-052: safety data from HVTN 
300 study 
Item 6    Added in Section 7.2, Exclusion criteria; and Section 7.4.1, Delaying 
vaccinations for a participant: considerations for timing of receipt of 
vaccines for Monkeypox 
Item 7 Revised in Section 9.10, Assessments of reactogenicity; Appendix T, 
Procedures at HVTN CRS for Part B (no lymph node FNA) and Part C: 
reactogenicity period increased from 7 to 14 days 
Item 8 Added in Section 12, Protocol conduct: Stipulation for Protocol monitoring 
Item 9 Updated Appendix U, HVTN low risk guidelines for the US: Sub-heading 
and PrEP language 

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Item 10 Updated in Title page; Section 13, Version history; Section 15, Acronyms 
and abbreviations; and Section 16, Literature cited: Contents of this 
amendment 
Item 11  Updated throughout the Protocol: Name of the study product provider 
Item 12 Corrected throughout the Protocol: Minor errors in grammar, typography, 
formatting 
Item 13 Updated throughout the Protocol: Section numbering and cross-references 
Item 14 Updated per Protocol Version 4.0, Letter of Amendment 1, dated May 12, 
2021 
Item 15 Updated per Protocol Version 4.0, Letter of Amendment 2, dated August 02, 
2021 
Item 16  Updated per Protocol Version 4.0, Clarification Memo 1, dated August 16, 
2022 
Date: August 16, 2022 
Protocol version: Version 4.0 
Protocol modification: Clarification Memo 1 
Item 1 
Added in Section 10.2, Total blood volume: alternate laboratory specimen 
tube types allowed for research samples upon HVTN laboratory center 
approval 
Date: August 02, 2021 
Protocol version: Version 4.0 
Protocol modification: Letter of Amendment 2 
Item 1 
Revised Section 7.1, Inclusion criteria, and Appendix S, HVTN low risk 
guidelines for the US: include persons stably taking PrEP 
Date: May 12, 2021 
Protocol version: Version 4.0 
Protocol modification: Letter of Amendment 1 
Item 1 
Corrected in Appendix I, Laboratory procedures for Part A with Optional 
Second Boost: Safety labs collection timepoint 
Date: March 10, 2021 
Protocol version: Version 4.0 
Protocol modification: Full Protocol Amendment 3 
Item 1 
Revised the protocol to expand the scientific rationale for the optional third 
vaccination in HVTN 137 Part A and inform participants 
Item 2 Revised the volume of bone marrow aspirate in Section 9.5, Optional 
Procedures and Appendix B, SICF for Part B, Item 14 

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Item 3 Updated Section 3.1, Protocol Team: protocol team membership 
Item 4 
Updated Title page, Table of contents, and Section 13, Version history: date, 
version number and contents of this amendment 
Date: February 10, 2021 
Protocol version: Version 3.0 
Protocol modification: Full Protocol Amendment 2 
Item 1 
Added a third vaccination as an optional second boost to HVTN 137 Part A 
Item 2 
Corrected minor document errors in Protocol Version 2, Letter of 
Amendment 4, dated December 21, 2020, Item 3 and Item 6: misplaced 
Appendix K (renamed to Appendix L in this Full Protocol Amendment), 
clarified footnotes referring to pregnancy testing, Appendix S (renamed to 
Appendix U) Visit Windows for HVTN 137 Part BA 
Item 3 
Updated per Clarification Memo 1 version 2.0, dated July 16, 2020 
Item 4 
Updated per Letter of Amendment 4, version 2.0, dated December 21, 2020 
Item 5 
Updated per Letter of Amendment 3, version 2.0, dated September 16, 2020 
Item 6 
Updated per Letter of Amendment 2, version 2.0, dated July 16, 2020 
Item 7 
Updated per Letter of Amendment 1, version 2.0, dated June 11, 2020 
Item 8 
Updated per Clarification Memo 3 version 2.0, dated March 24, 2020 
Item 9 
Updated per Clarification Memo 2 version 2.0, dated January 27, 2020 
Item 10 Updated per Clarification Memo 1 version 2.0, dated December 12, 2019 
Item 11 Corrected minor document errors 
Item 12 Updated Title page, Table of contents, and Section 13, Version history: date, 
version number and contents of this amendment 
Date: December 21, 2020 
Protocol version: Version 2.0 
Protocol modification: Letter of Amendment 4 
Item 1 Revised in Section 7.1, Inclusion criteria: language referring to pregnancy 
testing for optional study procedures in inclusion criterion 21 
Item 2 Revised in Section 9.5, Optional procedures: clarified timing of negative 
pregnancy test prior to rectal and vaginal sampling and removed requirement 
that pregnancy test must be performed on urine samples prior to 
leukapheresis, bone marrow aspiration, and lymph node FNA as blood 
samples can also be used 
Item 3 Appendices I - L, Laboratory procedures for Part B: consolidated footnotes 
for pregnancy testing of participants that will provide optional procedure 
samples and updated table footnotes 

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Item 4 Removed in Appendix B, SICF for Part B, item 4: manufacturer of the Alum 
adjuvant 
Item 5 Revised in Appendices I and J, Laboratory procedures for Part B: blood 
collection volumes at Visit 9 
Item 6 Updated in Appendix S, Visit Windows: footnote 1 to HVTN 137 Part A 
Visit Windows table, referring to visit target dates 
Item 7 Updated in Section 3.1, Protocol team: Membership 
Date: September 16, 2020 
Protocol version: Version 2.0 
Protocol modification: Letter of Amendment 3 
Item 1 Removed in Section 6.2, Randomization: stratified randomization and 
requirement for at least half of the participants in Part B to consent to the 
fine needle aspiration procedure 
Item 2 Removed in Laboratory Procedure Tables for Part B (Appendices I, J, K, 
and L): Prothrombin time / INR testing 
Item 3 Corrected in Appendix B, SICF for Part B, item 15: participant instructions 
for rectal tissue collection 
Item 4 
Updated in Section 3.1, Protocol team: Membership 
Item 5 
Corrected a document error in Protocol Version 2, Letter of Amendment 2, dated 
July 16, 2020: upper allowable visit window for the Final Visit (Visit 14.0) in Part 
A 
Date: July 16, 2020 
Protocol version: Version 2.0 
Protocol modification: Letter of Amendment 2 
Item 1 
Updated Appendix S Visits Windows to expand the upper allowable window 
for Visit 7/Vaccination 2 from 120 days to 180 days 
Date: June 11, 2020 
Protocol version: Version 2.0 
Protocol modification: Letter of Amendment 1 
Item 1 Updated with changes described in Protocol Version 2, Clarification Memo 
3, dated March 24, 2020 
Item 2 Updated in Section 3.1, Protocol team: Membership 
Date: March 24, 2020 
Protocol version: Version 2.0 

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Protocol modification: Clarification Memo 3 
Item 1 
Clarified in Appendix S, Visit windows: Allowable visit windows for Part A 
Item 2 
Clarified throughout protocol: “Clinic visits” 
Date: January 27, 2020 
Protocol version: Version 2.0 
Protocol modification: Clarification Memo 2 
Item 1 
Reconciled in Section 7.2, Exclusion criteria: Exclusion for autoimmune 
conditions 
Date: December 12, 2019 
Protocol version: Version 2.0 
Protocol modification: Clarification Memo 1 
Item 1 
Clarified in Section 6.3, Blinding: Treatment assignment but not group 
assignment blinded throughout trial 
Item 2 
Clarified in Inclusion criterion 23 in Section 7.1: No alternative pregnancy 
methods until 6 months after last vaccination 
Item 3 
Clarified in Appendices H through M: Lab procedures table footnotes 
regarding optional blood draws and blood draw totals 
Item 4 
Corrected in Section 13: Version history 
Date: October 30, 2019 
Protocol version: Version 2.0 
Protocol modification: Full Protocol Amendment 1 
Item 1 
IND number added to title page 
Item 2 
Age eligibility clarified 
Item 3 
SAE and MAAE reporting added throughout protocol duration 
Item 4 
Safety experience of CpG 1018 revised in Section 4.5.1 and Appendix B 
Item 5 
Fill volumes clarified in Sections 8.2.1 and 8.2.2 
Item 6 
Extraneous text removed from Appendix B 
Date: August 28, 2019 
Protocol version: 1.0 
Protocol modification: NA 
 
Original Protocol 
 

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14 
Document references (other than literature 
citations) 
Other documents referred to in this protocol, and containing information relevant 
to the conduct of this study, include: 
• Assessment of Understanding. Accessible through the HVTN protocol-
specific website. 
• Current CDC Guidelines: 
▪ Revised Recommendations for HIV Testing of Adults, Adolescents, and 
Pregnant Women in Health-Care Settings. Available at 
http://www.cdc.gov/mmwr/PDF/rr/rr5514.pdf  
▪ Revised Guidelines for HIV Counseling, Testing, and Referral. Available 
at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5019a1.htm 
• Division of AIDS (DAIDS) Clinical Research Policies and Standard 
Procedures Documents. Available at 
https://www.niaid.nih.gov/research/daids-clinical-research-policies-standard-
procedures 
• Division of AIDS Protocol Registration Manual. Available at 
https://www.niaid.nih.gov/sites/default/files/prmanual.pdf  
• Division of AIDS Table for Grading the Severity of Adult and Pediatric 
Adverse Events. Corrected Version 2.1, July 2017. Available at 
https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-
tables 
• The Manual for Expedited Reporting of Adverse Events to DAIDS. Version 
2.0, January 2010. Available at https://rsc.niaid.nih.gov/clinical-research-
sites/manual-expedited-reporting-adverse-events-daids 
• HVTN Certificate of Confidentiality. Accessible through the HVTN website. 
• HVTN 137 Special Instructions. Accessible through the HVTN protocol-
specific website. 
• HVTN 137 Study Specific Procedures. Accessible through the HVTN 
protocol-specific website. 
• HVTN 137 Site Lab Instructions. Accessible through the HVTN protocol-
specific website. 
• HVTN Manual of Operations. Accessible through the HVTN website. 

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• Dangerous Goods Regulations (updated annually), International Air Transport 
Association. Available for purchase at 
https://www.iata.org/publications/dgr/Pages/index.aspx 
• Lab assay algorithm (available upon request) 
• International Council on Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) E6, Guideline for Good Clinical 
Practice: Section 4.8, Informed consent of trial subjects. Available at 
http://www.ich.org/products/guidelines/efficacy/article/efficacy-
guidelines.html 
• Participants’ Bill of Rights and Responsibilities. Accessible through the 
HVTN website. 
• NIH Policy on Reporting Race and Ethnicity Data: Subjects in Clinical 
Research. Available at https://grants.nih.gov/grants/guide/notice-files/NOT-
OD-01-053.html 
• Pharmacy Guidelines and Instructions for DAIDS Clinical Trials Networks, 
July 2008 
• Requirements for Source Documentation in DAIDS Funded and/or Sponsored 
Clinical Trials. Available at 
https://www.niaid.nih.gov/sites/default/files/daids-sourcedocpolicy.pdf  
• Title 21, Code of Federal Regulations, Part 50. Available at 
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFR
Part=50 
• Title 45, Code of Federal Regulations, Part 46. Available at 
https://www.hhs.gov/ohrp/regulations-and-policy/regulations/45-cfr-
46/index.html 
See Section 16 for literature cited in the background and statistics sections of this 
protocol. 

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15 
Acronyms and abbreviations 
A/G 
 
albumin/globulin (ratio) 
AAHI                    Access to Advanced Health Institute  
Ab 
 
antibody 
ADCC 
 
antibody-dependent cellular cytotoxicity 
ADCP 
 
antibody-dependent cellular phagocytosis 
ADNP 
 
antibody-dependent neutrophil phagocytosis 
AE 
 
adverse event 
AESI 
 
adverse event of special interest 
AF 
 
aqueous formulation 
ALT 
 
alanine aminotransferase 
AMI 
 
acute myocardial infarction 
APC 
 
antigen presenting cell 
APTT 
 
activated partial thromboplastin time 
ART 
 
antiretroviral therapy 
ASA 
 
Acetylsalicylic acid 
AST 
 
aspartate aminotransferase 
AUC-MB  
area-under-the-curve-magnitude-breadth 
β-HCG 
 
beta human chorionic gonadotropin 
BAMA 
 
binding antibody multiplex assay 
BAMA-AI  
BAMA avidity index 
BCR 
 
B cell receptor 
BLI 
 
biolayer interferometry 
BM 
 
bone marrow 
BMI 
 
body mass index 
bnAb 
 
broadly neutralizing antibody 
BRA 
 
behavioral risk assessment  
CAB 
 
Community Advisory Board 
CAVD 
 
Collaboration for AIDS Vaccine Discovery 
CAVIMC  
Comprehensive Antibody Vaccine Immune Monitoring 
Consortium 
CBC 
 
complete blood count 
CD4bs 
 
CD4 binding site 
CDC 
 
US Centers for Disease Control and Prevention 
CFR 
 
Code of Federal Regulations 
cGMP 
 
current Good Manufacturing Practice 
CHIL 
 
Cape Town HIV Immunology Laboratory 
CI 
 
confidence interval 
CMIA 
 
chemiluminescent microparticle immunoassay 

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COMPASS 
Combinatorial Polyfunctionality analysis of Antigen-Specific 
T-cell Subsets  
CpG 
 
cytidine phosphoguanosine 
CRF 
 
case report form 
CRP 
 
C-reactive protein 
CRPMC 
 
NIAID Clinical Research Products Management Center 
CRS 
 
clinical research site 
DAERS 
 
DAIDS Adverse Experience Reporting System 
DAIDS 
 
Division of AIDS (US NIH) 
DC 
 
dendritic cell 
DHHS 
 
(US) Department of Health and Human Services 
DSMB 
 
(NIAID) Data and Safety Monitoring Board 
EAE 
 
adverse events requiring expedited reporting to DAIDS 
EC 
 
Ethics Committee 
EIA 
 
enzyme immunoassay 
ELISA 
 
enzyme-linked immunosorbent assay 
EMH 
 
extramedullary hematopoiesis 
Env 
 
HIV envelope 
Fab 
 
fragment antigen-binding 
Fc 
 
fragment crystallizable 
FcR 
 
Fc receptor 
FDA 
 
(US) Food and Drug Administration 
FNA 
 
fine needle aspiration 
FPR 
 
false positive rate 
Fred Hutch 
Fred Hutchinson Cancer Research Center (FHCRC)  
FS 
 
functionality score 
GCLP 
 
Good Clinical Laboratory Practice 
GCP 
 
Good Clinical Practice 
GEE 
 
generalized estimating equation 
GLA 
 
glucopyranosyl lipid A 
GPA 
 
granulomatosis with polyangiitis 
GSK 
 
Glaxo Smith Kline 
GTI 
 
genital tract infection 
HBsAg 
 
hepatitis B surface antigen 
HBV 
 
hepatitis B virus 
HCD 
 
higher-energy collisional dissociation 
HCDR3 
 
heavy chain complementarity-determining region 3 
HCV 
 
hepatitis C virus 
Hg 
 
mercury 

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HIPAA 
 
Health Insurance Portability and Accountability Act 
HIV 
 
human immunodeficiency virus 
HLA 
 
human leukocyte antigen 
HVTN 
 
HIV Vaccine Trials Network 
IAVI 
 
International AIDS Vaccine Initiative 
IB 
 
Investigator’s Brochure 
ICABA 
 
infected cells antibody binding assay 
ICH 
 
International Council on Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use 
ICS 
 
intracellular cytokine staining 
IFN-α 
 
interferon alpha 
IFN-γ 
 
interferon gamma 
IgA 
 
immunoglobulin subtype A 
IgG 
 
immunoglobulin subtype G 
IHC 
 
immunohistochemistry 
IL 
 
interleukin 
IM 
 
intramuscular (injection) 
IMC 
 
infectious molecular clone 
IND 
 
Investigational New Drug 
IoR 
 
Investigator of record 
IP-10 
 
IFN-γ inducible protein 10 
IRB 
 
Institutional Review Board 
IRM 
 
immune response modifier 
ISCOM 
 
immune stimulating complex 
IUD 
 
intrauterine device 
kDa 
 
kilodalton 
LC 
 
Laboratory Center 
LC-MS 
 
liquid chromatography mass spectrometry 
LC-MS/MS 
liquid chromatography-tandem mass spectrometry 
LN 
 
lymph node 
MAAE 
 
medically attended adverse event 
mAb 
 
monoclonal antibody 
MAR 
 
missing at random 
M-B 
 
magnitude-breadth 
MCAR 
 
missing completely at random 
MCP-1 
 
monocyte chemoattractant protein 1 
mDC 
 
myeloid dendritic cell 
MDP 
 
muramyl dipeptide 
MedDRA  
Medical Dictionary for Regulatory Activities 

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MIMOSA  
Mixture Models for Single-cell Assays 
mIU/mL  
mill-international units per milliliter 
MMR 
 
measles, mumps, and rubella 
MOP 
 
Manual of Operations 
MPER 
 
membrane proximal external region 
MPL 
 
monophosphoryl lipid A 
MS 
 
mass spectrometry  
MS-MS 
 
tandem mass spectrometry 
MSD 
 
meso-scale discovery 
MTD 
 
maximum tolerated dose 
MTP-PE  
muramyl tripeptide phosphatidylethanolamine 
nAb 
 
neutralizing antibody 
NAEPP 
 
National Asthma Education and Prevention Program 
NFL 
 
native flexibly-linked 
NHP 
 
nonhuman primate 
NIAID 
 
National Institute of Allergy and Infectious Diseases (US NIH) 
NIH 
 
(US) National Institutes of Health 
NK 
 
natural killer 
NOD 
 
nucleotide-binding oligomerization domain 
NSAID 
 
non-steroidal anti-inflammatory drug 
ODN 
 
oligodeoxynucleotide 
OHRP 
 
US Office for Human Research Protections 
OPV 
 
oral polio vaccine 
PAB 
 
(DAIDS) Pharmaceutical Affairs Branch 
PBMC 
 
peripheral blood mononuclear cell 
PCA 
 
principal component analysis 
PCR 
 
polymerase chain reaction 
pDC 
 
plasmacytoid dendritic cell 
PFS 
 
polyfunctionality score 
PI 
 
Principal Investigator 
PLGA 
 
Poly(lactic-co-glycolic acid) 
PSRT 
 
Protocol Safety Review Team 
pTfh 
 
peripheral T follicular helper cells 
PTID 
 
participant ID 
QS-21 
 
Quillaja saponaria fraction 21 
RAB 
 
(DAIDS) Regulatory Affairs Branch 
RBC 
 
red blood cells 
RE 
 
regulatory entity 
RSC 
 
(DAIDS) Regulatory Support Center 

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SAE 
 
serious adverse event 
SAP 
 
Statistical Analysis Plan 
SC 
 
subcutaneous 
SCHARP  
Statistical Center for HIV/AIDS Research and Prevention 
SDMC 
 
statistical and data management center 
SE 
 
stable emulsion 
SHIV 
 
simian-human immunodeficiency virus 
SIV 
 
simian immunodeficiency virus 
SMB 
 
Safety Monitoring Board 
SPR 
 
surface plasmon resonance 
SPT 
 
(DAIDS) Safety and Pharmacovigilance Team 
SSP 
 
Study Specific Procedures 
STI 
 
sexually transmitted infection 
SVA-MLV 
simian virus amphotropic murine leukemia virus 
TB 
 
tuberculosis 
TBS 
 
Tris-NaCl buffer 
TCR 
 
T cell receptor 
Tfh 
 
T follicular helper 
TLR 
 
toll-like receptor 
TNF-α 
 
tumor necrosis factor alpha 
UCA 
 
unmutated common ancestor 
UFO 
 
uncleaved prefusion-optimized 
USP 
 
United States Pharmacopeia 
UW-VSL  
University of Washington Virology Specialty Laboratory 
VISC 
 
Vaccine Immunology Statistical Center 
VISP 
 
vaccine induced seropositivity 
VLP 
 
virus-like particle 
VRC 
 
Vaccine Research Center (NIAID) 
WHC 
 
white blood cells 
WFI 
 
water for injection 
 

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93. Gilbert PB, Sato A, Sun X, Mehrotra DV. Efficient and robust method for 
comparing the immunogenicity of candidate vaccines in randomized clinical 
trials. Vaccine. 2009;27(3):396-401. 
94. James G, Witten D, Hastie T, Tibshirani R. An introduction to statistical 
learning with applications in R. New York: R. Springer; 2013. 
95. Huang Y, Gilbert P, Montefiori D, Self S. Simultaneous evaluation of the 
magnitude and breadth of a left- and right-censored multivariate response, 
with application to HIV vaccine development. Statistics in Biopharmaceutical 
Research. 2009;1:81-91. 
96. Finak G, McDavid A, Chattopadhyay P, Dominguez M, De RS, Roederer M, 
et al. Mixture models for single-cell assays with applications to vaccine 
studies. Biostatistics. 2014;15(1):87-101. 
97. Lin L, Finak G, Ushey K, Seshadri C, Hawn TR, Frahm N, et al. COMPASS 
identifies T-cell subsets correlated with clinical outcomes. Nat Biotechnol. 
2015;33(6):610-6. 
98. van der Laan MJ, Polley EC, Hubbard AE. Super learner. Stat Appl Genet 
Mol Biol. 2007;6:Article25. 
99. Tay MZ, Liu P, Williams LD, McRaven MD, Sawant S, Gurley TC, et al. 
Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs 
among Antibody Isotypes and Subclasses. PLoS Pathog. 
2016;12(8):e1005817. 
100. Ackerman ME, Moldt B, Wyatt RT, Dugast AS, McAndrew E, Tsoukas S, et 
al. A robust, high-throughput assay to determine the phagocytic activity of 
clinical antibody samples. J Immunol Methods. 2011;366(1-2):8-19. 
101. Worley MJ, Fei K, Lopez-Denman AJ, Kelleher AD, Kent SJ, Chung AW. 
Neutrophils mediate HIV-specific antibody-dependent phagocytosis and 
ADCC. J Immunol Methods. 2018;457:41-52. 

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102. Perez LG, Martinez DR, deCamp AC, Pinter A, Berman PW, Francis D, et al. 
V1V2-specific complement activating serum IgG as a correlate of reduced 
HIV-1 infection risk in RV144. PLoS One. 2017;12(7):e0180720. 
103. Tomaras GD, Yates NL, Liu P, Qin L, Fouda GG, Chavez LL, et al. Initial B-
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2008;82(24):12449-63. 
 

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Appendix A 
Sample informed consent form for Part A 
Title: A phase 1 clinical trial to evaluate the safety and immunogenicity of HIV-1 
BG505 SOSIP.664 gp140 with TLR agonist and/or Alum adjuvants and VRC 
HIV Env Trimer 4571 and 3M-052-AF with Alum in healthy, HIV uninfected 
adults 
 
HVTN protocol number: HVTN 137 
Site: [Insert site name] 
Thank you for your interest in our research study. Please read this consent form or 
ask someone to read it to you. If you decide to join the study, we will ask you to 
sign or make your mark on this form. We will offer you a copy to keep. We will 
ask you questions to see if we have explained everything clearly. You can also 
ask us questions about the study. 
Research is not the same as treatment or medical care. The purpose of a research 
study is to answer scientific questions. 
Key information 
These are some of the things you should know about this study: 
The purpose of the study is to test an experimental HIV vaccine. The study 
vaccine is made from two parts: a man-made piece of protein that looks like a 
protein found on the outside of HIV and an adjuvant. An adjuvant is a substance 
that helps the immune system respond better. The study will see if the protein and 
two different amounts of the same adjuvant are safe and if people can get them 
without being too uncomfortable. The study will also test how people’s immune 
systems respond to the vaccine made with two different amounts of the same 
adjuvant. This is the first study to give this vaccine to people.  
If you join the study, you will have about 5 clinic visits over about 8 months. 
Clinic visits will involve physical exams, collection of blood and urine for routine 
laboratory tests (including pregnancy tests if you can get pregnant), HIV testing at 
some visits, and collection of blood samples to look at your immune responses to 
the vaccine. Some visits will involve questionnaires, some of which ask very 
personal questions. You will get vaccine injections at two visits. After your clinic 
visits are over, you will get a phone call to check on your health about 6 months 
later. 
Some of the risks of getting vaccines are fever, chills, rash, aches and pains, 
nausea, headache, dizziness, feeling tired, and pain, redness, swelling, or itching 
where you get the injection. On rare occasions, a vaccine can cause an allergic 
reaction. These can even be life threatening. Very rarely, a vaccine causes a 
person to have an autoimmune disease or makes an autoimmune disease worse. 

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Because this vaccine has not been given to people yet, we do not know what all of 
the risks may be.  We think the risks will be similar to these general risks. There 
may be other side effects that we don’t yet know, even serious ones. 
We do not expect the study vaccine to benefit you in any way. You do not have to 
join, and you are free to leave at any time. 
The rest of this form provides a more complete description of the study. Please 
read it carefully. 
About the study 
The HIV Vaccine Trials Network (HVTN) and [Insert site name]  are doing a 
study to test an HIV vaccine. HIV is the virus that causes AIDS. The study 
vaccine is made from two parts: a protein and an adjuvant. Adjuvants are 
substances that help the immune system respond better. (Your immune system 
protects you from disease.) In this study we will test one protein with different 
adjuvants. 
About 105 people will take part in this study at multiple sites. The researcher in 
charge of this study at this clinic is [Insert name of site PI]. The US National 
Institutes of Health (NIH) is paying for the study. 
This study is divided into two parts, part A and part B. About 17 people will be in 
part A. In part A, we will test 2 different doses (amounts) of the same adjuvant. 
The study vaccine we give to the first people to join will contain a low dose of the 
adjuvant. We will only give the study vaccine which contains the higher dose of 
the adjuvant after we know that there were no serious health problems in people 
who got the lower dose. 
After we see the results from part A, we will decide what dose of the adjuvant to 
include in the study vaccine in part B. In part B, 88 more people will join. In part 
B, the study vaccine will include either the adjuvant tested in part A or 1 of 3 
other adjuvants.  
You are being invited to join part A of the study. 
1. We are doing part A of this study to answer several questions. 
• Is the study vaccine safe to give to people? 
• Are people able to take the study vaccine without becoming too 
uncomfortable? 
• How do people’s immune systems respond to the study vaccine?  
• Does the study vaccine have different effects at different doses? 

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2. The study vaccine cannot give you HIV. 
The study vaccine is not made from actual HIV. It is impossible for the study 
vaccine to give you HIV. Also, it cannot cause you to give HIV to someone else. 
3. We do not know if the study vaccine will decrease, increase, or not change 
your risk of getting HIV if you are exposed to the virus. 
Site: Any change to the following boxed text requires approval from HVTN 
Regulatory Affairs at vtn.core.reg@hvtn.org. You can remove the box around the text. 
Several studies have tested whether HIV vaccines can reduce the risk of getting 
HIV from another person. In some studies, people who got the vaccine seemed to 
have the same risk of getting HIV as people who did not get the vaccine. In one 
study, people who got the vaccine seemed to have a lower risk of getting HIV 
than people who did not get the vaccine. In studies with a different vaccine, some 
people who got the vaccine had a higher risk of getting HIV than people who did 
not get the vaccine. 
This study differs from the studies in which people who got the vaccine had a 
higher or lower risk of getting HIV. We can tell you about the differences. 
We do not know whether the vaccine in this study will affect your risk of getting 
HIV from another person. The risk could be higher, lower, or unchanged. It’s very 
important to avoid exposure to HIV during and after the study. We will tell you 
how to avoid HIV. 
4. This study vaccine is experimental. 
The study vaccine in Part A of this study is BG505 SOSIP.664 gp140 + 3M-052-
AF. It includes two parts. BG505 SOSIP.664 gp140 is a man-made piece of 
protein that looks like a protein found on the outside of HIV. From here on we 
will call it “the protein.” The second part of the study vaccine is the adjuvant 
called 3M-052-AF + Alum. (An adjuvant is something that helps the immune 
system respond better.) From here on, we will call it “the adjuvant.” We will use 
the term “the study vaccine” to refer to the combination of the protein and the 
adjuvant. The study vaccine is an experimental HIV vaccine. That means we do 
not know if it will be safe to use in people, or if it will work to prevent HIV 
infection. This study vaccine is used only in research studies. 
The protein (BG505 SOSIP.664 gp140): 
The protein was designed to look like a piece of protein on HIV. This piece of 
protein has been engineered to stay in a shape much like that in HIV. In this way 
it is different from proteins in some other HIV study vaccines. The protein was 
developed by John Moore at Cornell Weill Medical Center in New York, New 

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York, USA. It is being provided for this study by the International AIDS Vaccine 
Initiative (IAVI) in New York, New York, USA.  
The adjuvant (3M-052-AF + Alum): 
3M-052 is one of many similar products developed by 3M to treat skin conditions, 
tumors, and to make vaccines more effective. These products are designed to 
stimulate parts of the immune system that recognize viral and bacterial invaders. 
In this study, 3M-052 is dissolved in water and is mixed with Alum. Alum has 
been used in many commercial vaccines for more than 90 years.  
3M-052 was developed by 3M Corporation in St. Paul, Minnesota, USA. In this 
study, the 3M-052 is dissolved in water and this mixture is being provided by the 
Access to Advanced Health Institute (AAHI) in Seattle, Washington, USA. The 
Alum was manufactured by Brenntag Biosector in Frederikssund, Denmark.It is 
being provided by the Division of AIDS (DAIDS) at the US National Institutes of 
Health in Rockville, Maryland, USA. 
The 3M-052 adjuvant has been given to 52 participants with advanced cancer in 
one experimental study. The cancer study differed from this vaccine study in 
important ways. The cancer study participants were very sick. The 3M-052 was 
mixed with sesame oil. It was injected directly into tumors at higher doses and for 
a different purpose. In the cancer study, one participant died four days after 
getting his second injection into a liver tumor. The exact cause of death could not 
be determined but was felt to be related to the 3M-052 adjuvant and the injection 
procedure. Two other participants in the cancer study developed a condition 
called cytokine release syndrome, which can be severe and require 
hospitalization. Both participants recovered with medical care. We don’t expect to 
see these outcomes due to the many differences described above. We can discuss 
this more with you if you would like. 
Risks of the protein and adjuvant: 
The protein has been tested for safety and for immune responses in rats, rabbits, 
monkeys, and cows. It is currently being tested with a different adjuvant in a 
study with people in Seattle, USA. The study is planned to include Boston, USA 
and Kenya. As of August 9, 2019, 6 people have joined this study. Reactions to 
the vaccine have so far been mild to moderate. There have not been any serious 
health problems. 
This combination of protein and adjuvant has been tested for safety and/or 
immune response in mice, rats, guinea pigs, rabbits, and monkeys. The adjuvant 
has also been tested for safety in animal studies of other vaccines, such as an 
experimental vaccine against influenza. In these studies, animals that got these 
products had symptoms consistent with the general risks of other vaccines (as 
described below). This combination of protein and adjuvant has not been tested in 
humans before. Even if something looks like it is safe or works in animals, it may 
not be true for people. 

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General risks of vaccines: 
All vaccines can cause fever, chills, rash, aches and pains, nausea, headache, 
dizziness, and feeling tired. Vaccines can also cause pain, redness, swelling, or 
itching where you got the injection. Most people can still do their planned 
activities after getting a vaccine. Rarely, people have side effects that limit their 
normal activities or make them go to the doctor. 
Rarely, a vaccine can cause an allergic reaction, including a rash, hives, or trouble 
breathing. Allergic reactions can be life-threatening. You should tell us if you 
have ever had a bad reaction to any injection or vaccine. 
Very rarely, a vaccine causes an autoimmune disease in a person, or makes an 
autoimmune disease worse. An autoimmune disease happens when your immune 
system attacks your own body, instead of attacking an infection. 
Joining the study 
5. It is completely up to you whether or not to join the study. 
Take your time in deciding. If it helps, talk to people you trust, such as your 
doctor, friends or family. If you decide not to join this study, or if you leave it 
after you have joined, your other care at this clinic and the benefits or rights you 
would normally have will not be affected. 
If you join this study, you may not be allowed to join other HIV vaccine or HIV 
prevention studies now or in the future. You cannot be in this study while you are 
in another study where you get a study product. Being in more than one study 
may not be safe. 
Also, during the study, you should not donate blood or tissue. 
If you choose not to join this study, you may be able to join another study. 
Site: Remove item 6 if you use a separate screening consent that covers these 
procedures. 
6. If you want to join the study, we will screen you to see if you are eligible. 
Screening involves a physical exam, HIV test and health history. A physical exam 
may include, but is not limited to: 
• Checking your weight, temperature and blood pressure 
• Looking in your mouth and throat 
• Listening to your heart and lungs 

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• Feeling your abdomen (stomach and liver) 
We will also do blood and urine tests. These tests tell us about some aspects of 
your health, such as how healthy your kidneys, liver, and immune system are. We 
will also test you for hepatitis B and hepatitis C. We will ask you about 
medications you are taking. We will ask you about behaviors that might put you 
at risk for getting HIV. If you were assigned female sex at birth, we will test you 
for pregnancy.  
We will review the screening results with you. The screening results may show 
you are not eligible to join the study, even if you want to.  
Site: adapt the following section so it is applicable to the care available at your site 
7. If we find that you have a health problem during screening or during the 
study, we will tell you about the care that we can give here for free. 
For the care that we cannot give, we will explain how we will help you get care 
elsewhere. For health problems that are unrelated to the study, we will not pay for 
care. 
8. If you were assigned female sex at birth and can become pregnant, you must 
agree to use birth control to join this study. 
Site: If you want to include Appendix E, Approved birth control methods (for sample 
informed consent form), in this consent form, paste it below and delete paragraph 
below. 
You should not become pregnant during the study because we do not know how 
the study vaccine could affect the developing baby. You must agree to use 
effective birth control from 21 days (3 weeks) before your first injection until 6 
months after your last study injection. We will talk to you about effective birth 
control methods. They are listed on a handout that we will give you. 
Being in the study 
If you meet the study requirements and want to join, here is what will happen: 
9. You will come to the clinic for scheduled visits about [#] times over 
[Insert period of time]. 
Site: Insert number of visits and range of visit lengths. (There is site-specific variation 
in screening protocols and in the number of possible follow-up visits between 
protocol-mandated visits.) 
Visits can last from [#] to [#] hours. 
You may have to come for more visits if you have a lab or health issue. 

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We may contact you after the main study ends (for example, to tell you about the 
study results). 
10. We will give you [Site: Insert compensation] for each study visit you 
complete. 
This amount is to cover the costs of [Site: Insert text] 
Site: Insert any costs to participants (eg, birth control costs for participants assigned 
female sex at birth who could become pregnant). 
US sites: Include the following paragraph. You can remove the box around the text. 
Payments you receive for being in the study may be taxable. We may need to ask 
you for your Social Security number for tax reasons. 
You do not have to pay anything to be in this study. 
11. We will give you either the study vaccine or a placebo. 
Not everyone in this study will get the study vaccine. Some people will get a 
placebo, a substance that does not contain vaccine. In this study, the placebo is a 
combination of salt water and a preservative (to keep the solution from becoming 
too acidic). 
You have a 15-in-17 chance of getting the study vaccine. Whether you get the 
study vaccine or the placebo is completely random, like flipping a coin. 
We have no say in whether you get the study vaccine or the placebo. We will not 
know which one you are getting, and neither will you. Only the pharmacist at this 
clinic will have this information while the study is going on. 
You will have to wait until everyone in Part B completes their final study visits to 
find out whether you got the study vaccine or the placebo. This could be several 
years. But, if you have a serious medical problem and need to know what you got 
before the end of the study, we can tell you. 
12. We will give you the study products on a schedule. 
You will be in one of 2 groups. Group 1 will get a low dose of the study vaccine. 
If there are no serious health problems with Group 1, then Group 2 will get a 
higher dose (with more adjuvant in it). You will get 2 injections during the study 
into the muscle of your upper arm. 
 

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Group 
Number of 
participants 
Injection schedule  
At enrollment 
At 2 months 
1 
5 
protein + low dose of 
adjuvant 
protein + low dose of 
adjuvant 
1 
Placebo 
Placebo 
2 
10 
protein + higher dose of 
adjuvant 
protein + higher dose of 
adjuvant 
1 
Placebo 
Placebo 
You will have to wait in the clinic for about a half hour after each injection to see 
if there are any problems. Then for that night and for 7 more days, you will need 
to keep track of how you are feeling and if you have any symptoms. Site: 
Customize the next sentence based on how you collect reactogenicity information. 
You will bring this information back to the clinic at your next visit. Within 3 days 
of each injection, we will also need to be in contact with you to ask how you are 
doing. Contact the clinic staff if you have any issues or concerns after getting an 
injection. If you have a problem, we will continue to check on you until it goes 
away. 
13. In addition to giving you the study products, we will: 
• Do regular HIV testing, as well as counseling on your results and on how to 
avoid getting HIV 
• Do physical exams 
• Do pregnancy tests if you were assigned female sex at birth 
• Ask questions about your health, including medications you may be taking 
• Ask questions about any personal problems or benefits you may have from 
being in the study 
• Take urine and blood samples. 
When we take blood, the amount will depend on the lab tests we need to do. It 
will be some amount between 20 mL and 200 mL (a little more than 1 tablespoon 
to a little less than 1 cup). Your body will make new blood to replace the blood 
we take out. 
Site: You may want to add a sentence to the end of the previous paragraph 
contextualizing the blood volumes described (eg, “To compare, people who donate 
blood in the US can give a total of about 500 mL in an 8-week period.”). Modify the 
example for cultural relevance and alter blood volumes as necessary. 

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Site: Insert Part A table from Appendix H, Table of procedures (for informed consent 
form) in this section or distribute it as a separate sheet if it is helpful to your study 
participants. You are not required to do either. 
We will be looking for side effects. We will review the results of these procedures 
and tests with you at your next visit, or sooner if necessary. If any of the results 
are important to your health, we will tell you. 
14. We will counsel you about protecting yourself from HIV. 
We will ask you personal questions about your HIV risk factors such as sexual 
behavior, alcohol, and drug use. We will talk with you about ways to keep your 
risk of getting HIV low. 
15. The HVTN will test your samples to see how your immune system responds 
to the study products. 
We will send your samples (without your name) to labs approved by the HVTN 
for this study, which are located in the United States and in South Africa. In rare 
cases, some of your samples may be sent to labs approved by the HVTN in other 
countries for research related to this study. 
Researchers may also do genetic testing related to this study on your samples. 
Your genes are passed to you from your birth parents. They affect how you look 
and how your body works. The differences in people’s genes can help explain 
why some people get a disease while others do not. The genetic testing will only 
involve some of your genes, not all of your genes (your genome). The researchers 
will study only the genes related to the immune system and HIV and those that 
affect how people get HIV. 
If you get HIV, the researchers may look at all of the genes of the virus found in 
your samples. The researchers will use this information to learn more about HIV 
and the study product(s). 
In some cases, researchers may take cells from your samples and grow more of 
them over time, so that they can continue to contribute to this study. 
These tests done on your samples are for research purposes, not to check your 
health. The labs will not give the results to you or this clinic because their tests 
are not approved for use in making health care decisions. These labs are only 
approved to do research tests. 
When your samples are no longer needed for this study, the HVTN will continue 
to store them. 
Site: Delete next section if using separate consent for use of samples and information 
in other studies 

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16. When samples are no longer needed for this study, the HVTN wants to use 
them in other studies and share them with other researchers.  
The HVTN calls these samples “extra samples”. The HVTN will only allow your 
extra samples to be used in other studies if you agree to this. You will mark your 
decision at the end of this form. If you have any questions, please ask. 
Do I have to agree? No. You are free to say yes or no, or to change your mind 
after you sign this form. At your request, we will destroy all extra samples that we 
have. Your decision will not affect your being in this study or have any negative 
consequences here. 
Where are the samples stored? Extra samples are stored in a secure central place 
called a repository. Your samples will be stored in the HVTN repository in the 
United States. 
How long will the samples be stored? There is no limit on how long your extra 
samples will be stored. [Site: Revise the previous sentence to insert limits if your 
regulatory authority imposes them.] 
Will I be paid for the use of my samples? No. Also, a researcher may make a new 
scientific discovery or product based on the use of your samples. If this happens, 
there is no plan to share any money with you. The researcher is not likely to ever 
know who you are. 
Will I benefit from allowing my samples to be used in other studies? Probably not. 
Results from these other studies are not given to you, this clinic, or your doctor. 
They are not part of your medical record. The studies are only being done for 
research purposes. 
Will the HVTN sell my samples and information? No, but the HVTN may share 
your samples with HVTN or other researchers. Once we share your samples and 
information, we may not be able to get them back. 
How do other researchers get my samples and information? When a researcher 
wants to use your samples and information, their research plan must be approved 
by the HVTN. Also, the researcher’s institutional review board (IRB) or ethics 
committee (EC) will review their plan. [Site: If review by your institution’s 
IRB/EC/RE is also required, insert a sentence stating this.] IRBs/ECs protect the 
rights and well-being of people in research. If the research plan is approved, the 
HVTN will send your samples to the researcher’s location. 
What information is shared with HVTN or other researchers? The samples and 
information will be labeled with a code number. The key to the code will stay at 
this clinic. It will not be shared with the HVTN, other researchers, or with anyone 
else who does not need to know your name. Your name will not be part of the 
information. However, some information that we share may be personal, such as 
your race, ethnicity, sex, health information from the study, and HIV status. We 

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may share information about the study product you received and how your body 
responded to the study product. 
What kind of studies might be done with my extra samples and information? The 
studies will be related to HIV, vaccines, the immune system and other diseases. 
Researchers may also do genetic testing on your samples. 
In some cases, researchers may take cells from your samples and grow more of 
them over time, so that they can continue to do research with them. 
If you agree, your samples could also be used for genome-wide studies. In these 
studies, researchers will look at all of your genes (your genome). The researchers 
compare the genomes of many people, looking for common patterns of genes that 
could help them understand diseases. The researchers may put the information 
from the genome-wide studies into a protected database so that other researchers 
can access it, but your name and other personal information will not be included. 
Usually, no one would be able to look at your genome and link it to you as a 
person. However, if another database exists that also has information on your 
genome and your name, someone might be able to compare the databases and 
identify you. If others found out, it could lead to discrimination or other problems. 
The risk of this is very small. There may be other unknown risks. 
Who will have access to my information in studies using my extra samples? 
People who may see your information are: 
• Researchers who use your extra samples and information for other research 
• Government agencies that fund or monitor the research using your extra 
samples and information 
• The researcher’s Institutional Review Board or Ethics Committee 
• Any regulatory agency that reviews clinical trials 
• The people who work with the researcher 
All of these people will do their best to protect your information. The results of 
any new studies that use your extra samples and information may be published. 
No publication will use your name or identify you personally. 
17. We will do our best to protect your private information. 
US sites: Check HIPAA authorization for conflicts with this section. 
Your study records and samples will be kept in a secure location. We will label all 
of your samples and most of your records with a code number, not your name or 

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other personal information. However, it is possible to identify you, if necessary. 
We will not share your name with the lab that does the tests on your samples, or 
with anyone else who does not need to know your name. 
Site: Any change to the following boxed text requires approval from HVTN 
Regulatory Affairs. You can remove the box around the text.  
We do need to share your name with the HVTN in case you need proof in the 
future that you participated in an HIV vaccine study. The HVTN will keep your 
name in a secure file with these items:  
• The name of your study 
• Your age or date of birth 
• Your study ID number 
• What study product(s) you received 
There are no HIV test results kept in this file. The HVTN will not share any 
information that could identify you without your agreement. The HVTN will 
remove your name from the file if you do not want it there. 
Clinic staff will have access to your study records. Your records may also be 
reviewed by groups who watch over this study to see that we are protecting your 
rights, keeping you safe, and following the study plan. These groups include: 
• The US National Institutes of Health and its study monitors, 
• The US Food and Drug Administration, 
• Any regulatory agency that reviews clinical trials, 
• [Insert name of local IRB/EC] , 
• DAIDS, IAVI, AAHI and people who work for them, 
• The HVTN and people who work for them, 
• The HVTN Safety Monitoring Board (SMB) and 
• The US Office for Human Research Protections. 
All reviewers will take steps to keep your records private. 

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We cannot guarantee absolute privacy. If you are found to have a medical 
condition that we are required to report by law, then some of your information 
may be shared. At this clinic, we have to report the following information:  
Site: Include any public health or legal reporting requirements. Bulleted examples 
should include all appropriate cases (reportable communicable disease, risk of harm 
to self or others, etc.) If your site does not have public health or legal reporting 
requirements, you may delete the last sentence in the paragraph above, along with 
the bullets below. 
• [Item 1] 
• [Item 2] 
• [Item 3] 
US sites: Include the following boxed text. You can remove the box around the text. 
We have a Certificate of Confidentiality from the US government, to help protect 
your privacy. With the certificate, we do not have to release information about 
you to someone who is not connected to the study, such as the courts or police. 
Sometimes we can’t use the certificate. Since the US government funds this 
research, we cannot withhold information from it. Also, you can still release 
information about yourself and your study participation to others. 
The results of this study may be published. No publication will use your name or 
identify you personally. 
We may share information from the study with other researchers. We will not 
share your name or information that can identify you. 
A description of this clinical trial will be available on 
http://www.ClinicalTrials.gov. This website will not include information that can 
identify you. At most, the website will include a summary of the results. You can 
search this website at any time. 
18. There are several reasons why we may stop your injections. We may stop 
them even if you want to stay in the study and even if you were scheduled for 
more injections. 
We will stop your injections if you become pregnant. We will encourage you to 
stay in the study if you choose. We will discuss your study options with you. If 
you leave the study while you are still pregnant, we will contact you after your 
due date to ask some questions about your pregnancy and delivery. 
We will stop your injections if you get HIV. We will also take fewer samples, and 
we will help you get care and support. We will encourage you to stay in the study 
for up to 12 weeks after your last injection if you choose. We will discuss your 

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study options with you. We will counsel you about having HIV and about telling 
your partner(s). Site: Modify the following sentence as appropriate. We will not 
provide or pay for any of your HIV care directly.  
We will stop your injections if you enroll in another study where you receive a 
study product.  
If we stop your injections, we may ask you to stay in the study to complete other 
study procedures. 
19. We may take you out of the study at any time.  
We may take you out of the study if: 
• you do not follow instructions, 
• we think that staying in the study might harm you, or 
• the study is stopped for any reason. 
Other Risks 
20. There are other risks to being in this study. 
This section describes the other risks and restrictions we know about. There may 
also be unknown risks, even serious ones. We will tell you if we learn anything 
new that may affect your willingness to stay in the study. 
Risks of routine medical procedures: 
In this study, we will do some routine medical procedures. These are taking blood 
and giving injections. These procedures can cause bruising, pain, fainting, 
soreness, redness, swelling, itching, a sore, bleeding, and (rarely) muscle damage 
or infection where you got the injection. Taking blood can cause a low blood cell 
count (anemia), making you feel tired. 
Personal problems/discrimination/testing HIV antibody positive: 
About 10 to 20% of people who join HVTN studies report personal problems or 
discrimination because of joining an HIV vaccine study. Family or friends may 
worry, get upset or angry, or assume that you have HIV or at high risk and treat 
you unfairly as a result. Rarely, a person has lost a job because the study took too 
much time away from work, or because their employer thought they had HIV. 
The body makes antibodies to fight or prevent infection. Most vaccines cause the 
body to make antibodies as a way of preventing infection. Your body may make 
antibodies to HIV because you received an HIV study vaccine. The study vaccine 
may cause you to test positive on some types of HIV antibody tests, even if you 

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do not have HIV. This is called vaccine-induced seropositivity (VISP). VISP 
means that after you get the study vaccine, a routine HIV test done outside this 
clinic may say you have HIV, even if you don’t. For this reason, you should plan 
to get HIV tests only at this clinic during the study. Our tests can tell the 
difference between true HIV infection and a positive result that is caused by the 
study vaccine. 
If you have a positive test result caused by the study vaccine at any time, we can 
arrange free HIV testing for as long as you need it. If this happens, we do not 
know how long you will test positive due to the study vaccine. If you receive a 
positive HIV test result and we determine it is because you have HIV, we will 
refer you for follow-up care. 
It is unlikely, but you could test negative at the end of the study and positive some 
time later, even though you don’t have HIV. This could happen if different HIV 
tests come into use. We will give you a phone number to call for more 
information. 
Site: Modify the following paragraph if applicable. If someone believes you have 
HIV even if you do not, you could face discrimination and other problems. For 
example, in some countries, you could be denied medical or dental care, 
employment, insurance, a visa, or entry into the military. If you do have a positive 
HIV antibody test caused by the study vaccine, you will not be able to donate 
blood or organs. Your family and friends may treat you differently. We will give 
you a brochure that tells you more about testing HIV positive because of an HIV 
vaccine, and how you can avoid some of these problems. 
If you become pregnant during or after the study and have VISP, we don't know if 
the antibodies could be passed to your baby. We know that this happens with 
other vaccines, like tetanus vaccine. These antibodies from the mother are not a 
danger to the baby, and they go away over time. For most babies antibodies from 
the mother last for about six months. 
You should always tell the delivery staff if you have VISP. However, you may 
still be tested for HIV using the antibody test when you deliver your baby. If your 
test is positive and the delivery staff believes you have HIV, your baby may be 
started on antiretroviral treatment when it is not needed. If this happens, we can 
arrange for you and the baby to have a test that can tell the difference between 
true HIV infection and a VISP result. If you or the baby continue to have VISP, 
we can arrange this testing for free for as long as it is needed. 
Embarrassment/anxiety: 
You may feel embarrassed when we ask about your HIV risks, such as having sex 
and using drugs. Also, waiting for your HIV test results or other health test results 
could make you feel anxious. You could feel worried if your test results show that 
you have HIV. If you feel embarrassed or anxious, please tell us and we will try to 
help you. 

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Risks of disclosure of your personal information: 
We will take several steps to protect your personal information. Although the risk 
is very low, it is possible that your personal information could be given to 
someone who should not have it. If that happened, you could face discrimination, 
stress, and embarrassment. We can tell you more about how we will protect your 
personal information if you would like it. 
Risks of genetic testing: 
It is unlikely, but the genetic tests done on your samples could show you may be 
at risk for certain diseases. If others found out, it could lead to discrimination or 
other problems. However, it is almost impossible for you or others to know your 
test results from the genetic testing. The results are not part of your study records 
and are not given to you. 
In the very unlikely event that your genetic information becomes linked to your 
name, a federal law called the Genetic Information Nondiscrimination Act 
(GINA) helps protect you. GINA keeps health insurance companies and 
employers from seeing results of genetic testing when deciding about giving you 
health insurance or offering you work. GINA does not help or protect you against 
discrimination by companies that sell life, disability or long-term care insurance. 
Unknown risks: 
We do not know if the study vaccine will increase, decrease, or not change your 
risk of getting HIV if exposed. If you get HIV, we do not know how the study 
vaccine might affect your HIV infection or how long it takes to develop AIDS. 
We do not know if getting this study vaccine will affect how you respond to any 
future approved HIV vaccine. Currently, no HIV vaccine has been approved for 
use. 
We do not know how the study vaccine will affect a pregnant participant or a 
developing baby. 
Benefits 
21. The study may not benefit you. 
We do not expect the study vaccine to benefit you in any way. However, being in 
the study might still help you in some ways. The counseling that you get as part of 
the study may help you avoid getting HIV. The lab tests and physical exams that 
you get while in this study might detect health problems you don’t yet know 
about. 

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This study may help in the search for a vaccine to prevent HIV. However, if the 
study vaccine later becomes approved and sold, there are no plans to share any 
money with you. 
Your rights and responsibilities 
22. If you join the study, you have rights and responsibilities. 
You have many rights that we will respect. You also have responsibilities. We list 
these in the Participant’s Bill of Rights and Responsibilities. We will give you a 
copy of it. 
Leaving the study 
23. Tell us if you decide to leave the study. 
You are free to leave the study at any time and for any reason. Your care at this 
clinic and your legal rights will not be affected, but it is important for you to let us 
know. 
We will ask you to come back to the clinic one last time for a physical exam, and 
we may ask to take some blood and urine samples. We will also ask about any 
personal problems or benefits you have experienced from being in the study. We 
believe these steps are important to protecting your health, but it is up to you 
whether to complete them. 
Injuries 
Sites: Approval from HVTN Regulatory Affairs (at vtn.core.reg@hvtn.org) is needed 
for any change (other than those that the instructions specifically request or those 
previously approved by HVTN Regulatory Affairs) to the boxed text. You can remove 
the box around the text. 
24. If you get sick or injured during the study, contact us immediately. 
Your health is important to us. (Sites: adjust the following 2 sentences if 
applicable to the care available at your site) We will tell you about the care that 
we can give here. For the care that we cannot provide, we will explain how we 
will help you get care elsewhere. 
If you become sick or injured in this study, the HVTN has a process to decide if it 
is related to the study products and/or procedures. If it is, we call it a study-related 
injury. There are funds to pay for treatment of study-related injuries if certain 
conditions are met. 
Some of the study product providers may pay medical costs for study-related 
injuries that are determined to be caused by their own study products. If provider 
funds are not available or are not enough, or if the injury is determined to be 

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caused by study procedures, the HVTN has limited funds to pay medical costs 
that it determines are reasonable. (Sites: insert locale- appropriate medical 
insurance language in the following sentence) If the injury is not study related, 
then you and/or your health insurance will be responsible for treatment costs. 
Some injuries are not physical. For example, you might be harmed emotionally by 
being in an HIV vaccine study. Or you might lose wages because you cannot go 
to work. However, there are no funds to pay for these kinds of injuries, even if 
they are study related. 
You may disagree with the decision about whether your injury is study related. If 
you wish, the HVTN will ask independent experts to review the decision. You 
always have the right to use the court system if you are not satisfied. 
Health contact  
25. After your clinic visits end, we will contact you to check on your health.  
We will contact you by phone, email, or text message [Site: Modify mode of 
contact as appropriate; consult IRB/EC if necessary] about 12 months after your 
last injection to ask some questions about your health. If you prefer to answer 
these questions in person, you can come to the clinic to do this. 
If we have any concerns about your health, we may need to have more contact 
with you. You are welcome to contact us at any time if you have concerns about 
your health related to being in the study. 
If we ask you to come to the clinic, we will give you 
[Site: Insert compensation amount] for each visit. This amount is to cover the 
costs of [Site: Insert text]. 
If someone outside this study clinic told you that you have HIV, we will ask you 
to come back to the clinic for another HIV test. We will draw about 15 mL (1 
tablespoon) of blood. We may ask you to come back more than once for this 
testing. 
Because we will want to contact you, please tell us if your contact information 
changes, if you are moving away, or if you do not want us to contact you 
anymore. 
You can tell us at any time that you don’t want any more contacts. If you do so, 
you will not lose any benefits or rights you would normally have. 
All other information that is discussed earlier in this consent also applies to this 
contact. 

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Questions  
26. If you have questions or problems at any time during your participation in 
this study, use the following important contacts. 
If you have questions about this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
If you have any symptoms that you think may be related to this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
This study has been reviewed and approved by a committee called the 
[name of local IRB/EC]. If you have questions about your rights as a research 
participant, or problems or concerns about how you are being treated in this study, 
contact [name or title and telephone number of person on IRB/EC] , at the 
committee. 
If you want to leave this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
Your permissions and signature  
Site: Delete this section if using a separate consent for use of samples and 
information in other studies 
27. In Section 16 of this form, we told you about possible other uses of your extra 
samples and information, outside this study. Please choose only one of the 
options below and write your initials or make your mark in the box next to it. 
Whatever you choose, the HVTN keeps track of your decision about how 
your samples and information can be used. You can change your mind after 
signing this form. 
 

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I allow my extra samples and information to be used for other studies related to 
HIV, vaccines, the immune system, and other diseases. This may include 
genetic testing and keeping my cells growing over time.  
OR 
 
 
I agree to the option above and also to allow my extra samples and information 
to be used in genome wide studies. 
OR 
 
 
I do not allow my extra samples to be used in any other studies. This includes 
not allowing genetic testing, growing more of my cells, or genome wide studies. 
28. If you agree to join this study, you will need to sign or make your mark 
below. Before you sign or make your mark on this consent form, make sure 
of the following: 
• You have read this consent form, or someone has read it to you. 
• You feel that you understand what the study is about and what will happen to 
you if you join. You understand what the possible risks and benefits are. 
• You have had your questions answered and know that you can ask more. 
• You agree to join this study. 
You will not be giving up any of your rights by signing this consent form. 
 
 
 
 
 
 
 
Participant’s name (print) 
 
Participant’s signature or mark 
 
Date 
 
Time 
 
 
 
 
 
 
 
Clinic staff conducting consent 
discussion (print) 
 
Clinic staff signature 
 
Date 
 
Time 
For participants who are unable to read or write, a witness should complete the 
signature block below: 
 
 
 
 
 
 
 
Witness’s name (print) 
 
Witness’s signature  
 
Date 
 
Time 
*Witness is impartial and was present for the entire discussion of this consent form. 

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Appendix B 
Sample informed consent form for Part B 
Title: A phase 1 clinical trial to evaluate the safety and immunogenicity of HIV-1 
BG505 SOSIP.664 gp140 with TLR agonist and/or Alum adjuvants and VRC 
HIV Env Trimer 4571 and 3M-052-AF with Alum in healthy, HIV uninfected 
adults 
HVTN protocol number: HVTN 137 
Site: [Insert site name] 
Thank you for your interest in our research study. Please read this consent form or 
ask someone to read it to you. If you decide to join the study, we will ask you to 
sign or make your mark on this form. We will offer you a copy to keep. We will 
ask you questions to see if we have explained everything clearly. You can also 
ask us questions about the study. 
Research is not the same as treatment or medical care. The purpose of a research 
study is to answer scientific questions. 
Key information 
These are some of the things you should know about this study: 
The purpose of the study is to test 4 experimental HIV vaccines. The study 
vaccines are made from two parts: a man-made piece of protein that looks like a 
protein found on the outside of HIV and an adjuvant. Adjuvants are substances 
that help the immune system respond better. The study vaccines all have the same 
protein but different adjuvants. The study will see if the study vaccines are safe 
for people and how people’s immune systems respond to them. This is the first 
study to give these study vaccines to people. 
If you join the study, you will have about 15 clinic visits over about a year and a 
half. Clinic visits will involve physical exams, collection of blood and urine for 
routine laboratory tests (including pregnancy tests if you are capable of getting 
pregnant), HIV testing at some visits, and collection of blood samples to look at 
your immune responses to the study vaccines. Some visits will involve 
questionnaires, some of which ask very personal questions. You will get 
injections at three visits. 
Some of the risks of getting vaccines are fever, chills, rash, aches and pains, 
nausea, headache, dizziness, feeling tired, and pain, redness, swelling, or itching 
where you get the injection. On rare occasions, a vaccine can cause an allergic 
reaction. These can even be life threatening. Very rarely, a vaccine causes a 
person to have an autoimmune disease or makes an autoimmune disease worse. 
Because this protein and these adjuvants have not been given to many people yet, 
we do not know what all of the risks may be.  We think the risks will be similar to 
these general risks. There may be other side effects that we don’t yet know, even 
serious ones. 

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We do not expect the study vaccine to benefit you in any way. You do not have to 
join, and you are free to leave at any time. 
The rest of this form provides a more complete description of the study. Please 
read it carefully. 
About the study 
The HIV Vaccine Trials Network (HVTN) and [Insert site name] are doing a 
study to test HIV vaccines. HIV is the virus that causes AIDS. The study vaccines 
are made from two parts: a protein and an adjuvant. Adjuvants are substances that 
help the immune system respond better. (Your immune system protects you from 
disease.) In this study we will test one protein with different adjuvants.  
About 105 people will take part in this study at multiple sites. The researcher in 
charge of this study at this clinic is [Insert name of site PI]. The US National 
Institutes of Health (NIH) is paying for the study. 
This study is divided into two parts, part A and part B. About 17 people will be in 
part A. In part A, we tested 2 different doses (amounts) of 1 adjuvant. We may be 
recruiting people for Part B before we know the results from Part A. After we see 
the results from part A, we will decide whether or not to do part B of the study. If 
we decide to do part B, 88 more people will join. The results from part A will also 
help us decide on the dose of that 1 adjuvant to use in part B. In part B, we will 
test 4 study vaccines. In each of them, the protein will be the same but the 
adjuvant will be different. 
1. You are being invited to join part B of the study. We are doing part B of this 
study to answer several questions. 
• Are the study vaccines safe to give to people? 
• Are people able to take the study vaccines without becoming too 
uncomfortable? 
• How do people’s immune systems respond to the study vaccines?  
2. The study vaccines cannot give you HIV. 
The study vaccines are not made from actual HIV. It is impossible for the study 
vaccines to give you HIV. Also, they cannot cause you to give HIV to someone 
else. 
3. We do not know if the study vaccines will decrease, increase, or not change 
your risk of getting HIV if you are exposed to the virus. 
Site: Any change to the following boxed text requires approval from HVTN 
Regulatory Affairs at vtn.core.reg@hvtn.org. You can remove the box around the text. 

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Several studies have tested whether HIV vaccines can reduce the risk of getting 
HIV from another person. In some studies, people who got the vaccine seemed to 
have the same risk of getting HIV as people who did not get the vaccine. In one 
study, people who got the vaccine seemed to have a lower risk of getting HIV 
than people who did not get the vaccine. In studies with a different vaccine, some 
people who got the vaccine had a higher risk of getting HIV than people who did 
not get the vaccine. 
This study differs from the studies in which people who got the vaccine had a 
higher or lower risk of getting HIV. We can tell you about the differences. 
We do not know whether the vaccines in this study will affect your risk of getting 
HIV from another person. The risk could be higher, lower, or unchanged. It’s very 
important to avoid exposure to HIV during and after the study. We will tell you 
how to avoid HIV. 
4. These study vaccines are experimental. 
We are testing 4 study vaccines. The study vaccines are made up of two parts, the 
protein and the adjuvant. (An adjuvant is something that helps the immune system 
respond better.) The protein is BG505 SOSIP.664 gp140. This is a man-made 
piece of protein that looks like a protein found on the outside of HIV. From here 
on we will call it “the protein.” The protein will be included in all 4 study 
vaccines. The second part of the study vaccine, the adjuvant, will be different in 
each study vaccine. The adjuvants are Alum, CpG 1018 + Alum, 3M-052-AF + 
Alum, and GLA-LSQ. 
We are calling each of these combinations of protein and adjuvant “a study 
vaccine.” These are experimental HIV vaccines. That means we do not know if 
the vaccines will be safe to use in people, or if they will work to prevent HIV 
infection. These vaccines are used only in research studies. 
The protein (BG505 SOSIP.664 gp140): 
The protein was designed to look like a piece of protein on HIV. This piece of 
protein has been engineered to stay in a shape much like that in HIV. In this way 
it is different from proteins in some other HIV study vaccines. The protein was 
developed by John Moore at Cornell Weill Medical Center in New York, New 
York, USA. It is being provided for this study by the International AIDS Vaccine 
Initiative (IAVI) in New York, New York, USA.  

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The adjuvants: 
Alum: 
Alum alerts the immune system and attracts immune cells to the injection site. It 
is being provided for this study by the Division of AIDS (DAIDS) at the US 
National Institutes of Health in Rockville, Maryland, USA. 
CpG 1018 + Alum: 
The CpG 1018 adjuvant was developed by Dynavax Corporation in Berkeley, 
California, USA and is being provided for this study by DAIDS. It includes short 
man-made bits of DNA that stimulate a part of the immune system that recognizes 
invading viruses and bacteria. This adjuvant has been tested in clinical trials of 
vaccines to prevent flu, anthrax, and malaria. CpG 1018 is used in an FDA-
approved vaccine against hepatitis B. Before it was approved by the FDA, that 
vaccine was tested in more than 9500 people. Overall the side effects were similar 
to the side effects seen with other vaccines. In one study, people who got the 
vaccine with CpG 1018 had a heart attack more often than people who got a 
different vaccine against hepatitis B. The heart attacks were rare. After careful 
review by experts, no relationship between heart attack and the vaccine with CpG 
1018 was found. In this study, CpG 1018 is mixed with Alum. The FDA-
approved vaccine does not contain Alum. 
3M-052-AF + Alum: 
The 3M-052 is one of many similar products developed by 3M to treat skin 
conditions, tumors, and to make vaccines more effective. These products are 
designed to stimulate parts of the immune system that recognize viral and 
bacterial invaders. In this study, 3M-052 is dissolved in water and is mixed with 
Alum. 
3M-052 was developed by 3M Corporation in St. Paul, Minnesota, USA. In this 
study, the 3M-052 is dissolved in water and this mixture is being provided by the 
Access to Advanced Health Institute (AAHI) in Seattle, Washington, USA.  
The 3M-052 adjuvant has been given to 52 participants with advanced cancer in 
one experimental study. The cancer study differed from this vaccine study in 
important ways. The cancer study participants were very sick. The 3M-052 was 
mixed with sesame oil. It was injected directly into tumors at higher doses and for 
a different purpose. In the cancer study, one participant died four days after 
getting his second injection into a liver tumor. The exact cause of death could not 
be determined but was felt to be related to the 3M-052 adjuvant and the injection 
procedure. Two other participants in the cancer study developed a condition 
called cytokine release syndrome, which can be severe and require 
hospitalization. Both participants recovered with medical care. We don’t expect to 
see these outcomes due to the many differences described above. We can discuss 
this more with you if you would like. 

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HVTN 137 Part A tested 2 different doses (amounts) of the 3M-052-AF + Alum 
adjuvant. As there were no serious health problems in Part A participants, the 
decision was made to use the higher dose of adjuvant in the study vaccine in Part 
B of the study. 
Two participants in Part A did have reactions to their study injections that we 
want to tell you about. Both had redness and swelling over a large area on their 
arm where they got the injection that started about 1 week after a study injection. 
The redness lasted for about 2 to 3 days. For one of these people, the swelling 
went away within 2 to 3 days. The second person had significant swelling for 
about 3 days. The swelling went down but it took about 5 weeks to completely go 
away. They had mild pain which did not prevent them from going to work. 
Because the study is ongoing and is blinded, we do not know if these people got 
the study vaccine or placebo. 
 
GLA-LSQ: 
The GLA-LSQ adjuvant was developed by AAHI and is being provided for this 
study by DAIDS. It simulates parts of the immune system that recognize the cell 
walls of invading bacteria. GLA-LSQ has been tested in clinical trials of vaccines 
against TB, malaria, and some tropical diseases  
Risks of the protein and adjuvants: 
For more than 90 years, Alum has been used as an adjuvant in commercial 
vaccines. Hundreds of millions of people have gotten vaccines containing Alum.  
The protein has been tested for safety and immune response in rats, rabbits, 
monkeys, and cows. It is currently being tested with a different adjuvant in people 
in Seattle, USA. The study is planned to include Boston, USA and Kenya. As of 
August 9, 2019, 6 people have joined this study. Reactions to the vaccine have so 
far been mild to moderate. There have not been any serious health problems. 
All the study vaccines have been tested for safety in rats. Some of them have been 
tested for safety in rabbits and monkeys. All of the study vaccines have been 
tested for immune response in rats, guinea pigs, rabbits, and monkeys. In these 
studies, animals that got the study vaccines had symptoms consistent with the 
general risks of other vaccines (as described below). The study vaccines have not 
been tested in humans before. Even if something looks like it is safe or works in 
animals, it may not be true for people. 
General risks of vaccines: 
All vaccines can cause fever, chills, rash, aches and pains, nausea, headache, 
dizziness, and feeling tired. Vaccines can also cause pain, redness, swelling, or 
itching where you got the injection. Most people can still do their planned 

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activities after getting a vaccine. Rarely, people have side effects that limit their 
normal activities or make them go to the doctor. 
Rarely, a vaccine can cause an allergic reaction, including a rash, hives, or trouble 
breathing. Allergic reactions can be life-threatening. You should tell us if you 
have ever had a bad reaction to any injection or vaccine. 
Very rarely, a vaccine causes an autoimmune disease in a person, or makes an 
autoimmune disease worse. An autoimmune disease happens when your immune 
system attacks your own body, instead of attacking an infection. 
Joining the study 
5. It is completely up to you whether or not to join the study. 
Take your time in deciding. If it helps, talk to people you trust, such as your 
doctor, friends or family. If you decide not to join this study, or if you leave it 
after you have joined, your other care at this clinic and the benefits or rights you 
would normally have will not be affected. 
If you join this study, you may not be allowed to join other HIV vaccine or HIV 
prevention studies now or in the future. You cannot be in this study while you are 
in another study where you get a study product. Being in more than one study 
may not be safe. 
Also, during the study, you should not donate blood or tissue. 
If you choose not to join this study, you may be able to join another study. 
Site: Remove item 6 if you use a separate screening consent that covers these 
procedures. 
6. If you want to join the study, we will screen you to see if you are eligible. 
Screening involves a physical exam, HIV test and health history. A physical exam 
may include, but is not limited to: 
• Checking your weight, temperature and blood pressure 
• Looking in your mouth and throat 
• Listening to your heart and lungs 
• Feeling your abdomen (stomach and liver) 
We will also do blood and urine tests. These tests tell us about some aspects of 
your health, such as how healthy your kidneys, liver, and immune system are. We 
will also test you for hepatitis B and hepatitis C. We will ask you about 

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medications you are taking. We will ask you about behaviors that might put you 
at risk for getting HIV. If you were assigned female sex at birth, we will test you 
for pregnancy.  
We will review the screening results with you. The screening results may show 
you are not eligible to join the study, even if you want to.  
Site: adapt the following section so it is applicable to the care available at your site 
7. If we find that you have a health problem during screening or during the 
study, we will tell you about the care that we can give here for free. 
For the care that we cannot give, we will explain how we will help you get care 
elsewhere. For health problems that are unrelated to the study, we will not pay for 
care. 
8. If you were assigned female sex at birth and can become pregnant, you must 
agree to use birth control to join this study. 
Site: If you want to include Appendix F, Approved birth control methods (for sample 
informed consent form), in this consent form, paste it below and delete paragraph 
below. 
You should not become pregnant during the study because we do not know how 
the study vaccines could affect the developing baby. You must agree to use 
effective birth control from 21 days (3 weeks) before your first injection until 6 
months after your last study injection. We will talk to you about effective birth 
control methods. They are listed on a handout that we will give you. 
Being in the study 
If you meet the study requirements and want to join, here is what will happen: 
9. You will come to the clinic for scheduled visits about [#] times over 
[Insert period of time]. 
Site: Insert number of visits and range of visit lengths. (There is site-specific variation 
in screening protocols and in the number of possible follow-up visits between 
protocol-mandated visits.) 
Visits can last from [#] to [#] hours. 
You may have to come for more visits if you have a lab or health issue. 
We may contact you after the main study ends (for example, to tell you about the 
study results). 

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10. We will give you [Site: Insert compensation] for each study visit you 
complete. 
This amount is to cover the costs of [Site: Insert text] 
Site: Insert any costs to participants (eg, birth control costs for participants assigned 
female sex at birth who could become pregnant). 
US sites: Include the following paragraph. You can remove the box around the text. 
Payments you receive for being in the study may be taxable. We may need to ask 
you for your Social Security number for tax reasons. 
You do not have to pay anything to be in this study. 
11. We will give you either the study vaccines or a placebo. 
Not everyone in this study will get the study vaccines. Some people will get a 
placebo, a substance that does not contain vaccine. In this study, the placebo is a 
combination of salt water and a preservative (to keep the solution from becoming 
too acidic). We will compare the results from people who got the different study 
vaccines. We will also compare results from people who got the placebo with 
results from people who got the study vaccines.  
You have a 10-in-11 chance of getting the study vaccines. Site: Modify the 
randomization metaphor in the next sentence as appropriate to your local culture. 
Whether you get one of the study vaccines or the placebo is completely random, 
like flipping a coin. 
We have no say in whether you get the study vaccines or the placebo. We will not 
know which one you are getting, and neither will you. Only the pharmacist at this 
clinic will have this information while the study is going on. 
You will have to wait until everyone completes their final study visits to find out 
whether you got the study vaccines or the placebo. This could be several years. 
But, if you have a serious medical problem and need to know what you got before 
the end of the study, we can tell you. 
12. We will give you the study products on a schedule. 
You will be in one of 4 groups. You will get 3 injections into the upper arm 
during the study. 
 

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Group 
Number of 
participants 
Injection schedule  
At enrollment 
At 2 months 
At 6 months 
3 
20 
protein + 
(CpG 1018 + Alum) 
protein + 
(CpG 1018 + Alum) 
protein + 
(CpG 1018 + Alum) 
2 
Placebo 
Placebo 
Placebo 
4 
20 
protein +  
(3M-052-AF + Alum) 
protein +  
(3M-052-AF + Alum) 
protein +  
(3M-052-AF + Alum) 
2 
Placebo 
Placebo 
Placebo 
5 
20 
protein +  
GLA-LSQ 
protein +  
GLA-LSQ 
protein + 
GLA-LSQ 
2 
Placebo 
Placebo 
Placebo 
6 
20 
protein +  
Alum 
protein +  
Alum 
protein + 
Alum 
2 
Placebo 
Placebo 
Placebo 
You will have to wait in the clinic for about a half hour after each injection to see 
if there are any problems. Then for that night and for 7 more days, you will need 
to keep track of how you are feeling and if you have any symptoms. Site: 
Customize the next sentence based on how you collect reactogenicity information. 
You will bring this information back to the clinic at your next visit. Within 3 days 
of each injection, we will also need to be in contact with you to ask how you are 
doing. Contact the clinic staff if you have any issues or concerns after getting an 
injection. If you have a problem, we will continue to check on you until it goes 
away. 
13. In addition to giving you the study products, we will: 
• Do regular HIV testing, as well as counseling on your results and on how to 
avoid getting HIV 
• Do physical exams 
• Do pregnancy tests if you were assigned female sex at birth 
• Ask questions about your health, including medications you may be taking 
• Ask questions about any personal problems or benefits you may have from 
being in the study 
• Take urine and blood samples. 
When we take blood, the amount will depend on the lab tests we need to do. It 
will be some amount between 17 mL and 325 mL (about 1½ tablespoon to a little 

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more than ⅔ of a pint). Your body will make new blood to replace the blood we 
take out. 
Site: You may want to add a sentence to the end of the previous paragraph 
contextualizing the blood volumes described (eg, “To compare, people who donate 
blood in the US can give a total of about 500 mL in an 8-week period.”). Modify the 
example for cultural relevance and alter blood volumes as necessary. 
Site: Insert appropriate table from Appendix H, Tables of procedures (for informed 
consent form) in this section or distribute it as a separate sheet if it is helpful to your 
study participants. You are not required to do either. 
We will be looking for side effects. We will review the results of these procedures 
and tests with you at your next visit, or sooner if necessary. If any of the results 
are important to your health, we will tell you. 
14. If you agree, we may collect other samples to test your immune responses. 
Immune responses to vaccines involve different parts of the body. These include 
the cells in blood, in lymph nodes near the injection site, and in bone marrow. We 
would like to collect samples from these parts of the body to learn more about 
how the immune system responds to the study vaccines. Every additional sample 
provides more information. Not every type of sample will be collected by every 
clinic participating in the study. Some of the sample collection will be done at 
other locations. Those institutions may require additional forms of consent.  
At the end of this form, we will ask if you agree to each of these sampling 
procedures. You can agree now and change your mind later. Even if you agree to 
give these samples, you may not be eligible to do so but you will remain in the 
study. You can decide not to give any of these samples and still be in the study.  
Site: Of the following procedures, include only those available to your participants 
and edit the information as needed to reflect how they will be done at the 
site/procedure facility. 
Site: Images of the optional procedures in this section have been provided in a 
separate protocol appendix. You may insert then next to the narrative descriptions 
below or provide them as a separate document if it is helpful for your study 
participants. You are not required to do so.  
Leukapheresis procedure: 
This procedure collects large amounts of white blood cells. Blood is made up of 
red cells that carry oxygen, white cells that fight infection, platelets that help form 
clots, and plasma, the fluid left over when all the cells are removed. During 
leukapheresis, white blood cells are removed and the rest of the blood is put back 
into the body.  

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The leukapheresis procedure will be done at [site: insert location]. Your 
eligibility to have this procedure will be assessed by staff at our clinic and at the 
procedure facility.  
For the procedure, a clinician will insert a sterile needle into a vein in each of 
your arms. The needles are attached to tubes. Your blood will go out of your body 
through one tube and into a machine that separates the blood and takes out the 
white blood cells. When the white blood cells are taken out, the rest of the blood 
will go back into your body through the tube going into your other arm. 
Sometimes the fluid lost during the procedure is replaced by a sterile salt solution 
or a solution containing a protein called albumin. This protein is normally found 
in human blood. An anticoagulant called ACD-A may be added to your blood 
during the procedure. Anticoagulants prevent blood from clotting. 
It is normal to feel tired for up to 24 hours after leukapheresis.  
If you agree to have leukapheresis, it will happen about 2 weeks after your second 
injection. It will take about [site insert timeframe] for the procedure. 
We will give you [Site: Insert compensation] for having leukapheresis. This 
amount is to cover the costs of [Site: Insert text]. 
Risks of leukapheresis 
Generally, the risks of leukapheresis include nausea, vomiting, fainting or 
dizziness, pain, bruising or swelling at the needle sites, low blood pressure, 
increased pulse rate, seizures, blood loss, and infection. Rarely, albumin can cause 
an allergic reaction. If the leukapheresis procedure has to be stopped, it could 
result in the loss of as much as 1 cup of blood. Your body makes new blood 
within 2 weeks.  
The side effects of ACD-A can include muscle cramping, tingling sensations 
around the mouth, feeling chilled, numbness, or a feeling that the body is 
vibrating. 
If you notice any symptoms during leukapheresis, please let the nurse know 
immediately. Usually the symptoms can be reversed quickly by adding fluid or by 
slowing the procedure. If there are any problems, the staff will use the appropriate 
medical procedures to treat you.  
Lymph node cell collection procedure 
This procedure collects cells from lymph nodes. Lymph nodes are one of the key 
places where immune responses develop. In this procedure, a doctor will use a 
very thin needle guided by ultrasound to collect cells from a lymph node near the 
injection site.  

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The lymph node cell collection procedure will be done at [site: insert location]. 
Your eligibility to have this procedure will be assessed by staff at our clinic and at 
the procedure facility.  
For the procedure, a clinician will locate the appropriate lymph node by applying 
a cold gel and pressing a hand-held ultrasound device against your skin. If 
necessary, a small area near the lymph node may be shaved. A cleaning solution 
will be applied to the skin in that area. The area will be numbed by an injection of 
a local anesthetic, such as Lidocaine, which is like Novocaine. The doctor will 
insert a very thin needle and use the images from the ultrasound to guide it into 
the lymph node. The needle may be moved up and down to collect cells from the 
lymph node. Fluid may also be collected through the needle into a syringe or 
bottle. Each cell collection lasts about 10-15 seconds. It usually takes about 4 
separate cell collections to get enough cells. 
After the procedure is done, the area will be cleaned with warm water. You will 
be given a band-aid to cover the needle site. 
If you agree to have lymph node cell collection, it will happen about 3 weeks after 
your second injection. It will take about [site insert timeframe] for the procedure. 
We will give you [Site: Insert compensation] for having a lymph node cell 
collection. This amount is to cover the costs of [Site: Insert text]. 
Risks of lymph node cell collection 
The main risks of this procedure include pain and bruising where the needle is 
inserted and infection at that spot. The cleaning solution, or shaving the area, may 
cause irritation. Injecting the local anesthetic may sting or burn for a little while 
until the numbing takes effect. Very rarely, damage to tissues, nerves, or blood 
vessels may happen. Examining the lymph node area may be uncomfortable or 
cause embarrassment. There may be bleeding during or after the procedure. If 
there is an infection, antibiotic treatment may be needed. 
If discomfort, problems, or side effects happen during or after lymph node cell 
collection, the staff will use the appropriate medical procedures to treat you. 
Bone marrow cell collection procedure 
This procedure collects cells that make antibodies for a long time and cells that 
remember immune responses to the vaccine. Cell collection involves removing 
some marrow from your hip bone. The bone marrow cell collection procedure 
will be done at [site: insert location]. Your eligibility to have this procedure will 
be assessed by staff at our clinic and at the procedure facility.  
For the procedure, a clinician will locate the back of your hip bone just below 
your waist near your spine. A cleaning solution will be applied to the skin in that 
area. The area will be numbed by an injection of a local anesthetic, such as 

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Lidocaine, which is like Novocaine. This makes the procedure less 
uncomfortable. The doctor will insert a single needle into your hip bone to get up 
to 20 cc (up to ¾ of an ounce or a little less than 1 ½  tablespoons) of bone 
marrow.  
Once the bone marrow has been removed, a sterile dressing will be applied. A 
nurse will instruct you on how to care for this area. Your hip bone may be sore for 
a few days. You may feel tired for several days until your body can replace the 
bone marrow that was taken out. 
If you agree to bone marrow cell collection, it will happen about a year after your 
last injection. 
We will give you [Site: Insert compensation] for having bone marrow cell 
collection. This amount is to cover the costs of [Site: Insert text]. 
Risks of bone marrow cell collection 
Removing bone marrow may cause pain and bruising that may last 1 to 3 days. It 
may cause tiredness for a few days. Rarely, people have sweating, nausea, 
lightheadedness, or fainting. Very rarely there are more serious side effects. These 
include damage to normal blood vessels or bone structures or an infection where 
the bone marrow was removed. The cleaning solution may cause irritation. 
Injecting the local anesthetic may sting or burn for a little while until the numbing 
takes effect. Very rarely, damage to tissues, nerves, or blood vessels may happen. 
Examining the hip bone area may be uncomfortable or cause embarrassment. 
There may be bleeding during or after the procedure. If there is an infection, 
antibiotic treatment may be needed. 
If discomfort, problems, or side effects happen during or after bone marrow cell 
collection, the staff will use appropriate medical procedures to treat you. 
15. If you agree, we may also collect rectal and vaginal fluid and tissue. 
We want to see how the study vaccines affect the parts of the body where people 
may be exposed to HIV: their rectum and vagina. We would like to collect rectal 
fluid and tissue from all participants and vaginal fluid and tissue from participants 
assigned female sex at birth. We will collect these samples at our clinic.  
At the end of this form we will ask if you agree to provide these samples. You can 
agree now and change your mind later. Even if you agree to give these samples, 
you may not be eligible to do so but you will remain in the study. You can decide 
not to give any of these samples and still be in the study.  
We will ask you to avoid some activities before we collect these samples. This 
will help make sure your samples give accurate lab readings. 

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If you were assigned female sex at birth, we may test you for trichomonas 
vaginalis, yeast and/or bacterial vaginosis if clinically indicated when we collect 
these samples.  If you are providing tissue samples we will test you for gonorrhea 
and chlamydia when we collect them. 
We will give you your test results. If you need care, we will tell you about the 
care we can give you here. We will also tell you about care we can help you get 
elsewhere. 
Site: localize measurement units throughout this section as needed 
Rectal fluid collection (for all participants)  
We will perform a rectal exam to make sure it is safe to collect rectal fluids. We 
will collect rectal fluid by first placing a plastic tube about 2 cm wide (a little less 
than an inch) into your rectum to hold it open. The tube will go in about 6½ cm 
(about 2½ inches). A small balloon will be placed through the tube and into the 
rectum. The balloon will stay in for less than a minute. The balloon will be 
inflated to about half the size of a chicken egg after it is inside your rectum and 
deflated before it is removed. We will collect rectal fluid at 2 visits. 
For the 2 days before we collect your rectal fluid, we will ask you to follow these 
instructions:  
• Do not have receptive anal sex.  
• Do not put anything into your anus, including cleaning products (creams, gels, 
lotions, pads, etc.), lubricant, enemas or douches (even with water). 
• Do not use any steroid or other anti-inflammatory creams in or around your 
anus. 
We will not collect rectal fluid if we think you may have an anal or rectal 
infection. You should tell us if your rectal area is sore. 
We will give you [Site: Insert compensation] for rectal fluid collection. This 
amount is to cover the costs of [Site: Insert text]. 
Rectal tissue collection (for all participants) 
We will perform a rectal exam to make sure it is safe to collect rectal tissue 
samples. We will collect small samples of tissue about the size of half a grain of 
rice from the lining of your rectum. These are called rectal biopsies. We will 
collect up to 5 biopsies at 2 visits. To take the samples, we will place a plastic 
tube about 2 cm wide (a little less than an inch) into the anus to view the lower 
part of the rectum. You may feel some discomfort, but the biopsies are almost 
always painless. It will take 5 to 10 minutes.  

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You may see blood in your first few stools. This is normal after a biopsy. If you 
think the bleeding is excessive, contact us immediately. 
For the 2 days before we collect your rectal tissue, we will ask you to follow these 
instructions:  
• Do not have receptive anal sex.  
• Do not put anything into your anus, including cleaning products (creams, gels, 
lotions, pads, etc.), lubricant, enemas or douches (even with water). 
• Do not use any steroid or other anti-inflammatory creams in or around your 
anus. 
For the 5 days after we collect your rectal tissue, we will ask you to follow these 
instructions:  
• Do not have receptive anal sex.  
• Do not put anything into your anus, including cleaning products (creams, gels, 
lotions, pads, etc.), lubricant, enemas or douches (even with water).  
We will not collect rectal tissue if we think you may have an anal or rectal 
infection. You should tell us if your rectal area is sore. 
We will give you [Site: Insert compensation] for rectal tissue collection. This 
amount is to cover the costs of [Site: Insert text]. 
Vaginal fluid collection (for participants assigned female sex at birth) 
We will perform a pelvic exam to make sure it is safe to collect vaginal fluids. To 
collect vaginal fluid, a disposable menstrual cup will be inserted into your vagina. 
You will wear the cup for 1 to 6 hours and remove it at the clinic. The study staff 
will explain how to insert and remove the cup, or they can do it for you here. We 
will collect vaginal fluid at 2 visits. 
For the 2 days before we collect your vaginal fluid, we will ask you to follow 
these instructions:  
• Do not have vaginal sex or insert anything into your vagina, including 
tampons. 
• Do not douche or use anything in or around your vagina with spermicide, 
lubricants, or medication (such as topical yeast infection treatments). 
We will not collect vaginal fluid if you are menstruating or pregnant or if we 
think you may have a cervical or vaginal infection. If you are menstruating, we 
may ask you to return to collect this sample. 

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We will give you [Site: Insert compensation] for vaginal fluid collection. This 
amount is to cover the costs of [Site: Insert text]. 
Vaginal tissue collection (for participants assigned female sex at birth) 
We will perform a pelvic exam to make sure it is safe to collect vaginal tissue 
samples. We will collect small samples of tissue about the size of half a grain of 
rice from your vagina. These are called vaginal biopsies. We will collect up to 5 
biopsies at 2 visits. We will insert a speculum into your vagina. A speculum is a 
metal or plastic tool that looks like a bird’s beak. It is used to help open your 
vagina a few inches. After the speculum is put into your vagina, the vaginal wall 
will be cleaned with a clean cotton ball or swab.  
Biopsies will be taken with clean forceps. Forceps are a metal tool to help get the 
tissue from inside your vagina. You may feel cramping, pain, or discomfort. We 
will check to make sure that there is no bleeding from where the biopsies are 
taken. If there is bleeding, we will use a medication to stop it. One type of 
medication, silver nitrate, has a gray color. You may see gray flecks in your 
vaginal discharge after the biopsy. This is normal. The procedure will take about 
10 minutes. 
For the 2 days before and the 7 days after we collect your vaginal tissue, we will 
ask you to follow these instructions:  
• Do not have vaginal sex or insert anything into your vagina, including 
tampons. 
• Do not douche or use anything in or around your vagina with spermicide, 
lubricants, or medication (such as topical yeast infection treatments).  
We will not collect vaginal tissue if you are menstruating or pregnant or if we 
think you may have a cervical or vaginal infection. If you are menstruating, we 
may ask you to return to collect this sample. 
We will give you [Site: Insert compensation] for vaginal tissue collection. This 
amount is to cover the costs of [Site: Insert text]. 
Risks of rectal and vaginal fluid and tissue collection 
We will ask you to stop some activities before and after we collect these samples. 
You may find this inconvenient. These sample collections may cause some 
anxiety, temporary discomfort, and embarrassment. We will try to make you as 
comfortable as possible.  
All biopsies may cause a small amount of bleeding, which usually stops on its 
own. In rare cases, excess bleeding or infection may occur from a biopsy. If you 
need care, we will tell you about the care we can give you here. We will also tell 
you about care we can help you get elsewhere. Until the areas where the biopsies 

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were taken heal, you may be at increased risk for HIV or other sexually 
transmitted infection (STI) infection if you are exposed. Most people heal within 
5 to 14 days, but some may take longer. 
16. We will counsel you about protecting yourself from HIV. 
We will ask you personal questions about your HIV risk factors such as sexual 
behavior, alcohol, and drug use. We will talk with you about ways to keep your 
risk of getting HIV low. 
17. The HVTN will test your samples to see how your immune system responds 
to the study products. 
We will send your samples (without your name) to labs approved by the HVTN 
for this study, which are located in the United States and South Africa. In rare 
cases, some of your samples may be sent to labs approved by the HVTN in other 
countries for research related to this study. 
Researchers may also do genetic testing related to this study on your samples. 
Your genes are passed to you from your birth parents. They affect how you look 
and how your body works. The differences in people’s genes can help explain 
why some people get a disease while others do not. The genetic testing will only 
involve some of your genes, not all of your genes (your genome). The researchers 
will study only the genes related to the immune system and HIV and those that 
affect how people get HIV. 
If you get HIV, the researchers may look at all of the genes of the virus found in 
your samples. The researchers will use this information to learn more about HIV 
and the study product(s). 
In some cases, researchers may take cells from your samples and grow more of 
them over time, so that they can continue to contribute to this study. 
These tests done on your samples are for research purposes, not to check your 
health. The labs will not give the results to you or this clinic because their tests 
are not approved for use in making health care decisions. These labs are only 
approved to do research tests. 
When your samples are no longer needed for this study, the HVTN will continue 
to store them. 
Site: Delete next section if using separate consent for use of samples and information 
in other studies 

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18. When samples are no longer needed for this study, the HVTN wants to use 
them in other studies and share them with other researchers.  
The HVTN calls these samples “extra samples”. The HVTN will only allow your 
extra samples to be used in other studies if you agree to this. You will mark your 
decision at the end of this form. If you have any questions, please ask. 
Do I have to agree? No. You are free to say yes or no, or to change your mind 
after you sign this form. At your request, we will destroy all extra samples that we 
have. Your decision will not affect your being in this study or have any negative 
consequences here. 
Where are the samples stored? Extra samples are stored in a secure central place 
called a repository. Your samples will be stored in the HVTN repository in the 
United States. 
How long will the samples be stored? There is no limit on how long your extra 
samples will be stored. [Site: Revise the previous sentence to insert limits if your 
regulatory authority imposes them.] 
Will I be paid for the use of my samples? No. Also, a researcher may make a new 
scientific discovery or product based on the use of your samples. If this happens, 
there is no plan to share any money with you. The researcher is not likely to ever 
know who you are. 
Will I benefit from allowing my samples to be used in other studies? Probably not. 
Results from these other studies are not given to you, this clinic, or your doctor. 
They are not part of your medical record. The studies are only being done for 
research purposes. 
Will the HVTN sell my samples and information? No, but the HVTN may share 
your samples with HVTN or other researchers. Once we share your samples and 
information, we may not be able to get them back. 
How do other researchers get my samples and information? When a researcher 
wants to use your samples and information, their research plan must be approved 
by the HVTN. Also, the researcher’s institutional review board (IRB) or ethics 
committee (EC) will review their plan. [Site: If review by your institution’s 
IRB/EC/RE is also required, insert a sentence stating this.] IRBs/ECs protect the 
rights and well-being of people in research. If the research plan is approved, the 
HVTN will send your samples to the researcher’s location. 
What information is shared with HVTN or other researchers? The samples and 
information will be labeled with a code number. The key to the code will stay at 
this clinic. It will not be shared with the HVTN, other researchers, or with anyone 
else who does not need to know your name. Your name will not be part of the 
information. However, some information that we share may be personal, such as 
your race, ethnicity, sex, health information from the study, and HIV status. We 

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may share information about the study product you received and how your body 
responded to the study product. 
What kind of studies might be done with my extra samples and information? The 
studies will be related to HIV, vaccines, the immune system and other diseases. 
Researchers may also do genetic testing on your samples. 
In some cases, researchers may take cells from your samples and grow more of 
them over time, so that they can continue to do research with them. 
If you agree, your samples could also be used for genome-wide studies. In these 
studies, researchers will look at all of your genes (your genome). The researchers 
compare the genomes of many people, looking for common patterns of genes that 
could help them understand diseases. The researchers may put the information 
from the genome-wide studies into a protected database so that other researchers 
can access it, but your name and other personal information will not be included. 
Usually, no one would be able to look at your genome and link it to you as a 
person. However, if another database exists that also has information on your 
genome and your name, someone might be able to compare the databases and 
identify you. If others found out, it could lead to discrimination or other problems. 
The risk of this is very small. There may be other unknown risks. 
Who will have access to my information in studies using my extra samples? 
People who may see your information are: 
• Researchers who use your extra samples and information for other research 
• Government agencies that fund or monitor the research using your extra 
samples and information 
• The researcher’s Institutional Review Board or Ethics Committee 
• Any regulatory agency that reviews clinical trials 
• The people who work with the researcher 
All of these people will do their best to protect your information. The results of 
any new studies that use your extra samples and information may be published. 
No publication will use your name or identify you personally. 
19. We will do our best to protect your private information. 
US sites: Check HIPAA authorization for conflicts with this section 
Site: Explain any personal information sharing between your site and any 
institution(s) to which you will be referring participants for optional sample 

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collection(s) either here or in the section(s) where the sample collection(s) are 
described. 
Your study records and samples will be kept in a secure location. We will label all 
of your samples and most of your records with a code number, not your name or 
other personal information. However, it is possible to identify you, if necessary. 
We will not share your name with the lab that does the tests on your samples, or 
with anyone else who does not need to know your name. 
Site: Any change to the following boxed text requires approval from HVTN 
Regulatory Affairs. You can remove the box around the text.  
We do need to share your name with the HVTN in case you need proof in the 
future that you participated in an HIV vaccine study. The HVTN will keep your 
name in a secure file with these items:  
• The name of your study 
• Your age or date of birth 
• Your study ID number 
• What study product(s) you received 
There are no HIV test results kept in this file. The HVTN will not share any 
information that could identify you without your agreement. The HVTN will 
remove your name from the file if you do not want it there. 
Clinic staff will have access to your study records. Your records may also be 
reviewed by groups who watch over this study to see that we are protecting your 
rights, keeping you safe, and following the study plan. These groups include: 
• The US National Institutes of Health and its study monitors, 
• The US Food and Drug Administration, 
• Any regulatory agency that reviews clinical trials, 
• [Insert name of local IRB/EC] , 
• IAVI, Dynavax, AAHI, DAIDS, and people who work for them, 
• The HVTN and people who work for them, 
• The HVTN Safety Monitoring Board (SMB) and 
• The US Office for Human Research Protections. 

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All reviewers will take steps to keep your records private. 
We cannot guarantee absolute privacy. If you are found to have a medical 
condition that we are required to report by law, then some of your information 
may be shared. At this clinic, we have to report the following information:  
Site: Include any public health or legal reporting requirements. Bulleted examples 
should include all appropriate cases (reportable communicable disease, risk of harm 
to self or others, etc.) If your site does not have public health or legal reporting 
requirements, you may delete the last sentence in the paragraph above, along with 
the bullets below. 
• [Item 1] 
• [Item 2] 
• [Item 3] 
US sites: Include the following boxed text. You can remove the box around the text. 
We have a Certificate of Confidentiality from the US government, to help protect 
your privacy. With the certificate, we do not have to release information about 
you to someone who is not connected to the study, such as the courts or police. 
Sometimes we can’t use the certificate. Since the US government funds this 
research, we cannot withhold information from it. Also, you can still release 
information about yourself and your study participation to others. 
The results of this study may be published. No publication will use your name or 
identify you personally. 
We may share information from the study with other researchers. We will not 
share your name or information that can identify you. 
A description of this clinical trial will be available on 
http://www.ClinicalTrials.gov. This website will not include information that can 
identify you. At most, the website will include a summary of the results. You can 
search this website at any time. 
20. There are several reasons why we may stop your injections. We may stop 
them even if you want to stay in the study and even if you were scheduled for 
more injections. 
We will stop your injections if you become pregnant. We will encourage you to 
stay in the study if you choose. We will discuss your study options with you. If 
you leave the study while you are still pregnant, we will contact you after your 
due date to ask some questions about your pregnancy and delivery. 

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We will stop your injections if you get HIV. We will also take fewer samples, and 
we will help you get care and support. We will encourage you to stay in the study 
for up to 12 weeks after your last injection if you choose. We will discuss your 
study options with you. We will counsel you about having HIV and about telling 
your partner(s). Site: Modify the following sentence as appropriate. We will not 
provide or pay for any of your HIV care directly.  
We will stop your injections if you enroll in another study where you receive a 
study product.  
In the unlikely event that you get a bad reaction to a study injection we may stop 
your injections. 
If we stop your injections, we may ask you to stay in the study to complete other 
study procedures. 
21. We may take you out of the study at any time.  
We may take you out of the study if: 
• you do not follow instructions, 
• we think that staying in the study might harm you, or 
• the study is stopped for any reason. 
Other Risks 
22. There are other risks to being in this study. 
This section describes the other risks and restrictions we know about. There may 
also be unknown risks, even serious ones. We will tell you if we learn anything 
new that may affect your willingness to stay in the study. 
Risks of routine medical procedures: 
In this study, we will do some routine medical procedures. These are taking blood 
and giving injections. These procedures can cause bruising, pain, fainting, 
soreness, redness, swelling, itching, a sore, bleeding, and (rarely) muscle damage 
or infection where you got the injection. Taking blood can cause a low blood cell 
count (anemia), making you feel tired. 
Personal problems/discrimination/testing HIV antibody positive: 
About 10 to 20% of people who join HVTN studies report personal problems or 
discrimination because of joining an HIV vaccine study. Family or friends may 
worry, get upset or angry, or assume that you have HIV or at high risk and treat 

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you unfairly as a result. Rarely, a person has lost a job because the study took too 
much time away from work, or because their employer thought they had HIV. 
The body makes antibodies to fight or prevent infection. Most vaccines cause the 
body to make antibodies as a way of preventing infection. Your body may make 
antibodies to HIV because you received an HIV study vaccine. The study 
vaccines may cause you to test positive on some types of HIV antibody tests, even 
if you do not have HIV. This is called vaccine-induced seropositivity (VISP). 
VISP means that after you get the study vaccines, a routine HIV test done outside 
this clinic may say you have HIV, even if you don’t. For this reason, you should 
plan to get HIV tests only at this clinic during the study. Our tests can tell the 
difference between true HIV infection and a positive result that is caused by the 
study vaccines. 
If you have a positive test result caused by the study vaccines at any time, we can 
arrange free HIV testing for as long as you need it. If this happens, we do not 
know how long you will test positive due to the study vaccines. If you receive a 
positive HIV test result and we determine it is because you have HIV, we will 
refer you for follow-up care. 
It is unlikely, but you could test negative at the end of the study and positive some 
time later, even though you don’t have HIV. This could happen if different HIV 
tests come into use. We will give you a phone number to call for more 
information. 
Site: Modify the following paragraph if applicable. If someone believes you have 
HIV even if you do not, you could face discrimination and other problems. For 
example, in some countries, you could be denied medical or dental care, 
employment, insurance, a visa, or entry into the military. If you do have a positive 
HIV antibody test caused by the study vaccines, you will not be able to donate 
blood or organs. Your family and friends may treat you differently. We will give 
you a brochure that tells you more about testing HIV positive because of an HIV 
vaccine, and how you can avoid some of these problems. 
If you become pregnant during or after the study and have VISP, we don't know if 
the antibodies could be passed to your baby. We know that this happens with 
other vaccines, like tetanus vaccine. These antibodies from the mother are not a 
danger to the baby, and they go away over time. For most babies, antibodies from 
the mother last for about six months. 
You should always tell the delivery staff if you have VISP. However, you may 
still be tested for HIV using the antibody test when you deliver your baby. If your 
test is positive and the delivery staff believes you have HIV, your baby may be 
started on antiretroviral treatment when it is not needed. If this happens, we can 
arrange for you and the baby to have a test that can tell the difference between 
true HIV infection and a VISP result. If you or the baby continue to have VISP, 
we can arrange this testing for free for as long as it is needed. 

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Embarrassment/anxiety: 
You may feel embarrassed when we ask about your HIV risks, such as having sex 
and using drugs. Also, waiting for your HIV test results or other health test results 
could make you feel anxious. You could feel worried if your test results show that 
you have HIV. If you feel embarrassed or anxious, please tell us and we will try to 
help you. 
Risks of disclosure of your personal information: 
We will take several steps to protect your personal information. Although the risk 
is very low, it is possible that your personal information could be given to 
someone who should not have it. If that happened, you could face discrimination, 
stress, and embarrassment. We can tell you more about how we will protect your 
personal information if you would like it. 
Risks of genetic testing: 
It is unlikely, but the genetic tests done on your samples could show you may be 
at risk for certain diseases. If others found out, it could lead to discrimination or 
other problems. However, it is almost impossible for you or others to know your 
test results from the genetic testing. The results are not part of your study records 
and are not given to you. 
In the very unlikely event that your genetic information becomes linked to your 
name, a federal law called the Genetic Information Nondiscrimination Act 
(GINA) helps protect you. GINA keeps health insurance companies and 
employers from seeing results of genetic testing when deciding about giving you 
health insurance or offering you work. GINA does not help or protect you against 
discrimination by companies that sell life, disability or long-term care insurance. 
Unknown risks: 
We do not know if the study vaccines will increase, decrease, or not change your 
risk of getting HIV if exposed. If you get HIV, we do not know how the study 
vaccines might affect your HIV infection or how long it takes to develop AIDS. 
We do not know if getting these study vaccines will affect how you respond to 
any future approved HIV vaccine. Currently, no HIV vaccine has been approved 
for use. 
We do not know how the study vaccines will affect a pregnant participant or a 
developing baby. 

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Benefits 
23. The study may not benefit you. 
We do not expect the study vaccines to benefit you in any way. However, being in 
the study might still help you in some ways. The counseling that you get as part of 
the study may help you avoid getting HIV. The lab tests and physical exams that 
you get while in this study might detect health problems you don’t yet know 
about. 
This study may help in the search for a vaccine to prevent HIV. However, if the 
study vaccines later become approved and sold, there are no plans to share any 
money with you. 
Your rights and responsibilities 
24. If you join the study, you have rights and responsibilities. 
You have many rights that we will respect. You also have responsibilities. We list 
these in the Participant’s Bill of Rights and Responsibilities. We will give you a 
copy of it. 
Leaving the study 
25. Tell us if you decide to leave the study. 
You are free to leave the study at any time and for any reason. Your care at this 
clinic and your legal rights will not be affected, but it is important for you to let us 
know. 
We will ask you to come back to the clinic one last time for a physical exam, and 
we may ask to take some blood and urine samples. We will also ask about any 
personal problems or benefits you have experienced from being in the study. We 
believe these steps are important to protecting your health, but it is up to you 
whether to complete them. 
Injuries 
Sites: Approval from HVTN Regulatory Affairs (at vtn.core.reg@hvtn.org) is needed 
for any change (other than those that the instructions specifically request or those 
previously approved by HVTN Regulatory Affairs) to the boxed text. You can remove 
the box around the text. 
26. If you get sick or injured during the study, contact us immediately. 
Your health is important to us. (Sites: adjust the following 2 sentences if 
applicable to the care available at your site) We will tell you about the care that 

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we can give here. For the care that we cannot provide, we will explain how we 
will help you get care elsewhere. 
If you become sick or injured in this study, the HVTN has a process to decide if it 
is related to the study products and/or procedures. If it is, we call it a study-related 
injury. There are funds to pay for treatment of study-related injuries if certain 
conditions are met. 
Some of the study product providers may pay medical costs for study-related 
injuries that are determined to be caused by their own study products. If provider 
funds are not available or are not enough, or if the injury is determined to be 
caused by study procedures, the HVTN has limited funds to pay medical costs 
that it determines are reasonable. (Sites: insert locale- appropriate medical 
insurance language in the following sentence) If the injury is not study related, 
then you and/or your health insurance will be responsible for treatment costs. 
Some injuries are not physical. For example, you might be harmed emotionally by 
being in an HIV vaccine study. Or you might lose wages because you cannot go 
to work. However, there are no funds to pay for these kinds of injuries, even if 
they are study related. 
You may disagree with the decision about whether your injury is study related. If 
you wish, the HVTN will ask independent experts to review the decision. You 
always have the right to use the court system if you are not satisfied. 
Questions  
27. If you have questions or problems at any time during your participation in 
this study, use the following important contacts. 
If you have questions about this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
If you have any symptoms that you think may be related to this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
This study has been reviewed and approved by a committee called the 
[name of local IRB/EC]. If you have questions about your rights as a research 
participant, or problems or concerns about how you are being treated in this study, 
contact [name or title and telephone number of person on IRB/EC] , at the 
committee. 
If you want to leave this study, contact 
[name or title and telephone number of the investigator or other study staff]. 

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Your permissions and signature  
28. In Section 14 of this form, we told you about 3 other optional sample 
collection procedures. Please write your initials or make your mark in the 
boxes next to the procedure(s) that you agree to have done. You can change 
your mind after signing this form. 
Site: Include only boxes below for the procedures available to your participants. 
 
 
I agree to leukapheresis.  
 
 
 
I agree to lymph node cell collection. 
 
 
 
I agree to bone marrow cell collection.  
29. In section 15 of this form, we told you about 4 other types of optional sample 
collections. Please write your initials or make your mark in the boxes next to 
the sample(s) you agree to provide. You can change your mind after signing 
this form. 
 
 
I agree to provide rectal fluid.  
 
 
 
I agree to provide rectal tissue. 
 
 
 
I agree to provide vaginal fluid.  
 
 
 
I agree to provide vaginal tissue.  
Site: Delete the following blue section if using a separate consent for use of samples 
and information in other studies 
30. In Section 18 of this form, we told you about possible other uses of your extra 
samples and information, outside this study. Please choose only one of the 
options below and write your initials or make your mark in the box next to it. 
Whatever you choose, the HVTN keeps track of your decision about how 

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your samples and information can be used. You can change your mind after 
signing this form. 
 
 
I allow my extra samples and information to be used for other studies related to 
HIV, vaccines, the immune system, and other diseases. This may include 
genetic testing and keeping my cells growing over time.  
OR 
 
 
I agree to the option above and also to allow my extra samples and information 
to be used in genome wide studies. 
OR 
 
 
I do not allow my extra samples to be used in any other studies. This includes 
not allowing genetic testing, growing more of my cells, or genome wide studies. 
31. If you agree to join this study, you will need to sign or make your mark 
below. Before you sign or make your mark on this consent form, make sure 
of the following: 
• You have read this consent form, or someone has read it to you. 
• You feel that you understand what the study is about and what will happen to 
you if you join. You understand what the possible risks and benefits are. 
• You have had your questions answered and know that you can ask more. 
• You agree to join this study. 
You will not be giving up any of your rights by signing this consent form. 
 
 
 
 
 
 
 
Participant’s name (print) 
 
Participant’s signature or mark 
 
Date 
 
Time 
 
 
 
 
 
 
 
Clinic staff conducting consent 
discussion (print) 
 
Clinic staff signature 
 
Date 
 
Time 
For participants who are unable to read or write, a witness should complete the 
signature block below: 

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Witness’s name (print) 
 
Witness’s signature  
 
Date 
 
Time 
*Witness is impartial and was present for the entire discussion of this consent form. 

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Appendix C 
Sample informed consent form for Part C 
Title: A phase 1 clinical trial to evaluate the safety and immunogenicity of HIV-1 
BG505 SOSIP.664 gp140 with TLR agonist and/or Alum adjuvants and VRC 
HIV Env Trimer 4571 and 3M-052-AF with Alum in healthy, HIV uninfected 
adults 
HVTN protocol number: HVTN 137 
Site: [Insert site name] 
Thank you for your interest in our research study. Please read this consent form or 
ask someone to read it to you. If you decide to join the study, we will ask you to 
sign or make your mark on this form. We will offer you a copy to keep. We will 
ask you questions to see if we have explained everything clearly. You can also 
ask us questions about the study. 
Research is not the same as treatment or medical care. The purpose of a research 
study is to answer scientific questions. 
Key information 
These are some of the things you should know about this study: 
The purpose of the study is to test 2 experimental HIV vaccines. The study 
vaccines are made from two parts: a man-made piece of protein that looks like a 
protein found on the outside of HIV and an adjuvant. An adjuvant is a substance 
that helps the immune system respond better. The study will see if the study 
vaccines are safe and if people can get them without being too uncomfortable. 
The study will also test how people’s immune systems respond to the study 
vaccines. This is the first study to give these study vaccines to people. If you join 
the study, you will have about 15 clinic visits over about a year and a half. Clinic 
visits will involve physical exams, collection of blood and urine for routine 
laboratory tests (including pregnancy tests if you are capable of getting pregnant), 
HIV testing at some visits, and collection of blood samples to look at your 
immune responses to the study vaccines. Some visits will involve questionnaires, 
some of which ask very personal questions. You will get injections at three visits. 
Some of the risks of getting vaccines are fever, chills, rash, aches and pains, 
nausea, headache, dizziness, feeling tired, and pain, redness, swelling, or itching 
where you get the injection. On rare occasions, a vaccine can cause an allergic 
reaction. These can even be life threatening. Very rarely, a vaccine causes a 
person to have an autoimmune disease or makes an autoimmune disease worse. 
Because these proteins and these doses (amounts) of the adjuvant have not been 
given to many people yet, we do not know what all of the risks may be.  We think 
the risks will be similar to these general risks. There may be other side effects that 
we don’t yet know, even serious ones. 
We do not expect the study vaccine to benefit you in any way. You do not have to 
join, and you are free to leave at any time. 

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The rest of this form provides a more complete description of the study. Please 
read it carefully. 
About the study 
The HIV Vaccine Trials Network (HVTN) and [Insert site name] are doing a 
study to test HIV vaccines. HIV is the virus that causes AIDS. The study vaccines 
are made from two parts: a protein and an adjuvant. Adjuvants are substances that 
help the immune system respond better. (Your immune system protects you from 
disease.)  
About 127 people will take part in this study at multiple sites. The researcher in 
charge of this study at this clinic is [Insert name of site PI]. The US National 
Institutes of Health (NIH) is paying for the study. 
This study is divided into three parts: part A, part B, and part C. In part A, we 
tested 2 different doses (amounts) of the adjuvant with a protein. In part B, we 
tested the same protein as part A but with different adjuvants. 17 people were 
enrolled in part A and 88 were enrolled in Part B. We have completed enrollment 
for parts A and B. In part C of this study, we will test two proteins with 2 different 
doses of an adjuvant. About 22 people will be enrolled in part C. You are being 
invited to join part C of the study. 
1. We are doing part C of this study to answer several questions. 
• Are the study vaccines safe to give to people? 
• Are people able to take the study vaccines without becoming too 
uncomfortable? 
• How do people’s immune systems respond to the study vaccines?  
2. The study vaccines cannot give you HIV. 
The study vaccines are not made from actual HIV. It is impossible for the study 
vaccines to give you HIV. Also, they cannot cause you to give HIV to someone 
else. 
3. We do not know if the study vaccines will decrease, increase, or not change 
your risk of getting HIV if you are exposed to the virus. 
Site: Any change to the following boxed text requires approval from HVTN 
Regulatory Affairs at vtn.core.reg@hvtn.org. You can remove the box around the text. 
Several studies have tested whether HIV vaccines can reduce the risk of getting 
HIV from another person. In some studies, people who got the vaccine seemed to 
have the same risk of getting HIV as people who did not get the vaccine. In one 

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study, people who got the vaccine seemed to have a lower risk of getting HIV 
than people who did not get the vaccine. In studies with a different vaccine, some 
people who got the vaccine had a higher risk of getting HIV than people who did 
not get the vaccine. 
This study differs from the studies in which people who got the vaccine had a 
higher or lower risk of getting HIV. We can tell you about the differences. 
We do not know whether the vaccines in this study will affect your risk of getting 
HIV from another person. The risk could be higher, lower, or unchanged. It’s very 
important to avoid exposure to HIV during and after the study. We will tell you 
how to avoid HIV. 
4. These study vaccines are experimental. 
The study vaccines are made up of two parts, the protein and the adjuvant. (An 
adjuvant is something that helps the immune system respond better.) We are 
testing 2 study vaccines in part C. 
The first study vaccine is BG505 SOSIP.664 gp140 + 3M-052-AF + Alum. It 
includes two parts. BG505 SOSIP.664 gp140 is a man-made piece of protein that 
looks like a protein found on the outside of HIV. From here on we will call it 
“protein 1.” The second part of this study vaccine is the adjuvant called 3M-052-
AF + Alum. From here on, we will call it “the adjuvant.” 
The second study vaccine is Trimer 4571 + 3M-052-AF + Alum. It also includes 
two parts. Trimer 4571 is a man-made piece of protein that looks like a protein 
found on the outside of HIV. From here on we will call it “protein 2.” The second 
part of this study vaccine is the same adjuvant used in the first study vaccine but a 
different dose (amount) of it. This is the first study to give this study vaccine to 
people. 
These study vaccines are experimental HIV vaccines. That means we do not know 
if they will be safe to use in people, or if they will work to prevent HIV infection. 
These study vaccines are used only in research studies. 
Protein 1 (BG505 SOSIP.664 gp140): 
Protein 1 is a first-generation product that was designed to look like a piece of 
protein on HIV and engineered to stay in a shape much like that in HIV. In this 
way it is different from proteins in some other HIV study vaccines. The protein 
was developed by John Moore at Cornell Weill Medical Center in New York, 
New York, USA. It is being provided for this study by the International AIDS 
Vaccine Initiative (IAVI) in New York, New York. 

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Protein 2 (Trimer 4571): 
Protein 2 is like Protein 1 product but includes small changes to keep it fixed in 
one shape. Researchers think that this will lead to better antibodies when 
compared to proteins that don’t have these changes. The protein was developed 
and is being provided by the Dale and Betty Bumpers Vaccine Research Center 
(VRC) at the National Institute of Allergy and Infectious Diseases (NIAID). 
The adjuvant: 
3M-052-AF + Alum: 
The 3M-052 is one of many similar products developed by 3M to treat skin 
conditions, tumors, and to make vaccines more effective. These products are 
designed to stimulate parts of the immune system that recognize viral and 
bacterial invaders. In this study, 3M-052 is dissolved in water and is mixed with 
Alum.  
Alum is made from Aluminum Hydroxide. Alum is an adjuvant with a long-
standing safety record that has been used in approved vaccines for many years. 
3M-052 was developed by 3M Corporation in St. Paul, Minnesota, USA. In this 
study, the 3M-052 is dissolved in water and this mixture is being provided by the 
Access to Advanced Health Institute (AAHI) in Seattle, Washington, USA.  
The 3M-052 adjuvant has been given to 52 participants with advanced cancer in 
one experimental study. The cancer study differed from this vaccine study in 
important ways. The cancer study participants were very sick. The 3M-052 was 
mixed with sesame oil. It was injected directly into tumors at higher doses and for 
a different purpose. In the cancer study, one participant died four days after 
getting his second injection into a liver tumor. The exact cause of death could not 
be determined but was felt to be related to the 3M-052 adjuvant and the injection 
procedure. Two other participants in the cancer study developed a condition 
called cytokine release syndrome, which can be severe and require 
hospitalization. Both participants recovered with medical care. We don’t expect to 
see these outcomes due to the many differences described above. We can discuss 
this more with you if you would like. 
HVTN 137 Part A tested a high dose (amount) and a low dose of the 3M-052-AF 
+ Alum adjuvant. As there were no serious health problems in Part A participants, 
the decision was made to use the high dose of adjuvant in the study vaccines in 
part B of the study. There have been no serious health problems in Part B 
participants. In Part C, we will be testing the high dose and a medium dose of the 
adjuvant with two different proteins. We want to see if the medium dose can 
produce the same response as the high dose. 

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Risks of the study vaccines: 
Protein 1 + the adjuvant (at a higher and lower dose) have been tested in Part A 
and Part B of this study and there have been no serious health problems. Two 
participants in Part A who received the higher dose did have reactions to their 
study injections that we want to tell you about. Both had redness and swelling 
over a large area on their arm where they got the injection that started about 1 
week after a study injection. The redness lasted for about 2 to 3 days. For one of 
these people, the swelling went away within 2 to 3 days. The second person had 
significant swelling for about 3 days. The swelling went down but it took about 5 
weeks to completely go away. They had mild pain which did not prevent them 
from going to work. Because the study is ongoing and is blinded, we do not know 
if these people got the study vaccine or placebo. Redness and swelling are 
common reactions shortly after an injection but usually start within 1-2 days and 
not usually a week after the injection. No participants in Part B have had this type 
of delayed reaction. However, we will ask Part C participants to watch for 
reactions for a longer period of time than we did in Part A & B. 
Protein 2 mixed with another adjuvant was given to people as part of two different 
ongoing studies. In one study, 16 people got the vaccine mixed with the Alum 
adjuvant alone. Each person got 3 injections of the vaccine at the same dose or 
higher than the dose we will use in this study. The injections did not cause any 
serious health problems. 
Most people in that study had at least one of the side effects listed in the General 
risks of vaccines section below. They said the side effects were mild, and they 
went away within about a week. One person showed a slightly decreased number 
of one type of white blood cell at 7 days after their second injection. However, 
their count went back up to normal levels by the 8th day without any health 
concerns.  
In the second study, 3 people got a single dose of this protein vaccine combined 
with Alum at a higher dose than the one we will use in this study. These injections 
did not cause any serious health problems. Because this protein vaccine has only 
been given to a small number of people, we do not know all the side effects. 
There may be side effects, even serious or life-threatening ones, that we do not 
know about yet.  
Risks of the study adjuvant: 
For more than 90 years, Alum has been used as an adjuvant in commercial 
vaccines. Hundreds of millions of people have gotten vaccines containing Alum. 
Another protein vaccine and 3M-052-AF + Alum adjuvant combination is being 
tested for the first time in people in HVTN 300. Parts A and B of this study 
(HVTN 137) have also tested 3M-052-AF+ Alum with Protein 1. As of June 
2022, in these 2 studies, 48 people have had at least 1 study injection and at least 

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41 people have had 3 injections containing 3M-052-AF + Alum as an adjuvant. 
These injections have not caused any serious health problems. 
HVTN 300 enrolled 13 people. The most common side effects experienced by 
participants were headache and feeling unwell or tired.  
All people had some side effects that they described as mild to moderate. One (1) 
person had severe pain/tenderness in both the right and left injection sites 3 days 
following the fourth vaccination, though it lasted only one day. Five (5) people 
had severe side effects, including chills, headache, muscle aches, and generally 
feeling unwell. These severe side effects went away within 2 days. Of the 5 
people who had severe side effects, 2 decided to stop getting study injections 
because they felt generally unwell after injections, and it was affecting their daily 
lives. Another 2 of the 5 people who had severe side effects got more injections; 
one of them had more severe side effects while the other did not. And one (1) of 
the 5 people who had severe side effects has not yet received another injection.  
Two more people also decided to stop getting the study injections and dropped 
out of the study. One stopped because they experienced a panic attack after the 
first injection. However, this person had a history of panic attacks before being 
part of this study. The other did not return for their next injection visit and is no 
longer in the study. We do not know the reason for this. 
Given the side effects experienced in HVTN 300 and HVTN 137, we can expect 
that many people in this study will have some side effects. The side effects we 
expect would be similar to those listed in the General risks of vaccines section 
below. 
These are the side effects we know about. There may be others that we don’t 
know about. We will tell you if we learn about new side effects that could affect 
your willingness to stay in the study. 
General risks of vaccines: 
All vaccines can cause fever, chills, rash, aches and pains, nausea, headache, 
dizziness, and feeling tired. Vaccines can also cause pain, redness, swelling, or 
itching where you got the injection. Most people can still do their planned 
activities after getting a vaccine. Rarely, people have side effects that limit their 
normal activities or make them go to the doctor. 
Rarely, a vaccine can cause an allergic reaction, including a rash, hives, or trouble 
breathing. Allergic reactions can be life-threatening. You should tell us if you 
have ever had a bad reaction to any injection or vaccine. 
Very rarely, a vaccine causes an autoimmune disease in a person, or makes an 
autoimmune disease worse. An autoimmune disease happens when your immune 
system attacks your own body, instead of attacking an infection. 

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Joining the study 
5. It is completely up to you whether or not to join the study. 
Take your time in deciding. If it helps, talk to people you trust, such as your 
doctor, friends or family. If you decide not to join this study, or if you leave it 
after you have joined, your other care at this clinic and the benefits or rights you 
would normally have will not be affected. 
If you join this study, you may not be allowed to join other HIV vaccine or HIV 
prevention studies now or in the future. You cannot be in this study while you are 
in another study where you get a study product. Being in more than one study 
may not be safe. 
Also, during the study, you should not donate blood or tissue. 
If you choose not to join this study, you may be able to join another study. 
Site: Remove item 6 if you use a separate screening consent that covers these 
procedures. 
6. If you want to join the study, we will screen you to see if you are eligible. 
Screening involves a physical exam, HIV test and health history. A physical exam 
may include, but is not limited to: 
• Checking your weight, temperature and blood pressure 
• Looking in your mouth and throat 
• Listening to your heart and lungs 
• Feeling your abdomen (stomach and liver) 
We will also do blood and urine tests. These tests tell us about some aspects of 
your health, such as how healthy your kidneys, liver, and immune system are. We 
will also test you for hepatitis B and hepatitis C. We will ask you about 
medications you are taking, including HIV pre-exposure prophylaxis (PrEP). We 
will ask you about behaviors that might put you at risk for getting HIV. If you 
were assigned female sex at birth, we will test you for pregnancy.  
We will review the screening results with you. The screening results may show 
you are not eligible to join the study, even if you want to.  
Site: adapt the following section so it is applicable to the care available at your site 

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7. If we find that you have a health problem during screening or during the 
study, we will tell you about the care that we can give here for free. 
For the care that we cannot give, we will explain how we will help you get care 
elsewhere. For health problems that are unrelated to the study, we will not pay for 
care. 
8. If you were assigned female sex at birth and can become pregnant, you must 
agree to use birth control to join this study. 
Site: If you want to include Appendix F, Approved birth control methods (for sample 
informed consent form), in this consent form, paste it below and delete paragraph 
below. 
You should not become pregnant during the study because we do not know how 
the study vaccines could affect the developing baby. You must agree to use 
effective birth control from 21 days (3 weeks) before your first injection until 6 
months after your last study injection. We will talk to you about effective birth 
control methods. They are listed on a handout that we will give you. 
Being in the study 
If you meet the study requirements and want to join, here is what will happen: 
9. You will come to the clinic for scheduled visits about [#] times over 
[Insert period of time]. 
Site: Insert number of visits and range of visit lengths. (There is site-specific variation 
in screening protocols and in the number of possible follow-up visits between 
protocol-mandated visits.) 
Visits can last from [#] to [#] hours. 
You may have to come for more visits if you have a lab or health issue. 
We may contact you after the main study ends (for example, to tell you about the 
study results). 
10. We will give you [Site: Insert compensation] for each study visit you 
complete. 
This amount is to cover the costs of [Site: Insert text] 
Site: Insert any costs to participants (eg, birth control costs for participants assigned 
female sex at birth who could become pregnant). 
US sites: Include the following paragraph. You can remove the box around the text. 

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Payments you receive for being in the study may be taxable. We may need to ask 
you for your Social Security number for tax reasons. 
You do not have to pay anything to be in this study. 
11. We will give you either the study vaccines or a placebo. 
Not everyone in part C of this study will get the study vaccines. Some people will 
get a placebo, a substance that does not contain vaccine. In this study, the placebo 
is a combination of salt water and a preservative (to keep the solution from 
becoming too acidic). We will compare the results from people who got the 
different study vaccines. We will also compare results from people who got the 
placebo with results from people who got the study vaccines. 
Site: Modify the randomization metaphor in the next sentence as appropriate to 
your local culture. 
You have a 10-in-11 chance of getting the study vaccines. Whether you get one of 
the study vaccines or the placebo is completely random, like flipping a coin.  
We have no say in whether you get the study vaccines or the placebo. We will not 
know which one you are getting, and neither will you. Only the pharmacist at this 
clinic will have this information while the study is going on. 
You will have to wait until everyone completes their final study visits to find out 
whether you got the study vaccines or the placebo. This could be several years. 
But, if you have a serious medical problem and need to know what you got before 
the end of the study, we can tell you. 
12. We will give you the study products on a schedule. 
You will be in one of 2 groups. Group 7 will get protein 1 with medium dose of 
adjuvant or the placebo and Group 8 will get protein 2 with high dose of adjuvant 
or the placebo. You will get 3 injections into the upper arm during the study. 
The protein 2 + adjuvant study vaccine is being given to people for the first time 
in this study, to participants in Group 8. We will enroll only 1 participant per day 
in this group for the first 5 participants. If there are no serious health problems 
with these 5, we will enroll the remaining 5 participants in Group 8.  
 

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Group 
Number of 
participants 
Injection schedule 
At enrollment 
At 2 months 
At 6 months 
7 
10 
protein 1 + medium dose of 
adjuvant 
protein 1 + 
medium dose of adjuvant 
protein 1 + 
medium dose of adjuvant 
1 
Placebo 
Placebo 
Placebo 
8 
10 
protein 2 + 
high dose of adjuvant 
protein 2 + 
high dose of adjuvant 
protein 2 + 
high dose of adjuvant 
1 
Placebo 
Placebo 
Placebo 
You will have to wait in the clinic for about a half hour after each injection to see 
if there are any problems. Then for that night and for 14 more days, you will need 
to keep track of how you are feeling and if you have any symptoms. Site: 
Customize the next sentence based on how you collect reactogenicity information. 
You will bring this information back to the clinic at your next visit. Within 3 days 
of each injection, we will also need to be in contact with you to ask how you are 
doing. Contact the clinic staff if you have any issues or concerns after getting an 
injection. If you have a problem, we will continue to check on you until it goes 
away. 
13. In addition to giving you the study products, we will: 
• Do regular HIV testing, as well as counseling on your results and on how to 
avoid getting HIV 
• Do physical exams 
• Do pregnancy tests if you were assigned female sex at birth 
• Ask questions about your health, including medications you may be taking 
• Ask questions about any personal problems or benefits you may have from 
being in the study 
• Take urine and blood samples. 
When we take blood, the amount will depend on the lab tests we need to do. It 
will be some amount between 17 mL and 325 mL (about 1½ tablespoon to a little 
more than ⅔ of a pint). Your body will make new blood to replace the blood we 
take out. 
Site: You may want to add a sentence to the end of the previous paragraph 
contextualizing the blood volumes described (eg, “To compare, people who donate 
blood in the US can give a total of about 500 mL in an 8-week period.”). Modify the 
example for cultural relevance and alter blood volumes as necessary. 

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Site: Insert appropriate table from Appendix H, Tables of procedures (for informed 
consent form) in this section or distribute it as a separate sheet if it is helpful to your 
study participants. You are not required to do either. 
We will be looking for side effects. We will review the results of these procedures 
and tests with you at your next visit, or sooner if necessary. If any of the results 
are important to your health, we will tell you. 
14. We will counsel you about protecting yourself from HIV. 
We will ask you personal questions about your HIV risk factors such as sexual 
behavior, alcohol, and drug use. We will talk with you about ways to keep your 
risk of getting HIV low. 
15. The HVTN will test your samples to see how your immune system responds 
to the study products. 
We will send your samples (without your name) to labs approved by the HVTN 
for this study, which are located in the United States and South Africa. In rare 
cases, some of your samples may be sent to labs approved by the HVTN in other 
countries for research related to this study. 
Researchers may also do genetic testing related to this study on your samples. 
Your genes are passed to you from your birth parents. They affect how you look 
and how your body works. The differences in people’s genes can help explain 
why some people get a disease while others do not. The genetic testing will only 
involve some of your genes, not all of your genes (your genome). The researchers 
will study only the genes related to the immune system and HIV and those that 
affect how people get HIV. 
If you get HIV, the researchers may look at all of the genes of the virus found in 
your samples. The researchers will use this information to learn more about HIV 
and the study product(s). 
In some cases, researchers may take cells from your samples and grow more of 
them over time, so that they can continue to contribute to this study. 
These tests done on your samples are for research purposes, not to check your 
health. The labs will not give the results to you or this clinic because their tests 
are not approved for use in making health care decisions. These labs are only 
approved to do research tests. 
When your samples are no longer needed for this study, the HVTN will continue 
to store them. 
Site: Delete next section if using separate consent for use of samples and information 
in other studies 

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16. When samples are no longer needed for this study, the HVTN wants to use 
them in other studies and share them with other researchers.  
The HVTN calls these samples “extra samples”. The HVTN will only allow your 
extra samples to be used in other studies if you agree to this. You will mark your 
decision at the end of this form. If you have any questions, please ask. 
Do I have to agree? No. You are free to say yes or no, or to change your mind 
after you sign this form. At your request, we will destroy all extra samples that we 
have. Your decision will not affect your being in this study or have any negative 
consequences here. 
Where are the samples stored? Extra samples are stored in a secure central place 
called a repository. Your samples will be stored in the HVTN repository in the 
United States. 
How long will the samples be stored? There is no limit on how long your extra 
samples will be stored. [Site: Revise the previous sentence to insert limits if your 
regulatory authority imposes them.] 
Will I be paid for the use of my samples? No. Also, a researcher may make a new 
scientific discovery or product based on the use of your samples. If this happens, 
there is no plan to share any money with you. The researcher is not likely to ever 
know who you are. 
Will I benefit from allowing my samples to be used in other studies? Probably not. 
Results from these other studies are not given to you, this clinic, or your doctor. 
They are not part of your medical record. The studies are only being done for 
research purposes. 
Will the HVTN sell my samples and information? No, but the HVTN may share 
your samples with HVTN or other researchers. Once we share your samples and 
information, we may not be able to get them back. 
How do other researchers get my samples and information? When a researcher 
wants to use your samples and information, their research plan must be approved 
by the HVTN. Also, the researcher’s institutional review board (IRB) or ethics 
committee (EC) will review their plan. [Site: If review by your institution’s 
IRB/EC/RE is also required, insert a sentence stating this.] IRBs/ECs protect the 
rights and well-being of people in research. If the research plan is approved, the 
HVTN will send your samples to the researcher’s location. 
What information is shared with HVTN or other researchers? The samples and 
information will be labeled with a code number. The key to the code will stay at 
this clinic. It will not be shared with the HVTN, other researchers, or with anyone 
else who does not need to know your name. Your name will not be part of the 
information. However, some information that we share may be personal, such as 
your race, ethnicity, sex, health information from the study, and HIV status. We 

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may share information about the study product you received and how your body 
responded to the study product. 
What kind of studies might be done with my extra samples and information? The 
studies will be related to HIV, vaccines, the immune system and other diseases. 
Researchers may also do genetic testing on your samples. 
In some cases, researchers may take cells from your samples and grow more of 
them over time, so that they can continue to do research with them. 
If you agree, your samples could also be used for genome-wide studies. In these 
studies, researchers will look at all of your genes (your genome). The researchers 
compare the genomes of many people, looking for common patterns of genes that 
could help them understand diseases. The researchers may put the information 
from the genome-wide studies into a protected database so that other researchers 
can access it, but your name and other personal information will not be included. 
Usually, no one would be able to look at your genome and link it to you as a 
person. However, if another database exists that also has information on your 
genome and your name, someone might be able to compare the databases and 
identify you. If others found out, it could lead to discrimination or other problems. 
The risk of this is very small. There may be other unknown risks. 
Who will have access to my information in studies using my extra samples? 
People who may see your information are: 
• Researchers who use your extra samples and information for other research 
• Government agencies that fund or monitor the research using your extra 
samples and information 
• The researcher’s Institutional Review Board or Ethics Committee 
• Any regulatory agency that reviews clinical trials 
• The people who work with the researcher 
All of these people will do their best to protect your information. The results of 
any new studies that use your extra samples and information may be published. 
No publication will use your name or identify you personally. 
17. We will do our best to protect your private information. 
US sites: Check HIPAA authorization for conflicts with this section 
Site: Explain any personal information sharing between your site and any 
institution(s) to which you will be referring participants for optional sample 

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collection(s) either here or in the section(s) where the sample collection(s) are 
described. 
Your study records and samples will be kept in a secure location. We will label all 
of your samples and most of your records with a code number, not your name or 
other personal information. However, it is possible to identify you, if necessary. 
We will not share your name with the lab that does the tests on your samples, or 
with anyone else who does not need to know your name. 
Site: Any change to the following boxed text requires approval from HVTN 
Regulatory Affairs. You can remove the box around the text.  
We do need to share your name with the HVTN in case you need proof in the 
future that you participated in an HIV vaccine study. The HVTN will keep your 
name in a secure file with these items:  
• The name of your study 
• Your age or date of birth 
• Your study ID number 
• What study product(s) you received 
There are no HIV test results kept in this file. The HVTN will not share any 
information that could identify you without your agreement. The HVTN will 
remove your name from the file if you do not want it there. 
Clinic staff will have access to your study records. Your records may also be 
reviewed by groups who watch over this study to see that we are protecting your 
rights, keeping you safe, and following the study plan. These groups include: 
• The US National Institutes of Health and its study monitors, 
• The US Food and Drug Administration, 
• Any regulatory agency that reviews clinical trials, 
• [Insert name of local IRB/EC] , 
• IAVI, Dynavax, AAHI, DAIDS, and people who work for them, 
• The HVTN and people who work for them, 
• The HVTN Safety Monitoring Board (SMB) and 
• The US Office for Human Research Protections. 

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All reviewers will take steps to keep your records private. 
We cannot guarantee absolute privacy. If you are found to have a medical 
condition that we are required to report by law, then some of your information 
may be shared. At this clinic, we have to report the following information:  
Site: Include any public health or legal reporting requirements. Bulleted examples 
should include all appropriate cases (reportable communicable disease, risk of harm 
to self or others, etc.) If your site does not have public health or legal reporting 
requirements, you may delete the last sentence in the paragraph above, along with 
the bullets below. 
• [Item 1] 
• [Item 2] 
• [Item 3] 
US sites: Include the following boxed text. You can remove the box around the text. 
We have a Certificate of Confidentiality from the US government, to help protect 
your privacy. With the certificate, we do not have to release information about 
you to someone who is not connected to the study, such as the courts or police. 
Sometimes we can’t use the certificate. Since the US government funds this 
research, we cannot withhold information from it. Also, you can still release 
information about yourself and your study participation to others. 
The results of this study may be published. No publication will use your name or 
identify you personally. 
We may share information from the study with other researchers. We will not 
share your name or information that can identify you. 
A description of this clinical trial will be available on 
http://www.ClinicalTrials.gov. This website will not include information that can 
identify you. At most, the website will include a summary of the results. You can 
search this website at any time. 
18. There are several reasons why we may stop your injections. We may stop 
them even if you want to stay in the study and even if you were scheduled for 
more injections. 
We will stop your injections if you become pregnant. We will encourage you to 
stay in the study if you choose. We will discuss your study options with you. If 
you leave the study while you are still pregnant, we will contact you after your 
due date to ask some questions about your pregnancy and delivery. 

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We will stop your injections if you get HIV. We will also take fewer samples, and 
we will help you get care and support. We will encourage you to stay in the study 
for up to 12 weeks after your last injection if you choose. We will discuss your 
study options with you. We will counsel you about having HIV and about telling 
your partner(s). Site: Modify the following sentence as appropriate. We will not 
provide or pay for any of your HIV care directly.  
We will stop your injections if you enroll in another study where you receive a 
study product.  
In the unlikely event that you get a bad reaction to a study injection we may stop 
your injections. 
If we stop your injections, we may ask you to stay in the study to complete other 
study procedures. 
19. We may take you out of the study at any time.  
We may take you out of the study if: 
• you do not follow instructions, 
• we think that staying in the study might harm you, or 
• the study is stopped for any reason. 
Other Risks 
20. There are other risks to being in this study. 
This section describes the other risks and restrictions we know about. There may 
also be unknown risks, even serious ones. We will tell you if we learn anything 
new that may affect your willingness to stay in the study. 
Risks of routine medical procedures: 
In this study, we will do some routine medical procedures. These are taking blood 
and giving injections. These procedures can cause bruising, pain, fainting, 
soreness, redness, swelling, itching, a sore, bleeding, and (rarely) muscle damage 
or infection where you got the injection. Taking blood can cause a low blood cell 
count (anemia), making you feel tired. 
Personal problems/discrimination/testing HIV antibody positive: 
About 10 to 20% of people who join HVTN studies report personal problems or 
discrimination because of joining an HIV vaccine study. Family or friends may 
worry, get upset or angry, or assume that you have HIV or at high risk and treat 

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you unfairly as a result. Rarely, a person has lost a job because the study took too 
much time away from work, or because their employer thought they had HIV. 
The body makes antibodies to fight or prevent infection. Most vaccines cause the 
body to make antibodies as a way of preventing infection. Your body may make 
antibodies to HIV because you received an HIV study vaccine. The study 
vaccines may cause you to test positive on some types of HIV antibody tests, even 
if you do not have HIV. This is called vaccine-induced seropositivity (VISP). 
VISP means that after you get the study vaccines, a routine HIV test done outside 
this clinic may say you have HIV, even if you don’t. For this reason, you should 
plan to get HIV tests only at this clinic during the study. Our tests can tell the 
difference between true HIV infection and a positive result that is caused by the 
study vaccines. 
If you have a positive test result caused by the study vaccines at any time, we can 
arrange free HIV testing for as long as you need it. If this happens, we do not 
know how long you will test positive due to the study vaccines. If you receive a 
positive HIV test result and we determine it is because you have HIV, we will 
refer you for follow-up care. 
It is unlikely, but you could test negative at the end of the study and positive some 
time later, even though you don’t have HIV. This could happen if different HIV 
tests come into use. We will give you a phone number to call for more 
information. 
Site: Modify the following paragraph if applicable. If someone believes you have 
HIV even if you do not, you could face discrimination and other problems. For 
example, in some countries, you could be denied medical or dental care, 
employment, insurance, a visa, or entry into the military. If you do have a positive 
HIV antibody test caused by the study vaccines, you will not be able to donate 
blood or organs. Your family and friends may treat you differently. We will give 
you a brochure that tells you more about testing HIV positive because of an HIV 
vaccine, and how you can avoid some of these problems. 
If you become pregnant during or after the study and have VISP, we don't know if 
the antibodies could be passed to your baby. We know that this happens with 
other vaccines, like tetanus vaccine. These antibodies from the mother are not a 
danger to the baby, and they go away over time. For most babies, antibodies from 
the mother last for about six months. 
You should always tell the delivery staff if you have VISP. However, you may 
still be tested for HIV using the antibody test when you deliver your baby. If your 
test is positive and the delivery staff believes you have HIV, your baby may be 
started on antiretroviral treatment when it is not needed. If this happens, we can 
arrange for you and the baby to have a test that can tell the difference between 
true HIV infection and a VISP result. If you or the baby continue to have VISP, 
we can arrange this testing for free for as long as it is needed. 

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Embarrassment/anxiety: 
You may feel embarrassed when we ask about your HIV risks, such as having sex 
and using drugs. Also, waiting for your HIV test results or other health test results 
could make you feel anxious. You could feel worried if your test results show that 
you have HIV. If you feel embarrassed or anxious, please tell us and we will try to 
help you. 
Risks of disclosure of your personal information: 
We will take several steps to protect your personal information. Although the risk 
is very low, it is possible that your personal information could be given to 
someone who should not have it. If that happened, you could face discrimination, 
stress, and embarrassment. We can tell you more about how we will protect your 
personal information if you would like it. 
Risks of genetic testing: 
It is unlikely, but the genetic tests done on your samples could show you may be 
at risk for certain diseases. If others found out, it could lead to discrimination or 
other problems. However, it is almost impossible for you or others to know your 
test results from the genetic testing. The results are not part of your study records 
and are not given to you. 
In the very unlikely event that your genetic information becomes linked to your 
name, a federal law called the Genetic Information Nondiscrimination Act 
(GINA) helps protect you. GINA keeps health insurance companies and 
employers from seeing results of genetic testing when deciding about giving you 
health insurance or offering you work. GINA does not help or protect you against 
discrimination by companies that sell life, disability or long-term care insurance. 
Unknown risks: 
We do not know if the study vaccines will increase, decrease, or not change your 
risk of getting HIV if exposed. If you get HIV, we do not know how the study 
vaccines might affect your HIV infection or how long it takes to develop AIDS. 
We do not know if getting these study vaccines will affect how you respond to 
any future approved HIV vaccine. Currently, no HIV vaccine has been approved 
for use. 
We do not know how the study vaccines will affect a pregnant participant or a 
developing baby. 

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Benefits 
21. The study may not benefit you. 
We do not expect the study vaccines to benefit you in any way. However, being in 
the study might still help you in some ways. The counseling that you get as part of 
the study may help you avoid getting HIV. The lab tests and physical exams that 
you get while in this study might detect health problems you don’t yet know 
about. 
This study may help in the search for a vaccine to prevent HIV. However, if the 
study vaccines later become approved and sold, there are no plans to share any 
money with you. 
Your rights and responsibilities 
22. If you join the study, you have rights and responsibilities. 
You have many rights that we will respect. You also have responsibilities. We list 
these in the Participant’s Bill of Rights and Responsibilities. We will give you a 
copy of it. 
Leaving the study 
23. Tell us if you decide to leave the study. 
You are free to leave the study at any time and for any reason. Your care at this 
clinic and your legal rights will not be affected, but it is important for you to let us 
know. 
We will ask you to come back to the clinic one last time for a physical exam, and 
we may ask to take some blood and urine samples. We will also ask about any 
personal problems or benefits you have experienced from being in the study. We 
believe these steps are important to protecting your health, but it is up to you 
whether to complete them. 
Injuries 
Sites: Approval from HVTN Regulatory Affairs (at vtn.core.reg@hvtn.org) is needed 
for any change (other than those that the instructions specifically request or those 
previously approved by HVTN Regulatory Affairs) to the boxed text. You can remove 
the box around the text. 
24. If you get sick or injured during the study, contact us immediately. 
Your health is important to us. (Sites: adjust the following 2 sentences if 
applicable to the care available at your site) We will tell you about the care that 

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we can give here. For the care that we cannot provide, we will explain how we 
will help you get care elsewhere. 
If you become sick or injured in this study, the HVTN has a process to decide if it 
is related to the study products and/or procedures. If it is, we call it a study-related 
injury. There are funds to pay for treatment of study-related injuries if certain 
conditions are met. 
Some of the study product providers may pay medical costs for study-related 
injuries that are determined to be caused by their own study products. If provider 
funds are not available or are not enough, or if the injury is determined to be 
caused by study procedures, the HVTN has limited funds to pay medical costs 
that it determines are reasonable. (Sites: insert locale- appropriate medical 
insurance language in the following sentence) If the injury is not study related, 
then you and/or your health insurance will be responsible for treatment costs. 
Some injuries are not physical. For example, you might be harmed emotionally by 
being in an HIV vaccine study. Or you might lose wages because you cannot go 
to work. However, there are no funds to pay for these kinds of injuries, even if 
they are study related. 
You may disagree with the decision about whether your injury is study related. If 
you wish, the HVTN will ask independent experts to review the decision. You 
always have the right to use the court system if you are not satisfied. 
Questions  
25. If you have questions or problems at any time during your participation in 
this study, use the following important contacts. 
If you have questions about this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
If you have any symptoms that you think may be related to this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
This study has been reviewed and approved by a committee called the 
[name of local IRB/EC]. If you have questions about your rights as a research 
participant, or problems or concerns about how you are being treated in this study, 
contact [name or title and telephone number of person on IRB/EC] , at the 
committee. 
If you want to leave this study, contact 
[name or title and telephone number of the investigator or other study staff]. 

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Your permissions and signature  
Site: Delete the following blue section if using a separate consent for use of samples 
and information in other studies 
26. In Section 18 of this form, we told you about possible other uses of your extra 
samples and information, outside this study. Please choose only one of the 
options below and write your initials or make your mark in the box next to it. 
Whatever you choose, the HVTN keeps track of your decision about how 
your samples and information can be used. You can change your mind after 
signing this form. 
 
 
I allow my extra samples and information to be used for other studies related to 
HIV, vaccines, the immune system, and other diseases. This may include 
genetic testing and keeping my cells growing over time.  
OR 
 
 
I agree to the option above and also to allow my extra samples and information 
to be used in genome wide studies. 
OR 
 
 
I do not allow my extra samples to be used in any other studies. This includes 
not allowing genetic testing, growing more of my cells, or genome wide studies. 
27. If you agree to join this study, you will need to sign or make your mark 
below. Before you sign or make your mark on this consent form, make sure 
of the following: 
• You have read this consent form, or someone has read it to you. 
• You feel that you understand what the study is about and what will happen to 
you if you join. You understand what the possible risks and benefits are. 
• You have had your questions answered and know that you can ask more. 
• You agree to join this study. 
You will not be giving up any of your rights by signing this consent form. 

HVTN 137 Version 5.0 / September 26, 2022 
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Participant’s name (print) 
 
Participant’s signature or mark 
 
Date 
 
Time 
 
 
 
 
 
 
 
Clinic staff conducting consent 
discussion (print) 
 
Clinic staff signature 
 
Date 
 
Time 
For participants who are unable to read or write, a witness should complete the 
signature block below: 
 
 
 
 
 
 
 
Witness’s name (print) 
 
Witness’s signature  
 
Date 
 
Time 
*Witness is impartial and was present for the entire discussion of this consent form. 
 

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Appendix D 
Sample addendum to informed consent form 
for Part A with Optional Third Vaccination 
participants only 
Title: A phase 1 clinical trial to evaluate the safety and immunogenicity of HIV-1 
BG505 SOSIP.664 gp140 with TLR agonist and/or Alum adjuvants and VRC 
HIV Env Trimer 4571 and 3M-052-AF with Alum in healthy, HIV uninfected 
adults 
HVTN protocol number: HVTN 137 
Site: [Insert site name] 
1.Key information 
• Enrollment in Part A is complete with 17 participants and injections have been 
completed. We are now adding an optional third injection of the same study 
product already received for all Part A participants. Getting a third study 
injection is optional. 
• Participants who do not agree to have a third injection will not sign this 
consent form. They will continue on in the study according to the consent form 
they signed when they joined it. 
• Participants who agree to have a third injection will need to sign this consent 
form. They will have the same study procedures as were described in the 
original consent form but their schedule of study visits will change. Their study 
duration will also change. They will be in the study for 12 months after getting 
the third injection 
• Because this is the first study to give this study vaccine to people, the risks of a 
third injection of study vaccine are unknown at this time.  However, we expect 
the risks will be the same as we told you in the main study informed consent 
form. 
1. Study progress update 
In HVTN 137 Part A, we are testing 2 different doses (amounts) of the same 
adjuvant. Enrollment in Part A is complete with 17 participants and injections 
have been completed. The study vaccine we gave to the first people to join 
contained a low dose of the adjuvant. There were no serious health problems in 
those people, so as planned, we gave people who later joined the study the 
vaccine with the higher dose of the adjuvant. As there were no serious health 
problems in those people either, the decision was made to use the higher dose of 
adjuvant in the study vaccine in Part B of the study, which is now open and 
enrolling participants.   

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Two participants in Part A did have reactions to their study injections that we 
want to tell you about. Both had redness and swelling over a large area on their 
arm where they got the injection that started about 1 week after a study injection. 
The redness lasted for about 2 to 3 days. For one of these people, the swelling 
went away within 2 to 3 days. The second person had significant swelling for 
about 3 days. The swelling went down but it took about 5 weeks to completely go 
away. They had mild pain which did not prevent them from going to work. 
Because the study is ongoing and is blinded, we do not know if these people got 
the study vaccine or placebo. 
2. New optional study plan for Part A participants 
The researchers would like to offer all Part A participants the option to receive a 
third injection of the same dose and combination of study products they already 
received. This study opened just before the COVID-19 pandemic started and is 
taking longer than planned because of it. The delay allowed the researchers to 
take an early look at Part A participants’ immune responses to their study 
injections and they found that some were very good. The researchers would like 
to see if these responses can be improved with one more injection. The 
researchers would also like to make up for the delay and quickly learn more about 
the adjuvant given in Part A. 
Getting a third study injection is optional. Participants who agree to it will follow 
a revised study visit schedule. We are calling the third injection and revised study 
visit schedule ‘the Part A Optional Third Vaccination’. The optional third 
injection will be about 6 to 12 months after your first injection. If you join the 
Part A Optional Third Vaccination portion of the study, the study procedures will 
be the same but your study visit schedule will change. Your study duration will 
also change. You will be in the study for 12 months after you get the third 
injection. We will tell you more about this below. 
As we told you in the main study informed consent form, we do not know 
whether the study vaccine will affect your risk of getting HIV from another 
person. The risk could be higher, lower, or unchanged. It’s very important to 
avoid exposure to HIV during and after the study. We will tell you how to avoid 
HIV. If you get HIV, we do not know how the study vaccine might affect your 
HIV infection or how long it takes to develop AIDS. We do not know if getting 
this study vaccine will affect how you respond to any future approved HIV 
vaccine. 
Please review this information carefully. You are free to ask questions at any 
time.  
3. You are free to choose whether or not to join the Part A Optional Third 
Vaccination.  
2.If you do not want to join the Part A Optional Third Vaccination, you will not 
sign this consent form and you will continue on in the study following the consent 

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form you signed when you joined it. If you decide you want to join the Part A 
Optional Third Vaccination, we will ask you to sign this consent form. We will 
give you a copy to keep. 
4. If you join the Part A Optional Third Vaccination, the study procedures will 
be the same but your study visit schedule and study duration will change.   
You will be in the study for 12 months after you get the third injection. You will 
come to the clinic for scheduled visits about 4 times over the 12 months following 
the third injection. 
Visits can last from [#] to [#] hours. 
You may have to come for more visits if you have a lab or health issue.  
5. Many things described in the informed consent form you signed previously 
remain the same. 
These include: 
• The study procedures we will do; 
• The potential risks and benefits of being in the study; 
• Your rights and responsibilities in the study; 
• How your samples will be used; 
• What we will do if we find you have a health problem; 
• How we will protect your private information and who can access your study 
records; 
• Reasons we might take you out of the study; 
• There may be some restrictions on blood or tissue donation; and 
• What will happen if you get sick or injured during the study. 
As before, there is no cost to you for being in the study. Participants who agree to 
have a third injection will be given [Site: Insert additional compensation] for each 
study visit completed for the optional third vaccination. 
In the consent form you signed when you joined this study, you chose whether the 
HVTN could use your extra samples and information in other studies. The HVTN 
will continue to honor the choice you made in that consent form. You can change 
your mind if you want. Your decision will not affect your being in this study or 
have any negative consequences here. 

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As stated in the Key Information section, the potential additional risks of a third 
injection of study vaccine are unknown at this time. 
6. If you have questions or problems at any time during this study, use the 
following important contacts. 
If you have questions about this study, contact [name or title and telephone 
number of the investigator or other study staff]. 
If you have any symptoms that you think may be related to this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
This study has been reviewed and approved by a committee called the [name of 
local IRB/EC]. If you have questions about your rights as a research participant, 
or problems or concerns about how you are being treated in this study, contact 
[name or title and telephone number of person on IRB/EC], at the committee. 
If you want to leave this study, contact [name or title and telephone number of the 
investigator or other study staff]. 
You can reach a study staff member 24-hours a day at [telephone number]. 
7. If you agree to join the Part A Optional Third Vaccination, you will need to 
sign or make your mark below. Before you sign or make your mark on this 
consent form, make sure of the following: 
• You have read this consent form, or someone has read it to you. 
• You feel that you understand what the Part A Optional Third Vaccination is 
about and what will happen to you if you join it. You understand what the 
possible risks and benefits are. 
• You have had your questions answered and know that you can ask more. 
• You agree to join the Part A Optional Third Vaccination. 
You will not be giving up any of your rights by signing this consent form. 

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Participant’s name (print) 
 
Participant’s signature or mark 
 
Date 
 
Time 
 
 
 
 
 
 
 
Clinic staff conducting consent 
discussion (print) 
 
Clinic staff signature 
 
Date 
 
Time 
For participants who are unable to read or write, a witness should complete the 
signature block below: 
 
 
 
 
 
 
 
Witness’s name (print) 
 
Witness’s signature  
 
Date 
 
Time 
*Witness is impartial and was present for the consent process. 
 
 

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Appendix E 
Approved birth control methods for persons 
assigned female sex at birth (for Part A sample 
informed consent form) 
Site: Any change to the following boxed text requires approval from HVTN 
Regulatory Affairs at vtn.core.reg@hvtn.org. You can remove the box around the text. 
You should not become pregnant during the study because we do not know how 
the study vaccine could affect the developing baby. 
You must agree to use effective birth control from 21 days before your first 
injection until 6 months after your last study injection.  
Effective birth control means using any of the following methods every time you 
have sex: 
• Birth control drugs that prevent pregnancy—given by pills, shots, patches, 
vaginal rings, or inserts under the skin; 
• Male or female condoms, with or without a cream or gel that kills sperm; 
• Diaphragm or cervical cap with a cream or gel that kills sperm; 
• Intrauterine device (IUD); or 
• Any other contraceptive method approved by the researchers. 
You do not have to use birth control if: 
• You are only having sex with a partner or partners who have had a vasectomy. 
(We will ask you some questions to confirm that the vasectomy was 
successful.); 
• You have reached menopause, with no menstrual periods for one year; 
• You have had a hysterectomy (your uterus removed); 
• You have had your ovaries removed; 
• You have a tubal ligation (your “tubes tied”) or confirmed successful 
placement of a product that blocks the fallopian tubes; 
• You are having sex only with a partner(s) assigned female sex at birth; 
• You only have oral sex; or, 

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• You are sexually abstinent (no sex at all). 
Remember: If you are having sex, male and female condoms are the only birth 
control methods that also provide protection against HIV and other sexually 
transmitted infections. 
If you join the study, we will test you for pregnancy at some visits, including 
before each study injection. 
 

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Appendix F 
Approved birth control methods for persons 
assigned female sex at birth (for Part B and Part C 
sample informed consent form) 
Site: Any change to the following boxed text requires approval from HVTN 
Regulatory Affairs at vtn.core.reg@hvtn.org. You can remove the box around the text. 
You should not become pregnant during the study because we do not know how 
the study vaccines could affect the developing baby. 
You must agree to use effective birth control from 21 days before your first 
injection until 6 months after your last study injection.  
Effective birth control means using any of the following methods every time you 
have sex: 
• Birth control drugs that prevent pregnancy—given by pills, shots, patches, 
vaginal rings, or inserts under the skin; 
• Male or female condoms, with or without a cream or gel that kills sperm; 
• Diaphragm or cervical cap with a cream or gel that kills sperm; 
• Intrauterine device (IUD); or 
• Any other contraceptive method approved by the researchers. 
You do not have to use birth control if: 
• You are only having sex with a partner or partners who have had a vasectomy. 
(We will ask you some questions to confirm that the vasectomy was 
successful.); 
• You have reached menopause, with no menstrual periods for one year; 
• You have had a hysterectomy (your uterus removed); 
• You have had your ovaries removed; 
• You have a tubal ligation (your “tubes tied”) or confirmed successful 
placement of a product that blocks the fallopian tubes; 
• You are having sex only with a partner(s) assigned female sex at birth; 
• You only have oral sex; or, 

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• You are sexually abstinent (no sex at all). 
Remember: If you are having sex, male and female condoms are the only birth 
control methods that also provide protection against HIV and other sexually 
transmitted infections. 
If you join the study, we will test you for pregnancy at some visits, including 
before each study injection. 
 

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Appendix G 
Sample consent form for use of samples and 
information in other studies 
Title: A phase 1 clinical trial to evaluate the safety and immunogenicity of HIV-1 
BG505 SOSIP.664 gp140 with TLR agonist and/or Alum adjuvants and VRC 
HIV Env Trimer 4571 and 3M-052-AF with Alum in healthy, HIV uninfected 
adults 
 
HVTN protocol number: HVTN 137 
Site: [Insert site name] 
When samples are no longer needed for this study, the HVTN wants to use them 
in other studies and share them with other researchers. The HVTN calls these 
samples “extra samples.” The HVTN will only allow your extra samples to be 
used in other studies if you agree to this. You will mark your decision at the end 
of this form. If you have any questions, please ask. 
Key information 
These are some of the things you should know about the use of your samples and 
information for other studies: 
• The extra samples will be labeled with a code number and some personal 
information. They will not be labeled with your name. The extra samples are 
stored in a secure place.  At your request, the HVTN will destroy all your 
extra samples. You can still join the main study even if you do not agree to 
use of your extra samples in other studies. 
• Researchers may do genetic testing on your samples, which could include 
genome wide studies. It is unlikely, but these tests could show you may be at 
risk for certain diseases. In the very unlikely event that others found out, this 
could lead to discrimination or other problems.  
• You will not be paid or otherwise benefit from allowing your extra samples to 
be used in other studies.   
The rest of this form gives more information about use of your extra samples for 
other studies. Please read it carefully. 
1. Do I have to agree? 
No. You are free to say yes or no, or to change your mind after you sign this form. 
At your request, we will destroy all extra samples that we have. Your decision 
will not affect your being in this study or have any negative consequences here. 

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2. Where are the samples stored? 
Extra samples are stored in a secure central place called a repository. Your 
samples will be stored in the HVTN repository in the United States. 
3. How long will the samples be stored? 
There is no limit on how long your extra samples will be stored. [Site: Revise the 
previous sentence to insert limits if your regulatory authority imposes them.] 
4. Will I be paid for the use of my samples? 
No. Also, a researcher may make a new scientific discovery or product based on 
the use of your samples. If this happens, there is no plan to share any money with 
you. The researcher is not likely to ever know who you are. 
5. Will I benefit from allowing my samples to be used in other studies? 
Probably not. Results from these other studies are not given to you, this clinic, or 
your doctor. They are not part of your medical record. The studies are only being 
done for research purposes. 
6. Will the HVTN sell my samples and information? 
No, but the HVTN may share your samples with HVTN or other researchers. 
Once we share your samples and information, we may not be able to get them 
back. 
7. How do other researchers get my samples and information? 
When a researcher wants to use your samples and information, their research plan 
must be approved by the HVTN. Also, the researcher’s institutional review board 
(IRB) or ethics committee (EC) will review their plan. [Site: If review by your 
institution’s IRB/EC/RE is also required, insert a sentence stating this.] IRBs/ECs 
protect the rights and well-being of people in research. If the research plan is 
approved, the HVTN will send your samples to the researcher’s location. 
8. What information is shared with HVTN or other researchers?  
The samples and information will be labeled with a code number. The key to the 
code will stay at this clinic. It will not be shared with the HVTN, other 
researchers, or with anyone else who does not need to know your name. Your 
name will not be part of the information. However, some information that we 
share may be personal, such as your race, ethnicity, gender, health information 
from the study, and HIV status. We may share information about the study 
product you received and how your body responded to the study product. 

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9. What kind of studies might be done with my extra samples and information? 
The studies will be related to HIV, vaccines, the immune system and other 
diseases. 
Researchers may also do genetic testing on your samples. 
In some cases, researchers may take cells from your samples and grow more of 
them over time, so that they can continue to do research with them. 
If you agree, your samples could also be used for genome wide studies. In these 
studies, researchers will look at all of your genes (your genome). The researchers 
compare the genomes of many people, looking for common patterns of genes that 
could help them understand diseases. The researchers may put the information 
from the genome-wide studies into a protected database so that other researchers 
can access it, but your name and other personal information will not be included. 
Usually, no one would be able to look at your genome and link it to you as a 
person. However, if another database exists that also has information on your 
genome and your name, someone might be able to compare the databases and 
identify you. If others found out, it could lead to discrimination or other problems. 
The risk of this is very small. There may be other unknown risks. 
10. What are the risks of genetic testing? 
It is unlikely, but the genetic tests done on your samples could show you may be 
at risk for certain diseases. If others found out, it could lead to discrimination or 
other problems. However, it is almost impossible for you or others to know your 
test results from the genetic testing. The results are not part of your study records 
and are not given to you. 
In the very unlikely event that your genetic information becomes linked to your 
name, a federal law called the Genetic Information Nondiscrimination Act 
(GINA) helps protect you. GINA keeps health insurance companies and 
employers from seeing results of genetic testing when deciding about giving you 
health insurance or offering you work. GINA does not help or protect you against 
discrimination by companies that sell life, disability or long-term care insurance. 
11. Who will have access to my information in studies using my extra samples? 
People who may see your information are: 
• Researchers who use your extra samples and information for other research 
• Government agencies that fund or monitor the research using your extra 
samples and information 
• The researcher’s Institutional Review Board or Ethics Committee 

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• Any regulatory agency that reviews clinical trials 
• The people who work with the researcher 
All of these people will do their best to protect your information. The results of 
any new studies that use your extra samples and information may be published. 
No publication will use your name or identify you personally. 
Questions  
12. If you have questions or problems about allowing your samples and 
information to be used in other studies, use the following important contacts. 
If you have questions about the use of your samples or information or if you want 
to change your mind about their use, contact 
[name or title and telephone number of the investigator or other study staff]. 
If you think you may have been harmed because of studies using your samples or 
information, contact 
[name or title and telephone number of the investigator or other study staff]. 
If you have questions about your rights as a research participant, contact 
[name or title and telephone number of person on IRB/EC . 
13. Please choose only one of the options below and write your initials or make 
your mark in the box next to it. Whatever you choose, the HVTN keeps track 
of your choice about how your samples and information can be used. You 
can change your mind after signing this form. 
 
 
I allow my extra samples and information to be used for other studies related to 
HIV, vaccines, the immune system, and other diseases. This may include 
genetic testing and keeping my cells growing over time. 
OR 
 
 
I agree to the option above and also to allow my extra samples and information 
to be used in genome wide studies. 
 
OR 
 
 
I do not allow my extra samples to be used in any other studies. This includes 
not allowing genetic testing, growing more of my cells, or genome wide studies.  
 
 
 

HVTN 137 Version 5.0 / September 26, 2022 
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Participant’s name (print) 
 
Participant’s signature or mark 
 
Date 
 
Time 
 
 
 
 
 
 
 
Clinic staff conducting consent 
discussion (print) 
 
Clinic staff signature 
 
Date 
 
Time 
For participants who are unable to read or write, a witness should complete the 
signature block below: 
 
 
 
 
 
 
 
Witness’s name (print) 
 
Witness’s signature  
 
Date 
 
Time 
*Witness is impartial and was present for the entire discussion of this consent form.

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Appendix H 
Tables of procedures (for sample informed consent form) 
Part A 
 
 
 
 
Time after first injection visit 
 
Procedure 
Screening 
visit(s) 
First 
Injection 
visit 
2 
weeks 
2 
months 
2½ 
months 
8 
months 
14 
months** 
Injection 
 
√ 
 
√ 
 
 
 
Medical history 
√ 
 
 
 
 
 
 
Complete physical 
√ 
 
 
 
 
√ 
 
Brief physical 
 
√ 
√ 
√ 
√ 
 
 
Urine test 
√ 
 
√ 
 
√ 
 
 
Blood drawn 
√ 
√ 
√ 
 
√ 
√ 
 
Pregnancy test (participants assigned female sex at birth)* 
√ 
√ 
 
√ 
 
√ 
 
HIV testing and pretest counseling 
√ 
 
 
 
√ 
√ 
 
Risk reduction counseling 
√ 
√ 
√ 
√ 
√ 
√ 
 
Interview/questionnaire 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Not shown in this table is a time after all study participants have completed their last scheduled visit when you can find out what products you received.  
* Persons who had a hysterectomy (removal of the uterus) or removal of both ovaries (verified by medical records), are not required to have a pregnancy test. 
** Phone contact about one year after last injection to check on certain aspects of participant health. 
 
 

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Part A with Optional Third Vaccination 
 
 
 
Time after first injection visit 
Procedure 
Screening 
visit(s) 
Injection 
visit 
2 weeks 
2 months 
2½ months 
6 months 
6¼ months 
6½ months 
12 months 
18 months 
Injection 
 
√ 
 
√ 
 
√ 
 
 
 
 
Medical history 
√ 
 
 
 
 
 
 
 
 
 
Complete physical 
√ 
 
 
 
 
 
 
 
 
√ 
Brief physical 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Urine test 
√ 
 
√ 
 
√ 
 
 
√ 
 
 
Blood drawn 
√ 
√ 
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
Pregnancy test (participants assigned female sex at birth)* 
√ 
√ 
 
√ 
 
√ 
 
 
√ 
 
HIV testing and pretest counseling 
√ 
 
 
 
√ 
√ 
 
 
√ 
√ 
Risk reduction counseling 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Interview/questionnaire 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Not shown in this table is a time after all study participants have completed their last scheduled visit when you can find out what products you received.  
* Persons who had a hysterectomy (removal of the uterus) or removal of both ovaries (verified by medical records), are not required to have a pregnancy test. 
 
 

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Part B 
 
 
Time after first injection visit 
Procedure 
Screening 
visit(s) 
First injection 
visit 
1 day 
3 days 
1 week 
2 weeks 
2 months 
2¼ months  
2½ months 
2¾ months 
6 months 
6¼ months 
6½ months 
12 months 
18 months 
Injection 
 
√ 
 
 
 
 
√ 
 
 
 
√ 
 
 
 
 
Medical history 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
√ 
Brief physical 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Urine test 
√ 
√** 
 
 
 
√ 
 
 
 
 
 
 
√ 
 
 
Blood drawn 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Rectal and vaginal swabs 
 
√** 
 
 
 
 
 
 
 
 
 
 
√** 
 
 
Pregnancy test (participants assigned female sex at 
birth)* 
√ 
√ 
 
 
 
 
√ 
 
√** 
√** 
√ 
 
√** 
√ 
√** 
HIV testing and pretest counseling 
√ 
 
 
 
 
 
 
 
√ 
 
√ 
 
 
√ 
√ 
Risk reduction counseling 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Interview/questionnaire 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Site: Include only rows below for the procedures available to your participants  
 
 
 
 
 
 
 
 
 
 
 
 
 
Leukapheresis (optional) 
 
 
 
 
 
 
 
 
√ 
 
 
 
 
 
 
Lymph node cell collection (optional) 
 
 
 
 
 
 
 
 
 
√ 
 
 
 
 
 
Bone marrow cell collection (optional) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
√ 
Vaginal and/or rectal fluid collection (optional) *** 
 
√ 
 
 
 
 
 
 
 
 
 
 
√ 
 
 
Vaginal and/or rectal biopsy (optional) *** 
 
√ 
 
 
 
 
 
 
 
 
 
 
√ 
 
 
 
Greyed out visit is only applicable for participants doing lymph node cell collection. 
Not shown in this table is a time after all study participants have completed their last scheduled visit when you can find out what products you received.  
* Persons who had a hysterectomy (removal of the uterus) or removal of both ovaries (verified by medical records), are not required to have a pregnancy test. 
** For participants having any of the optional procedures at these visits.  
*** Procedure involves a rectal and/or pelvic exam, as appropriate. 
 
 
 
 
 

HVTN 137 Version 5.0 / September 26, 2022 
HVTN137_v5.0_Final_26Sep22 / Page 251 of 281 
 
Part C 
 
 
Time after first injection visit 
Procedure 
Screening 
visit(s) 
First injection 
visit 
1 day 
3 days 
1 week 
2 weeks 
2 months 
2¼ months 
2½ months 
2¾ months 
6 months 
6¼ months 
6½ months 
12 months 
18 months 
Injection 
 
√ 
 
 
 
 
√ 
 
 
 
√ 
 
 
 
 
Medical history 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
√ 
Brief physical 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Urine test 
√ 
 
 
 
 
√ 
 
 
 
 
 
 
√ 
 
 
Blood drawn 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Pregnancy test (participants assigned female sex at 
birth)* 
√ 
√ 
 
 
 
 
√ 
 
 
 
√ 
 
 
√ 
 
HIV testing and pretest counseling 
√ 
 
 
 
 
 
 
 
√ 
 
√ 
 
 
√ 
√ 
Risk-reduction counseling 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Interview/questionnaire 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Grayed out visit are not applicable. 
Not shown in this table is a time after all study participants have completed their last scheduled visit when you can find out what products you received. 
* Persons who had a hysterectomy (removal of the uterus) or removal of both ovaries (verified by medical records) are not required to have a pregnancy test. 

HVTN 137 Version 5.0 / September 26, 2022 
HVTN137_v5.0_Final_26Sep22 / Page 252 of 281 
Appendix I 
Optional procedure images for Part B 
Sample informed consent form 
Leukapheresis procedure 
 
 
Lymph node cell collection 
 
2. The blood passes through an apheresis 
machine, which separates out the white 
blood cells.  
3. The white blood cells are collected 
for storage. 

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Bone marrow cell collection 
 
 
 
 
 
 
 
 
 
 
 

HVTN 137 Version 5.0 / September 26, 2022 
HVTN137_v5.0_Final_26Sep22 / Page 254 of 281 
Appendix J 
Laboratory procedures for Part A  
 
 
Grayed out visits are not applicable to these groups. 
1 CSR = Central Specimen Repository; UW-VSL = University of Washington Virology Specialty Laboratory (Seattle, Washington, USA). 
2 HVTN Laboratories include: Fred Hutchinson Cancer Research Center (Seattle, Washington, USA); Duke University Medical Center (Durham, North Carolina, USA). 
3 Local labs may assign appropriate alternative tube types for locally performed tests. 
4 Screening may occur over the course of several contacts/visits up to and including day 0 prior to vaccination. 
5 Chemistry panels are defined in Section 9.2 (pre-enrollment procedures) and Section 9.4 (follow-up visits). 
6 And microscopy if needed. 
7 For participants assigned female sex at birth. Pregnancy test may be performed on blood specimens. Persons who are NOT of reproductive potential due to having undergone total 
hysterectomy or bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing 
8 At an early termination visit for a withdrawn or terminated participant who is not HIV-infected (see Section 9.12), blood should be drawn for HIV diagnostic testing, as shown for visit 14 
above. If a participant has a confirmed diagnosis of HIV infection, do not collect blood for HIV diagnostic testing (see Section 9.14) 
9 For information concerning the AESI contact, see Section 9.6. Clinic visits are not required except that any participant reporting a diagnosis of HIV infection from testing outside of the 
HVTN will be asked to come to the clinic to collect specimens for HIV testing with HVTN HIV diagnostic algorithms. 
10 Specimens indicated for Day 0 may be obtained within the 14 days prior to vaccination, except for a pregnancy test which must be performed on urine or blood specimens within 24 hours 
of vaccination with negative results received prior to vaccination. 
Visit:
1
210
3
4
5
6
7
8
9
10
11
12
13
14
AESI9
Day:
D0
D1
D3
D7
D14
D56
D63
D70
D77
D168
D175
D182
D224
D425
Week:
W0
W1
W2
W8
W9
W10
W11
W24
W25
W26
W32
W61
Month:
M0
M0.25
M0.5
M2
M2.25
M2.5
M2.75
M6
M6.25
M6.5
M8
M14
VAC1
VAC2
Procedure
Total
BLOOD COLLECTION
Screening/Diagnostic
HIV screening test
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
5
HBsAg/ anti-HCV
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
5
HIV diagnostics8
UW-VSL
UW-VSL
EDTA
10mL
—
—
—
—
10
20
—
30
Safety labs
CBC/ Diff/ Platelets
Local lab
Local lab
EDTA
5mL
5
—
5
—
5
5
—
20
Chemistry panel5
Local lab
Local lab
SST
5mL
5
—
5
—
5
5
—
20
Immunogenicity assays
Cellular assays
Ag-specific B-cell phenotyping
CSR
HVTN Labs
ACD
8.5mL
—
34
34
—
34
34
—
136
ICS
CSR
HVTN Labs
ACD
8.5mL
—
34
34
—
34
34
—
136
Humoral assays
Neutralizing Ab assay
CSR
HVTN Labs
SST
8.5mL
—
8.5
8.5
—
8.5
8.5
—
34
Binding Ab assay
CSR
HVTN Labs
SST
8.5mL
—
8.5
8.5
—
8.5
8.5
—
34
STORAGE
PBMC 
CSR
—
ACD
8.5mL
—
34
34
—
34
34
—
136
Serum 
CSR
—
SST
8.5mL
—
25.5
25.5
—
25.5
25.5
—
102
Visit total
20
145
155
0
165
175
0
658
56-Day total
 
20
165
319
319
319
175
0
URINE COLLECTION
Urine dipstick6
Local lab
Local lab
X
X
X
Pregnancy test7
Local lab
Local lab
X
X
X
X
Screening 
visit4
(vol. 
capacity)
Tube type3
Assay 
location2
Ship to1

HVTN 137 Version 5.0 / September 26, 2022 
HVTN137_v5.0_Final_26Sep22 / Page 255 of 281 
Appendix K 
Laboratory procedures for Part A with Optional Second Boost 
 
 
Grayed out visits are not applicable to these groups. 
1 CSR = Central Specimen Repository; UW-VSL = University of Washington Virology Specialty Laboratory (Seattle, Washington, USA). 
2 HVTN Laboratories include: Fred Hutchinson Cancer Research Center (Seattle, Washington, USA); Duke University Medical Center (Durham, North Carolina, USA). 
3 Local labs may assign appropriate alternative tube types for locally performed tests. 
4 Screening may occur over the course of several contacts/visits up to and including day 0 prior to vaccination. 
5 Chemistry panels are defined in Section 9.2 (pre-enrollment procedures) and Section 9.4 (follow-up visits). 
6 And microscopy if needed. 
7 For participants assigned female sex at birth. Pregnancy test may be performed on blood specimens. Persons who are NOT of reproductive potential due to having undergone total 
hysterectomy or bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing. 
8 At an early termination visit for a withdrawn or terminated participant who is not HIV-infected (see Section 9.12), blood should be drawn for HIV diagnostic testing, as shown for visit 16 
above. If a participant has a confirmed diagnosis of HIV infection, do not collect blood for HIV diagnostic testing (see Section 9.14). 
9 Specimens indicated for Day 0 may be obtained within the 14 days prior to vaccination, except for a pregnancy test which must be performed on urine or blood specimens within 24 hours 
of vaccination with negative results received prior to vaccination. 
10 For participants who agree to undergo boost vaccination, collection of Month 8 samples (as shown in the Lab procedures table for Part A, see Appendix J) will not occur. Participants who 
have already undergone sample collection at Month 8 will be placed on the Part A with Optional Second Boost schedule at Visit 11. 
Visit:
1
29
3
4
5
6
7
8
9
10
1110
12
13
14
15
16
Day:
D0
D1
D3
D7
D14
D56
D63
D70
D77
D168
D175
D182
D224
D364
D546
Week:
W0
W1
W2
W8
W9
W10
W11
W24
W25
W26
W32
W52
W78
Month:
M0
M0.25
M0.5
M2
M2.25
M2.5
M2.75
M6
M6.25
M6.5
M8
M12
M18
VAC1
VAC2
BOOST
Procedure
Total
BLOOD COLLECTION
Screening/Diagnostic
HIV screening test
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
5
HBsAg/ anti-HCV
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
5
HIV diagnostics8
UW-VSL
UW-VSL
EDTA
10mL
—
—
—
—
10
10
—
—
—
10
20
50
Safety labs
CBC/ Diff/ Platelets
Local lab
Local lab
EDTA
5mL
5
—
5
—
5
—
—
5
—
5
—
25
Chemistry panel5
Local lab
Local lab
SST
5mL
5
—
5
—
5
—
—
5
—
5
—
25
Immunogenicity assays
Cellular assays
Ag-specific B-cell phenotyping
CSR
HVTN Labs
ACD
8.5mL
—
34
34
—
34
—
—
34
—
34
34
204
ICS
CSR
HVTN Labs
ACD
8.5mL
—
34
34
—
34
—
—
34
—
34
34
204
Humoral assays
Neutralizing Ab assay
CSR
HVTN Labs
SST
8.5mL
—
8.5
8.5
—
8.5
8.5
—
8.5
—
8.5
8.5
60
Binding Ab assay
CSR
HVTN Labs
SST
8.5mL
—
8.5
8.5
—
8.5
8.5
—
8.5
—
8.5
8.5
60
STORAGE
PBMC 
CSR
—
ACD
8.5mL
—
34
34
—
34
—
68
68
—
34
42.5
315
Serum 
CSR
—
SST
8.5mL
—
25.5
25.5
—
25.5
—
—
25.5
—
25.5
25.5
153
Visit total
20
145
155
0
165
27
68
189
165
173
1105
56-Day total
 
20
165
319
319
319
27
95
284
165
173
URINE COLLECTION
Urine dipstick6
Local lab
Local lab
X
—
X
—
X
—
—
X
—
—
Pregnancy test7
Local lab
Local lab
X
X
—
X
—
X
—
—
X
—
Screening 
visit4
Ship to1
Assay 
location2
Tube type3
(vol. 
capacity)

HVTN 137 Version 5.0 / September 26, 2022 
HVTN137_v5.0_Final_26Sep22 / Page 256 of 281 
Appendix L 
Laboratory procedures for Part B with leukapheresis and lymph node FNA 
 
 
Grayed out visits are not applicable to this subgroup.  
Visit:
1
213
3
4
5
6
7
8
9
1011
11
12
13
14
15
16
Day:
D0
D1
D3
D7
D14
D56
D63
D70
D77
D168
D175
D182
D224
D364
D546
Week:
W0
W1
W2
W8
W9
W10
W11
W24
W25
W26
W32
W52
W78
Month:
M0
M0.25
M0.5
M2
M2.25
M2.5
M2.75
M6
M6.25
M6.5
M8
M12
M18
VAC1
VAC2
VAC3
Procedure
 
Total
BLOOD COLLECTION
Screening/Diagnostic
HIV screening test
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HBsAg/ anti-HCV
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HIV diagnostics 8
UW-VSL
UW-VSL
EDTA
10mL
—
—
—
—
—
—
—
—
10
—
10
—
—
10
20
50
Safety labs
CBC/ Diff/ Platelets
Local lab
Local lab
EDTA
5mL
5
—
—
—
—
5
—
—
5
—
—
—
5
5
—
25
Chemistry panel5
Local lab
Local lab
SST
5mL
5
—
—
—
—
5
—
—
5
—
—
—
5
5
—
25
Immunogenicity assays
Cellular assays
Tfh/pTfh phenotyping
CSR
HVTN Labs
ACD
8.5mL
—
25.5
—
—
25.5
—
—
25.5
—
25.5
—
25.5
—
—
25.5
153
Ag-specific B-cell phenotyping
CSR
HVTN Labs
ACD
8.5mL
—
17
—
—
—
34
—
—
z
34
—
—
34
34
17
170
Ag-specific Plasmablast phenotyping
CSR
HVTN Labs
ACD
8.5mL
—
—
—
—
17
—
—
34
—
—
—
34
—
—
34
119
B-cell repertoire analysis
CSR
HVTN Labs
ACD
8.5mL
—
34
—
—
—
—
—
—
z
—
—
—
34
34
34
136
ICS
CSR
HVTN Labs
ACD
8.5mL
—
—
—
—
—
—
—
—
z
—
—
—
34
34
34
102
Humoral assays
Binding Ab assay
CSR
HVTN Labs
SST
8.5mL
—
8.5
—
—
—
—
—
—
8.5
—
—
—
8.5
8.5
8.5
43
Neutralizing Ab assay
CSR
HVTN Labs
SST
8.5mL
—
8.5
—
—
—
—
—
—
8.5
—
—
—
8.5
8.5
8.5
43
Fc-mediated Ab functions 9
CSR
HVTN Labs
SST
8.5mL
—
y
—
—
—
—
—
—
y
—
—
—
y
y
y
Innate immunity and inflammation assays
Phenotyping
CSR
HVTN Labs
ACD
8.5mL
—
8.5
8.5
8.5
8.5
—
8.5
—
—
—
8.5
—
—
—
—
51
RNA gene expression
CSR
HVTN Labs
Tempus
3mL
—
3
3
3
3
—
3
—
3
—
3
—
3
—
—
24
Serum cytokines/chemokines
CSR
HVTN Labs
SST
5mL
—
5
5
5
5
—
5
—
—
—
5
—
—
—
—
30
STORAGE
PBMC 
CSR
—
ACD
8.5mL
—
34
—
—
17
68
—
34
z
—
—
68
153
102
42.5
519
Serum17
CSR
—
SST
8.5mL
—
25.5
8.5
8.5
8.5
25.5
—
—
17
—
—
—
25.5
17
17
153
Visit total
20
170
25
25
85
138
17
94
57
60
27
128
311
258
241
1652
56-Day total10
 
20
190
215
240
324
462
478
332
305
227
27
154
465
258
241
URINE COLLECTION
Urine dipstick6
Local lab
Local lab
X
—
—
—
—
X
—
—
—
—
—
—
X
—
—
Pregnancy test7
Local lab
Local lab
X
X
—
—
—
—
X
—
X12
X12
X
—
X12
X
X12
Chlamydia/Gonorrhea14
Local lab
Local lab
—
X
—
—
—
—
—
—
—
—
—
—
X
—
—
RECTAL SWAB COLLECTION
Chlamydia/Gonorrhea14
Local lab
Local lab
—
X
—
—
—
—
—
—
—
—
—
—
X
—
—
CERVICAL/VAGINAL SWAB COLLECTION
Chlamydia/Gonorrhea14
Local lab
Local lab
—
X
—
—
—
—
—
—
—
—
—
—
X
—
—
Trichomonas vaginalis 15
Local lab
Local lab
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
Bacterial vaginosis 16
Local lab
Local lab
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
Yeast16
Local lab
Local lab
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
OTHER COLLECTIONS (OPTIONAL)
Lymph node FNA
CSR
HVTN Labs
—
—
—
—
—
—
—
—
—
X
—
—
—
—
—
Bone marrow aspirate
CSR
HVTN Labs
—
—
—
—
—
—
—
—
—
—
—
—
—
—
X
Leukapheresis
CSR
HVTN Labs
—
—
—
—
—
—
—
—
X
—
—
—
—
—
—
MUCOSAL SECRETION COLLECTION (OPTIONAL)
Cervicovaginal secretions
CSR
HVTN Labs 
—
X
—
—
—
—
—
—
—
—
—
—
X
—
—
Rectal secretions
CSR
HVTN Labs
—
X
—
—
—
—
—
—
—
—
—
—
X
—
—
MUCOSAL BIOPSY COLLECTION (OPTIONAL)
Vaginal biopsies
CSR
HVTN Labs
—
5
—
—
—
—
—
—
—
—
—
—
5
—
10
Colorectal biopsies
CSR
HVTN Labs
—
5
—
—
—
—
—
—
—
—
—
—
5
—
10
Screening 
visit4
Total Biopsies
Ship to1
Assay 
location2
Tube type3
(vol. 
capacity)

HVTN 137 Version 5.0 / September 26, 2022 
HVTN137_v5.0_Final_26Sep22 / Page 257 of 281 
1 CSR = Central Specimen Repository; UW-VSL = University of Washington Virology Specialty Laboratory (Seattle, Washington, USA). 
2 HVTN Laboratories include: Fred Hutchinson Cancer Research Center (Seattle, Washington, USA); Duke University Medical Center (Durham, North Carolina, USA). 
3 Local labs may assign appropriate alternative tube types for locally performed tests. 
4 Screening may occur over the course of several contacts/visits up to and including day 0 prior to vaccination. 
5 Chemistry panels are defined in Section 9.2 (pre-enrollment procedures) and Section 9.4 (follow-up visits). 
6 And microscopy if needed. 
7 For participants assigned female sex at birth. Pregnancy test may be performed on blood specimens. Persons who are NOT of reproductive potential due to having undergone total 
hysterectomy or bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing. 
8 At an early termination visit for a withdrawn or terminated participant who is not HIV-infected (see Section 9.12), blood should be drawn for HIV diagnostic testing, as shown for visit 16 
above. If a participant has a confirmed diagnosis of HIV infection, do not collect blood for HIV diagnostic testing (see Section 9.14). 
9 Fc-mediated Ab functions may include FcR binding assay, ADCC, ADNP ADCP, and complement assay. 
10 The 56-day total blood volume does not include up to 16.5 mL blood collected for a reaction (see Section 9.10.1); however, the 56-day limit is not exceeded at any visit by this possible 
collection. 
11 Visit 10 will only apply to participants who are providing lymph node FNA collections. 
12 Pregnancy testing at indicated visit is only required of participants who were assigned female sex at birth and are providing optional procedure samples (leukapheresis, lymph node FNA, 
bone marrow aspirate, and rectal or vaginal mucosal secretion or biopsy). See Section 9.5 for the timing of the pregnancy test in order to meet eligibility requirements for the optional 
procedures. 
13 Specimens indicated for Day 0 may be obtained within the 14 days prior to vaccination, except for a pregnancy test which must be performed on urine or blood specimens within 24 hours 
of vaccination with negative results received prior to vaccination. 
14 Chlamydia/gonorrhea testing will only be performed for participants providing biopsy samples. In males, chlamydia/gonorrhea testing will be done on both rectal swabs and urine. In 
females, chlamydia/gonorrhea testing will be done on rectal swabs and on urine or vaginal swabs. 
15 Trichomonas testing will be done with cervical/vaginal swabs or urine and will only be performed when clinically indicated for participants who agree to provide cervicovaginal secretion 
or vaginal biopsy samples. 
16 Cervical/vaginal swabs for yeast and bacterial vaginosis testing will only be performed when clinically indicated for participants who agree to provide cervicovaginal secretion or vaginal 
biopsy samples 
17 Antibody avidity, peptide microarray, metabolomic profiles, and proteomics assays may be done with serum collected for storage. 
y = SST blood collected for the Binding Ab and Neutralizing Ab assays will also cover specimen needs for the Fc-mediated Ab function assays; no separate blood draw is needed.  
z = Leukapheresis samples collected will cover specimen needs for the Ag-specific B-cell phenotyping, B-cell repertoire analysis and ICS assays; no separate blood draw is needed. 

HVTN 137 Version 5.0 / September 26, 2022 
HVTN137_v5.0_Final_26Sep22 / Page 258 of 281 
Appendix M 
Laboratory procedures for Part B with leukapheresis (no lymph node FNA) 
 
 
Grayed out visits are not applicable to this subgroup. 
1 CSR = Central Specimen Repository; UW-VSL = University of Washington Virology Specialty Laboratory (Seattle, Washington, USA). 
2 HVTN Laboratories include: Fred Hutchinson Cancer Research Center (Seattle, Washington, USA); Duke University Medical Center (Durham, North Carolina, USA). 
3 Local labs may assign appropriate alternative tube types for locally performed tests. 
4 Screening may occur over the course of several contacts/visits up to and including day 0 prior to vaccination. 
5 Chemistry panels are defined in Section 9.2 (pre-enrollment procedures) and Section 9.4 (follow-up visits). 
Visit:
1
212
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Day:
D0
D1
D3
D7
D14
D56
D63
D70
D77
D168
D175
D182
D224
D364
D546
Week:
W0
W1
W2
W8
W9
W10
W11
W24
W25
W26
W32
W52
W78
Month:
M0
M0.25
M0.5
M2
M2.25
M2.5
M2.75
M6
M6.25
M6.5
M8
M12
M18
VAC1
VAC2
VAC3
Procedure
 
Total
BLOOD COLLECTION
Screening/Diagnostic
HIV screening test
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HBsAg/ anti-HCV
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HIV diagnostics 8
UW-VSL
UW-VSL
EDTA
10mL
—
—
—
—
—
—
—
—
10
10
—
—
10
20
50
Safety labs
CBC/ Diff/ Platelets
Local lab
Local lab
EDTA
5mL
5
—
—
—
—
5
—
—
5
—
—
5
5
—
25
Chemistry panel5
Local lab
Local lab
SST
5mL
5
—
—
—
—
5
—
—
5
—
—
5
5
—
25
Immunogenicity assays
Cellular assays
Tfh/pTfh phenotyping
CSR
HVTN Labs
ACD
8.5mL
—
25.5
—
—
25.5
—
—
25.5
—
—
25.5
—
—
25.5
128
Ag-specific B-cell phenotyping
CSR
HVTN Labs
ACD
8.5mL
—
17
—
—
—
34
—
—
z
—
—
34
34
17
136
Ag-specific Plasmablast phenotyping
CSR
HVTN Labs
ACD
8.5mL
—
—
—
—
17
—
—
34
—
—
34
—
—
34
119
B-cell repertoire analysis
CSR
HVTN Labs
ACD
8.5mL
—
34
—
—
—
—
—
—
z
—
—
34
34
34
136
ICS
CSR
HVTN Labs
ACD
8.5mL
—
—
—
—
—
—
—
—
z
—
—
34
34
34
102
Humoral assays
Binding Ab assay
CSR
HVTN Labs
SST
8.5mL
—
8.5
—
—
—
—
—
—
8.5
—
—
8.5
8.5
8.5
43
Neutralizing Ab assay
CSR
HVTN Labs
SST
8.5mL
—
8.5
—
—
—
—
—
—
8.5
—
—
8.5
8.5
8.5
43
Fc-mediated Ab functions 9
CSR
HVTN Labs
SST
8.5mL
—
y
—
—
—
—
—
—
y
—
—
y
y
y
Innate immunity and inflammation assays
Phenotyping
CSR
HVTN Labs
ACD
8.5mL
—
8.5
8.5
8.5
8.5
—
8.5
—
—
8.5
—
—
—
—
51
RNA gene expression
CSR
HVTN Labs
Tempus
3mL
—
3
3
3
3
—
3
—
3
3
—
3
—
—
24
Serum cytokines/chemokines
CSR
HVTN Labs
SST
5mL
—
5
5
5
5
—
5
—
—
5
—
—
—
—
30
STORAGE
PBMC 
CSR
—
ACD
8.5mL
—
34
—
—
17
68
—
34
z
—
68
153
102
42.5
519
Serum16
CSR
—
SST
8.5mL
—
25.5
8.5
8.5
8.5
25.5
—
—
17
—
—
25.5
17
17
153
Visit total
20
170
25
25
85
138
17
94
57
27
128
311
258
241
1592
56-Day total10
 
20
190
215
240
324
462
478
332
305
27
154
465
258
241
URINE COLLECTION
Urine dipstick6
Local lab
Local lab
X
—
—
—
—
X
—
—
—
—
—
X
—
—
Pregnancy test7
Local lab
Local lab
X
X
—
—
—
—
X
—
X11
X
—
X11
X
X11
Chlamydia/Gonorrhea13
Local lab
Local lab
—
X
—
—
—
—
—
—
—
—
—
X
—
—
RECTAL SWAB COLLECTION
Chlamydia/Gonorrhea13
Local lab
Local lab
—
X
—
—
—
—
—
—
—
—
—
X
—
—
CERVICAL/VAGINAL SWAB COLLECTION
Chlamydia/Gonorrhea13
Local lab
Local lab
—
X
—
—
—
—
—
—
—
—
—
X
—
—
Trichomonas vaginalis 14
Local lab
Local lab
—
—
—
—
—
—
—
—
—
—
—
—
—
—
Bacterial vaginosis 15
Local lab
Local lab
—
—
—
—
—
—
—
—
—
—
—
—
—
—
Yeast15
Local lab
Local lab
—
—
—
—
—
—
—
—
—
—
—
—
—
—
OTHER COLLECTIONS (OPTIONAL)
Bone marrow aspirate
CSR
HVTN Labs
—
—
—
—
—
—
—
—
—
—
—
—
—
X
Leukapheresis
CSR
HVTN Labs
—
—
—
—
—
—
—
—
X
—
—
—
—
—
MUCOSAL SECRETION COLLECTION (OPTIONAL)
Cervicovaginal secretions
CSR
HVTN Labs 
—
X
—
—
—
—
—
—
—
—
—
X
—
—
Rectal secretions
CSR
HVTN Labs
—
X
—
—
—
—
—
—
—
—
—
X
—
—
MUCOSAL BIOPSY COLLECTION (OPTIONAL)
Vaginal biopsies
CSR
HVTN Labs
—
5
—
—
—
—
—
—
—
—
—
5
—
10
Colorectal biopsies
CSR
HVTN Labs
—
5
—
—
—
—
—
—
—
—
—
5
—
10
Screening 
visit4
Total Biopsies
Ship to1
Assay 
location2
Tube type3
(vol. 
capacity)

HVTN 137 Version 5.0 / September 26, 2022 
HVTN137_v5.0_Final_26Sep22 / Page 259 of 281 
6 And microscopy if needed. 
7 For participants assigned female sex at birth. Pregnancy test may be performed on blood specimens. Persons who are NOT of reproductive potential due to having undergone total 
hysterectomy or bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing 
8 At an early termination visit for a withdrawn or terminated participant who is not HIV-infected (see Section 9.12), blood should be drawn for HIV diagnostic testing, as shown for visit 16 
above. If a participant has a confirmed diagnosis of HIV infection, do not collect blood for HIV diagnostic testing (see Section 9.14). 
9 Fc-mediated Ab functions may include FcR binding assay, ADCC, ADNP ADCP, and complement assay. 
10 The 56-day total blood volume does not include up to 16.5 mL blood collected for a reaction (see Section 9.10.1); however, the 56-day limit is not exceeded at any visit by this possible 
collection. 
11 Pregnancy testing at indicated visit is only required of participants who were assigned female sex at birth and are providing optional procedure samples (leukapheresis, bone marrow 
aspirate, and rectal or vaginal mucosal secretion or biopsy). See Section 9.5 for the timing of the pregnancy test in order to meet eligibility requirements for the optional procedures.  
12 Specimens indicated for Day 0 may be obtained within the 14 days prior to vaccination, except for a pregnancy test which must be performed on urine or blood specimens within 24 hours 
of vaccination with negative results received prior to vaccination. 
13 Chlamydia/gonorrhea testing will only be performed for participants providing biopsy samples. In males, chlamydia/gonorrhea testing will be done on both rectal swabs and urine. In 
females, chlamydia/gonorrhea testing will be done on rectal swabs and on urine or vaginal swabs. 
14 Trichomonas testing will be done with cervical/vaginal swabs or urine and will only be performed when clinically indicated for participants who agree to provide cervicovaginal secretion 
or vaginal biopsy samples. 
15 Cervical/vaginal swabs for yeast and bacterial vaginosis testing will only be performed when clinically indicated for participants who agree to provide cervicovaginal secretion or vaginal 
biopsy samples. 
16 Antibody avidity, peptide microarray, metabolomic profiles, and proteomics assays may be done with serum collected for storage. 
y = SST blood collected for the Binding Ab and Neutralizing Ab assays will also cover specimen needs for the Fc-mediated Ab function assays; no separate blood draw is needed.  
z = Leukapheresis samples collected will cover specimen needs for the Ag-specific B-cell phenotyping, B-cell repertoire analysis and ICS assays; no separate blood draw is needed. 

HVTN 137 Version 5.0 / September 26, 2022 
HVTN137_v5.0_Final_26Sep22 / Page 260 of 281 
Appendix N 
Laboratory procedures for Part B with lymph node FNA (no leukapheresis) 
 
Visit:
1
213
3
4
5
6
7
8
9
1011
11
12
13
14
15
16
Day:
D0
D1
D3
D7
D14
D56
D63
D70
D77
D168
D175
D182
D224
D364
D546
Week:
W0
W1
W2
W8
W9
W10
W11
W24
W25
W26
W32
W52
W78
Month:
M0
M0.25
M0.5
M2
M2.25
M2.5
M2.75
M6
M6.25
M6.5
M8
M12
M18
VAC1
VAC2
VAC3
Procedure
 
Total
BLOOD COLLECTION
Screening/Diagnostic
HIV screening test
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HBsAg/ anti-HCV
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HIV diagnostics 8
UW-VSL
UW-VSL
EDTA
10mL
—
—
—
—
—
—
—
—
10
—
10
—
—
10
20
50
Safety labs
CBC/ Diff/ Platelets
Local lab
Local lab
EDTA
5mL
5
—
—
—
—
5
—
—
5
—
—
—
5
5
—
25
Chemistry panel5
Local lab
Local lab
SST
5mL
5
—
—
—
—
5
—
—
5
—
—
—
5
5
—
25
Immunogenicity assays
Cellular assays
Tfh/pTfh phenotyping
CSR
HVTN Labs
ACD
8.5mL
—
25.5
—
—
25.5
—
—
25.5
—
25.5
—
25.5
—
—
25.5
153
Ag-specific B-cell phenotyping
CSR
HVTN Labs
ACD
8.5mL
—
17
—
—
—
34
—
—
34
34
—
—
34
34
17
204
Ag-specific Plasmablast phenotyping
CSR
HVTN Labs
ACD
8.5mL
—
—
—
—
17
—
—
34
—
—
—
34
—
—
34
119
B-cell repertoire analysis
CSR
HVTN Labs
ACD
8.5mL
—
34
—
—
—
—
—
—
34
—
—
—
34
34
34
170
ICS
CSR
HVTN Labs
ACD
8.5mL
—
—
—
—
—
—
—
—
34
—
—
—
34
34
34
136
Humoral assays
Binding Ab assay
CSR
HVTN Labs
SST
8.5mL
—
8.5
—
—
—
—
—
—
8.5
—
—
—
8.5
8.5
8.5
43
Neutralizing Ab assay
CSR
HVTN Labs
SST
8.5mL
—
8.5
—
—
—
—
—
—
8.5
—
—
—
8.5
8.5
8.5
43
Fc-mediated Ab functions 9
CSR
HVTN Labs
SST
8.5mL
—
y
—
—
—
—
—
—
y
—
—
—
y
y
y
Innate immunity and inflammation assays
Phenotyping
CSR
HVTN Labs
ACD
8.5mL
—
8.5
8.5
8.5
8.5
—
8.5
—
—
—
8.5
—
—
—
—
51
RNA gene expression
CSR
HVTN Labs
Tempus
3mL
—
3
3
3
3
—
3
—
3
—
3
—
3
—
—
24
Serum cytokines/chemokines
CSR
HVTN Labs
SST
5mL
—
5
5
5
5
—
5
—
—
—
5
—
—
—
—
30
STORAGE
PBMC 
CSR
—
ACD
8.5mL
—
34
—
—
17
68
—
34
68
—
—
68
153
102
42.5
587
Serum17
CSR
—
SST
8.5mL
—
25.5
8.5
8.5
8.5
25.5
—
—
17
—
—
—
25.5
17
17
153
Visit total
20
170
25
25
85
138
17
94
227
60
27
128
311
258
241
1822
56-Day total10
 
20
190
215
240
324
462
478
332
475
397
27
154
465
258
241
URINE COLLECTION
Urine dipstick6
Local lab
Local lab
X
—
—
—
—
X
—
—
—
—
—
—
X
—
—
Pregnancy test7
Local lab
Local lab
X
X
—
—
—
—
X
—
—
X12
X
—
X12
X
X12
Chlamydia/Gonorrhea14
Local lab
Local lab
—
X
—
—
—
—
—
—
—
—
—
—
X
—
—
RECTAL SWAB COLLECTION
Chlamydia/Gonorrhea14
Local lab
Local lab
—
X
—
—
—
—
—
—
—
—
—
—
X
—
—
CERVICAL/VAGINAL SWAB COLLECTION
Chlamydia/Gonorrhea14
Local lab
Local lab
—
X
—
—
—
—
—
—
—
—
—
—
X
—
—
Trichomonas vaginalis 15
Local lab
Local lab
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
Bacterial vaginosis 16
Local lab
Local lab
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
Yeast16
Local lab
Local lab
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
OTHER COLLECTIONS (OPTIONAL)
Lymph node FNA
CSR
HVTN Labs
—
—
—
—
—
—
—
—
—
X
—
—
—
—
—
Bone marrow aspirate
CSR
HVTN Labs
—
—
—
—
—
—
—
—
—
—
—
—
—
—
X
MUCOSAL SECRETION COLLECTION (OPTIONAL)
Cervicovaginal secretions
CSR
HVTN Labs 
—
X
—
—
—
—
—
—
—
—
—
—
X
—
—
Rectal secretions
CSR
HVTN Labs
—
X
—
—
—
—
—
—
—
—
—
—
X
—
—
MUCOSAL BIOPSY COLLECTION (OPTIONAL)
Vaginal biopsies
CSR
HVTN Labs
—
5
—
—
—
—
—
—
—
—
—
—
5
—
10
Colorectal biopsies
CSR
HVTN Labs
—
5
—
—
—
—
—
—
—
—
—
—
5
—
10
Ship to1
Screening 
visit4
Total Biopsies
(vol. 
capacity)
Tube type3
Assay 
location2
 
Grayed out visits are not applicable to this subgroup. 
1 CSR = Central Specimen Repository; UW-VSL = University of Washington Virology Specialty Laboratory (Seattle, Washington, USA). 
2 HVTN Laboratories include: Fred Hutchinson Cancer Research Center (Seattle, Washington, USA); Duke University Medical Center (Durham, North Carolina, USA). 
3 Local labs may assign appropriate alternative tube types for locally performed tests. 
4 Screening may occur over the course of several contacts/visits up to and including day 0 prior to vaccination. 
5 Chemistry panels are defined in Section 9.2 (pre-enrollment procedures) and Section 9.4 (follow-up visits). 

HVTN 137 Version 5.0 / September 26, 2022 
HVTN137_v5.0_Final_26Sep22 / Page 261 of 281 
6 And microscopy if needed. 
7 For participants assigned female sex at birth. Pregnancy test may be performed on blood specimens. Persons who are NOT of reproductive potential due to having undergone total 
hysterectomy or bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing 
8 At an early termination visit for a withdrawn or terminated participant who is not HIV-infected (see Section 9.12), blood should be drawn for HIV diagnostic testing, as shown for visit 16 
above. If a participant has a confirmed diagnosis of HIV infection, do not collect blood for HIV diagnostic testing (see Section 9.14). 
9 Fc-mediated Ab functions may include FcR binding assay, ADCC, ADNP ADCP, and complement assay. 
10 The 56-day total blood volume does not include up to 16.5 mL blood collected for a reaction (see Section 9.10.1); however, the 56-day limit is not exceeded at any visit by this possible 
collection. 
11 Visit 10 will only apply to participants who are providing lymph node FNA collections. 
12 Pregnancy testing at indicated visit is only required of participants who were assigned female sex at birth and are providing optional procedure samples (lymph node FNA, bone marrow 
aspirate, and rectal or vaginal mucosal secretion or biopsy). See Section 9.5 for the timing of the pregnancy test in order to meet eligibility requirements for the optional procedures. 
13 Specimens indicated for Day 0 may be obtained within the 14 days prior to vaccination, except for a pregnancy test which must be performed on urine or blood specimens within 24 hours 
of vaccination with negative results received prior to vaccination. 
14 Chlamydia/gonorrhea testing will only be performed for participants providing biopsy samples. In males, chlamydia/gonorrhea testing will be done on both rectal swabs and urine. In 
females, chlamydia/gonorrhea testing will be done on rectal swabs and on urine or vaginal swabs. 
15 Trichomonas testing will be done with cervical/vaginal swabs or urine and will only be performed when clinically indicated for participants who agree to provide cervicovaginal secretion 
or vaginal biopsy samples. 
16 Cervical/vaginal swabs for yeast and bacterial vaginosis testing will only be performed when clinically indicated for participants who agree to provide cervicovaginal secretion or vaginal 
biopsy samples. 
17 Antibody avidity, peptide microarray, metabolomic profiles, and proteomics assays may be done with serum collected for storage. 
y = SST blood collected for the Binding Ab and Neutralizing Ab assays will also cover specimen needs for the Fc-mediated Ab function assays; no separate blood draw is needed. 

HVTN 137 Version 5.0 / September 26, 2022 
HVTN137_v5.0_Final_26Sep22 / Page 262 of 281 
Appendix O 
Laboratory procedures for Part B (no leukapheresis and no lymph node FNA) 
 
Visit:
1
212
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Day:
D0
D1
D3
D7
D14
D56
D63
D70
D77
D168
D175
D182
D224
D364
D546
Week:
W0
W1
W2
W8
W9
W10
W11
W24
W25
W26
W32
W52
W78
Month:
M0
M0.25
M0.5
M2
M2.25
M2.5
M2.75
M6
M6.25
M6.5
M8
M12
M18
VAC1
VAC2
VAC3
Procedure
 
Total
BLOOD COLLECTION
Screening/Diagnostic
HIV screening test
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HBsAg/ anti-HCV
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HIV diagnostics 8
UW-VSL
UW-VSL
EDTA
10mL
—
—
—
—
—
—
—
—
10
10
—
—
10
20
50
Safety labs
CBC/ Diff/ Platelets
Local lab
Local lab
EDTA
5mL
5
—
—
—
—
5
—
—
5
—
—
5
5
—
25
Chemistry panel5
Local lab
Local lab
SST
5mL
5
—
—
—
—
5
—
—
5
—
—
5
5
—
25
Immunogenicity assays
Cellular assays
Tfh/pTfh phenotyping
CSR
HVTN Labs
ACD
8.5mL
—
25.5
—
—
25.5
—
—
25.5
—
—
25.5
—
—
25.5
128
Ag-specific B-cell phenotyping
CSR
HVTN Labs
ACD
8.5mL
—
17
—
—
—
34
—
—
34
—
—
34
34
17
170
Ag-specific Plasmablast phenotyping
CSR
HVTN Labs
ACD
8.5mL
—
—
—
—
17
—
—
34
—
—
34
—
—
34
119
B-cell repertoire analysis
CSR
HVTN Labs
ACD
8.5mL
—
34
—
—
—
—
—
—
34
—
—
34
34
34
170
ICS
CSR
HVTN Labs
ACD
8.5mL
—
—
—
—
—
—
—
—
34
—
—
34
34
34
136
Humoral assays
Binding Ab assay
CSR
HVTN Labs
SST
8.5mL
—
8.5
—
—
—
—
—
—
8.5
—
—
8.5
8.5
8.5
43
Neutralizing Ab assay
CSR
HVTN Labs
SST
8.5mL
—
8.5
—
—
—
—
—
—
8.5
—
—
8.5
8.5
8.5
43
Fc-mediated Ab functions 9
CSR
HVTN Labs
SST
8.5mL
—
y
—
—
—
—
—
—
y
—
—
y
y
y
Innate immunity and inflammation assays
 
Phenotyping
CSR
HVTN Labs
ACD
8.5mL
—
8.5
8.5
8.5
8.5
—
8.5
—
—
8.5
—
—
—
—
51
RNA gene expression
CSR
HVTN Labs
Tempus
3mL
—
3
3
3
3
—
3
—
3
3
—
3
—
—
24
Serum cytokines/chemokines
CSR
HVTN Labs
SST
5mL
—
5
5
5
5
—
5
—
—
5
—
—
—
—
30
STORAGE
PBMC 
CSR
—
ACD
8.5mL
—
34
—
—
17
68
—
34
68
—
68
153
102
42.5
587
Serum16
CSR
—
SST
8.5mL
—
25.5
8.5
8.5
8.5
25.5
—
—
17
—
—
25.5
17
17
153
Visit total
20
170
25
25
85
138
17
94
227
27
128
311
258
241
1762
56-Day total10
 
20
190
215
240
324
462
478
332
475
27
154
465
258
241
URINE COLLECTION
Urine dipstick6
Local lab
Local lab
X
—
—
—
—
X
—
—
—
—
—
X
—
—
Pregnancy test7
Local lab
Local lab
X
X
—
—
—
—
X
—
—
X
—
X11
X
X11
Chlamydia/Gonorrhea13
Local lab
Local lab
—
X
—
—
—
—
—
—
—
—
—
X
—
—
RECTAL SWAB COLLECTION
Chlamydia/Gonorrhea13
Local lab
Local lab
—
X
—
—
—
—
—
—
—
—
—
X
—
—
CERVICAL/VAGINAL SWAB COLLECTION
Chlamydia/Gonorrhea13
Local lab
Local lab
—
X
—
—
—
—
—
—
—
—
—
X
—
—
Trichomonas vaginalis 14
Local lab
Local lab
—
—
—
—
—
—
—
—
—
—
—
—
—
—
Bacterial vaginosis 15
Local lab
Local lab
—
—
—
—
—
—
—
—
—
—
—
—
—
—
Yeast15
Local lab
Local lab
—
—
—
—
—
—
—
—
—
—
—
—
—
—
OTHER COLLECTIONS (OPTIONAL)
Bone marrow aspirate
CSR
HVTN Labs
—
—
—
—
—
—
—
—
—
—
—
—
—
X
MUCOSAL SECRETION COLLECTION (OPTIONAL)
Cervicovaginal secretions
CSR
HVTN Labs 
—
X
—
—
—
—
—
—
—
—
—
X
—
—
Rectal secretions
CSR
HVTN Labs
—
X
—
—
—
—
—
—
—
—
—
X
—
—
MUCOSAL BIOPSY COLLECTION (OPTIONAL)
Vaginal biopsies
CSR
HVTN Labs
—
5
—
—
—
—
—
—
—
—
—
5
—
10
Colorectal biopsies
CSR
HVTN Labs
—
5
—
—
—
—
—
—
—
—
—
5
—
10
Ship to1
Screening 
visit4
Total Biopsies
(vol. 
capacity)
Tube type3
Assay 
location2
 
Grayed out visits are not applicable to this subgroup. 
1 CSR = Central Specimen Repository; UW-VSL = University of Washington Virology Specialty Laboratory (Seattle, Washington, USA). 
2 HVTN Laboratories include: Fred Hutchinson Cancer Research Center (Seattle, Washington, USA); Duke University Medical Center (Durham, North Carolina, USA). 
3 Local labs may assign appropriate alternative tube types for locally performed tests. 
4 Screening may occur over the course of several contacts/visits up to and including day 0 prior to vaccination. 

HVTN 137 Version 5.0 / September 26, 2022 
HVTN137_v5.0_Final_26Sep22 / Page 263 of 281 
5 Chemistry panels are defined in Section 9.2 (pre-enrollment procedures) and Section 9.4 (follow-up visits). 
6 And microscopy if needed. 
7 For participants assigned female sex at birth. Pregnancy test may be performed on blood specimens. Persons who are NOT of reproductive potential due to having undergone total 
hysterectomy or bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing. 
8 At an early termination visit for a withdrawn or terminated participant who is not HIV-infected (see Section 9.12), blood should be drawn for HIV diagnostic testing, as shown for visit 16 
above. If a participant has a confirmed diagnosis of HIV infection, do not collect blood for HIV diagnostic testing (see Section 9.14). 
9 Fc-mediated Ab functions may include FcR binding assay, ADCC, ADNP ADCP, and complement assay. 
10 The 56-day total blood volume does not include up to 16.5 mL blood collected for a reaction (see Section 9.10.1); however, the 56-day limit is not exceeded at any visit by this possible 
collection. 
11 Pregnancy testing at indicated visit is only required of participants who were assigned female sex at birth and are providing optional procedure samples (bone marrow aspirate and rectal 
or vaginal mucosal secretion or biopsy). See Section 9.5 for the timing of the pregnancy test in order to meet eligibility requirements for the optional procedures. 
12 Specimens indicated for Day 0 may be obtained within the 14 days prior to vaccination, except for a pregnancy test which must be performed on urine or blood specimens within 24 hours 
of vaccination with negative results received prior to vaccination. 
13 Chlamydia/gonorrhea testing will only be performed for participants providing biopsy samples. In males, chlamydia/gonorrhea testing will be done on both rectal swabs and urine. In 
females, chlamydia/gonorrhea testing will be done on rectal swabs and on urine or vaginal swabs. 
14 Trichomonas testing will be done with cervical/vaginal swabs or urine and will only be performed when clinically indicated for participants who agree to provide cervicovaginal secretion 
or vaginal biopsy samples. 
15 Cervical/vaginal swabs for yeast and bacterial vaginosis testing will only be performed when clinically indicated for participants who agree to provide cervicovaginal secretion or vaginal 
biopsy samples. 
16 Antibody avidity, peptide microarray, metabolomic profiles, and proteomics assays may be done with serum collected for storage. 
y = SST blood collected for the Binding Ab and Neutralizing Ab assays will also cover specimen needs for the Fc-mediated Ab function assays; no separate blood draw is needed. 

HVTN 137 Version 5.0 / September 26, 2022 
HVTN137_v5.0_Final_26Sep22 / Page 264 of 281 
Appendix P 
Laboratory procedures for Part B (no optional procedures) and Part C  
 
Visit:
1
211
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Day:
D0
D1
D3
D7
D14
D56
D63
D70
D77
D168
D175
D182
D224
D364
D546
Week:
W0
W1
W2
W8
W9
W10
W11
W24
W25
W26
W32
W52
W78
Month:
M0
M0.25
M0.5
M2
M2.25
M2.5
M2.75
M6
M6.25
M6.5
M8
M12
M18
VAC1
VAC2
VAC3
Procedure
 
Total
BLOOD COLLECTION
Screening/Diagnostic
HIV screening test
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HBsAg/ anti-HCV
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HIV diagnostics8
UW-VSL
UW-VSL
EDTA
10mL
—
—
—
—
—
—
—
—
10
10
—
—
10
20
50
Safety labs
CBC/ Diff/ Platelets
Local lab
Local lab
EDTA
5mL
5
—
—
—
—
5
—
—
5
—
—
5
5
—
25
Chemistry panel5
Local lab
Local lab
SST
5mL
5
—
—
—
—
5
—
—
5
—
—
5
5
—
25
Immunogenicity assays
Cellular assays
Tfh/pTfh phenotyping
CSR
HVTN Labs
ACD
8.5mL
—
25.5
—
—
25.5
—
—
25.5
—
—
25.5
—
—
25.5
128
Ag-specific B-cell phenotyping
CSR
HVTN Labs
ACD
8.5mL
—
17
—
—
—
34
—
—
34
—
—
34
34
17
170
Ag-specific Plasmablast phenotyping
CSR
HVTN Labs
ACD
8.5mL
—
—
—
—
17
—
—
34
—
—
34
—
—
34
119
B-cell repertoire analysis
CSR
HVTN Labs
ACD
8.5mL
—
34
—
—
—
—
—
—
34
—
—
34
34
34
170
ICS
CSR
HVTN Labs
ACD
8.5mL
—
—
—
—
—
—
—
—
34
—
—
34
34
34
136
Humoral assays
Binding Ab assay
CSR
HVTN Labs
SST
8.5mL
—
8.5
—
—
—
—
—
—
8.5
—
—
8.5
8.5
8.5
43
Neutralizing Ab assay
CSR
HVTN Labs
SST
8.5mL
—
8.5
—
—
—
—
—
—
8.5
—
—
8.5
8.5
8.5
43
Fc-mediated Ab functions 9
CSR
HVTN Labs
SST
8.5mL
—
y
—
—
—
—
—
—
y
—
—
y
y
y
Innate immunity and inflammation assays
 
Phenotyping
CSR
HVTN Labs
ACD
8.5mL
—
8.5
8.5
8.5
8.5
—
8.5
—
—
8.5
—
—
—
—
51
RNA gene expression
CSR
HVTN Labs
Tempus
3mL
—
3
3
3
3
—
3
—
3
3
—
3
—
—
24
Serum cytokines/chemokines
CSR
HVTN Labs
SST
5mL
—
5
5
5
5
—
5
—
—
5
—
—
—
—
30
STORAGE
PBMC 
CSR
—
ACD
8.5mL
—
34
—
—
17
68
—
34
68
—
68
153
102
42.5
587
Serum12
CSR
—
SST
8.5mL
—
25.5
8.5
8.5
8.5
25.5
—
—
17
—
—
25.5
17
17
153
Visit total
20
170
25
25
85
138
17
94
227
27
128
311
258
241
1762
56-Day total10
 
20
190
215
240
324
462
478
332
475
27
154
465
258
241
URINE COLLECTION
Urine dipstick6
Local lab
Local lab
X
—
—
—
—
X
—
—
—
—
—
X
—
—
Pregnancy test7
Local lab
Local lab
X
X
—
—
—
—
X
—
—
X
—
—
X
—
Screening 
visit4
Ship to1
Assay 
location2
Tube type3
Tube size
(vol. 
 
Grayed out visits are not applicable to this subgroup. 
1 CSR = Central Specimen Repository; UW-VSL = University of Washington Virology Specialty Laboratory (Seattle, Washington, USA). 
2 HVTN Laboratories include: Fred Hutchinson Cancer Research Center (Seattle, Washington, USA); Duke University Medical Center (Durham, North Carolina, USA). 
3 Local labs may assign appropriate alternative tube types for locally performed tests. 
4 Screening may occur over the course of several contacts/visits up to and including day 0 prior to vaccination. 
5 Chemistry panels are defined in Section 9.2 (pre-enrollment procedures) and Section 9.4 (follow-up visits). 
6 And microscopy if needed. 
7 For participants assigned female sex at birth. Pregnancy test may be performed on blood specimens. Persons who are NOT of reproductive potential due to having undergone total 
hysterectomy or bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing 
8 At an early termination visit for a withdrawn or terminated participant who is not HIV-infected (see Section 9.12), blood should be drawn for HIV diagnostic testing, as shown for visit 16 
above. If a participant has a confirmed diagnosis of HIV infection, do not collect blood for HIV diagnostic testing (see Section 9.14). 
9 Fc-mediated Ab functions may include FcR binding assay, ADCC, ADNP ADCP, and complement assay. 
10 The 56-day total blood volume does not include up to 16.5 mL blood collected for a reaction (see Section 9.10.1); however, the 56-day limit is not exceeded at any visit by this possible 
collection. 
11 Specimens indicated for Day 0 may be obtained within the 14 days prior to vaccination, except for a pregnancy test which must be performed on urine or blood specimens within 24 hours 
of vaccination with negative results received prior to vaccination. 
12 Antibody avidity, peptide microarray, metabolomic profiles, and proteomics assays may be done with serum collected for storage. 
y = SST blood collected for the Binding Ab and Neutralizing Ab assays will also cover specimen needs for the Fc-mediated Ab function assays; no separate blood draw is needed. 

HVTN 137 Version 5.0 / September 26, 2022 
HVTN137_v5.0_Final_26Sep22 / Page 265 of 281 
Appendix Q 
Procedures at HVTN CRS for Part A 
Visit: 
011 
02 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
14 
AESI2 
Post 
Day: 
 
D0 
D1 
D3 
D7 
D14 
D56 
D63 
D70 
D77 
D168 
D175 
D182 
D224 
D425 
 
Week: 
 
W0 
 
 
W1 
W2 
W8 
W9 
W10 
W11 
W24 
W25 
W26 
W32 
W61 
 
Month: 
 
M0 
 
 
 
M0.5 
M2 
M2.25 
M2.5 
M2.75 
M6 
M6.25 
M6.5 
M8 
M14 
 
Procedure 
Scr. 
VAC1 
 
 
 
 
VAC2 
 
 
 
 
 
 
 
 
 
Study procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signed screening consent (if used) 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assessment of understanding 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol consent 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history  
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical exam 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
✓ 
 
 
Contraception status assessment3 
✓ 
✓ 
 
 
 
✓ 
✓ 
 
✓ 
 
 
 
 
✓ 
 
 
Behavioral risk assessment questionnaire4 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
✓ 
 
 
Risk reduction counseling5 
✓ 
✓ 
 
 
 
✓ 
✓ 
 
✓ 
 
 
 
 
✓ 
 
 
Confirm eligibility  
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Obtain demographics 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomize 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant medications 
✓ 
✓ 
 
 
 
✓ 
✓ 
 
✓ 
 
 
 
 
✓ 
 
 
HIV infection assessment6 
✓ 
 
 
 
 
 
 
 
✓ 
 
 
 
 
✓ 
 
 
Abbreviated physical exam 
 
✓ 
 
 
 
✓ 
✓ 
 
✓ 
 
 
 
 
 
 
 
Intercurrent illness/adverse experience 
 
✓ 
 
 
 
✓ 
✓ 
 
✓ 
 
 
 
 
✓ 
 
 
Social impact assessment 
 
✓ 
 
 
 
✓ 
✓ 
 
✓ 
 
 
 
 
✓ 
 
 
Social impact assessment questionnaire 
 
 
 
 
 
 
 
 
 
 
 
 
 
✓ 
 
 
Outside testing and belief questionnaire 
 
 
 
 
 
 
 
 
 
 
 
 
 
✓ 
 
 
AESI contact 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
✓ 
 
Specimen collection7 
✓ 
✓ 
 
 
 
✓ 
✓ 
 
✓ 
 
 
 
 
✓ 
 
 
Vaccination procedures8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vaccination9 
 
✓ 
 
 
 
 
✓ 
 
 
 
 
 
 
 
 
 
Reactogenicity assessments10 
 
✓ 
 
 
 
 
✓ 
 
 
 
 
 
 
 
 
 
Poststudy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unblind participant 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
✓ 
 
Grayed out visits are not applicable to Part A.  
1 Screening may occur over the course of several contacts/visits up to and including day 0 prior to vaccination. 
2 See section 9.6 (AESI health contact) 
3 Contraception status assessment is required only for participants assigned female sex at birth who are sexually active in a way that could cause pregnancy. Persons who are confirmed 
pregnant, pregnancy testing is not required, unless clinically indicated.  

HVTN 137 Version 5.0 / September 26, 2022 
HVTN137_v5.0_Final_26Sep22 / Page 266 of 281 
4 Not applicable to HIV-infected participants. Conduct before Risk Reduction Counseling if both occur at same visit. 
5 Includes brief risk screening and targeted risk reduction counseling, if indicated. Includes transmission risk reduction counseling for HIV-infected participants. Conduct after BRA 
questionnaire if both occur at same visit. 
6 Includes pretest steps and HIV testing. A subsequent follow-up contact is conducted to provide post-test steps and to report results to participant. If a participant has a confirmed diagnosis 
of HIV infection, do not perform HIV infection assessment. 
7 For specimen collection requirements, see Appendix J. For participants with a confirmed diagnosis of HIV infection, specimens listed under “Safety labs” in Appendix J, urinalysis, and 
urine pregnancy tests will be collected per the protocol schedule. 
8 Not applicable to HIV-infected participants. 
9 Blood draws required at vaccination visits must be performed prior to vaccination; however, it is not necessary to have results prior to vaccination, except for results of a urine or serum 
pregnancy test, if indicated. See Appendix J. 
10 Reactogenicity assessments performed daily for at least 7 days postvaccination (see Section 9.10). 
 
 

HVTN 137 Version 5.0 / September 26, 2022 
HVTN137_v5.0_Final_26Sep22 / Page 267 of 281 
Appendix R 
Procedures at HVTN CRS for Part A with Optional Second Boost 
 
Visit: 
011 
02 
03 
04 
05 
06 
07 
08 
09 
10 
1110 
12 
13 
14 
15 
16 
Post 
Day: 
 
D0 
D1 
D3 
D7 
D14 
D56 
D63 
D70 
D77 
D168 
D175 
D182 
D224 
D364 
D546 
 
Week: 
 
W0 
 
 
W1 
W2 
W8 
W9 
W10 
W11 
W24 
W25 
W26 
W32 
W52 
W78 
 
Month: 
 
M0 
 
 
 
M0.5 
M2 
M2.25 
M2.5 
M2.75 
M6 
M6.25 
M6.5 
M8 
M12 
M18 
 
Procedure 
Scr. 
VAC1 
 
 
 
 
VAC2 
 
 
 
BOOST 
 
 
 
 
 
 
Study procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signed screening consent (if used) 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assessment of understanding 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol consent 
✓ 
 
 
 
 
 
 
 
 
 
✓ 
 
 
 
 
 
 
Medical history  
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical exam 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
✓ 
 
Contraception status assessment2 
✓ 
✓ 
 
 
 
✓ 
✓ 
 
✓ 
 
✓ 
✓ 
✓ 
 
✓ 
✓ 
 
Behavioral risk assessment questionnaire3 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
✓ 
 
Risk reduction counseling4 
✓ 
✓ 
 
 
 
✓ 
✓ 
 
✓ 
 
✓ 
✓ 
✓ 
 
✓ 
✓ 
 
Confirm eligibility  
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Obtain demographics 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomize 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant medications 
✓ 
✓ 
 
 
 
✓ 
✓ 
 
✓ 
 
✓ 
✓ 
✓ 
 
✓ 
✓ 
 
HIV infection assessment5 
✓ 
 
 
 
 
 
 
 
✓ 
 
✓ 
 
 
 
✓ 
✓ 
 
Abbreviated physical exam 
 
✓ 
 
 
 
✓ 
✓ 
 
✓ 
 
✓ 
✓ 
✓ 
 
✓ 
 
 
Intercurrent illness/adverse experience 
 
✓ 
 
 
 
✓ 
✓ 
 
✓ 
 
✓ 
✓ 
✓ 
 
✓ 
✓ 
 
Social impact assessment 
 
✓ 
 
 
 
✓ 
✓ 
 
✓ 
 
✓ 
✓ 
✓ 
 
✓ 
✓ 
 
Social impact assessment questionnaire 
 
 
 
 
 
 
 
 
 
 
✓ 
 
 
 
 
 
 
Outside testing and belief questionnaire 
 
 
 
 
 
 
 
 
 
 
✓ 
 
 
 
 
 
 
Specimen collection6 
✓ 
✓ 
 
 
 
✓ 
✓ 
 
✓ 
 
✓ 
✓ 
✓ 
 
✓ 
✓ 
 
Vaccination procedures7 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vaccination8 
 
✓ 
 
 
 
 
✓ 
 
 
 
✓ 
 
 
 
 
 
 
Reactogenicity assessments9 
 
✓ 
 
 
 
 
✓ 
 
 
 
✓ 
 
 
 
 
 
 
Poststudy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unblind participant 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
✓ 
1 Screening may occur over the course of several contacts/visits up to and including day 0 prior to vaccination. 
2 Contraception status assessment is required only for participants assigned female sex at birth who are sexually active in a way that could cause pregnancy. Persons who are confirmed 
pregnant, pregnancy testing is not required, unless clinically indicated.  
3 Not applicable to HIV-infected participants. Conduct before Risk Reduction Counseling if both occur at same visit. 
4 Includes brief risk screening and targeted risk reduction counseling, if indicated. Includes transmission risk reduction counseling for HIV-infected participants. Conduct after BRA 
questionnaire if both occur at same visit. 

HVTN 137 Version 5.0 / September 26, 2022 
HVTN137_v5.0_Final_26Sep22 / Page 268 of 281 
5 Includes pretest steps and HIV testing. A subsequent follow-up contact is conducted to provide post-test steps and to report results to participant. If a participant has a confirmed diagnosis 
of HIV infection, do not perform HIV infection assessment. 
6 For specimen collection requirements, see Appendix K. For participants with a confirmed diagnosis of HIV infection, specimens listed under “Safety labs” in Appendix K, urinalysis, and 
urine pregnancy tests will be collected per the protocol schedule. 
7 Not applicable to HIV-infected participants. 
8 Blood draws required at vaccination visits must be performed prior to vaccination; however, it is not necessary to have results prior to vaccination, except for results of a urine or serum 
pregnancy test, if indicated. See Appendix K. 
9 Reactogenicity assessments performed daily for at least 7 days postvaccination (see Section 9.10). 
10 For participants who agreed to undergo boost vaccination collection of Month 8 samples (see Appendix J and Appendix Q) will not occur. If a participant has already undergone 
sample collection at Month 8 they will be placed on the boost schedule. 
 
 

HVTN 137 Version 5.0 / September 26, 2022 
HVTN137_v5.0_Final_26Sep22 / Page 269 of 281 
Appendix S 
Procedures at HVTN CRS for Part B (with lymph node FNA) 
Visit: 
011 
02 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
14 
15 
16 
Post 
Day: 
 
D0 
D1 
D3 
D7 
D14 
D56 
D63 
D70 
D77 
D168 
D175 
D182 
D224 
D364 
D546 
 
Week: 
 
W0 
 
 
W1 
W2 
W8 
W9 
W10 
W11 
W24 
W25 
W26 
W32 
W52 
W78 
 
Month: 
 
M0 
 
 
 
M0.5 
M2 
M2.25 
M2.5 
M2.75 
M6 
M6.25 
M6.5 
M8 
M12 
M18 
 
Procedure 
Scr. 
VAC1 
 
 
 
 
VAC2 
 
 
 
VAC3 
 
 
 
 
 
 
Study procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signed screening consent (if used) 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assessment of understanding 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol consent 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history  
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical exam 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
✓ 
 
Contraception status assessment2 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
 
✓ 
✓ 
 
Behavioral risk assessment questionnaire3 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
✓ 
 
Risk reduction counseling4 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
 
✓ 
✓ 
 
Confirm eligibility  
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Obtain demographics 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomize 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant medications 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
 
✓ 
✓ 
 
HIV infection assessment5 
✓ 
 
 
 
 
 
 
 
✓ 
 
✓ 
 
 
 
✓ 
✓ 
 
Abbreviated physical exam 
 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
 
✓ 
 
 
Intercurrent illness/adverse experience 
 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
 
✓ 
✓ 
 
Social impact assessment 
 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
 
✓ 
✓ 
 
Social impact assessment questionnaire 
 
 
 
 
 
 
✓ 
 
 
 
✓ 
 
 
 
 
 
 
Outside testing and belief questionnaire 
 
 
 
 
 
 
 
 
 
 
✓ 
 
 
 
 
 
 
Pelvic and/or rectal exam6 
 
✓ 
 
 
 
 
 
 
 
 
 
 
✓ 
 
 
 
 
Specimen collection7 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
 
✓ 
✓ 
 
Vaccination procedures8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vaccination9 
 
✓ 
 
 
 
 
✓ 
 
 
 
✓ 
 
 
 
 
 
 
Reactogenicity assessments10 
 
✓ 
 
 
 
 
✓ 
 
 
 
✓ 
 
 
 
 
 
 
Poststudy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unblind participant 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
✓ 
Grayed out visits are not applicable.  
1 Screening may occur over the course of several contacts/visits up to and including day 0 prior to vaccination. 
2 Contraception status assessment is required only for participants assigned female sex at birth who are sexually active in a way that could cause pregnancy. Persons who are confirmed 
pregnant, pregnancy testing is not required, unless clinically indicated. 
3 Not applicable to HIV-infected participants. Conduct before Risk Reduction Counseling if both occur at same visit. 

HVTN 137 Version 5.0 / September 26, 2022 
HVTN137_v5.0_Final_26Sep22 / Page 270 of 281 
4 Includes brief risk screening and targeted risk reduction counseling, if indicated. Includes transmission risk reduction counseling for HIV-infected participants. Conduct after BRA 
questionnaire if both occur at same visit. 
5 Includes pretest steps and HIV testing. A subsequent follow-up contact is conducted to provide post-test steps and to report results to participant. If a participant has a confirmed diagnosis 
of HIV infection, do not perform HIV infection assessment. 
6 As appropriate for participants providing rectal and/or vaginal mucosal samples (see Section 9.5). 
7 For specimen collection requirements, see Appendix L, and Appendix N. For participants with a confirmed diagnosis of HIV infection, specimens for urinalysis and urine pregnancy tests 
listed under “Safety labs” in Appendix L, and Appendix N will be collected per the protocol schedule. 
8 Not applicable to HIV-infected participants. 
9 Blood draws required at vaccination visits must be performed prior to vaccination; however, it is not necessary to have results prior to vaccination, except for results of a urine or serum 
pregnancy test, if indicated. See Appendix L and Appendix N. 
10 Reactogenicity assessments performed daily for at least 7 days postvaccination (see Section 9.10). 
 

HVTN 137 Version 5.0 / September 26, 2022 
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Appendix T 
Procedures at HVTN CRS for Part B (no lymph node FNA) and Part C 
Visit: 
011 
02 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
14 
15 
16 
Post 
Day: 
 
D0 
D1 
D3 
D7 
D14 
D56 
D63 
D70 
D77 
D168 
D175 
D182 
D224 
D364 
D546 
 
Week: 
 
W0 
 
 
W1 
W2 
W8 
W9 
W10 
W11 
W24 
W25 
W26 
W32 
W52 
W78 
 
Month: 
 
M0 
 
 
 
M0.5 
M2 
M2.25 
M2.5 
M2.75 
M6 
M6.25 
M6.5 
M8 
M12 
M18 
 
Procedure 
Scr. 
VAC1 
 
 
 
 
VAC2 
 
 
 
VAC3 
 
 
 
 
 
 
Study procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signed screening consent (if used) 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assessment of understanding 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol consent 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history  
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical exam 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
✓ 
 
Contraception status assessment2 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
 
✓ 
✓ 
✓ 
 
✓ 
✓ 
 
Behavioral risk assessment questionnaire3 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
✓ 
 
Risk reduction counseling4 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
 
✓ 
✓ 
✓ 
 
✓ 
✓ 
 
Confirm eligibility  
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Obtain demographics 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomize 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant medications 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
 
✓ 
✓ 
✓ 
 
✓ 
✓ 
 
HIV infection assessment5 
✓ 
 
 
 
 
 
 
 
✓ 
 
✓ 
 
 
 
✓ 
✓ 
 
Abbreviated physical exam 
 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
 
✓ 
✓ 
✓ 
 
✓ 
 
 
Intercurrent illness/adverse experience 
 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
 
✓ 
✓ 
✓ 
 
✓ 
✓ 
 
Social impact assessment 
 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
 
✓ 
✓ 
✓ 
 
✓ 
✓ 
 
Social impact assessment questionnaire 
 
 
 
 
 
 
✓ 
 
 
 
✓ 
 
 
 
 
 
 
Outside testing and belief questionnaire 
 
 
 
 
 
 
 
 
 
 
✓ 
 
 
 
 
 
 
Pelvic and/or rectal exam6 
 
✓ 
 
 
 
 
 
 
 
 
 
 
✓ 
 
 
 
 
Specimen collection7 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
 
✓ 
✓ 
✓ 
 
✓ 
✓ 
 
Vaccination procedures8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vaccination9 
 
✓ 
 
 
 
 
✓ 
 
 
 
✓ 
 
 
 
 
 
 
Reactogenicity assessments10 
 
✓ 
 
 
 
 
✓ 
 
 
 
✓ 
 
 
 
 
 
 
Poststudy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unblind participant 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
✓ 
Grayed out visits are not applicable.  
1 Screening may occur over the course of several contacts/visits up to and including day 0 prior to vaccination. 
2 Contraception status assessment is required only for participants assigned female sex at birth who are sexually active in a way that could cause pregnancy. Persons who are confirmed 
pregnant, pregnancy testing is not required, unless clinically indicated. 
3 Not applicable to HIV-infected participants. Conduct before Risk Reduction Counseling if both occur at same visit. 

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HVTN137_v5.0_Final_26Sep22 / Page 272 of 281 
4 Includes brief risk screening and targeted risk reduction counseling, if indicated. Includes transmission risk reduction counseling for HIV-infected participants. Conduct after BRA 
questionnaire if both occur at same visit. 
5 Includes pretest steps and HIV testing. A subsequent follow-up contact is conducted to provide post-test steps and to report results to participant. If a participant has a confirmed diagnosis 
of HIV infection, do not perform HIV infection assessment. 
6 As appropriate for participants providing rectal and/or vaginal mucosal samples (see Section 9.5). 
7 For specimen collection requirements, see Appendix M, Appendix O, and Appendix P. For participants with a confirmed diagnosis of HIV infection, specimens for urinalysis and urine 
pregnancy tests listed under “Safety labs” in Appendix M, Appendix O, and Appendix P will be collected per the protocol schedule. 
8 Not applicable to HIV-infected participants. 
9 Blood draws required at vaccination visits must be performed prior to vaccination; however, it is not necessary to have results prior to vaccination, except for results of a urine or serum 
pregnancy test, if indicated. See Appendix M, Appendix O, and Appendix P. 
10 Reactogenicity assessments performed daily for at least 7 days postvaccination for Part B. Reactogenicity assessments performed daily for at least 14 days postvaccination for Part C (see 
Section 9.10). 
 

HVTN 137 Version 5.0 / September 26, 2022 
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Appendix U 
HVTN low risk guidelines for the US 
The following are intended as guidelines for the investigator to help identify 
potential vaccine trial participants at “low risk” for HIV infection. These 
guidelines are based on behaviors within the last 6-12 months prior to enrollment; 
however, it may be appropriate to consider a person’s behavior over a longer 
period of time than specified to assess the person’s likelihood of maintaining low 
risk behavior. Some volunteers may not be appropriate for enrollment even if they 
meet these guidelines. These guidelines should be supplemented and interpreted 
with local epidemiologic information about HIV prevalence in your area and 
community networks. The investigator may review the risk level of any volunteer 
with the site PI and/or the Protocol Safety Review Team. 
A volunteer may be appropriate for inclusion if he/she/they meets these guidelines: 
 
A. For US volunteers NOT on stable Pre-exposure 
prophylaxis (PrEP) 
1 
SEXUAL BEHAVIORS 
In the last 12 months did not: 
• Have oral, vaginal or anal intercourse with an HIV-infected partner, or a 
partner who uses injection drugs  
• Give or receive money, drugs, gifts or services in exchange for oral, vaginal or 
anal sex 
 
AND 
 
In the last 6 months has abstained from penile/anal or penile/vaginal intercourse, OR 
 
In the last 6 months: 
• Had 4 or fewer partners of the opposite birth sex for vaginal and/or anal 
intercourse, OR 
 
Is an MSM (person born male with partner(s) born male) who, in the last 12 months: 
• Had 2 or fewer MSM partners for anal intercourse and had no unprotected 
anal sex with MSM, OR 
•  Had unprotected anal intercourse with only 1 MSM partner, within a 
monogamous relationship lasting at least 12 months (during which neither 
partner had any other partners). If the monogamous relationship ended, the 
volunteer may then have had protected anal intercourse with 1 other MSM 
partner (total 2 or fewer partners in the last 12 months).  
 
Is a transgender person, regardless of the point on the transition spectrum, having sex 
with men (born male) and/or other transgender persons, who in the last 12 months: 
• Had 2 or fewer partners for anal or vaginal intercourse, and had no 
unprotected anal or vaginal sex, OR  

HVTN 137 Version 5.0 / September 26, 2022 
HVTN137_v5.0_Final_26Sep22 / Page 274 of 281 
• Had unprotected anal or vaginal intercourse sex with 1 partner only within a 
monogamous relationship lasting at least 12 months (during which neither 
partner had any other partners). If the monogamous relationship ended, may 
then have had protected anal or vaginal sex with 1 other partner (total 2 or 
fewer partners in the last 12 months). 
 
AND 
 
Uses or intends to use condoms in situations which may include penile/anal or 
penile/vaginal intercourse with new partners of unknown HIV status, occasional 
partners, 
partners outside a primary relationship, and/or partners known to have other partners. 
 
2 
NON-SEXUAL BEHAVIORS 
 
In the last 12 months did not: 
• Inject drugs or other substances without a prescription 
• Use cocaine, methamphetamine, or excessive alcohol, which in the 
investigator’s judgment, rendered the participant at greater than low risk for 
acquiring HIV infection. 
The investigator’s judgment should consider local epidemiologic information 
about HIV prevalence in the area and community networks. 
 
A volunteer is NOT appropriate for inclusion if he/she: 
 
Acquired an STI (ie new infection) in the last 12 months: 
 
• Syphilis  
• Gonorrhea  
• Non-gonococcal urethritis  
• Herpes Simplex Virus type 2 (HSV2)  
• Chlamydia  
• Pelvic inflammatory disease (PID)  
• Trichomonas  
• Mucopurulent cervicitis  
• Epididymitis  
• Proctitis  
• Lymphogranuloma venereum  
• Chancroid  
• Hepatitis B 
 
                         
 

HVTN 137 Version 5.0 / September 26, 2022 
HVTN137_v5.0_Final_26Sep22 / Page 275 of 281 
B. For US volunteers on Pre-exposure prophylaxis (PrEP) 
1. PrEP ASSESSMENT 
• Reports 6 months (180 days) or more of protective PrEP use 
• For daily oral PrEP use: 
▪ For persons AMAB who have sex with persons AMAB: Reports equal 
to or greater than 70% when asked the following: “Thinking about the 
past 4 weeks, what percent of the time were you able to take all your 
PrEP medications?” 
▪ For people with a vagina having intravaginal intercourse: Reports 
equal to or greater than 90% when asked the following: “Thinking 
about the past 4 weeks, what percent of the time were you able to take 
all your PrEP medications?” 
• For event-driven (on-demand or “2-1-1”) PrEP use1 in persons AMAB 
who have sex with persons AMAB: Reports use consistent with the 
guidance of the professional education organization, the International 
Antiviral Society–USA (IAS-USA): 
▪ For individuals with frequent use (> 15 pills per month): At least 80% 
of condomless sex acts are covered with on-demand PrEP at the 
recommended dose schedule 
▪ For individuals with less frequent use (≤ 15 pills per month): 
o A past history of high adherence (> 90%) 
o Commitment to use on-demand PrEP for all condomless sex acts at 
the recommended dose schedule 
• Emtricitabine/tenofovir alafenamide (FTC/TAF, Descovy) and 
emtricitabine/tenofovir disoproxil fumarate (FTC/TDF, Truvada) when 
taken as PrEP do not interfere with pseudoneutralization assays. However, 
other antiretroviral medications may potentially interfere with 
immunogenicity assays. For PrEP medications other than FTC/TAF or 
FTC/TDF, refer to the SSP for details. 
• Commits to maintaining protective PrEP use throughout trial 
 
1 See Study-specific Procedures (SSP) for additional guidance on on-demand PrEP. 
2. SEXUAL BEHAVIORS 
• Persons stably taking PrEP as prescribed above for 6 months or longer are 
considered low risk of HIV infection, regardless of any sexual behavior that 
might otherwise be associated with high risk of HIV exposure. 
3. NON-SEXUAL BEHAVIORS 
In the last 12 months did not: 
• Inject drugs or other substances without a prescription 

HVTN 137 Version 5.0 / September 26, 2022 
HVTN137_v5.0_Final_26Sep22 / Page 276 of 281 
• Use cocaine, methamphetamine, or excessive alcohol, which in the 
investigator’s judgment, rendered the participant at greater than low risk for 
acquiring HIV infection. 
The investigator’s judgment should consider local epidemiologic information 
about HIV prevalence in the area and community networks. 

HVTN 137 Version 5.0 / September 26, 2022 
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Appendix V 
Adverse events of special interest 
AEs of special interest (AESI) for this protocol include but are not limited to potential 
immune-mediated diseases; representative examples of AESI are listed below. 
Updates to AESI will be provided as an appendix to the HVTN 137 Study Specific 
Procedures. 
Neuroinflammatory disorders 
Musculoskeletal disorders 
Skin disorders 
• 
Cranial nerve disorders, including 
paralyses/paresis (eg Bell’s palsy)  
• 
Optic neuritis 
• 
Multiple sclerosis 
• 
Transverse myelitis 
• 
Guillain-Barré syndrome, including 
Miller Fisher syndrome and other 
variants 
• 
Acute disseminated 
encephalomyelitis, including site 
specific variants: eg non-infectious 
encephalitis, encephalomyelitis, 
myelitis, myeloradiculoneuritis 
• 
Myasthenia gravis, including 
Lambert-Eaton myasthenic syndrome  
• 
Immune-mediated peripheral 
neuropathies and plexopathies, 
(including chronic inflammatory 
demyelinating polyneuropathy, 
multifocal motor neuropathy and 
polyneuropathies associated with 
monoclonal gammopathy). 
• 
Narcolepsy 
• 
Systemic lupus erythematosus and 
associated conditions 
• 
Systemic scleroderma (Systemic 
sclerosis), including diffuse systemic 
form and CREST syndrome 
• 
Idiopathic inflammatory myopathies, 
including dermatomyositis  
• 
Polymyositis  
• 
Antisynthetase syndrome 
• 
Rheumatoid arthritis, and associated 
conditions including juvenile chronic 
arthritis and Still’s disease 
• 
Polymyalgia rheumatica 
• 
Spondyloarthritis, including 
ankylosing spondylitis, reactive 
arthritis (Reiter's Syndrome) and 
undifferentiated spondyloarthritis  
• 
Psoriatic arthropathy 
• 
Relapsing polychondritis 
• 
Mixed connective tissue disorder 
• 
Psoriasis 
• 
Vitiligo 
• 
Erythema nodosum 
• 
Autoimmune bullous skin 
diseases (including pemphigus, 
pemphigoid and dermatitis 
herpetiformis) 
• 
Alopecia areata 
• 
Lichen planus 
• 
Sweet’s syndrome 
• 
Localized Scleroderma 
(Morphea)  
• 
Cutaneous lupus erythematosus 
 
Metabolic disorders 
• 
Addison’s disease 
• 
Autoimmune thyroiditis 
(including Hashimoto 
thyroiditis) 
• 
Diabetes mellitus type I 
• 
Grave's or Basedow’s disease 
Vasculitides 
Blood disorders 
Others 
• 
Large vessels vasculitis including: 
giant cell arteritis such as Takayasu’s 
arteritis and temporal arteritis.  
• 
Medium sized and/or small vessels 
vasculitis including: polyarteritis 
nodosa, Kawasaki's disease, 
microscopic polyangiitis, Wegener’s 
granulomatosis, Churg-Strauss 
syndrome (allergic granulomatous 
angiitis), Buerger’s disease 
(thromboangiitis obliterans), 
necrotizing vasculitis and anti-
neutrophil cytoplasmic antibody 
(ANCA) positive vasculitis (type 
unspecified), Henoch-Schonlein 
purpura, Behcet’s syndrome, 
leukocytoclastic vasculitis. 
• 
Autoimmune hemolytic anemia 
• 
Autoimmune thrombocytopenia 
• 
Antiphospholipid syndrome 
• 
Pernicious anemia 
• 
Autoimmune aplastic anemia 
• 
Autoimmune neutropenia  
• 
Autoimmune pancytopenia 
 
Gastrointestinal disorders 
• 
Celiac disease 
• 
Crohn’s disease 
• 
Ulcerative colitis 
• 
Ulcerative proctitis 
 
Liver disorders 
• 
Autoimmune cholangitis 
• 
Autoimmune hepatitis 
• 
Primary biliary cirrhosis 
• 
Primary sclerosing cholangitis 
• 
Autoimmune 
glomerulonephritis (including 
IgA nephropathy, 
glomerulonephritis rapidly 
progressive, membranous 
glomerulonephritis, 
membranoproliferative 
glomerulonephritis, and 
mesangioproliferative 
glomerulonephritis) 
• 
Ocular autoimmune diseases 
(including autoimmune uveitis 
and autoimmune retinopathy) 
• 
Autoimmune 
myocarditis/cardiomyopathy 
• 
Sarcoidosis 
• 
Stevens-Johnson syndrome 
• 
Sjögren’s syndrome 
• 
Idiopathic pulmonary fibrosis 
• 
Goodpasture syndrome 
• 
Raynaud’s phenomenon 

HVTN 137 Version 5.0 / September 26, 2022 
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Appendix W Visit Windows 
HVTN 137 Part A Visit Windows 
Visit 
Number 
Visit Type 
Lower 
Allowable 
Window  
(-) 
Lower 
Target 
Window  
(-) 
Target 
Day 
Upper 
Target 
Window 
(+) 
Upper 
Allowable 
Window  
(+) 
01.0 
Screening 
 
-56 
- 
0 
- 
+0 
02.0 
Enrollment/Vaccination 1 
 
- 
- 
0 
- 
- 
03.0 
 
 
 
 
 
 
04.0 
 
 
 
 
 
 
05.0 
 
 
 
 
 
 
06.0 
2 weeks postvaccination 1 
- 
-4 
14 
+4 
+7 
07.0 
Vaccination 2 
- 
-7 
56 
+9 
+180 
08.0 
 
 
 
 
 
 
09.0 
2 weeks postvaccination 2 
Primary Immunogenicity 
- 
-4 
70 
+4 
+7 
10.0 
 
 
 
 
 
 
11.0 
 
 
 
 
 
 
12.0 
 
 
 
 
 
 
13.0 
 
 
 
 
 
 
14.0 
Final Visit 
(Should be scheduled ~6 
months post-Vaccination 
2) 
-28 
-14 
224 
+14 
+120 
AESI 
AESI Contact 
(Should be scheduled ~12 
months post-Vaccination 
2) 
-28 
-14 
425 
+14 
120 
All target dates are relative to Day 0, with the exception of the postvaccination visits, visits 6.0 and 
9.0, which are relative to the vaccination immediately preceding the visit. 
The highlighted (blue) visits are not required for Part A participants. 
 
 

HVTN 137 Version 5.0 / September 26, 2022 
HVTN137_v5.0_Final_26Sep22 / Page 279 of 281 
HVTN 137 Part A with Optional Second Boost Visit Windows 
Visit 
Number 
Visit Type 
Lower 
Allowable 
Window  
(-) 
Lower 
Target 
Window  
(-) 
Target 
Day 
Upper 
Target 
Window 
(+) 
Upper 
Allowable 
Window  
(+) 
01.0 
Screening 
 
-56 
- 
0 
- 
+0 
02.0 
Enrollment/Vaccination 1 
 
- 
- 
0 
- 
- 
03.0 
 
 
 
 
 
 
04.0 
 
 
 
 
 
 
05.0 
 
 
 
 
 
 
06.0 
2 weeks postvaccination 1 
- 
-4 
14 
+4 
+7 
07.0 
Vaccination 2 
- 
-7 
56 
+9 
+180 
08.0 
 
 
 
 
 
 
09.0 
2 weeks postvaccination 2 
Primary Immunogenicity 
- 
-4 
70 
+4 
+7 
10.0 
 
 
 
 
 
 
11.0 
Vaccination 3 
- 
-7 
168 
+9 
+365 
12.0 
7 days postvaccination 3 
-1 
- 
175 
- 
+1 
13.0 
2 weeks postvaccination 3 
Primary Immunogenicity 
- 
-4 
182 
+4 
+7 
14.0 
 
 
 
 
 
 
15.0 
Follow-up Visit 
-84 
-14 
364 
+14 
+84 
16.0 
Final Visit 
-56 
-14 
546 
+14 
+84 
All target dates are relative to Day 0, with the exception of the postvaccination visits 9.0, 12.0, 13.0, 
15.0, and 16.0, which are relative to the vaccination immediately preceding the visit. 
The highlighted (blue) visits are not required for any Part A Boost participants. 
 
 

HVTN 137 Version 5.0 / September 26, 2022 
HVTN137_v5.0_Final_26Sep22 / Page 280 of 281 
HVTN 137 Part B and Part C Visit Windows 
Visit 
Number 
Visit Type 
Lower 
Allowable 
Window  
(-) 
Lower 
Target 
Window  
(-) 
Target 
Day1 
Upper 
Target 
Window 
(+) 
Upper 
Allowable 
Window  
(+) 
01.0 
Screening 
 
-56 
- 
0 
- 
+0 
02.0 
Enrollment/Vaccination 1 
 
- 
- 
0 
- 
- 
03.0 
1 day postvaccination 1 
-0 
- 
1 
- 
+0 
04.0 
3 days postvaccination 1 
-0 
- 
3 
- 
+0 
05.0 
7 days postvaccination 1 
-1 
- 
7 
- 
+1 
06.0 
2 weeks postvaccination 1 
- 
-4 
14 
+4 
+7 
07.0 
Vaccination 2 
- 
-7 
56 
+9 
+14 
08.0 
7 days postvaccination 2 
-1 
- 
63 
- 
+1 
09.0 
2 weeks postvaccination 2 
Primary Immunogenicity 
- 
-4 
70 
+1 
+4 
10.02 
FNA visit 
-3 
-1 
77 
+4 
+7 
11.0 
Vaccination 3 
- 
-7 
168 
+9 
+14 
12.0 
7 days postvaccination 3 
-1 
- 
175 
- 
+1 
13.0 
2 weeks postvaccination 3 
Primary Immunogenicity 
- 
-4 
182 
+4 
+7 
14.03 
 
 
 
 
 
 
15.0 
Follow-up Visit 
-84 
-14 
364 
+14 
+84 
16.0 
Final Visit 
-56 
-14 
546 
+14 
+28 
1 All target dates are relative to Day 0, with the exception of the postvaccination visits, visits 8.0, 
9.0, 10.0, 12.0, and 13.0, which are relative to the vaccination immediately preceding the visit. 
2 The green highlighted visit is only required for participants who are providing lymph node FNA 
collections in Part B. 
3 The highlighted (blue) visit is not required for any Part B or Part C participants. 

HVTN 137 Version 5.0 / September 26, 2022 
HVTN137_v5.0_Final_26Sep22 / Page 281 of 281 
Appendix X 
Protocol Signature Page 
 
A phase 1 clinical trial to evaluate the safety and immunogenicity of HIV-1 
BG505 SOSIP.664 gp140 with TLR agonist and/or Alum adjuvants and VRC 
HIV Env Trimer 4571 and 3M-052-AF with Alum in healthy, HIV-uninfected 
adults 
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 (U.S.) 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 (eg, U.S. National Institutes of Health, Division of AIDS) and 
institutional policies 
 
 
 
 
 
 
 
 
 
Investigator of Record Name (print) 
 
Investigator of Record Signature 
 
Date 
 
 
DAIDS Protocol Number: HVTN 137 
DAIDS Protocol Version: Version 5.0 
Protocol Date: September 26, 2022