A Phase 1, Open-Label Clinical Trial to Evaluate Safety, Tolerability, and Immunogenicity of Adjuvanted HIV-1 Fusion Peptide Conjugate Vaccine (VRC-HIVVCP0108-00-VP) Alone or in Prime-Boost Regimens With Adjuvanted HIV-1 Envelope Trimer 4571 (VRC-HIVRGP096-00-VP) and HIV-1 Trimer 6931 (VRC-HIVRGP0106-00-VP) Vaccines in Healthy Adults
Phase: PHASE1
Conditions: HIV
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

PROTOCOL 
HVTN 303 
A Phase 1, Open-Label Clinical Trial to Evaluate Safety, 
Tolerability, and Immunogenicity of Adjuvanted HIV-1 
Fusion Peptide Conjugate Vaccine (VRC-HIVVCP0108-
00-VP) Alone or in Prime-Boost Regimens with
Adjuvanted HIV-1 Envelope Trimer 4571 (VRC-
HIVRGP096-00-VP) and HIV-1 Trimer 6931 (VRC-
HIVRGP0106-00-VP) Vaccines in Healthy Adults 
DAIDS DOCUMENT ID 38835 
IND 028412 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 
Vaccine Research Center (VRC) 
NIAID, NIH, DHHS 
Bethesda, Maryland, USA 
September 21, 2023 
Final 
HVTN 303 
Version 2.0 

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HVTN 303 enrolled (vaccinated) its first participant on August 15, 2022, with the goal to enroll 60 
participants in the study. As of Dec 20, 2022, 44 participants were enrolled (no enrollments occurred 
after this date). Part A (Groups 1, 2, 3, 4, and 5) completed enrollment of 15 participants from 
August 15 to October 14, 2022.  
Part B enrolled 29 participants from November 3 to December 20, 2022: Group 6 enrolled 10 ppts, 
all of whom received 1 vaccination; Group 7 enrolled 10 participants, 5 of whom received 2 
vaccinations; Group 8 enrolled 9 participants, 6 of whom received 2 vaccinations. No participants 
received a 3rd vaccination.  
Over time, the PSRT observed trends in local and systemic reactogenicity (grade 3 fever, grade 3 
injection site erythema, and/or induration/swelling), unsolicited adverse events (urticaria, rash, and 
serum sickness), and temporary increases in absolute eosinophil counts (AECs) post-vaccination. 
Certain of these events resulted in pauses in all vaccinations, and the PSRT requested the HVTN 
Safety Monitoring Board (SMB) perform an ad hoc review of all safety data. Following this review 
on January 11, 2023, the SMB recommended that all vaccinations in the study be permanently 
discontinued, and that participants be continued in safety follow-up, and these recommendations 
were implemented.  
On January 13, 2023, a protocol memo was distributed informing the clinical research sites that all 
vaccinations in HVTN 303 were permanently discontinued. Vaccinations in Part A were completed 
on October 14, 2022, and specimen collection for safety labs was completed 4 weeks after the 
vaccination on November 10, 2022. Discontinuation of vaccinations applied to Part B only. On 
March 13, 2023, FDA informed DAIDS that the IND has been placed on Clinical Hold and 
confirmed that all protocol-related activities must cease except for any participant safety follow-up 
assessments. Safety follow-up assessments, including specimen collection for safety labs, have been 
conducted for at least 7 months after last vaccination for all participants in Part B and no safety 
concerns have been identified during this follow-up period.  
All participants have been informed using “Dear Participant” letters.  
HVTN 303 Protocol sections 1, 2, 3, 6, 7 and 8 have been revised to include language in prior 
protocol modifications and protocol changes that resulted from the permanent discontinuation of 
vaccinations in the study. Procedures specified for remaining follow-up visits have been revised.  
• For participants in Groups 7 and 8 that received two doses of their respective vaccines, 
Leukapheresis or 204 ml of blood draw has been added at 10 months +/- 2 month past their 
last vaccination to investigate immunological outcomes.  
• The revised study procedures for Part A participants are shown in new Appendix B and for 
Part B participants are shown in new Appendix D.  
• The revised visit windows for participants are shown in new Appendix F. New Appendix H 
and Appendix J contains addendums to the sample consent forms for Part A and Part B 
participants respectively that updates study information and new tables of procedures. 

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Protocol Signature Page 
A Phase 1, Open-Label Clinical Trial to Evaluate Safety, Tolerability, and 
Immunogenicity of Adjuvanted HIV-1 Fusion Peptide Conjugate Vaccine (VRC- 
HIVVCP0108-00-VP) Alone or in Prime-Boost Regimens with Adjuvanted HIV-
1 Envelope Trimer 4571 (VRC-HIVRGP096-00-VP) and HIV-1 Trimer 6931 
(VRC-HIVRGP0106-00-VP) Vaccines in Healthy 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 (US) Health and Human Service regulations (45 
CFR 46); applicable US 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, US National Institutes of Health, Division of AIDS) and 
institutional policies 
 
 
 
 
 
 
 
 
 
Investigator of Record Name (print) 
 
Investigator of Record Signature 
 
Date 
 
 
 
DAIDS Protocol Number: HVTN 303 
DAIDS Protocol Version: Version 2.0 
Protocol Date: September 21, 2023 
 
 

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Acronyms and abbreviations 
Ab 
 
antibody 
AE 
 
adverse event 
AEC 
 
absolute eosinophil count 
AESI 
 
adverse events of special interest 
Ag 
 
antigen 
ALT 
 
Alanine aminotransferase  
AoU 
 
Assessment of Understanding 
ART 
 
antiretroviral therapy  
AUC-MB  
area-under-the-magnitude breadth curve 
β-HCG 
 
beta human chorionic gonadotropin 
BAMA 
 
binding antibody multiplex assay 
bnAb 
 
broadly neutralizing antibody 
BP 
 
blood pressure 
CAB 
 
community advisory board 
CBC 
 
complete blood count 
cGMP 
 
current Good Manufacturing Practice 
CHO 
 
Chinese hamster ovary 
CI 
 
confidence interval 
CMIA 
 
chemiluminescent microparticle immunoassay 
ConC 
 
consensus clade C sequence 
COVID-19 
coronavirus disease 2019 
CRF 
 
case report form 
CRPMC 
 
Clinical Research Products Management Center 
CRS 
 
clinical research site  
CSS 
 
clinical safety specialist 
CTL 
 
CD8+ T lymphocyte(s) 
DAERS 
 
DAIDS Adverse Experience Reporting System 
DAIDS 
 
Division of AIDS 
DHHS 
 
Department of Health and Human Services 
d/v 
 
dose per volume 
DS 
 
disulfide mutation 
EAE 
 
expedited adverse event 
EC 
 
ethics committee  
eGFR 
 
estimated glomerular filtration rate  
EIA 
 
enzyme immunoassay  
ELICA 
 
electrochemiluminescence 
Env 
 
HIV-1 envelope glycoprotein  

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EUA 
 
emergency use authorized/authorization 
EUL 
 
emergency use listing 
FDA 
 
Food and Drug Administration 
FP 
 
fusion peptide 
FP8v1-rTTHC 
fusion peptide conjugate vaccine 
FP8v2 
 
eight N-terminal FP residues 
FS 
 
functionality score  
GCP 
 
Good Clinical Practice 
GEE 
 
generalized estimating equations 
GLP 
 
good laboratory practice 
GPP 
 
Good Participatory Practices 
HA 
 
hemagglutinin 
HCV 
 
hepatitis C virus 
ICH 
 
international council for harmonization  
IB 
 
investigator’s brochure 
ICS 
 
intracellular cytokine staining assay 
IDR 
 
immunodominant region  
IM 
 
intramuscular/intramuscularly 
IND 
 
investigational new drug (application) 
IRB 
 
institutional review board 
IV 
 
intravenous  
KLH 
 
keyhole limpet hemocyanin 
MAAE 
 
medically attended adverse events  
MAR 
 
missing at random 
MCAR 
 
missing completely at random 
mcg 
 
microgram 
mg 
 
milligram 
mL 
 
milliliter 
MOP 
 
manual of procedures 
MPL 
 
monophosphoryl lipid A  
MSD 
 
Meso Scale Discovery 
MSM 
 
person born male with partner(s) born male 
nAb 
 
neutralizing antibody 
NAT 
 
nucleic acid test  
NIAID 
 
National Institute of Allergy and Infectious Diseases 
NIH 
 
National Institutes of Health 
OHRP 
 
Office for Human Research Protections 
PAB 
 
Pharmaceutical Affairs Branch 

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PBMC 
 
peripheral blood mononuclear cell 
PBS 
 
phosphate buffered saline 
PCA 
 
principal component analysis 
PCR 
 
polymerase chain reaction 
PEF 
 
peak expiratory flow 
PFS 
 
polyfunctionality score 
PI 
 
Principal Investigator 
PIMMC 
 
potential immune-mediated medical condition 
PrEP 
 
pre-exposure prophylaxis  
PSRT 
 
Protocol Safety Review Team 
RAB 
 
Regulatory Affairs Branch 
RE 
 
Regulatory Entity 
RSC 
 
Regulatory Support Center  
rTTHC 
 
recombinant tetanus toxoid heavy chain fragment C 
SAE 
 
serious adverse event 
SAP 
 
statistical analysis plan 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SAS 
 
statistical analysis system 
SC 
 
subcutaneous/subcutaneously 
SICF 
 
sample informed consent form 
SMB 
 
safety monitoring board 
SOP 
 
Standard Operating Procedure 
SPT 
 
Safety and Pharmacovigilance Team 
SSP 
 
study specific procedures 
SUSAR 
 
suspected unexpected serious adverse reaction 
ULN 
 
upper limit of normal 
VCMP 
 
Vaccine Clinical Materials Program 
VISP 
 
vaccine-induced seropositivity  
VRC 
 
Vaccine Research Center 
WBC 
 
white blood cell 
WHO 
 
World Health Organization 

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Contents 
1 Executive summary ......................................................................................................10 
1.1 
Title ..............................................................................................................10 
1.2 
Design ...........................................................................................................10 
1.3 
Study products ..............................................................................................10 
1.4 
Study population ..........................................................................................11 
1.5 
Study plan and schema table ........................................................................11 
1.6 
Duration per participant ...............................................................................14 
1.7 
Estimated total study duration ......................................................................14 
1.8 
Study sites ....................................................................................................14 
2 Introduction ..................................................................................................................15 
2.1 
Study rationale ..............................................................................................15 
2.2 
Rationale for evaluation of FP8v1-rTTHC ..................................................17 
2.3 
Rationale for evaluation of FP8v1-rTTHC and Trimer 6931 (ConC-FP8v2 
RnS-3mut-2G-SOSIP.664) ...........................................................................18 
2.4 
Rationale for Use of the Adjuplex Adjuvant ................................................18 
2.5 
Rationale for Vaccine Regimen and Dose Selections ..................................19 
2.6 
Assessment of Immunogenicity ...................................................................21 
2.7 
Rationale for Leukapheresis .........................................................................22 
2.8 
Study Products ..............................................................................................22 
2.9 
Preclinical Studies with FP conjugate vaccine, Trimer 4571 and Trimer 
6931 and Adjuplex .......................................................................................23 
2.10 Previous Human Experience ........................................................................25 
2.11 Risks and benefits .........................................................................................31 
3 Objectives and endpoints .............................................................................................34 
3.1 
Primary objectives and endpoints ................................................................34 
3.2 
Exploratory objectives ..................................................................................35 
4 Laboratory strategy ......................................................................................................36 
5 Study design .................................................................................................................37 
5.1 
Study population ..........................................................................................37 
5.2 
Participant departure from vaccination schedule or withdrawal ..................42 
6 Statistical considerations ..............................................................................................47 
6.1 
Accrual and sample size calculations ...........................................................47 
6.2 
Sample size calculations for safety ..............................................................47 
6.3 
Randomization .............................................................................................51 
6.4 
Blinding ........................................................................................................51 
6.5 
Statistical analyses ........................................................................................51 
7 Study product preparation, storage, and administration ..............................................61 
7.1 
Vaccine Regimen .........................................................................................61 
7.2 
Study Product Formulation and Storage ......................................................63 
7.3 
Preparation of Study Products ......................................................................64 
7.4 
Labeling of Study Products ..........................................................................74 
7.5 
Study Product Administration ......................................................................75 

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7.6 
Acquisition of study products ......................................................................75 
7.7 
Study Product Accountability ......................................................................75 
7.8 
Final Disposition of study product ...............................................................75 
8 Clinical procedures ......................................................................................................76 
8.1 
Screening ......................................................................................................76 
8.2 
Definition of Study Day and Study Visit .....................................................76 
8.3 
Reactogenicity Assessments ........................................................................76 
8.4 
Leukapheresis for Part B participants ..........................................................78 
8.5 
Visit windows and missed visits ..................................................................78 
8.6 
Monitoring for COVID-19 symptoms ..........................................................78 
8.7 
Monitoring for HIV infection .......................................................................79 
8.8 
Early termination visit ..................................................................................79 
9 Safety and adverse events ............................................................................................81 
9.1 
Adverse events .............................................................................................81 
9.2 
Serious adverse events .................................................................................82 
9.3 
Safety monitoring .........................................................................................84 
9.4 
Safety reviews ..............................................................................................84 
9.5 
Safety pause and prompt PSRT AE review..................................................86 
9.6 
Total blood volume ......................................................................................88 
9.7 
Study termination .........................................................................................88 
9.8 
Pregnancy .....................................................................................................89 
10 Protocol conduct and informed consent .......................................................................90 
10.1 Protocol conduct ...........................................................................................90 
10.2 Informed consent ..........................................................................................90 
11 Exploratory studies ......................................................................................................92 
11.1 Specimen storage and other use of specimens .............................................92 
12 Literature cited .............................................................................................................93 
 Schedule of procedures for Part A (Groups 1-5) ..........................................99 
Appendix B Follow-up schedule of procedures for Part A (Groups 1-5) post termination 
of vaccinations ............................................................................................101 
Appendix C Schedules of procedures for Part B (Tables for Group 6, Group 7, and 
Group 8) .....................................................................................................103 
Appendix D Follow-up schedule of procedures for Part B (Tables for Group 6, Group 7, 
and Group 8) post termination of vaccinations ..........................................107 
Appendix E Visit windows .............................................................................................111 
Appendix F Follow up visit windows post termination of vaccination .........................115 
Appendix G Sample informed consent form for Part A (Groups 1-5) ...........................119 
Appendix H Sample addendum to informed consent form for Part A (Groups 1-5) post 
termination of vaccinations ........................................................................140 
Appendix I Sample informed consent form for Part B (Groups 6-8) ............................144 

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Appendix J Sample addendum to informed consent form for Part B (Groups 6-8) post 
termination of vaccinations ........................................................................171 
Appendix K Low risk guidelines for US ........................................................................180 
Appendix L Approved birth control methods ................................................................183 
Appendix M Adverse events of special interest ..............................................................185 
Appendix N Protocol team ..............................................................................................186 
Appendix O Version history ...........................................................................................187 

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1 
Executive summary 
1.1 
Title  
A Phase 1, Open-Label Clinical Trial to Evaluate Safety, Tolerability, and 
Immunogenicity of Adjuvanted HIV-1 Fusion Peptide Conjugate Vaccine (VRC- 
HIVVCP0108-00-VP) Alone or in Prime-Boost Regimens with Adjuvanted HIV-
1 Envelope Trimer 4571 (VRC-HIVRGP096-00-VP) and HIV-1 Trimer 6931 
(VRC-HIVRGP0106-00-VP) Vaccines in Healthy Adults. 
1.2 
Design 
This is a phase 1, open-label, dose-escalation study to evaluate the dose, safety, 
tolerability and immunogenicity of adjuvanted HIV-1 Fusion Peptide (FP) 
conjugate vaccine (FP8v1-rTTHC) alone or in prime-boost regimens with 
adjuvanted HIV-1 Trimer 4571 and adjuvanted HIV-1 Trimer 6931. The primary 
hypothesis is that FP8v1-rTTHC, HIV-1 Trimer 4571, and HIV-1 Trimer 6931 
adjuvanted vaccines are safe and tolerable when administered alone and when co-
administered with HIV-1 Trimer 4571, in prime-boost regimens.  
1.3 
Study products 
• FP8v1-rTTHC (FP conjugate vaccine) is an HIV-1 fusion peptide conjugated 
to recombinant tetanus toxoid heavy chain fragment C (rTTHC) via sulfo-
SIAB chemical linker. FP8v1 corresponds to the amino-terminal eight 
residues of the most prevalent HIV fusion peptide sequence. FP conjugate 
vaccine will be provided at a 1-milligram (mg)/milliliter (mL) concentration 
in 3-mL glass vials filled to 0.7 mL. 
• HIV-1 Trimer 4571 (Trimer 4571) is a synthetic soluble HIV-1 envelope 
product that consists of an HIV-1 envelope (Env) trimer variant, derived from 
clade A, strain BG505. Trimer 4571 is provided at a 500-mcg/mL 
concentration in 3-mL glass vials filled to 1.2 mL 
• HIV-1 Trimer 6931 (Trimer 6931) is a synthetic soluble HIV-1 envelope 
product that consists of an HIV-1 envelope (Env) trimer variant, derived from 
consensus clade C sequence (ConC). Trimer 6931 will be provided at a 1-
mg/mL concentration in 3-mL glass vials filled to 1.2 mL. 
• Adjuplex is the adjuvant and will be provided in a sterile, pyrogen-free, 
homogeneous suspension at 0.7 mL in 3-mL glass vials. Adjuplex will be 
mixed with study products in the pharmacy during preparation prior to 
vaccination at a 20% dose by volume. 

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• PBS (labeled as Phosphate Buffered Saline pH 7.2): Diluent. 
1.4 
Study population 
Healthy adults aged 18 to 50 years, inclusive. 
1.5 
Study plan and schema table 
This study has two parts. Part A will evaluate the safety, tolerability, and 
immunogenicity of single doses of the FP conjugate, Trimer 4571 and Trimer 
6931 vaccines, in a dose-escalation design. Each product must be assessed as safe 
prior to use in Part B. Trimer 4571 with alum adjuvant has been previously 
evaluated in humans but will be tested in Part A with Adjuplex. Part B will 
evaluate the safety, tolerability, and immunogenicity of FP conjugate prime, 
Trimer 4571 prime, or an FP plus Trimer 4571 prime, all followed by subsequent 
doses of Trimer 4571, Trimer 6931 and both Trimers combined. Study vaccines 
will be administered intramuscularly (IM) via needle and syringe in two injection 
sites. The study schema is in Table 1-1 below: 
 
 

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Table 1-1 Schema  
Part A: Dose Escalation** 
Group 
N 
W0 
 
 
 
 
 
 
 
 
 
1 
3 
25 mcg FP conjugate 
vaccine 
 
 
 
 
 
 
 
 
 
2 
3 
200 mcg FP 
conjugate vaccine 
 
 
 
 
 
 
 
 
 
3 
3 
100 mcg Trimer 6931 
 
 
 
 
 
 
 
 
 
4 
3 
200 mcg Trimer 6931 
 
 
 
 
 
 
 
 
 
5 
3 
200 mcg Trimer 4571 
 
 
 
 
 
 
 
 
 
Part A 
Total 
15* 
 
Part B: Prime Boost Regimen** 
Group 
N 
W0 
W4 
W8*** 
W12*** 
W20*** 
W24*** 
W32*** 
W36*** 
W44*** 
W48*** 
6 
15 10 
 
200 mcg 
Trimer 4571 
 
 
200 mcg 
Trimer 4571 
 
200 mcg Trimer 
6931 
 
100 mcg 
Trimer 
4571 
+ 
100 mcg 
Trimer 
6931 
 
100 mcg 
Trimer 
4571 
+ 
100 mcg 
Trimer 
6931 
7 
15 10 
 
200 mcg 
FP conjugate vaccine 
200 mcg 
FP conjugate 
vaccine 
200 mcg 
FP conjugate 
vaccine 
200 mcg 
Trimer 4571 
 
200 mcg 
Trimer 4571 
 
200 mcg 
Trimer 
6931 
 
100 mcg 
Trimer 
4571 
+ 
100 mcg 
Trimer 
6931 
8 
15 9 
200 mcg 
FP conjugate vaccine 
+ 
200 mcg 
Trimer 4571 
200 mcg 
FP conjugate 
vaccine 
+ 
200 mcg 
Trimer 4571 
200 mcg 
FP conjugate 
vaccine 
+ 
200 mcg 
Trimer 4571 
 
200 mcg 
Trimer 
6931 
 
100 mcg 
Trimer 
4571 
+ 
100 mcg 
Trimer 
6931 
 
100 mcg 
Trimer 
4571 
+ 
100 mcg 
Trimer 
6931 
 
Part B total 
45§ 29 
 
Overall 
Total 
60† 44 
 
 
 

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Table 1-1 Footnotes: 
**Adjuplex adjuvant will be mixed with all study products in Part A and Part B at 20% by volume in the pharmacy during product preparation for all vaccinations. 
Once mixed, all study injections will be divided into 2 syringes, and each syringe will be administered intramuscularly to one of the deltoids. 
 
* In Part A, up to 20 participants may be enrolled if needed for safety evaluations. Additional participants may be enrolled to ensure the availability of 2-week safety 
data from at least 3 participants per group. Refer to the HVTN 303 Study Specific Procedures (SSP) for further details. 
 
§ In Part B, up to 50 participants may be enrolled if needed for safety evaluations. Additional participants may be enrolled to ensure the availability of 2-week safety 
data from at least 15 participants per group. Refer to the HVTN 303 SSP for further details.  
 
† Total up to 70 participants can be enrolled if needed for safety evaluations. Refer to the HVTN 303 SSP for further details. 
Notes:  
Part A of the study may begin with direct enrollment of participants into the following groups simultaneously: 
• 
Group 1 with no more than 1 participant enrolled per day for the 3 participants. 
• 
Group 3 with no more than 1 participant enrolled per day for the 3 participants. 
 
After Groups 1 and 3 have been fully enrolled, the study will be placed on a safety hold. No additional enrollments will proceed until the Protocol Safety Review 
Team (PSRT) has determined it is safe to do so. Once all of the reactogenicity and 2-week safety data from at least 6 participants have been submitted to the 
database, the PSRT must assess the accumulated product-specific data as showing no significant safety concerns before proceeding with enrollment of Groups 2, 4 
and 5. If the PSRT has determined it is safe to proceed after reviewing data from Groups 1 and 3, the following groups may begin simultaneously:  
• 
Group 2 with no more than 1 participant enrolled per day for the 3 participants 
• 
Group 4 with no more than 1 participant enrolled per day for the 3 participants 
• 
Group 5 with no more than 1 participant enrolled per day for the 3 participants 
Once Groups 2, 4 and 5 have been fully enrolled, the study will be placed on a safety hold before proceeding with Part B. Once all of the reactogenicity and 2-week 
safety data from at least 9 participants have been submitted to the database, the PSRT must assess the accumulated product-specific data as showing no significant 
safety concerns before proceeding with enrollment of Part B. 
Part B enrollments may only proceed if no safety concerns have been identified for any of the product administrations in Part A of the study. 
If at any time there is insufficient data to conduct a formal PSRT Safety Review because of participant discontinuations from the study before sufficient data are 
collected, then additional participants may be enrolled into that group to acquire the requisite data on the required number of participants specified above. 
Moreover, the PSRT may recommend additional participants be enrolled into a given treatment group if additional safety evaluations are requested. 
Consultation with the HVTN Safety Monitoring Board (SMB), Institutional Review Board (IRB) and Food and Drug Administration (FDA), if needed, as specified 
by study pause criteria (per Section 9.5.1), will occur if indicated. 
***Vaccination in Part B starting from Week 8 onwards did not take place.  
Actual Ns for Group 6, 7 and 8 were 10, 10 and 9 respectively. In Part B total 29 participants were enrolled.  

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1.6 
Duration per participant 
For participants in Part A (Groups 1-5): 52 weeks of scheduled clinic visits. 
For participants in Part B (Groups 6 and 7): 100 weeks of scheduled clinic visits. 
For participants in Part B (Group 8): 96 weeks of scheduled clinic visits. 
1.7 
Estimated total study duration 
Total study duration is 36 months (includes enrollment, planned safety holds and 
follow-up). 
1.8 
Study sites  
HVTN Clinical Research Sites (HVTN CRSs) to be specified in the Site 
Announcement Memo. 
On January 13, 2023, a protocol memo was distributed informing the clinical 
research sites that all vaccinations in HVTN 303 were permanently 
discontinued. Procedures specified for remaining follow-up visits have been 
revised. Duration for Part A participants remained unchanged. Duration for 
Part B participants (for Groups 6 -8) is 56 weeks. 
Following cessation of vaccination and reduction of follow-up duration the 
estimated total study duration is reduced to approximately 18 months. 

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2 
Introduction 
In the nearly 4 decades since AIDS was first observed and described (1-5), its 
virologic etiologic agent, HIV-1 (6-8), has continued to be a worldwide threat to 
public health. In 2018, in the United States alone, an estimated 37,968 new 
infections occurred, with 1.2 million people living with confirmed infection, and 
15,820 deaths among those diagnosed with HIV (9). Global statistics reported in 
2019 were even more sobering, with approximately 38 million people living with 
HIV worldwide, including 1.7 million new HIV cases and 690,000 deaths (9). For 
individuals who received a diagnosis of HIV-1 during the years spanning 1980 
and 1996, median survival was less than a year (10, 11). Advances in therapeutic 
drug development have transformed the survival prognosis to one of an 
essentially normal life span for individuals newly diagnosed since 2017 and who 
have access to effective antiretroviral therapy (ART) (12, 13). Although the rate 
of new cases of HIV infections is decreasing globally, additional widespread 
measures are needed to accelerate the reduction of new infections. Development 
of a protective HIV-1 vaccine thus remains a global health priority to control and 
eliminate the AIDS pandemic (14). 
A central goal of HIV-1 vaccine development remains the elicitation of protective 
antibodies capable of neutralizing diverse tier 2 (neutralization-resistant) isolates 
that typify naturally circulating HIV-1 strains. A primary vaccine target has been 
the HIV-1 envelope glycoprotein (Env), the sole viral component exposed on the 
virion surface and principal target for neutralizing antibodies. HIV Env is 
synthesized as a gp160 precursor protein, cleaved to gp120 exterior and gp41 
transmembrane subunits by a furin-family protease, and assembled via 
noncovalent interactions into a trimer of gp120-gp41 heterodimers (15). To infect 
a target cell, the gp120 subunit binds the primary host CD4 receptor, thereby 
triggering conformational rearrangements in HIV Env that enable binding to a co-
receptor, either CCR5 or CXCR4 chemokine receptor. Co-receptor binding 
induces further Env-conformational rearrangements, including formation of the 
pre hairpin intermediate and insertion of the fusion peptide (FP) at the N-terminus 
of gp41 into the host cell membrane. Subsequent refolding of gp41 into a post 
fusion six helical bundle leads to fusion of virion and host cell membranes, and 
entry of HIV-1 into the host cell (16, 17). Extensive glycosylation, sequence 
variation, and conformational masking of key neutralizing epitopes on the Env 
allow circulating HIV strains to evade the immune response, and thus poses 
serious challenges for vaccine development. 
2.1 
Study rationale 
In order to test the effect of vaccination with a well-formed HIV envelope trimer 
in humans, the Vaccine Research Center (VRC) has previously developed BG505 
DS-SOSIP.664 (herein Trimer 4571, VRC-HIVRGP096-00-VP; IND 18602), a 
soluble, cleaved HIV-1 Env trimer derived from the clade A BG505 Env gene. 

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The new 201C 433C disulfide mutation (DS) introduced within the gp120 subunit 
of BG505 DS-SOSIP.664 maintains the Env trimer in a prefusion-closed state that 
is resistant to CD4-induced conformational change (18). In preclinical testing, 
Trimer 4571 exhibited the desired target antigenicity with specific recognition by 
broadly neutralizing antibodies (bnAbs) but little to weak binding by non-
neutralizing antibodies, even in the presence of CD4 (18, 19). Immunization with 
prefusion-stabilized SOSIP trimers in multiple animal models has been shown to 
elicit neutralizing responses against autologous or closely matched heterologous 
HIV-1 viruses, although with limited breadth (20-26). Trimer 4571 was tested in 
the VRC 018 study (NCT03783130), a phase 1 clinical trial in healthy adults. As 
of June 2020, the study has been completed, no serious adverse events (SAEs) 
were reported, and study data became available in ClinicalTrials.gov. Overall, the 
Trimer 4571 data demonstrated a good phase 1 safety profile and immunogenicity 
in humans, thus indicating it may be useful as a boosting immunogen in HIV-1 
vaccination protocols. 
One vaccine strategy to induce epitope targeting bnAbs with significant 
neutralization breadth involves the use of epitope-focused immunogens as 
priming reagents followed by boosting with stabilized soluble Env trimers, in 
combination with an adjuvant. Recently, the VRC identified the fusion peptide 
(FP) as a vulnerable region targeted by neutralizing antibodies (27). The FP is a 
hydrophobic stretch of 15-20 residues at the N-terminus of gp41 that plays an 
essential role in the viral entry process. FP embeds in the target cell membrane 
during the pre hairpin intermediate step, where it anchors the rearranging viral 
spike and facilitates fusion of the viral and cell membranes. The N-terminal 
portion of FP is recognized by several broadly neutralizing human antibodies, 
including N123-VRC34.01 (27), PGT151 (28, 29), and ACS202 (30, 31). These 
antibodies are derived from natural infection, and analysis of their recognition 
established the exposed N-terminal half of FP as a site of vulnerability for 
antibody-mediated neutralization (27). 
To evaluate the utility of FP-targeting immunogens to elicit neutralization 
breadth, the VRC created FP-carrier protein conjugates by covalently linking the 
N-terminal 6-10 residues corresponding to the most prevalent sequence of FP 
(FPv1) with an appended cysteine to lysine residues on the keyhole limpet 
hemocyanin (KLH) carrier protein using a heterobifunctional crosslinker. 
Adjuvanted FP-carrier conjugate immunogens could induce broad neutralizing 
FP-directed immune responses in mice capable of neutralizing up to 31% of a 
cross-clade panel of 208 diverse HIV-1 strains (32). Boosting with Trimer 4571, 
administered with the lecithin-carbomer based adjuvant Adjuplex, was found to 
significantly enhance neutralizing titers, especially in guinea pigs and rhesus 
macaques, with vaccine-elicited rhesus antibodies obtained after FP-carrier 
priming and stabilized Env-trimer boosting capable of neutralizing up to 59% of 
the 208-strain panel (33). 

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In a follow-up study, priming with a cocktail of FP-carrier conjugate and Trimer 
4571, prior to boosting with just Trimer 4571, improved autologous potency and 
elicited earlier cross-clade neutralizing responses in rhesus macaques compared to 
priming with FP-carrier conjugate alone (34). This finding suggests that priming 
with an FP-carrier and Trimer 4571 cocktail followed by boosting with HIV-1 
Env Trimer alone could serve as an alternate vaccine strategy capable of 
achieving broad neutralization with potentially fewer immunizations. 
Finally, a heterologous trimer boost strategy was recently shown to further 
improve breadth in guinea pigs. In this study, the animals were given a FP-tetanus 
toxoid carrier (FP8v1-rTTHC) prime, followed by sequential boosts with Trimer 
4571, then Trimer 6931 (a consensus C trimer engineered with a slightly altered 
FP [see Section 2.9]), and finally boosted with a trimer cocktail (Trimer 4571 + 
Trimer 6931). The consistency, breadth and potency of neutralization against a 
panel of representative pseudoviruses was further enhanced with this regimen (34, 
35). 
Overall, these proof-of-concept studies provide substantial evidence that an 
epitope-focused vaccine approach using an FP-carrier protein conjugate and 
prefusion-closed stabilized Env trimers (Trimer 4571 and Trimer 6931) 
administered with an adjuvant (ie, Adjuplex) in prime-boost regimens can elicit 
reproducible, neutralizing immune responses against diverse tier-2 primary 
isolates in animals. This vaccine strategy will be used in the proposed HVTN 303 
clinical study. 
Overall, the goal of the trial is to elicit tier-2 neutralizing antibodies against FP 
with breadth. Key immunological questions to be addressed include: 1) Will 
somatic hypermutation allow focusing on FP during the priming phase?, 2) What 
is the impact of FP priming on inducing a cross-reactive HIV-1 neutralizing 
response?, 3) What are the differences in immune responses and types of 
antibodies elicited by different priming regimens, either priming with FP alone or 
FP in combination with a stabilized Env trimer?, and 4) Will boosting with 
diverse trimers and trimer cocktails induce and expand breadth of neutralization 
responses? This trial continues a project establishing first-in-human data for 
adjuvanted stabilized Env trimers in combination with the adjuvanted FP vaccine, 
which has already shown promise in animal models. Data from this trial will be 
used in design of future antigens and vaccine regimens to increase breadth and 
potency of FP-directed neutralization as a critical step towards development of a 
protective HIV-1 vaccine. 
2.2 
Rationale for evaluation of FP8v1-rTTHC 
Initial studies evaluating an FP-focused vaccine approach used FP conjugated to 
the KLH carrier protein. However, the KLH used as a carrier protein in these 
earlier studies is a multi-subunit metalloprotein of approximately 8 MDa and is 
derived from a natural source, posing challenges to standard manufacturing 

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processes, characterization, and quality control. To identify an FP-based 
immunogen suitable for clinical development, the VRC evaluated several FP-
carrier conjugates made with different carrier proteins used in licensed vaccines, 
and found a non-toxic, truncated variant of tetanus toxoid, recombinant tetanus 
toxoid heavy chain fragment C (rTTHC) (36, 37) to be a suitable candidate carrier 
protein for inducing FP-directed responses (38). The N-terminal eight amino acids 
of the most prevalent FP sequence (FP8v1: AVGIGAVF) conjugated to rTTHC 
carrier protein (FP8v1-rTTHC) elicits FP-directed neutralizing responses in 
multiple animal models when used with the Adjuplex adjuvant. Based on these 
promising attributes, FP8v1-rTTHC was advanced as a candidate vaccine 
immunogen for product development and current good manufacturing practice 
(cGMP) manufacture. 
2.3 
Rationale for evaluation of FP8v1-rTTHC and Trimer 6931 (ConC-
FP8v2 RnS-3mut-2G-SOSIP.664) 
Priming with the most prevalent N-terminal eight residues of the fusion peptide 
(FP8v1) followed by boosting with Trimer 4571 (BG505 DS-SOSIP.664) that 
contains the matching FP8v1 sequence elicits 20-30% neutralization breadth in 
sera from vaccine-test animals (32). While the FP-carrier protein priming is 
important for initiating FP-directed responses (33), Env trimer boosts are critical 
for maturing responses to achieve broad neutralization (32, 33). Additional 
boosting with a heterologous clade C HIV-1 Env trimer increased consistency of 
eliciting broad cross-clade neutralizing responses (33), suggesting a vaccine 
strategy that uses sequential boosting with a heterologous trimer can enhance 
cross-clade FP-directed neutralizing responses. 
To evaluate the utility of a heterologous HIV-1 Env trimer to boost FP-directed 
responses, the VRC designed Trimer 6931 (ConC-FP8v2 RnS-3mut-2G-
SOSIP.664), a prefusion-closed stabilized trimer with a consensus clade C 
sequence and a different fusion peptide sequence from that found in FP8v1-
rTTHC and Trimer 4571. Trimer 6931 is based on the ConC_Base0 variant (39) 
and contains additional stabilizing mutations, 302M, 320L, and 329P (3mut), at 
the trimer apex, two glycine substitutions in gp41 (2G) (40) to further improve 
stability and antigenicity of the trimer in a prefusion-closed form, as well as the 
standard SOSIP substitutions (41) and 7 other stabilizing mutations (39). In 
preclinical studies, Trimer 6931 elicited higher neutralization breadth when used 
as a heterologous trimer boost in guinea pigs immunized with FP8v1-rTTHC and 
Trimer 4571 prime-boost regimen, compared to boosting with Trimer 4571 only, 
as discussed in Section 2.9. 
2.4 
Rationale for Use of the Adjuplex Adjuvant 
Adjuvants improve the elicited immune response to many vaccines (42). Adjuplex 
is a novel adjuvant based on a purified lecithin and carbomer homopolymer. 

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Adjuplex has been established as an effective and well tolerated adjuvant for use 
with different antigens and immunization regimens in animals (43, 44). There is 
limited human experience with Adjuplex (see Section 2.10.2). 
In animal studies, soluble influenza hemagglutinin (HA) protein administered 
subcutaneously (SC) or intranasally with Adjuplex adjuvant at 1-20% by volume 
induced robust antigen-specific CD8+ T lymphocytes (CTLs) responses in mice 
(44). Through histological images of the IM and SC injection sites in the 
Ovalbumin-Adjuplex model in mice, significant correlation was observed 
between increasing dose of Adjuplex and the extent and cellularity of the 
inflammatory infiltrate at the injection site (44). 
In another study in mice, soluble HA of influenza A virus adjuvanted with 
Adjuplex and administered SC has been shown to elicit robust humoral immunity 
and T-cell responses (43). The optimal dose of Adjuplex for immunogenicity was 
1% by volume; HA adjuvanted with 1% of Adjuplex induced high titers of HA-
specific IgG with insignificant weight loss in mice. The vaccine administered with 
the optimal dose of Adjuplex completely protected mice from the lethal influenza 
virus challenge and was comparatively as effective as the adjuvants 
monophosphoryl lipid A (MPL) and alum in preventing disease. No signs of local 
toxicity or intolerance, assessed by swelling or scratching caused by irritation, 
were noted at any Adjuplex dose, suggesting the Adjuplex to be a potent and 
well-tolerated adjuvant for subunit vaccines (43). 
HIV vaccine candidates adjuvanted with the Adjuplex dose of 20% by volume 
were found to elicit reproducible, neutralizing immune responses against diverse 
tier-2 primary isolates in a prime-boost regimen (32). Boosting with Trimer 4571 
after FP priming, with Adjuplex adjuvant, was found to significantly enhance 
neutralizing titers, especially in guinea pigs and rhesus macaques, with vaccine-
elicited rhesus antibodies neutralizing up to 59% of the 208-strain panel (33). 
Adjuplex adjuvant has been shown to enhance immunogenicity of HIV-1 Env 
trimers compared to alum in non-human primates (45). 
Based on VRC pre-clinical data, using the Adjuplex adjuvant elicited a 
statistically significant higher neutralizing responses compared to the alum and 
unadjuvanted groups; therefore, Adjuplex was selected for clinical evaluations in 
HVTN 303 study and further discussed in Section 2.9. 
2.5 
Rationale for Vaccine Regimen and Dose Selections 
The consecutive immunization strategy through the sequential prime-boost 
regimens allows for the ability to induce potent HIV-1 broadly neutralizing 
antibodies (bnAb) in animal studies (46). Investigation of different prime-boost 
regimens may inform on the next generation of HIV-1 vaccines and the 
immunization regimens capable of eliciting durable, cross-reactive serum 
neutralizing antibody responses in humans. The pre-clinical studies provide 

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substantial evidence that an epitope-focused vaccine approach using an FP-carrier 
protein conjugate (FP8v1-rTTHC) and prefusion-closed stabilized Env trimer(s) 
(Trimer 4571 and Trimer 6931) administered with an adjuvant (ie, Adjuplex) in a 
prime-boost regimen can elicit reproducible, neutralizing immune responses 
against diverse tier-2 primary isolates in animals. In addition, they indicate that a 
FP-fusion protein + Trimer 4571 prime cocktail, followed by heterologous boosts 
by each individual trimer and then with a cocktail of the two trimers, has induced 
the broadest neutralizing response to the FP epitope. These animal studies provide 
the rationale for Groups 7 and 8 in Part B of this study, which tests the difference 
in the two priming regimens of FP-conjugate alone (Group 7) or FP-conjugate + 
Trimer 4571 cocktail (Group 8). Group 6 is an essential control arm, which tests 
the relative effects of each booster regimen for Groups 7 and 8. The first 4 doses 
in Group 6 mirror the boosts for Group 7 and the last 3 doses mirror the boost 
doses in Group 8. This will provide important data on the trimers alone and in 
cocktail to induce immunity in combination with Adjuplex and importantly, will 
allow a precise determination the impact of FP and FP + trimer priming. These 
data can confirm whether the animal study results were predictive, and thus can 
inform future product development. 
Doses were chosen to ensure safety of new products and to maximize immune 
response. The recombinant tetanus toxoid heavy chain fragment C (rTTHC) has 
been shown to be safe and effective in multiple vaccines with doses up to at least 
200 mcg (a polysaccharide quadrivalent [A, C, W135, Y]). Neisseria meningitis 
tetanus toxoid conjugate vaccine (47), the FP-conjugate (FP8v1-RTTHC), has not 
been used in humans and will be tested first at 25 mcg (Group 1), the dose used in 
mice (38) and then at the target dose of 200 mcg (Group 2). Given the proven 
safety track record for tetanus toxoid conjugate vaccines, an intermediate step 
dose is not felt to be necessary for safety, and instead the immunological target 
dose will be tested directly in Group 2. In VRC 018, Trimer 4571 was tested at 
100 mcg and 500 mcg in combination with 500 mcg of Alum. Both doses were 
tolerated well and there was a trend towards improved immune response at the 
higher dose of immunogen. Consequently, the target doses for each trimer in this 
study will be 200 mcg, both for improved immunogenicity and to allow a total 
dose of 400 mcg immunogen when trimers are used in combination with the FP-
tetanus toxoid conjugate. As Trimer 6931 has not yet been tested in humans, 
Group 3 will start with 100 mcg of this immunogen. Groups 4 and 5 will test 
maximum dosing of each respective trimer at 200 mcg each. 
Based on previous VRC experience (48), product injections will be split and 
completed at 2 injection sites, 1 on each arm. Separating injections into 2 sites 
would increase germinal center recruitment and therefore could enhance vaccine 
immunogenicity (unpublished animal data). 

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2.6 
Assessment of Immunogenicity 
 
Specimens to evaluate immunogenicity will be collected at baseline and at 
specified time points throughout the study after the administration of product. 
HIV-specific humoral immune responses will be assessed by neutralization 
antibody assays. The primary immunogenicity time point is 2 weeks after the last 
vaccination. 
Trimer 4571- and Trimer 6931-specific antibody titers will be measured by 
Electrochemiluminescence (ELICA) using a Meso Scale Discovery (MSD) 
platform. Other exploratory assays to assess humoral and cellular immune 
responses may be performed with stored samples. 
Measurements of antibody, B-cell and T-cell responses may be assessed from 
stored samples for timepoints throughout the study as exploratory evaluations. 
This includes a number of high-throughput functional assays and high-throughput 
biophysical profiling tools to comprehensively characterize the humoral immune 
response elicited by vaccination regimens. 
Vaccinations were stopped on January 13, 2023, resulting in most (33) 
participants receiving only 1 vaccination and eleven participants in Groups 7 
and 8 receiving 2 vaccinations. Specimens to evaluate immunogenicity were 
collected at baseline and at the specified timepoints after the administration 
of product until March 13, 2023, when the FDA informed DAIDS that the 
IND has been placed on Clinical Hold and confirmed that all protocol-related 
activities must cease except for any participant safety follow-up assessments. 
The primary immunogenicity time point, after the changes to the vaccination 
and collection schedule, remains 2 weeks after the last vaccination, however 
participants only received 1 or 2 vaccinations. Antibody titers will be 
measured by Electrochemiluminescence (ELICA) using a Meso Scale 
Discovery (MSD) platform for all participants with one or two vaccinations 
in Groups 5, 6, 7 and 8. 
Additional exploratory assays to assess humoral and cellular immune 
responses may be performed, including B cell response and neutralization 
antibody assays. 
A specimen collection has been added at approximately 10 months post the 

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2.7 
Rationale for Leukapheresis 
 
Subjects in Groups 6-8 will be encouraged to complete leukapheresis at 2 weeks 
post–last vaccination to collect blood cells of special interest for research. It is 
expected that a subset of participants (about half of the participants in Part B, 
groups 6-8) will agree to undergo leukapheresis. Leukapheresis will be performed 
2 weeks post–last vaccination for subjects who receive the full vaccination 
regimen. The rationale for performing leukapheresis at these timepoints is to 
assess whether rare-epitope–specific B cells and T cells have been stimulated. 
While peripheral blood draws of ~500 mL allow isolation of up to 500 million 
peripheral blood mononuclear cells (PBMCs), these number of cells are often not 
enough to detect an epitope-specific response in the periphery. Leukapheresis, 
however, can provide 6-10 billion PBMCs without depleting red blood cells or 
other blood components and significantly increase the likelihood of detecting 
antigen-specific B and T cells outside lymph nodes. 
2.8 
Study Products 
Study products are manufactured under cGMP regulations by VRC/National 
Institute of Allergy and Infectious Diseases (NIAID)/NIH at the VRC Pilot Plant, 
operated under contract by the Vaccine Clinical Materials Program (VCMP), 
Leidos Biomedical Research, Inc., Frederick, MD USA. 
Manufacturing and preclinical information is included in the Investigator’s 
Brochures (IBs) for each product. Quality assurance lot release testing by the 
manufacturer and ongoing stability programs verify conformance to product 
specifications throughout use in clinical trial. 
The adjuvant in this study, Adjuplex, is a sterile, pyrogen-free suspension 
produced by VRC Pilot Plant. Adjuplex comprises highly purified de-oiled soy 
lecithin and benzene-free carbomer homopolymer formulated in phosphate 
buffered saline (PBS). Adjuplex adjuvant will be mixed with study products 
mentioned below at 20% by volume in the pharmacy during product preparation 
for all vaccinations. 
2.8.1 
VRC-HIVVCP0108-00-VP (FP8v1-rTTHC or FP conjugate vaccine), 
Investigational Vaccine 
The VRC-HIVRGP0108-00-VP vaccine (FP8v1-rTTHC) is a sterile, aqueous, 
buffered solution filled into single-dose vials. The peptide-carrier conjugate, 
Only participants who received two vaccinations in Part B (Groups 7-8) and 
who consent to leukapheresis will undergo leukapheresis at 10 months +/- 2 
months post–last vaccination in order to collect blood cells for research.  

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FP8v1-rTTHC, consists of a carrier tetanus toxoid–derived protein plus a linker to 
chemically attach the fusion peptide (FP). 
2.8.2 
VRC-HIVRGP096-00-VP (Trimer 4571), Investigational Vaccine  
The VRC-HIVRGP096-00-VP vaccine (Trimer 4571) is a sterile, aqueous, 
buffered solution filled into single-dose vials. Trimer 4571 consists of an HIV-1 
envelope trimer variant derived from the clade A HIV-1 strain BG505. It is 
produced in a Chinese Hamster Ovary (CHO) DG44 cell line. 
2.8.3 
VRC-HIVRGP0106-00-VP (Trimer 6931), Investigational Vaccine 
The VRC-HIVRGP0106-00-VP vaccine (Trimer 6931) is a sterile, aqueous, 
buffered solution filled into single-dose vials. Trimer 6931 is a recombinant, 
consensus clade C HIV-1 trimeric envelope glycoprotein. It is produced in a CHO 
DG44 cell line. The envelope glycoprotein molecule contains the second-most 
prevalent sequence for the eight N-terminal FP residues (FP8v2) and additional 
stabilizing mutations (RnS, 3mut, and 2G) to maintain a closed conformation in 
the presence of CD4, further enhancing the likelihood of cross-clade HIV-1 
neutralization when administered as a heterologous trimer boost to FP8v1-
rTTHC. 
2.9 
Preclinical Studies with FP conjugate vaccine, Trimer 4571 and 
Trimer 6931 and Adjuplex 
Preliminary immunogenicity studies in standard vaccine-test animals have 
demonstrated that boosting with Trimer 4571 significantly enhanced neutralizing 
titers in animals primed with an FP-carrier conjugate (32), and subsequent 
boosting with a diverse HIV-1 Env trimer derived from a clade C strain of donor 
CH505 increased consistency of elicited cross-clade neutralizing responses in 
guinea pigs (49). To demonstrate FP8v1-rTTHC immunogenicity and to evaluate 
the utility of Trimer 6931 as a heterologous Env trimer to boost FP-directed 
immune responses, guinea pigs were immunized using a FP8v1-rTTHC/Trimer 
4571 prime-boost regimen and then further boosted with either Trimer 4571 or 
Trimer 6931, with Adjuplex adjuvant (35). Female Hartley guinea pigs were 
immunized intramuscularly (IM) with 25 mcg FP8v1-rTTHC at weeks 0, 4 and 8 
weeks and immunized with 25 mcg Trimer 4571 at weeks 12 and 16. One group 
of animals (n = 6 per group) was boosted further with 25 mcg adjuvanted Trimer 
4571 at weeks 20, 24 and 36. A second group (n = 6 per group) was boosted with 
25 mcg adjuvanted Trimer 6931 at weeks 20 and 24 and given a final 
immunization of 25 mcg of a trimer cocktail at week 36. At week 38, 2 weeks 
after the final immunization, the group boosted with Trimer 6931 showed higher 
serum-neutralization breadth on a panel of 10 heterologous, cross-clade HIV-1 
pseudoviruses compared to the group boosted only with HIV-1 Trimer 4571. 
Overall, this study showed that priming with adjuvanted FP8v1-rTTHC and 
sequential boosting with Trimer 4571 and Trimer 6931 could induce a broadly 

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neutralizing response in guinea pigs and demonstrated the utility of Trimer 6931 
in boosting FP-directed responses. 
Additional preclinical studies were conducted in mice and guinea pigs to evaluate 
immunogenicity of development-grade FP8v1-rTTHC, Trimer 4571 and Trimer 
6931 immunogens, with Adjuplex adjuvant, using different prime-boost regimens. 
Animals (n = 10 per group) were immunized using the following vaccine 
regimens: 1) FP8v1-rTTHC prime followed by sequential boosting with Trimer 
4571, Trimer 6931 and a trimer cocktail or 2) co administration of FP8v1-rTTHC 
and Trimer 4571 followed by boosting with Trimer 6931 and a trimer cocktail. 
Mice were immunized once every 2 weeks and guinea pigs were immunized 
monthly, except for a 2-month interval used between trimer cocktail boosts. For 
both mice and guinea pigs, 25 mcg of a single immunogen or 25 mcg of a trimer 
cocktail or 50 mcg of FP8v1-rTTHC + Trimer 4571 cocktail were administered 
intramuscularly with Adjuplex adjuvant at a 20% (v/v) dose. The data indicated 
that development-grade FP8v1-rTTHC, Trimer 4571 and Trimer 6931 are 
immunogenic in both mice and guinea pigs. Priming with FP8v1-rTTHC 
conjugate, either alone or in combination with Trimer 4571, followed by 
heterologous boosting with Trimer 6931, elicited consistent, autologous BG505 
neutralizing responses in both mice and guinea pigs. Moreover, both FP-primed 
and FP + trimer cocktail-primed vaccine regimens with heterologous Env trimer 
boosts induced cross-clade HIV-1 neutralization in guinea pigs, and boosting with 
a cocktail of Env trimers expanded the breadth and potency of heterologous 
neutralizing responses. Additional details for these preclinical immunogenicity 
studies can be found in the IB. 
A repeat-dose toxicity study of Trimer 4571 formulated with alum adjuvant was 
conducted to evaluate the safety of Trimer 4571 vaccine formulated with adjuvant 
in New Zealand white rabbits when administered intramuscularly (IM) or 
subcutaneously (SC) once every 3 weeks for 4 injections (study days 1, 22, 43, 
and 64). Treatment with the Trimer 4571 vaccine and adjuvant mixture induced 
appropriate antibody responses in the rabbits. All study injections were well 
tolerated, and the study rabbits used in this study survived to the scheduled 
necropsies. Any findings noted did not result in any adverse or limiting toxicity, 
were considered to be of minimal toxicological significance (eg, noted in only 1 
sex, reversible, transient, no alteration in organ function), and were anticipated 
findings (such as fibrinogen increases and mixed cell infiltration at the injection 
sites) following administration of immunogenic substances. 
A repeat-dose toxicity study to evaluate the safety of the 3 HIV-1 vaccine 
candidates (FP8v1-r TTHC, HIV-1 Trimer 4571, and HIV-1 Trimer 6931, 200 
mcg each) alone or in combination with and without Adjuplex adjuvant (20% v/v) 
when administered intramuscularly (IM) every 3 weeks for 3 (FP8v1-rTTHC with 
or without Trimer 4571) or 4 (Trimers 4571 and 6931) injections was conducted 
in New Zealand white rabbits. Toxicity and reversibility of effects were evaluated 
after acute and recovery time points. The study was conducted in compliance with 

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the US Food and Drug Administration (FDA) Good Laboratory Practice (GLP) 
Regulations (21 CFR Part 58). Treatment with the HIV-1 vaccine candidates was 
well tolerated, did not result in any animal deaths and induced appropriate 
antibody responses in the rabbits. The treatments did not result in any treatment-
related adverse clinical signs or toxicologically significant or adverse findings. 
2.10 
Previous Human Experience 
There is no human experience with the FP conjugate vaccine (VRC-HIVVCP018-
00-VP) or Trimer 6931 (VRC-HIVRGP0106-00-VP) prior to this trial. 
2.10.1 
Trimer 4571 
2.10.1.1 
Prevention studies 
I. VRC 018 
Trimer 4571 was evaluated under protocol VRC 018, “A Phase 1 Dose 
Escalation, Randomized, Open-Label Clinical Trial to Evaluate Dose, Safety, 
Tolerability and Immunogenicity of a HIV-1 Vaccine, VRC-HIVRGP096-00-VP, 
with Alum in Healthy Adults” (NCT03783130). This first-in-human study, 
conducted at the NIH Clinical Center in Bethesda, MD, was completed in June 
2020. The VRC018 study evaluated Trimer 4571 at doses of 100 mcg or 500 mcg, 
field mixed with 500 mcg of aluminum hydroxide suspension (alum) adjuvant 
prior to injection, and administered via IM or SC injections at day 0, week 8 and 
week 20. Sixteen healthy adults, ages 22-48 years old, enrolled in the study; 6 
participants received a 100-mcg dose (3 participants by IM and 3 by SC route) of 
Trimer 4571 and 10 participants received a 500-mcg dose (5 by IM and 5 by SC 
route). 
As of August 2021, final data from this study are available and have been posted 
on ClinicalTrials.gov (NCT03783130). Overall, Trimer 4571 with alum adjuvant 
was well-tolerated with no reported SAEs or unexpected reactions, and no study 
pause criteria were met at any time. 
Mild injection site pruritis following second or third product administration was 
the most frequently recorded unsolicited adverse event (AE), reported for 6/16 
(37.5%) participants. All injection site pruritis events were assessed as related to 
study product, lasted between 1 and 9 days, and resolved with no residual effects.  
The only other AE assessed as related to study product was a mild asymptomatic 
neutropenia recorded for a Group 3 (500 mcg IM) participant 7 days after the 
second product administration, and which resolved 8 days after onset with no 
residual effects. Solicited local and systemic reactogenicity symptoms were 
reported through 7 days post Trimer 4571 product administration. Symptoms of 
local reactogenicity were reported by 14 of 16 participants (87.6%), with mild 
pain/tenderness at the injection site being the most frequently reported symptom. 

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Symptoms of solicited systemic reactogenicity were reported by 11 of 16 
participants (68.8%). 
Local Reactogenicity 
For the 100-mcg recipients, mild pain/tenderness at the injection site was the most 
frequent local symptom reported by 2 of 3 (66.7%) participants who received the 
IM or the SC injection, respectively. No other local symptoms were reported by 
participants who received 100-mcg IM. Among participants who received the 
100-mcg SC injection, 2 of 3 (66.7%) participants reported mild to moderate 
swelling and 2 of 3 (66.7%) participants reported moderate redness. All solicited 
events in the 100-mcg groups resolved within the 7-day solicited period except for 
1 report of pain/tenderness by a 100-mcg IM recipient, which occurred after the 
first product administration and resolved on day 8. 
For the 500-mcg groups, 100% of the participants who received IM or SC 
injections reported at least 1 local symptom, with mild pain/tenderness at the 
injection site reported by 10/10 (100%) participants. One of 5 (20.0%) IM 
recipients reported moderate swelling after the second product administration and 
moderate redness after the third product administration. One of 5 (20.0%) SC 
recipients reported moderate swelling and severe redness, and 1 of 5 (20%) SC 
recipients reported mild redness after the first product administration. The 
moderate swelling resolved 1 day after the solicited period on day 8. All other 
events resolved within the solicited period. 
Systemic Reactogenicity  
Overall, for the 100-mcg groups, 1 of 3 (33.3%) participants who received the IM 
injection and 2 of 3 (66.7%) participants who received the SC injection reported 
at least 1 mild systemic symptom. Mild headache was the most frequent 
symptom, reported by 1 of 3 (33.3%) IM recipients and 2 of 3 (66.7%) SC 
recipients. One SC recipient reported moderate malaise and moderate nausea after 
the first product administration, and mild malaise after the second and third 
product administration. All events resolved within the 7-day solicited period 
except for 1 report of mild myalgia by a 100-mcg IM recipient, which occurred 
after the third product administration and resolved 6 days after the solicited 
period. 
For the 500-mcg groups, 5 of 5 (100.0%) IM recipients and 3 of 5 (60.0%) SC 
recipients reported at least 1 mild systemic symptom. Mild myalgia was the most 
frequent symptom, reported by 4 of 5 (80.0%) IM recipients and 1 of 5 (20.0%) 
SC recipients. Mild malaise was reported by 2 of 5 (40.0%) IM and SC recipients, 
respectively. Mild headache was reported by 1 of 5 (20.0%) IM recipients and 1 
of 5 (20.0%) SC recipients. Mild nausea was reported by 1 of 5 (20.0%) SC 
recipients. All events resolved within the solicited period. There were no reports 
of fever or severe systemic solicited reactogenicity symptoms. 

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Immunogenicity: 
Immunogenicity of Trimer 4571 was evaluated by measurement of the trimer-
specific antibody in serum samples by Electrochemiluminescence (ECLIA) using 
a Meso Scale Discovery (MSD) platform at baseline and at 2 weeks after the third 
product administration. Trimer 4571–specific antibody titers were below the 
negative cut off values in all groups at baseline. All dose groups displayed 
detectable antibody responses at 2 weeks after regimen completion (week 22) 
with the geometric mean AUCs of 674 (95% CI 50-9011), 924 (95% CI 175-
4880), 2,529 (95% CI 387-16515), and 1,368 (95% CI 551-3397) for the 100-mcg 
IM, 100-mcg SC, 500-mcg IM, and 500-mcg SC dose groups, respectively. 
Trimer 4571 induced antibodies that were detected by antigen (Ag)/antibody (Ab) 
Combination HIV testing in participants who confirmed to be HIV negative by 
polymerase chain reaction (PCR). This reaction is referred to as vaccine-induced 
seropositivity (VISP). The VRC 018 trial used the VITROS 3600 system Ag/Ab 
detection assay at the NIH Clinical Center for clinical testing. Samples collected 
from 7 of 16 participants (43.8%) were reactive in the assay, and therefore 
seropositive, but participants were confirmed as HIV negative by PCR. Of the 7 
participants who were seropositive, 1 was a 100-mcg recipient and 6 were 500-
mcg recipients. Six of 7 participants with VISP reverted back to non-reactive on 
later testing. It is unknown whether the remaining 1 participant (500-mcg 
recipient) reverted back to non-reactive, as the final follow-up visits were 
conducted by the telephone, but blood samples were not collected due to the 
coronavirus disease 2019 (COVID-19) public health emergency stay-at-home 
orders. 
II. NIH-19-I-0069 Phase 1 Study (NCT03878121) [Source: Information 
provided by Vaccine Research Center (VRC)] 
Protocol NIH-19-I-0069 is an open-label phase 1 study of recombinant adenovirus 
serotype 4 (Ad4)-based HIV envelope (Env) vaccines administered intranasally to 
healthy volunteers. Each study vaccinee (n~100) will receive 1 of 2 Ad4-HIV 
vaccines at months 0 and 2, followed by a booster vaccination with 500 mcg of 
the heterologous soluble trimeric protein VRCHIVRGP096-00-VP (HIV-1 Trimer 
4571) with alum, administered as an intramuscular (IM) injection at month 6. 
The study was initiated in February 2019 and is ongoing.  
As of March 31, 2023, 21participants have enrolled in the trial and 15 participants 
have received HIV-1 Trimer 4571 with alum adjuvant, 500 mcg by IM route at 
Month 6 of trial participation. Doses of Trimer 4571 were given as a boost 4 
months after administration of the second dose of Ad4-Env145NFL or Ad4-
Env150KN intranasally (administered at months 0 and 2). 
Overall, Trimer 4571 product administrations have been generally well tolerated 
with 39 reported reactogenicity events after trimer 4571 dosing, 8 of which were 

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judged to be definitely, possibly or possibly related to Trimer 4571 
administration. Solicited local reactions of mild pain at the injection site was 
reported by 1 of 15 (6.7%) participants. Mild to moderate headache reported by 5 
(33.3%) participants and mild to moderate fatigue reported by 3 (20%) 
participants. No unsolicited events were assessed as related to study product. 
There were no SAEs reported and no adverse events resulted in the Trimer 4571 
product discontinuation in any participant. There have been no SUSARs reported 
to the FDA and no study pauses due to safety concerns. 
III. HVTN 137 (NCT04177355) 
HVTN 137 is 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 
specifically, VRC HIV Env Trimer 4571 and TLR agonist, 3M-052-AF, with 
alum in healthy, HIV-uninfected adults. Part C Group 8, the only group including 
Trimer 4571, will enroll 10 participants (10:1 vaccine to placebo ratio) to receive 
Trimer 4571 100 mcg adjuvanted with 5 g 3M-052-AF and 500 g alum 
administered IM and placebo (N = 1) at Days 0 and 56 with an optional third dose 
at Day 168.  
The study began enrolling on February 5, 2023. As of May 1, 2023, 11 
participants have received the first of 3 planned administrations of Trimer 4571 
with 3M-052-AF or placebo. Five (5) participants have received the second dose. 
Overall product administrations have been generally well-tolerated with reported 
reactogenicity of mostly mild to moderate in severity. Solicited injection site pain 
and/or tenderness was reported by 8 of 11 (73%) participants (7 mild, 1 
moderate). Mild induration at the injection site was reported by 1 (9%) 
participant. No participants reported gradable injection site erythema. Solicited 
systemic reactions were reported by 9 (81.8% participants, including 2 (18%) 
with mild symptoms, 6 (55%) with moderate symptoms, and 1 (9% with severe 
symptoms. Systemic events included: malaise/fatigue (n=2 mild, n=5 moderate, 
n=1 severe); myalgia (n=2 mild, n=4 moderate, n=1 severe); headache (n=2 mild, 
n=3 moderate, n=1 severe); nausea (n=3 mild, n=2 moderate); chills (n=2 mild, 
n=1 moderate, n=1 severe); arthralgia (n=2 mild, n=1 severe); and fever (n=3 
mild).  
Three (3) unsolicited adverse events have been reported by 2 (18.2%) 
participants. One participant reported 2 events that were determined to be related 
to study product: mild decreased appetite of 10 days duration and mild brain fog 
lasting 2 days. Both events resolved without sequelae.  
There have been no SAEs and no adverse events resulting in product 
discontinuation of Trimer 4571. 

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2.10.1.2 
Therapeutic studies 
Native-like Envelope Trimer Immunization (NETI) Phase 1 Study 
(NCT04985760) [Source: information provided by Vaccine Research Center 
(VRC)] 
The NETI protocol is a phase 1; randomized, double-blind, dose escalation 
clinical trial to assess the safety, tolerability, and immunogenicity of vaccination 
with Trimer 4571 in adults living with HIV-1 on suppressive ART. Both groups 
are randomized 3:1 Trimer 4571: vaccine control with alum and administered 
study product by IM injection as follows: 
• Group 1 will receive 100 g of Trimer 4571 with 500 mcg of alum (active, 
n=6) or volume matched PBS with 500 g alum (control, n= 2) at weeks 0, 8 
and 20. 
• Group 2 will receive 500 g of Trimer 4571 with 500 mcg of alum (active, 
n=18) or volume matched PBS with 500 g alum (control, n=6) at weeks 0, 8 
and 20. 
• Group 2A (n=8) will enroll participants without evidence of precursor broadly 
neutralizing antibody at screening. 
• Group 2B (n=16) will enroll participants with evidence of precursor broadly 
neutralizing antibody at screening. 
The first participant enrolled and received study product on September 30, 2021. 
As of March 31, 2023, the study is ongoing and 16 participants have received 
either a 100 mcg dose of Trimer 4571 with alum or vaccine control by IM route. 
A total of 16 participants have received two doses of study product and 9 have 
received three doses of study product. Overall product administrations have been 
generally well tolerated with all reported reactogenicity of grade 1 or grade 2 in 
severity. 
Solicited local reactions were reported by 14 of 16 (87.5%) participants including 
injection site tenderness (n=11, 68.8%) and injection site pain (n=6, 37.5%). 
Local symptoms were mild in severity with the exception of 1 participant 
reporting moderate tenderness. Solicited systemic reactions were reported by 7 
(43.8%) participants including fatigue (n=5, 31.3%), arthralgia (n=2, 12.5%), 
myalgia (n=3, 18.8%), headache (n=2, 12.5%) and 1 (6.3%) reported instance 
each for chills, malaise, and nausea. One (6.3%) participant reported headache; 
one (6.3%) reported fatigue; and one (6:3%) reported myalgia after both first and 
second dose of study product. Of the 40 solicited events reported, 34 (85.0%) 
were mild and 6 (15.0%) were moderate in severity. 
Thirteen (81.3%) participants reported unsolicited adverse events, and 4 events 
were determined to be possibly or probably related to study product due to 

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temporal association. One participant experienced new onset eczema, moderate in 
severity 14 days after first dose of study product, which resolved but recurred 2 
days prior to second dose of study product in a localized area after application of 
local heat. This participant noted mild worsening two days after third dose of 
study product, which improved with topical steroid application. One subject 
reporting flushing of the left face, neck and shoulder on the day of first product 
administration and a tender lymph node in the neck on the day of second study 
product administration. Both events resolved the same day. 
There were 2 SAEs reported: 1 hospitalization due to acute cholecystitis and 1 
hospitalization due to COVID-19 pneumonia, both events were assessed as 
unrelated to study product. A planned interval cholecystectomy for the participant 
with acute cholecystitis demonstrated incidental finding of gallbladder 
adenocarcinoma on the resected gallbladder pathology, assessed as unrelated to 
study product, and subsequently, per investigator discretion, the third dose of the 
study product was not administered. The participant with COVID-19 pneumonia 
received a contraindicated medication and per study protocol the third dose of 
study product was discontinued. There were no related SAEs. There have been no 
SUSARs reported to the FDA or other regulatory agency and no study pauses due 
to safety concerns. 
2.10.2 
Adjuplex 
Adjuplex is currently being tested in the following studies: 
• A Phase 1 clinical study of a mosaic quadrivalent influenza vaccine 
(NCT04896086). 
• A Phase 1 clinical study of an adenovirus-vectored vaccine against cocaine 
(NCT02455479). A summary of the cocaine vaccine study objectives and 
endpoints, a well as study contact information, can be found on the 
ClinicalTrials.gov website. 
• A Phase 1 clinical study (HVTN 303, NCT05470400) with Adjuplex 
combined with HIV vaccine antigens 
2.10.3 
Experience in this study (HVTN 303) to date 
Local and systemic reactogenicity, adverse events, and transient increases in 
absolute eosinophil counts  
Two participants reported grade 3 fever on day 1 after first vaccination that 
resolved the same day (Group 7) or the next day (Group 8). 
Across Groups 3, 5, 6, 7, and 8, there were 6 participants who reported grade 3 
injection site reactions of erythema (4 participants); induration/swelling (1 
participant); or both (1 participant) after first or second vaccination, with onset on 

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days 1, 2, 5, 6, 7 or 8 post-vaccination. A Group 5 participant with grade 3 
erythema and grade 3 induration/swelling also reported pain in thumb and knee 
with possible swelling over his right metacarpal joint; however, at the time of 
reporting, possible alternative etiologies for these joint symptoms were 
considered. 
One group 8 participant was diagnosed with serum sickness, with onset on day 8 
post first vaccination. The participant was prescribed oral corticosteroids, and all 
symptoms resolved within approximately 2 weeks. The participant was 
discontinued from study vaccinations.  
A second Group 8 participant experienced grade 3 fever one day post first 
vaccination that lasted 1 day. Two weeks post-vaccination, the participant 
reported a small area of erythema on the chest that was pruritic, bruising above 
the right antecubital fossa, right armpit pain/tenderness, and sore throat. All 
symptoms were resolved after 7 days. One week post 2nd vaccination, the 
participant reported a nickel-sized area of urticaria/erythema on the right shin that 
was pruritic and blanched slightly with pressure; the rash resolved after 8 days.  
A Group 7 participant reported pruritis and slightly area of redness at/near the 
injection sites of both arms, with onset two days post second vaccination. The 
symptoms resolved after 4 days. 
In addition, several participants had a transient increase in absolute eosinophil 
count (AEC) after vaccination. None of the participants with elevated AECs had 
grade 3 erythema, induration or fever; none had symptoms associated with the 
AEC increase; none required any treatment or medical care. All elevated values 
returned to within laboratory reference range. 
2.11 
Risks and benefits 
2.11.1 
Risks of the Vaccines: 
This is the first study in humans of the investigational vaccines FP8v1-rTTHC 
and Trimer 6931; therefore, risks are unknown at the time of study start. 
The signs and symptoms associated with administration of a similar vaccine, 
Trimer 4571, are discussed in Section 2.10.1. 
Most of the risks noted are based on risks of vaccines in general. Potential side 
effects resulting from intramuscular injections include stinging, discomfort, 
redness of skin, or mild bruising at vaccine injection site. As with any injection 
procedure, infection at the site of injection is a possible risk. Signs of infection at 
the injection site include severe pain, redness, swelling, warmth or drainage. 

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Participants may exhibit general signs and symptoms associated with 
administration of the vaccine injection, including fever, chills, rash, aches and 
pains, nausea, dizziness and fatigue. These side effects will be monitored, but are 
generally short term, mild to moderate severity and usually do not require 
treatment. 
There may be side effects from the study products, which may be serious or life 
threatening, that we do not know about yet. 
These vaccines are intended to generate antibodies, which may cause a positive or 
indeterminate HIV antibody result in standard diagnostic tests that may have a 
negative employment and social impact. HIV PCR will be used to exclude or 
confirm HIV infection.  
The majority of the human population is immune to tetanus toxoid via 
vaccination. Since the fragment used in FP8v1-rTTHC (FP conjugate) vaccine is 
not a complete tetanus toxoid, but rather just the heavy chain it is most likely will 
not be immunogenic. No risks are expected from the tetanus toxoid fragment. 
2.11.2 
Risks of Adjuplex 
Adjuplex is a novel adjuvant platform and therefore, risks are broadly unknown at 
the time of study start. As described in Section 2.8, one of Adjuplex components 
is soy lecithin. Highly purified soy lecithin that is used for Adjuplex preparation 
does not contain soy protein residues that are linked to induction of an allergic 
reaction to soy, and therefore an allergic reaction to the Adjuplex is highly 
unlikely (50, 51). 
Based on experience with Adjuplex in animal studies described in Section 2.4, 
potential inflammatory reactions at injection site may be expected, similar to the 
injection site reactions observed with other adjuvants. 
In a single human phase 1 study described in Section 2.10.2 (NCT02455479), 
injections of either a vaccine adjuvanted with Adjuplex or Adjuplex alone have 
been well tolerated, with injection site pain, soreness and tenderness, and 
occasional fever reported. As of 10 December 2021, there was only one SAE 
reported in the study, and it was attributed to cocaine drug use, not the vaccine or 
adjuvant. 
Potential inflammatory reactions at the injection site may be expected, similar to 
the injection site reactions observed with other adjuvants. This can manifest as 
mild to severe pain, redness, and swelling at the site of administration. When 
combined with a vaccine, Adjuplex may cause more frequent or severe systemic 
reactions, such as fever, chills, myalgia, or malaise, compared to formulations 
containing the vaccine only. Rash, urticaria and transient elevated absolute 
eosinophil counts and one event of serum sickness have been observed after 
administration of Adjuplex-adjuvanted vaccines.  

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There is a limited experience with Adjuplex in humans, there may be other 
unknown side effects. 
2.11.3 
Other risks 
A skin biopsy is a generally safe procedure. However, complications such as 
bleeding, pain, bruising, and scarring, and rarely an infection can occur. 
2.11.4 
Benefits 
Study participants will not receive direct health benefit from study participation. 
Others may benefit from knowledge gained in this study that may aid in the 
development of an HIV vaccine. The investigational vaccine is not expected to 
provide protection from HIV infection. 
Participants may benefit from more frequent counseling, laboratory tests and 
physical exams while enrolled in the study. Participants may also experience 
positive social impacts as a benefit of study participation. When asked, 
participants say that being in a study made them feel good about helping others, 
increased their knowledge about HIV, and improved their self-esteem. 

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3 
Objectives and endpoints 
3.1 
Primary objectives and endpoints 
Primary objective 1: 
To evaluate the safety and tolerability of the following regimens in healthy adults: 
• Adjuvanted FP conjugate vaccine administered IM at a dose of 25 or 200 mcg, 
• Adjuvanted Trimer 6931, administered IM at a dose of 100 or 200 mcg, 
• Adjuvanted Trimer 4571 administered IM at 200 mcg, or 
• Prime-boost vaccination regimen of FP conjugate and Trimer 4571. 
Primary endpoint 1: 
Local and systemic reactogenicity signs and symptoms, laboratory measures of 
safety, and adverse and serious adverse events. 
SAEs, medically attended adverse events (MAAEs), adverse events of special 
interest (AESIs) and AEs leading to early participant withdrawal or permanent 
discontinuation which will be collected throughout the study and for 12 months 
following any receipt of study product. Additionally, all adverse events will be 
collected for 28 days after any receipt of study vaccination. All safety lab related 
adverse events will be collected throughout duration of study. 
Primary objective 2: 
To evaluate the ability of FP-conjugate and Trimer 4571 vaccines to elicit FP-
specific binding antibodies in Part B participants. 
Primary endpoint 2:  
On January 13, 2023, a protocol memo was distributed informing the clinical 
research sites that all vaccinations in HVTN 303 were permanently 
discontinued. Due to permanent discontinuation of vaccinations, none of the 
participants received Trimer 6931 in prime-boost regimen. Collection of 
immunogenicity samples was stopped on March 13, 2023. Sections 2.6 and 3 
are the revised version of the original protocol (v1.0) as per the availability of 
the samples and the content of the current protocol version 2.0.  

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Magnitude and response rate of serum antibody binding of FP and envelope 
trimer antigens as measured by the MSD assay 2 weeks after the last vaccination. 
3.2 
Exploratory objectives 
Exploratory objective 1: 
Mapping of FP-specific serum neutralizing activity 
Exploratory objective 2: 
To evaluate the ability of the vaccine regimen to elicit early FP broad neutralizing 
antibody memory B-cell lineages. 
Exploratory objective 3: 
To evaluate the humoral and cellular immune response to vaccination regimens 
including FP-conjugate vaccine and Trimer 4571 to compare responses between 
the regimens. 
Exploratory objective 4: 
To conduct analyses related to furthering the understanding of HIV, immunology, 
vaccines, and clinical trial conduct. 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. 

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4 
Laboratory strategy  
The laboratory strategy for this protocol will focus on interrogations of the 
humoral and cellular immune response as it relates to the ability of FP-conjugate 
and Trimer 4571 vaccines to elicit FP-specific binding antibodies. the elicitation 
of broadly neutralizing antibodies. Magnitude, breadth, kinetics and durability of 
serum neutralizing antibodies will be assessed by using vaccine-matched and non-
matched (heterologous) tier 2 HIV-1 Env-pseudotyped viruses in the TZM-bl 
assay. Serum antibodies will be further interrogated by measuring IgG binding to 
the vaccine antigens and a specialized set of epitope domain-specific antigens. A 
role for T-cell help will be investigated by assessing antigen-specific CD4+ T 
cells by intracellular cytokine staining as measured by flow cytometry. To gain 
further insights into the requirements for broadly neutralizing antibody induction, 
exploratory studies may be conducted to assess antigen-specific B-cell 
frequencies and to interrogate B-cell lineages that give rise to FP-specific 
antibodies in vaccine recipients. Serum neutralizing antibodies may also be 
assessed in the TZM-bl assay. The detailed laboratory strategy and the technical 
details are described in the Central Assay Plan and will be updated as new 
reagents and techniques are incorporated into assay planning. This document will 
be available on the protocol webpage. Descriptions of the standard HVTN 
laboratory assays can be found online at 
https://www.hvtn.org/content/dam/hvtn/scientific-programs/hvtn-laboratory-
assay-descriptions.pdf 

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5 
Study design 
This is an open-label, dose-escalation study to examine the safety, tolerability, 
and immunogenicity dose of adjuvanted Fusion Peptide Vaccine alone or in 
prime-boost regimens with adjuvanted Trimer 4571 and Trimer 6931 vaccines in 
healthy adults. The hypothesis is that the vaccines will be safe, tolerable for 
human administration and will induce detectable immune response. 
5.1 
Study population 
All inclusion and exclusion criteria must be met for eligibility. Screening 
procedures to determine eligibility must be performed within 56 days prior to 
enrollment. 
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. 
5.1.1 
Inclusion criteria 
1. Able and willing to complete the informed consent process, including an 
Assessment of Understanding (AoU): volunteer demonstrates understanding of 
this study, completes a questionnaire prior to first vaccination with verbal 
demonstration of understanding of all questionnaire items answered incorrectly.  
2. 18-50 years old, inclusive, on day of enrollment. 
3. Agrees to comply with planned study procedures and be available for clinic 
follow-up through the last clinic visit. 
4. Agrees not to enroll in another study of an investigational agent during 
participation in the trial, including severe acute respiratory syndrome coronavirus 
2 (SARS-CoV-2) investigational agents that may subsequently obtain emergency 
use authorization (EUA) or undergo licensure by the FDA. If a potential 
participant is already enrolled in a SARS-CoV-2 clinical trial, prior approvals 
from the SARS-COV-2 study sponsor and HVTN 303 PSRT are required prior to 
enrollment in HVTN 303. 
5. In good general health without clinically significant medical history. 
6. Physical examination and laboratory results without clinically significant findings 
that would interfere with assessment of safety or reactogenicity.  

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7.  Body Mass Index (BMI) ≤ 40. 
8. Assessed as low risk for HIV acquisition as per Appendix K, agrees to discuss 
HIV infection risks, agrees to risk reduction counseling, and agrees to avoid 
behavior associated with high risk of HIV exposure through the final study visit. 
Low risk may include persons stably taking pre-exposure prophylaxis (PrEP) as 
prescribed for 6 months or longer (see Appendix K for protocol safety review 
team [PSRT)] consultation requirements). 
9. Suitable injection sites in the deltoid muscle of each arm, as assessed by a 
clinician. 
Laboratory Criteria within 56 days prior to enrollment: 
10. White blood cells (WBCs) 2,500-12,000/mm3 
11. WBC differential either within institutional normal range or approved by the 
Investigator of Record (IoR) as “not clinically significant.” 
12. Platelets = 125,000 – 500,000/mm3 
13.  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 participants who have been on hormone therapy for less than 
6 consecutive months, determine hemoglobin eligibility based on the sex 
assigned at birth  
14. Serum creatinine ≤ 1.1 x upper limit of normal (ULN) based on the institutional 
normal range. 
15. Alanine aminotransferase (ALT) ≤1.25 x ULN based on the institutional normal 
range. 
16. Negative for HIV infection by an (US) Food and Drug Administration (FDA)-
approved enzyme immunoassay (EIA) or chemiluminescent microparticle 
immunoassay (CMIA).  

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17. Negative for anti-Hepatitis C antibodies (anti-HCV) or negative HCV nucleic acid 
test (NAT) if anti-HCV antibodies are detected. 
18. Negative for Hepatitis B surface antigen. 
For a volunteer capable of becoming pregnant: 
19. Agrees to use effective means of birth control from at least 21 days prior to 
enrollment through 12 weeks after the last product administration. 
20. Negative β-HCG (beta human chorionic gonadotropin) pregnancy test (urine or 
serum) at screening and prior to each study product administration on the day of 
study product administration. 
5.1.2 
Exclusion criteria 
1. Active duty and reserve US military personnel 
For a volunteer capable of becoming pregnant:  
2. Breast-feeding or planning to become pregnant from at least 21 days prior to 
enrollment through 12 weeks after the last product administration. 
Participant has received any of the following:  
3. An investigational HIV vaccine (previous placebo recipients are not excluded). 
4. 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). 
5. Blood products within 60 days prior to enrollment 
6. Monoclonal antibodies (mAbs), whether licensed or investigational. Exceptions 
may be made by the HVTN 303 PSRT on a case-by-case basis 
7. Receipt of any of the following: 
• Within 4 weeks prior to enrollment: 
▪ Any licensed live, attenuated vaccine (except for the Jynneos monkeypox 
vaccine)  
▪ Any adenoviral-vectored SARS-CoV-2 vaccine with FDA Emergency Use 
Authorization (EUA), FDA licensure or World Health Organization 
(WHO) Emergency Use Listing (EUL) 

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▪  ACAM2000 vaccine for Monkeypox 
▪ ACAM2000 received greater than 4 weeks prior to enrollment but 
vaccination scab is still present 
• Within 2 weeks prior to enrollment: 
▪ Any licensed killed/subunit/inactivated vaccine 
▪ Any mRNA based or protein SARS-CoV-2 vaccines with FDA EUA, 
FDA licensure, or WHO EUL 
▪ Jynneos Monkeypox vaccine for Monkeypox 
Receipt of any SARS-CoV-2 vaccination series should be completed 4 weeks 
prior to enrollment when possible. 
8. Investigational research agents with a half-life of 7 or fewer days within 4 weeks 
prior to enrollment. If a potential participant has received investigational agents 
with a half-life greater than 7 days (or unknown half-life) within the past year, 
PSRT approval is required for enrollment.  
9. Current allergen immunotherapy with antigen injections, unless on maintenance 
schedule.  
10. Current anti-TB prophylaxis or therapy.  
Participant has any of the following:  
11. Serious adverse reactions to vaccines or vaccine components.  
12. Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema.  
13. Hypertension that is not well controlled.  
• 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. 

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14. Asthma is excluded if the participant has ANY of the following:  
• Required either oral or parenteral corticosteroids for an exacerbation two or 
more times within the past year; OR  
• Needed emergency care, urgent care, hospitalization, or intubation for an 
acute asthma exacerbation within the past year (eg, would NOT exclude 
individuals with asthma who meet all other criteria but sought 
urgent/emergent care solely for asthma medication refills or co-existing 
conditions unrelated to asthma); OR  
• Uses a short-acting rescue inhaler more than 2 days/week for acute asthma 
symptoms (ie, not for preventive treatment prior to athletic activity); OR  
• Uses medium-to-high-dose inhaled corticosteroids (greater than 250 mcg 
fluticasone or therapeutic equivalent per day), whether in single-therapy or 
dual-therapy inhalers (ie, with a long-acting beta agonist [LABA]); OR  
• Uses more than one medication for maintenance therapy daily. Inclusion of 
anyone on a stable dose of more than one medication for maintenance therapy 
daily for greater than two years requires PSRT approval.  
15. Autoimmune disease, current or history, including psoriasis. 
16. Clinically significant immunodeficiency. 
17. 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 M) 
18. 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.). 
19. Diabetes mellitus type 1 or type 2. 
20. Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or 
platelet disorder requiring special precautions) or significant bruising or bleeding 
difficulties with IM injections or blood draws.  
21. Seizure disorder other than: 1) febrile seizures, 2) seizures secondary to alcohol 
withdrawal more than 3 years ago, or 3) seizures that have not required treatment 
within the last 3 years.  
22. Asplenia or functional asplenia. 

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23. 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). 
24. Any other chronic or clinically significant condition that in the clinical judgement 
of the investigator would jeopardize the safety or rights of the study participant, 
including, but not limited to: clinically significant forms of drug or alcohol abuse, 
serious psychiatric disorders, or cancer that, in the clinical judgement of the site 
investigator, has a potential for recurrence (excluding basal cell carcinoma).  
5.1.3 
Leukapheresis Eligibility Criteria 
Part B (groups 6-8) participants who consent to leukapheresis (see Section 2.7) 
will be asked to undergo leukapheresis at 2 weeks post–last vaccination in order 
to collect blood cells of special interest for research. These participants must meet 
all of the following criteria: 
1. Weight ≥ 110 pounds 
2. Meeting local site requirements related to these procedures (eg, any specific 
hemoglobin level requirements by pheresis center) 
3. Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test (urine or 
serum) performed by a study clinician within 72 hours prior to the apheresis 
procedure 
5.2 
Participant departure from vaccination schedule or withdrawal  
 
5.2.1 
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: 
Only participants who received two vaccinations in Part B (Groups 7-8) and 
who consent to leukapheresis will undergo leukapheresis at 10 months +/- 2 
months post–last vaccination in order to collect blood cells for research. 
On January 13, 2023, a protocol memo was distributed informing the 
clinical research sites that all vaccinations in HVTN 303 were 
permanently discontinued. Hence, the language that are no longer 
relevant for this amendment is marked with strikethrough. 

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• Intercurrent illness or pre vaccination abnormal vital signs or clinical 
symptoms that may mask assessment of vaccine reaction 
• Treatment with systemic glucocorticoids (eg, prednisone or other 
glucocorticoid), with the exception that study injection may continue per 
principal investigator (PI) discretion if the next study injection occurs at least 
2 weeks following completion of glucocorticoid treatment 
• Receipt of any live attenuated vaccines within 4 weeks prior to study vaccine 
administration 
• Receipt of any inactivated vaccines within 2 weeks prior to study vaccine 
administration with exceptions as below: 
• Timing of study vaccination with respect to SARS-CoV-2 vaccination: if the 
SARS-CoV-2 vaccination series was not completed prior to enrollment, 
attempt to time SARS-CoV-2 vaccination no closer than 2 weeks (for protein 
vaccines and mRNA-based vaccines) or 4 weeks (for adenoviral-vectored) 
before or after study vaccination. 
• Timing of study vaccination with respect to Monkeypox vaccination: attempt 
to separate study vaccination from administration of Monkeypox vaccine prior 
to study enrollment, or during study based on the instruction below: 
▪ Jynneos vaccine:  
▪ after administration of Jynneos vaccine, a minimum of 2 weeks is 
required before administration of study vaccine  
▪ after study vaccine administration, a minimum of 2 weeks is required 
before administration of Jynneos vaccine 
▪ ACAM2000 vaccine: (Note: in addition to the instructions mentioned 
below, sites should consult with HVTN 303 PSRT for any participants who 
may be scheduled to receive ACAM2000 vaccine after enrollment) 
▪ after administration of ACAM2000 vaccine, a minimum of 4 weeks is 
required before administration of study vaccine; if vaccination scab is 
not present  
▪ if ACAM2000 vaccine is received greater than 4 weeks prior to 
enrollment but vaccination scab is still present, delay study vaccination 
until the scab is no longer present 
▪ after study vaccine administration, a minimum of 2 weeks is required 
before administration of ACAM2000 vaccine 
Vaccinations should not be administered outside the visit-window period 
specified in Appendix E and Appendix F. 

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5.2.2 
Discontinuation of study vaccine administration 
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: 
• SAE that is subsequently considered to be related to vaccination 
• Pregnancy (regardless of outcome) 
• HIV infection 
• Grade 3 AE assessed as related to study vaccine, with the following 
exceptions: 
▪ Grade 3 subjective reactogenicity and injection site reactions: injection 
site pain/tenderness and erythema/induration (grade 3 by size only), 
fatigue, generalized myalgia, generalized arthralgia, chills, headache, 
nausea (unless intravenous [IV] rehydration required) 
▪ AEs reviewed by the PSRT and approved for vaccination continuation 
• Grade 4 AE assessed as related to study vaccine 
• Clinically significant type 1 hypersensitivity associated with study vaccine 
For ease of reference and review, the clinically significant type 1 
hypersensitivity definition, as per the Second National Institute of Allergy and 
Infectious Disease/Food Allergy and Anaphylaxis Network symposium 
criteria for anaphylaxis (28), is provided below: 
Anaphylaxis is highly likely when any one of the following criteria are 
fulfilled: 
1. Acute onset of an illness (minutes to several hours) with involvement of the 
skin, mucosal tissue, or both (eg, generalized hives, pruritus or flushing, 
swollen lips-tongue-uvula) 
AND AT LEAST ONE OF THE FOLLOWING: 
a. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, 
reduced peak expiratory flow [PEF], hypoxemia) 
b. Reduced blood pressure (BP) or associated symptoms of end-organ 
dysfunction (eg, hypotonia [collapse], syncope, incontinence) 
2. Two or more of the following that occur rapidly after exposure to a likely 
allergen for that patient [participant] (minutes to several hours): 

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a. Involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush, 
swollen lips-tongue-uvula) 
b. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, 
reduced PEF, hypoxemia) 
c. Reduced BP or associated symptoms (eg, hypotonia [collapse], syncope, 
incontinence) 
d. Persistent gastrointestinal symptoms (eg, crampy abdominal pain, 
vomiting) 
3. Reduced BP after exposure to known allergen for that patient [participant] 
(minutes to several hours). Adults: systolic BP of less than 90 mm Hg or 
greater than 30% decrease from that person’s baseline 
• PI assessment that it is not in the best interest of the participant to continue 
receiving study vaccine 
• New diagnosis of or newly disclosed AESI (see Appendix MAppendix M) 
• 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 303 PSRT) 
Participants discontinuing study vaccine for reasons other than HIV infection 
should be encouraged to participate in follow-up visits and procedures per the 
protocol. At the discretion of the CRS clinician and the PSRT (for composition of 
PSRT see Section 9.3), some clinic procedures and sample collections may be 
modified or discontinued. 
If a participant becomes HIV-infected during the course of the study, no 
additional study vaccine will be administered. participants will be encouraged to 
continue scheduled study visits for up to 12 months following their last study 
vaccine administration. At post infection follow-up visits, only samples for 
protocol-specified clinical labs (with the exception of HIV diagnostic testing) will 
be collected. In addition, some clinic procedures may be modified or 
discontinued. 
5.2.3 
Participant departure from vaccine schedule 
If a participant misses a scheduled vaccination, they are eligible for future 
vaccinations. 

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5.2.4 
Discontinuation of study participation 
A participant may be discontinued from protocol participation for the following 
reasons: 
• Participant voluntarily withdraws; 
• CRS determines the participant is lost to follow-up; 
• The investigational new drug (IND) application Sponsor or regulatory 
authorities stop the study; or 
• PI assessment that it is not in the best interest of the participant to continue 
participation in the study or that the participant’s compliance with the study is 
not sufficient. 
If a participant terminates participation in the study early for any reason, the site 
principal investigator should consider if the following assessments are 
appropriate: end-of-study HIV test, complete blood count (CBC) with differential, 
serum chemistry, physical examination, and if indicated, a pregnancy test (see 
Appendix A, Appendix B, Appendix C and Appendix D). For participants with 
HIV infection, please see Section 8.7. If the site principal investigator has 
questions regarding a termination visit, they should consult with the PSRT. 

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6 
Statistical considerations 
 
6.1 
Accrual and sample size calculations 
Recruitment will target 60 (up to 70) healthy adult participants 18 to 50 years of 
age. However, due to the early termination, the study enrolled a total of 44 
participants (15 in Part A and 29 in Part B). The primary goal of this study is to 
identify safety concerns that may be associated with the study products. 
Since enrollment is concurrent with receiving the first study vaccination, all 
enrolled participants will provide some safety data. For immunogenicity analyses, 
the sample calculations are based on the available samples. 
6.2 
Sample size calculations for safety 
The goal of the safety evaluation for this study is to identify safety concerns 
associated with product administration. The ability of the study to detect SAEs 
(see Section 9.1) 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 each vaccine arm of the study (n = 3) 
in Part A, there is a 90% chance of observing at least 1 event if the true rate of 
such an event is 53.6% or more; and there is a 90% chance of observing no events 
if the true rate is 1% or less. For a vaccine arm in Part B (n = 9 or 10), there is a 
90% chance of observing at least 1 event if the true rate of such an event is 22.6% 
or 20.6% or more; and there is a 90% chance of observing no events if the true 
rate is 1% or less For a combined vaccine arm (Groups 1-5 in Part A and Groups 
6-8 in Part B) of the study (n = 44), there is a 90% chance of observing at least 1 
event if the true rate of such an event is 5.1% or more; and there is a 90% chance 
of observing no events if the true rate is 0.2% or less. As a reference, in HVTN 
vaccine trials from April 2008 through March 2018, about 1.7% 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 3, 9, 10, and 44 are presented in Table 6-1for a range of possible true 
adverse event rates. These calculations provide a more complete picture of the 
On January 13, 2023, a protocol memo was distributed informing the clinical 
research sites that all vaccinations in HVTN 303 were permanently 
discontinued. The sample size calculations for safety and immunogenicity were 
updated based on the actual numbers of participants who were enrolled in the 
study and the updated objectives in Section 3. The language shown below is the 
revised version of the original protocol (v1.0) as per the sample size and the 
design of the current protocol version 2.0.  

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sensitivity of this study design to identify potential safety problems with the 
vaccine. 
Table 6-1 Probability of observing 0 events, 1 or more events, and 2 or more events, among 
arms of size 3, 9, 10, and combined arms of size 44, for different true event rates 
True 
event 
rate (%) 
Pr(0/3) 
Pr(1+/3) 
Pr(2+/3) 
Pr(0/10) Pr(1+/10) Pr(2+/10) Pr(0/9) Pr(1+/9) Pr(2+/9) Pr(0/44) Pr(1+/44) Pr(2+/44) 
1 
97 
3 
0 
90.4 
9.6 
0.4 
91.4 
8.6 
0.3 
64.3 
35.7 
7.2 
4 
88.5 
11.5 
0.5 
66.5 
33.5 
5.8 
69.3 
30.7 
4.8 
16.6 
83.4 
53 
5 
85.7 
14.3 
0.7 
59.9 
40.1 
8.6 
63 
37 
7.1 
10.5 
89.5 
65.3 
10 
72.9 
27.1 
2.8 
34.9 
65.1 
26.4 
38.7 
61.3 
22.5 
1 
99 
94.3 
20 
51.2 
48.8 
10.4 
10.7 
89.3 
62.4 
13.4 
86.6 
56.4 
<0.1 
>99.9 
99.9 
30 
34.3 
65.7 
21.6 
2.8 
97.2 
85.1 
4 
96 
80.4 
<0.1 
>99.9 
>99.9 
40 
21.6 
78.4 
35.2 
0.6 
99.4 
95.4 
1 
99 
92.9 
<0.1 
>99.9 
>99.9 
50 
12.5 
87.5 
50 
0.1 
99.9 
98.9 
0.2 
99.8 
98 
<0.1 
>99.9 
>99.9 
60 
6.4 
93.6 
64.8 
0 
>99.9 
99.8 
0 
>99.9 
99.6 
<0.1 
>99.9 
>99.9 
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 6-2 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 (52). If none of the participants in a group of 
size of 3 (eg, Groups 1-5 in Part A) or in a group of size of 9 or 10 (eg, the 
Groups 6-8 in Part B) are experiencing a safety event, the 95% 2-sided upper 
confidence bound for the true rate of such events in the total vaccinated 
population is 56.1% or 29.9% or 29.2%, respectively. For the combined vaccine 
arms in Part A and Part B (Groups 1-8, n = 44), the 95% 2-sided upper confidence 
bound for this rate is 9.8%. 

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Table 6-2 Two-sided 95% confidence intervals based on observing a particular rate of safety 
endpoints for arms of size 3, 9, 10 or combined arms of size 44 
Observed event rate 
95% Confidence interval (%) 
0/3 
[0, 56.1] 
1/3 
[6.1, 79.2] 
2/3 
[20.8, 93.9] 
0/9 
[0, 29.9] 
1/9 
[2, 43.5] 
2/9 
[6.3, 54.7] 
0/10 
[0, 29.2] 
1/10 
[0.1, 30.5] 
2/10 
[0.2, 31.9] 
0/44 
[0.1, 9.8] 
1/44 
[0.3, 11.4] 
2/44 
[0.6, 12.9] 
6.2.1 
Sample size calculations for immunogenicity 
The main goals of this trial regarding immunogenicity outcomes involve assessing 
the ability of FP-conjugate and Trimer 4571 vaccines alone or co-administration 
to elicit antibody binding FP and envelop trimer antigens and mapping FP-
specific serum neutralizing activity induced by the prime vaccines regimens in 
Groups 5-8 and prime boost vaccines regimens in Groups 7-8. No adjustment for 
multiple comparisons will be made for the use of multiple assays. 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 6-3. Calculations are done using the score test 
method (52). The sample size of n = 13 (Groups 5-6) and n=9 for each of Groups 
7 and 8 will be used to evaluate the immunogenicity post the 1st vaccination 
induced by the vaccination; the sample sizes of n=4, 5 for Groups 7-8 will be used 
to evaluate the immunogenicity post the 2nd vaccination. 

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Table 6-3 Two-sided 95% confidence intervals for the true response rate based on observing 
a particular rate of responses in the vaccinees (n =4, 5, 9, 13) 
No. of responses 
Observed response rate (%) 
95% Confidence interval 
2/4 
50 
[15, 85] 
4/4 
100 
[51, 100] 
2/5 
40 
[11.8, 76.9] 
4/5 
80 
[37.6, 96.4] 
3/9 
33.3 
[12.1, 64.6] 
6/9 
66.7 
[35.4, 87.9] 
9/9 
100 
[70.1, 100] 
3/13 
23.1 
[8.2, 50.3] 
6/13 
46.2 
[23.2, 70.9] 
9/13 
69.2 
[42.4, 87.3] 
As shown in Table 6-4, there is limited power for a formal comparison of 
immunogenicity response rates between Group 7 (n=9) and Group 8 (n=9). For 
either 80% or 90% power, the sizes of differences that the trial is powered to 
detect are fairly large. These calculations use a Fisher exact 2-sided test with a 
type I error rate of 0.05. 
Table 6-4 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 
 
The response magnitudes will be compared between the arms among the positive 
responders. The response magnitudes will be transformed (eg, using log-
transformation for response magnitudes) prior to the comparisons if they are not 
normally distributed. The numbers presented in Table 6-5 are the minimum mean 
differences (in standard deviations [SDs]) between two arms that can be 
distinguished with a statistical power of 80% or 90% and a type I error rate of 
0.05 given a range of possible true response rates in both arms. The calculations 
are based on 5,000 simulations with the data being generated from normal 
distributions with different means and a common standard deviation in two arms 
and the Wilcoxon rank sum test for comparing the difference between arms. 

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Table 6-5 Minimum mean difference (in SDs) with 80% or 90% power to distinguish the 
response levels between Group 7 and Group 8 among positive responders. 
Common true response rate (%) 
Minimum mean difference in SDs 
(n1 = 9, n2 = 9) 
Power = 80% 
Power = 90% 
50 
2.7 
3.1 
60 
2.3 
2.6 
70 
2.0 
2.3 
80 
1.8 
2.0 
90 
1.6 
1.9 
100 
1.5 
1.8 
6.3 
Randomization  
In Part A, Groups 1 and 3 will be randomized and will enroll no more than 1 
participant per day for 3 participants per group. Contingent on the safety data 
from Groups 1 and 3, Groups 2, 4, and 5 will be randomized and may enroll 
simultaneously with no more than 1 participant per day for 3 participants for each 
group. Contingent on the safety data from Groups 1-5 in Part A, Groups 6-8 in 
Part B will be randomized and stratified by whether or not participants will be 
willing to consent to leukapheresis. A maximum of 7 participants per group that 
do NOT consent to leukapheresis collection will be enrolled. A participant’s 
randomization assignment will be computer generated and provided to the HVTN 
CRS pharmacist through a Web-based randomization system. 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 procedures [MOP]). 
6.4 
Blinding 
Participants and site staff will be unblinded to participants’ group assignments. 
Laboratory program staff will be unblinded to whether a sample is from Part A or 
Part B but will remain blinded to the treatment assignment within Part A or Part B 
during assay analysis. 
6.5 
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 

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are excluded. Because of the brief length of time between randomization and 
enrollment (typically no more than 4 working days), very few such individuals are 
expected. 
Analyses for primary endpoints will be performed using statistical analysis system 
(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). 
6.5.1 
Analysis variables 
The analysis variables consist of baseline participant characteristics, safety, and 
immunogenicity for primary- and secondary-objective analyses. 
6.5.2 
Baseline comparability 
Treatment arms will be compared for baseline participant characteristics using 
descriptive statistics. 
6.5.3 
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. 
6.5.3.1 
Reactogenicity 
The number and percentage of participants experiencing each type of 
reactogenicity sign or symptom will be tabulated by severity and treatment arm in 
Part A and Part B 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 across arms and Wilcoxon rank sum test will be 
used to test for difference in severity between 2 arms in Part B. 
6.5.3.2 
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 (in Part A and Part B) the number and percentage of participants 

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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 differences must rely heavily upon clinical judgment. 
A listing of SAEs reported to the Division of AIDS (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. 
6.5.3.3 
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 (Part A and Part 
B) 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 time point, as well as changes from baseline for post 
enrollment 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 (Section 9.1) will be tabulated by treatment arm for each post 
vaccination time point. Reportable clinical laboratory abnormalities without an 
associated clinical diagnosis will also be included in the tabulation of AEs 
described above. 
6.5.3.4 
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 (Part B). 
6.5.4 
Immunogenicity analysis 
6.5.4.1 
General approach 
For the statistical analysis of immunogenicity endpoints, data from enrolled 
participants in Part B will be used according to the initial randomization 
assignment regardless of how many injections the participants received. 
Additional analyses may be performed, limited to participants who received all 
scheduled injections per protocol. Assay results from specimens collected outside 
of the visit window, or from HIV-infected participants collected post infection, 
may be 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 

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sample and thereafter may be excluded. If an HIV-infected participant does not 
have a seronegative sample post enrollment, then all data from that participant 
may be excluded from the analysis. 
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% CI estimates 
calculated using the score test method (52). Barnard’s 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 (54). 
In addition to response rate estimates for each timepoint, the probability of 
observing at least 1 positive response by a given timepoint and the probability of 
observing more than 1 positive response by a given timepoint will be estimated, 
with corresponding CIs, for each vaccine arm using maximum likelihood-based 
methods (55). 
For quantitative assay data (eg, the vaccine-induced serum neutralizing antibody 
[nAb] as measured by the TZM-bl assay, HIV-specific serum IgG binding 
magnitude, breadth, and avidity to cross-clade panels of gp120 and V1V2 and to 
V3, CD4i, gp41 and gp41 immunodominant region [IDR] as assessed by the 
binding antibody multiplex assay [BAMA] or CD4+ T-cell responses to Gag and 
Env as assessed by ICS), 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. 
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. To test for 
differences among all vaccine arms, first a Kruskal-Wallis rank test or an F-test 
(depending on the normality assumption) will be used to test for overall 
differences. Secondly, if the overall test is significant at the 2-sided 0.05 level, 
then individual tests comparing between vaccine arms will be done. If rank-based 
tests are used, then the tests will be inverted to construct Hodges-Lehmann point 
estimates and 2-sided (1-0.05/# of comparisons) × 100% CIs about the differences 
in location centers of the number of comparisons between vaccine arms. If rank-
based tests are used, then the tests will be inverted to construct Hodges-Lehmann 
point estimates and 2-sided (1-0.05/# of comparisons) × 100% CIs about the 
differences in location centers of the number of comparisons between vaccine 
arms. When all pair-wise comparisons between the multiple vaccine arms are of 
interest, the Tukey procedure (56) will be used. If only specific comparisons 

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between pairs of the multiple vaccine arms are of interest, the Holm-Bonferroni 
procedure 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 2 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, nAb, BAMA, ICS). 
If treatment arm differences for these assays are best summarized by a mixture 
model, then either Lachenbruch’s test statistic (57) or an alternative 2-part test 
(58) (as defined in the SAP) will be used to evaluate the composite null 
hypothesis of equal response rates in the 2 arms and equal 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 [GEE]) may be utilized to incorporate immune responses 
over several timepoints and to test for differences over time. 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 15% 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 

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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 assessing repeated immunogenicity measurement, 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 (59) will be used 
because they accommodate the censoring. In addition, secondary analyses of 
repeated immunogenicity measurements may be done using weighted GEE (60) 
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. 
6.5.4.2 
Multivariate display of immunogenicity endpoints 
Data-visualization techniques may be used to explore the relationship among 
immunogenicity readouts. The set of readouts may be based on one of the primary 
endpoints (eg, nAb, BAMA, ICS), 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; for a larger number of readouts, a 
heatmap showing the degree of correlation between any two pairs may be used. 
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 (61). 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 [PFS], Env-specific CD8+ T cell total magnitude) from the origin to the 
point defined by its first 2 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 principal component. The 
angle between 2 arrows conveys information about the correlation of the 2 

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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. 
6.5.4.3 
Primary analyses of neutralization magnitude-breadth curves 
The area-under-the-magnitude-breadth curve (AUC-MB) to non matched 
(heterologous) tier 2 HIV-1 Env-pseudotyped viruses in the TZM-bl assay (62) 
will be computed for each participant with evaluable neutralization data, as 
described in Huang et al, 2009 (63). AUC-MB to a vaccine-matched panel may 
also be computed when the panel consists of at least 3 isolates. Dunnett’s 
procedure will be applied with 2-sided alpha = 0.05 to determine which of the 3 
vaccine groups (Groups 6-8 in Part B) have a significantly higher mean AUC-MB 
than that of the pooled baseline samples from Groups 6-8, as described in Liu et 
al, 1997 (64) (see their formula [1.1]). This procedure will be applied to construct 
95% CIs about the 3 differences in mean AUC-MB for each vaccine regimen 
(Groups 6-8) versus the pooled baseline samples from Groups 6-8, which 
simultaneously have at least 95% coverage probability. 
Select the best vaccine regimen among those passing the tier-2 
screen 
The vaccine regimens that passed the tier-2 screen will be ranked by the estimated 
mean of the AUC-MB curves. The vaccine regimen with the highest estimated 
mean will be selected as the best regimen. 
6.5.4.4 
Secondary analyses of neutralization magnitude-breadth curves 
Superiority comparisons of vaccine regimens passing the tier-2 
screen 
For the set of vaccine regimens that passed the tier-2 screen, an F-test will be 
performed for whether any of the mean AUC-MBs differ. If this test is not 
significant (p-value > 0.05), then the conclusion will be that there were no 
significant differences in mean AUC-MBs among the vaccine regimens that 
advanced. If the F-test is significant, then simultaneous 95% CIs about the mean-
differences in AUC-MBs will be reported. These CIs are computed as the 
estimated mean-difference plus or minus tN-m,025 multiplied by the square-root of 
S2 (1/ni + 1/nj), where tN-m,025 is the 97.5th percentile of a t-distribution with N – 
m degrees of freedom, where N is the total number of vaccine recipients evaluated 
(summing over the advanced vaccine regimens) and m is the number of advanced 
vaccine regimens. In addition, S2 is an estimate of the common sample variance 
of the AUC-MB, whereas ni and nj are the sample sizes of evaluable participants 

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for vaccine regimens i and j being compared. Following Fisher’s least significant 
difference procedure, the pairs of vaccine regimens with this CI, excluding zero, 
are deemed to have a significant difference. Nominal (unadjusted) 95% CIs about 
pairs of vaccine arms will also be reported. 
Omnibus comparison of magnitude-breadth distributions 
The analyses of magnitude-breadth described above are based on the endpoint 
area-under-the-curve, which is interpreted as the average log10 half-maximal 
inhibitory concentration (IC50) to the set of isolates in the test panel. Use of this 
endpoint is maximally statistically powerful if 1 vaccine arm has greater 
magnitude and breadth than the comparator vaccine arm, but may miss an effect 
wherein 1 vaccine arm has greater magnitude and the comparator vaccine arm has 
greater breadth. Therefore, a secondary analysis may compare the distribution of 
magnitude-breadth curves among vaccine arms using the test statistic max|BdG| 
from Huang, et al (63), which is designed to detect general differences in 
magnitude-breadth curve distributions. 
Selecting the best vaccine regimen among those passing the tier-2 
screen 
For each vaccine regimen that passes the tier-2 screen, the best vaccine regimen 
will be deemed as that with the greatest value of the max|BdG| test statistic 
comparing its distribution of magnitude-breadth curves versus the pooled placebo 
group. 
Superiority comparisons of vaccine regimens passing the tier-2 
screen 
Similarly, the max|BdG| test statistic will be used to compare the distribution of 
magnitude-breadth curves between each pair of advanced vaccine regimens. The 
Holm-Bonferroni procedure will be applied to determine the pairs of regimens 
with significant differences in distribution controlling the family-wise false 
positive error rate at no more than 0.05. Nominal (unadjusted) 95% CIs about 
pairs of vaccine arms will also be reported. 
6.5.4.5 
Analysis of binding antibody IgG/IgA responses measured by BAMA 
The analysis of IgG, IgG3, and IgA binding antibody response to gp120, V1V2 
and other antigens (V3, CD4i, gp41, and gp41 IDR) as measured by the BAMA 
assay will be evaluated and compared as described under the general approach. 
Scores measured the cross-reactivity among the gp120 and V1V2 will be derived. 
The details of the score derivations will be described in SAP. The derived scores 
will be evaluated and compared as described under the general approach. 

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6.5.4.6 
Analysis of CD4+ and CD8+ T-cell response as measured by the ICS 
assay  
The analysis of CD4+ and CD8+ 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 (65) 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 (66) 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. 
6.5.5 
Analyses 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 only. 
6.5.5.1 
Safety 
During the course of the trial, unblinded analyses of safety data will be prepared 
approximately every 4 months for review by the safety monitoring board (SMB). 
During the course of the trial, unblinded analyses of safety data will be prepared 
approximately every 4 months during the main study for review by the SMB. Ad 
hoc safety reports may also be prepared for SMB review at the request of the 
HVTN 303 PSRT. The HVTN leadership must approve any other requests for 
unblinded safety data prior to the end of the scheduled follow-up visits. 
6.5.5.2 
Immunogenicity 
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 

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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 at 
least 1 of the primary immunogenicity endpoints of the same class (humoral, cell-
mediated, innate or mucosal) or, if no primary endpoint of the same class, at least 
1 of the primary immunogenicity endpoints reaches the aforementioned threshold. 
The Laboratory Program will review the analysis report prior to distribution to the 
protocol chairs, DAIDS, vaccine developer, and other key HVTN members and 
investigators. 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 
Study product preparation, storage, 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 1-1. See the Investigator’s Brochures (IBs) for further 
information about study products. 
7.1 
Vaccine Regimen 
The schedule of study product administration is shown in Section 1.5 and 
additional information is given below. 
Part A 
Group 1 
Treatment 1 (T1): 
25 mcg FP Conjugate Vaccine (FP8v1-rTTHC; VRC-HIVVCP0108-00-VP) + 
20% dose/volume (d/v) Adjuplex, to be administered as 0.8 mL, divided into 2 
syringes (0.4 mL each), intramuscularly at Week 0. 
Group 2 
Treatment 2 (T2): 
200 mcg FP conjugate vaccine (FP8v1-rTTHC; VRC-HIVVCP0108-00-VP) + 
20% dose/volume (d/v) Adjuplex, to be administered as 0.8 mL, divided into 2 
syringes (0.4 mL each), intramuscularly at Week 0. 
Group 3 
Treatment 3 (T3): 
100 mcg Trimer 6931 (HIV-1 Trimer 6931 Vaccine; VRC-HIVRGP0106-00-VP) 
+ 20% dose/volume (d/v) Adjuplex, to be administered as 0.8 mL, divided into 2 
syringes (0.4 mL each), intramuscularly at Week 0. 
On January 13, 2023, a protocol memo was distributed informing the clinical 
research sites that all vaccinations in HVTN 303 were permanently 
discontinued. The vaccination that did not take place due to this has been 
marked with strikethrough.  

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Group 4 
Treatment 4 (T4): 
200 mcg Trimer 6931 (HIV-1 Trimer 6931 Vaccine; VRC-HIVRGP0106-00-VP) 
+ 20% dose/volume (d/v) Adjuplex, to be administered as 0.8 mL, divided into 2 
syringes (0.4 mL), intramuscularly at Week 0. 
Group 5 
Treatment 5 (T5): 
200 mcg Trimer 4571 (HIV-1 Trimer 4571 Vaccine; VRC-HIVRGP096-00-VP) + 
20% dose/volume (d/v) Adjuplex, to be administered as 0.8 mL, divided into 2 
syringes (0.4 mL each), intramuscularly at Week 0. 
Part B 
Group 6 
Treatment 6 (T6): 
200 mcg Trimer 4571 + 20% dose/volume (d/v) Adjuplex, to be administered as 
0.8 mL, divided into 2 syringes (0.4 mL each), intramuscularly at Weeks 0 and 
12. 
200 mcg Trimer 6931 + 20% dose/volume (d/v) Adjuplex, to be administered as 
0.8 mL, divided into 2 syringes (0.4 mL each), intramuscularly at Week 24. 
100 mcg Trimer 4571 + 100 mcg Trimer 6931 + 20% dose/volume (d/v) 
Adjuplex, to be administered as 0.8 mL, divided into 2 syringes (0.4 mL each), at 
Weeks 36 and 48. 
Group 7 
Treatment 7 (T7): 
200 mcg FP conjugate vaccine + 20% dose/volume (d/v) Adjuplex, to be 
administered as 0.8 mL, divided into 2 syringes (0.4 mL each), at Weeks 0 and 4 
and 8. 
200 mcg Trimer 4571 + 20% dose/volume (d/v) Adjuplex, to be administered as 
0.8 mL, divided into 2 syringes (0.4 mL each), intramuscularly at Weeks 12 and 
24. 
200 mcg Trimer 6931 + 20% dose/volume (d/v) Adjuplex, to be administered as 
0.8 mL, divided into 2 syringes (0.4 mL each), intramuscularly at Week 36. 

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100 mcg Trimer 4571 + 100 mcg Trimer 6931 + 20% dose/volume (d/v) 
Adjuplex, to be administered as 0.8 mL, divided into 2 syringes (0.4 mL each), at 
Week 48. 
Group 8 
Treatment 8 (T8): 
200 mcg FP conjugate vaccine + 200 mcg Trimer 4571 + 20% dose/volume (d/v) 
Adjuplex, to be administered as 0.8 mL, divided into 2 syringes (0.4 mL each), at 
Weeks 0 and 4 and 8. 
200 mcg Trimer 6931 + 20% dose/volume (d/v) Adjuplex, to be administered as 
0.8 mL, divided into 2 syringes (0.4 mL each), intramuscularly at Week 20. 
100 mcg Trimer 4571 + 100 mcg Trimer 6931 + 20% dose/volume (d/v) 
Adjuplex, to be administered as 0.8 mL, divided into 2 syringes (0.4 mL each), 
intramuscularly at Weeks 32 and 44. 
7.2 
Study Product Formulation and Storage 
This study includes 3 investigational vaccines, a diluent, and 1 adjuvant as 
follows: 
7.2.1 
FP Conjugate Vaccine Labeled as FP8v1-rTTHC Vaccine (VRC-
HIVVCP0108-00-VP) 
FP Conjugate Vaccine will be provided as 3-mL single-use glass vials with a 0.7-
mL fill volume, at a concentration of 1 mg/mL. After being thawed, each vial 
contains a clear, colorless, preservative-free sterile solution; some white or 
translucent particles may be present. 
FP Conjugate Vaccine must be stored until use at -35°C to -15°C. Unopened vials 
may be stored cumulatively for up to 48 hours at 2oC to 8oC and for up to 24 
hours at 15°C to 27°C post thaw. Vials should not be refrozen after being thawed. 
7.2.2 
Trimer 4571 Labeled as HIV Trimer 4571 Vaccine (VRC-HIVRGP096-
00-VP) 
Trimer 4571 will be provided as 3-mL single-use glass vials with a 1.2-mL fill 
volume, at a concentration of 500 mcg/mL. After being thawed, each vial contains 
a clear, colorless, preservative-free, sterile solution; some small white or 
translucent particles may be present. 

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Trimer 4571 must be stored until use at -35°C to -15°C. Unopened vials may be 
stored cumulatively for up to 48 hours at 2°C to 8°C and up to 24 hours at 15°C to 
27°C post-thaw. Vials should not be refrozen after being thawed. 
7.2.3 
Trimer 6931 Labeled as HIV Trimer 6931 Vaccine (VRC-HIVRGP0106-
00-VP) 
Trimer 6931 will be provided as 3-mL single-use glass vials with a 1.2-mL fill 
volume, at a concentration of 1 mg/mL. After being thawed, each vial contains a 
clear, colorless, preservative-free, sterile solution; some small white or translucent 
particles may be present. 
Trimer 6931 must be stored until use at -35°C to -15°C. Unopened vials may be 
stored cumulatively for up to 48 hours at 2°C to 8°C and up to 24 hours at 15°C to 
27°C post-thaw. Vials should not be refrozen after being thawed. 
7.2.4 
Adjuplex Adjuvant (VRC-GENADJ0110-AP-NV) 
Adjuplex adjuvant will be provided as 3-mL single-use glass vials with a fill 
volume of 0.7 mL. Each vial contains an off-white, semi-opaque (not transparent), 
preservative-free, sterile liquid with no visible particles and is homogenous after a 
gentle shake.  
Adjuplex will be mixed with study products in the pharmacy during preparation 
prior to vaccination to maintain a 20% (v/v) dose of Adjuplex. 
Adjuplex adjuvant vials must be stored until use at 2°C to 8°C. DO NOT 
FREEZE. Unopened vials may be stored for up to 8 hours at 15°C to 27°C. 
7.2.5 
PBS Diluent Labeled as Phosphate Buffered Saline pH 7.2 (VRC-
PBSPLA043-00-VP) 
PBS diluent will be provided as 3-mL single-use glass vials with a fill volume of 
1.5 mL. After being thawed, each vial contains a clear, colorless, preservative-
free, sterile buffered solution. 
PBS diluent must be stored until use at -35°C to -15°C. Unopened vials may be 
stored cumulatively for up to 48 hours at 2°C to 8°C and up to 24 hours at 15°C to 
27°Cpost-thaw. Vials should not be refrozen after being thawed. 
7.3 
Preparation of Study Products 
Prior to preparation, a new prescription will be sent to the pharmacy and must 
contain the participant’s PTID, group number assignment, and week number for 
the visit. 

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Pharmacists must follow appropriate aseptic technique and sterile preparation 
procedures as outlined in USP <797>, utilizing a pharmacy laminar flow hood or 
biosafety cabinet/isolator. Pharmacists should follow the requirements of their 
institution and their pharmacy regulatory authority regarding these procedures. 
Local regulations and site intuitional policies and procedures for use of personal 
protective equipment, such as gloves, gowns, masks, and safety glasses, must also 
be followed. 
Any unused portion of study product cannot be used for another participant. Any 
empty vials, unused portion of entered vials, or unused prepared study product 
should be discarded in a biohazard container and disposed of in accordance with 
institutional or pharmacy policy. 
Refer to the HVTN 303 Study Specific Procedures (SSP) for further details on 
study product preparation. 
7.3.1 
FP Conjugate Vaccine (25 mcg)  
The pharmacy will need to prepare a 25-mcg dose of FP Conjugate with adjuvant 
for the following participants at the listed study weeks: 
• Group 1; Week 0 
Preparation of 25-mcg FP Conjugate Vaccine with Adjuvant: 
When preparing doses, glass or polypropylene containers are preferred for 
compounding; avoid polystyrene and polytetrafluoroethylene (PTFE) materials. 
Pipettors with plastic disposable tips may be used in place of syringes for 
compounding. 
1. Remove 1 vial of FP8v1-rTTHC Vaccine (VRC-HIVVCP0108-00-VP) and 2 
vials of Phosphate Buffered Saline (PBS; VRC-PBSPLA043-00-VP) from frozen 
storage. Thaw and equilibrate vials at ambient temperature (15°C to 27°C) for a 
minimum of 30 minutes. Vials should NOT be moved directly from the freezer 
to a refrigerator to thaw. 
2. Remove 1 vial of Adjuplex adjuvant (VRC-GENADJ0110-AP-NV) from 2°C 
to 8°C storage and equilibrate vial at ambient temperature (15°C to 27°C) for a 
minimum of 30 minutes. 
3. Gently swirl the equilibrated FP8v1-rTTHC and PBS vials until the contents 
look homogenous. DO NOT SHAKE THE VIALS. If some white to translucent 
particles are observed, vials may be used for the preparation of the IM 
administration. 
4. Gently swirl the equilibrated vial of Adjuplex until the contents look 
homogenous. The Adjuplex adjuvant emulsion will retain some opacity. 

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5. Transfer 2.00 mL of PBS into a new empty sterile container using a 3.0 mL 
syringe and a large-bore needle (eg, 18G, 16G). 
6. Transfer an additional 0.46 mL of PBS into the same sterile container using a 
1.0-mL syringe and a new large-bore needle (eg, 18G, 16G). 
7. Transfer 0.1 mL of FP8v1-rTTHC Vaccine into the same sterile conatiner 
using a new 1-mL syringe and a new large-bore needle (eg, 18G, 16G). 
8. Transfer 0.64 mL Adjuplex into the same sterile container using a new 1-mL 
syringe and a new large-bore needle (eg, 18G, 16G). 
9. Close and invert the container gently 10 times to mix the compounded dose. 
10. Withdraw 0.4 mL of the compounded dose twice into 2 separate new 1-mL 
syringes using two new large-bore needles (eg, 18G, 16G). Each syringe will be 
administered IM to one of the deltoids for a total dose volume of 0.8 mL. 
11. Remove the needles used in Step 10 to withdraw compounded vaccine and 
attach appropriately sized needles for administration to the prepared syringes 
before dispensing. 
12. Place a participant-specific label on each prepared syringe for administration. 
NOTE: After preparation into a syringe for administration, the adjuvanted FP8v1-
rTTHC vaccine may be stored at 2°C to 8°C for up to 8 hours and/or at 15°C to 
27°C for a maximum of 4 hours, including administration time. The prepared 
study product may not be stored in direct sunlight. 
7.3.2 
FP Conjugate Vaccine (200 mcg) 
The pharmacy will need to prepare a 200-mcg dose of FP Conjugate with 
adjuvant for the following participants at the listed study weeks: 
• Group 2; Week 0 
• Group 7; Weeks 0, 4 and 8 
Preparation of 200-mcg FP Conjugate Vaccine with Adjuvant: 
When preparing doses, glass or polypropylene containers are preferred for 
compounding; avoid polystyrene and polytetrafluoroethylene (PTFE) materials. 
Pipettors with plastic disposable tips may be used in place of syringes for 
compounding 
1. Remove 1 vial of FP8v1-rTTHC Vaccine (VRC-HIVVCP0108-00-VP) and 1 
vial of Phosphate Buffered Saline (PBS; VRC-PBSPLA043-00-VP) from frozen 
storage. Thaw and equilibrate vials at ambient temperature (15°C to 27°C) for a 

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minimum of 30 minutes. Vials should NOT be moved directly from the freezer 
to a refrigerator to thaw. 
2. Remove 1 vial of Adjuplex adjuvant (VRC-GENADJ0110-AP-NV) from 2°C 
to 8°C storage and equilibrate vial at ambient temperature (15°C to 27°C) for a 
minimum of 30 minutes. 
3. Gently swirl the equilibrated FP8v1-rTTHC and PBS vials until the contents 
look homogenous. DO NOT SHAKE THE VIALS. If some white to translucent 
particles are observed, vials may be used for the preparation of the IM 
administration. 
4. Gently swirl the equilibrated vial of Adjuplex until the contents look 
homogenous. The Adjuplex adjuvant emulsion will retain some opacity. 
5. Transfer 0.66 mL of PBS into a new sterile container using a 1-mL syringe 
and a large-bore needle (eg, 18G, 16G). 
6. Transfer 0.3 mL of FP8v1-rTTHC Vaccine into the same sterile container 
using a new 1-mL syringe and a new large-bore needle (eg, 18G, 16G). 
7. Transfer 0.24 mL of adjuvant into the same sterile container using a new 1-
mL syringe and a new large-bore needle (eg, 18G, 16G). 
8. Close and invert the container gently 10 times to mix the compounded dose. 
9. Withdraw 0.4 mL of the compounded dose twice into 2 separate 1-mL 
syringes using 2 new large-bore needles (eg, 18G, 16G). Each syringe will be 
administered IM to one of the deltoids for a total dose volume of 0.8 mL 
10. Remove the needles used in Step 9 to withdraw compounded vaccine and 
attach appropriately sized needles for administration to the prepared syringes 
before dispensing. 
11. Place a participant-specific label on each prepared syringe for administration. 
NOTE: after preparation into a syringe for administration, the adjuvanted FP8v1-
rTTHC vaccine may be stored at 2°C to 8°C for up to 8 hours and/or at 15°C to 
27°C for a maximum of 4 hours, including administration time. The prepared 
study product may not be stored in direct sunlight. 
7.3.3 
Trimer 6931 (100 mcg) 
The pharmacy will need to prepare a 100-mcg dose of Trimer 6931 with adjuvant 
for the following participants at the listed study weeks: 
• Group 3; Week 0 

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Preparation of 100-mcg Trimer 6931 Vaccine with Adjuvant: 
When preparing doses, glass or polypropylene containers are preferred for 
compounding; avoid polystyrene and polytetrafluoroethylene (PTFE) materials. 
Pipettors with plastic disposable tips may be used in place of syringes for 
compounding 
1. Remove 1 vial of HIV-1 Trimer 6931 Vaccine (VRC-HIVRGP0106-00-VP) 
and 1 vial of Phosphate Buffered Saline (PBS; VRC-PBSPLA043-00-VP) from 
frozen storage. Thaw and equilibrate vials at ambient temperature (15°C to 27°C) 
for a minimum of 30 minutes. Vials should NOT be moved directly from the 
freezer to a refrigerator to thaw. 
2. Remove 1 vial of Adjuplex adjuvant (VRC-GENADJ0110-AP-NV) from 2°C 
to 8°C storage and equilibrate vial at ambient temperature (15°C to 27°C) for a 
minimum of 30 minutes. 
3. Gently swirl the equilibrated HIV-1 Trimer 6931 and PBS vials until the 
contents look homogenous. DO NOT SHAKE THE VIALS. If some white to 
translucent particles are observed, vials may be used for the preparation of the IM 
administration. 
4. Gently swirl the equilibrated vial of Adjuplex until the contents look 
homogenous. The Adjuplex adjuvant emulsion will retain some opacity. 
5. Transfer 0.81 mL of PBS into a new sterile container using 1-mL syringe and 
a large-bore needle (eg, 18G, 16G). 
6. Transfer 0.15 mL of HIV-1 Trimer 6931 into the same sterile container using 
a new 1-mL syringe and a new large-bore needle (eg, 18G, 16G). 
7. Transfer 0.24 mL of Adjuplex into the same sterile container using a new 1-
mL syringe and a new large-bore needle (eg, 18G, 16G). 
8. Close and invert the container gently 10 times to mix the compounded dose. 
9. Withdraw 0.4 mL of the compounded dose twice into 2 separate 1-mL 
syringes using 2 new large-bore needles (eg, 18G, 16G). Each syringe will be 
administered IM to one of the deltoids for a total dose volume of 0.8 mL. 
10. Remove the needles used in Step 9 to withdraw compounded vaccine and 
attach appropriately sized needles for administration to the prepared syringes 
before dispensing. 
11. Place a participant-specific label on each prepared syringe for administration. 
NOTE: after preparation into a syringe for administration, the adjuvanted Trimer 
6931 vaccine may be stored at 2°C to 8°C for up to 8 hours and/or at 15°C to 27°C 

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for a maximum of 4 hours, including administration time. The prepared study 
product may not be stored in direct sunlight. 
7.3.4 
Trimer 6931 (200 mcg) 
The pharmacy will need to prepare a 200-mcg dose of Trimer 6931 with adjuvant 
for the following participants at the listed study weeks: 
• Group 4; Week 0 
• Group 6; Week 24 
• Group 7; Week 36 
• Group 8; Week 20 
Preparation of 200-mcg Trimer 6931 Vaccine with Adjuvant: 
When preparing doses, glass or polypropylene containers are preferred for 
compounding; avoid polystyrene and polytetrafluoroethylene (PTFE) materials. 
Pipettors with plastic disposable tips may be used in place of syringes for 
compounding. 
1. Remove 1 vial of HIV-1 Trimer 6931 Vaccine (VRC-HIVRGP0106-00-VP) 
and 1 vial of Phosphate Buffered Saline (PBS; VRC-PBSPLA043-00-VP) from 
frozen storage. Thaw and equilibrate vials at ambient temperature (15°C to 27°C) 
for a minimum of 30 minutes. Vials should NOT be moved directly from the 
freezer to a refrigerator to thaw. 
2. Remove 1 vial of Adjuplex adjuvant (VRC-GENADJ0110-AP-NV) from 2°C 
to 8°C storage and equilibrate vial at ambient temperature (15°C to 27°C) for a 
minimum of 30 minutes. 
3. Gently swirl the equilibrated HIV-1 Trimer 6931 and PBS vials until the 
contents look homogenous. DO NOT SHAKE THE VIALS. If some white to 
translucent particles are observed, vials may be used for the preparation of the IM 
administration. 
4. Gently swirl the equilibrated vial of Adjuplex until the contents look 
homogenous. The Adjuplex adjuvant emulsion will retain some opacity. 
5. Transfer 0.66 mL of PBS into a new sterile container using a 1-mL syringe 
and a large-bore needle (eg, 18G, 16G). 
6. Transfer 0.3 mL of HIV-1 Trimer 6931 into the same sterile container using a 
new 1-mL syringe and a new large-bore needle (eg, 18G, 16G). 

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7. Transfer 0.24 mL of Adjuplex into the same sterile container using a new 1-
mL syringe and a new large-bore needle (eg, 18G, 16G). 
8. Close and invert the container gently 10 times to mix the compounded dose. 
9. Withdraw 0.4 mL of the compounded mixture twice into 2 separate 1-mL 
syringes using 2 new needles. Each syringe will be administered IM to one of the 
deltoids for a total dose volume of 0.8 mL. 
10. Remove the needles used in Step 9 to withdraw compounded vaccine and 
attach appropriately sized needles for administration to the prepared syringes 
before dispensing. 
11. Place a participant-specific label on each prepared syringe for administration. 
NOTE: after preparation into a syringe for administration, the adjuvanted Trimer 
6931 vaccine may be stored at 2°C to 8°C for up to 8 hours and/or at 15°C to 
27°C for a maximum of 4 hours, including administration time. The prepared 
study product may not be stored in direct sunlight. 
7.3.5 
Trimer 4571 (200 mcg) 
The pharmacy will need to prepare a 200-mcg dose of Trimer 4571 with adjuvant 
for the following participants at the listed study weeks: 
• Group 5; Week 0 
• Group 6; Weeks 0 and 12 
• Group 7; Weeks 12 and 24 
Preparation of 200-mcg Trimer 4571 Vaccine with Adjuvant: 
When preparing doses, glass or polypropylene containers are preferred for 
compounding; avoid polystyrene and polytetrafluoroethylene (PTFE) materials. 
Pipettors with plastic disposable tips may be used in place of syringes for 
compounding. 
1. Remove 1 vial of HIV-1 Trimer 4571 Vaccine (VRC-HIVRGP096-00-VP) 
and 1 vial of Phosphate Buffered Saline (PBS; VRC-PBSPLA043-00-VP) from 
frozen storage. Thaw and equilibrate vials at ambient temperature (15°C to 27°C) 
for a minimum of 30 minutes. Vials should NOT be moved directly from the 
freezer to a refrigerator to thaw. 
2. Remove 1 vial of Adjuplex adjuvant (VRC-GENADJ0110-AP-NV) from 2°C 
to 8°C storage and equilibrate vial at ambient temperature (15°C to 27°C) for a 
minimum of 30 minutes. 

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3. Gently swirl the equilibrated HIV-1 Trimer 4571 and PBS vials until the 
contents look homogenous. DO NOT SHAKE THE VIALS. If some white to 
translucent particles are observed, vials may be used for the preparation of the IM 
administration. 
4. Gently swirl the equilibrated vial of Adjuplex until the contents look 
homogenous. The Adjuplex adjuvant emulsion will retain some opacity. 
5. Transfer 0.36 mL of PBS into a new sterile container using a 1-mL syringe 
and a large-bore needle (eg, 18G, 16G). 
6. Transfer 0.6 mL of HIV-1 Trimer 4571 into the same sterile container using a 
new 1-mL syringe and a new large-bore needle (eg, 18G, 16G). 
7. Transfer 0.24 mL of Adjuplex into the same sterile container using a new 1-
mL syringe and a new large-bore needle (eg, 18G, 16G). 
8. Close and invert the container gently 10 times to mix the compounded dose. 
9. Withdraw 0.4 mL of the compounded dose twice into 2 separate 1-mL 
syringes using 2 new large-bore needles (eg, 18G, 16G). Each syringe will be 
administered IM to one of the deltoids for a total dose volume of 0.8 mL. 
10. Remove the needles used in Step 9 to withdraw compounded vaccine and 
attach appropriately sized needles for administration to the prepared syringes 
before dispensing. 
11. Place a participant-specific syringe on each prepared syringe for 
administration. 
NOTE: after preparation into a syringe for administration, the adjuvanted Trimer 
4571 vaccine may be stored at 2°C to 8°C for up to 8 hours and/or at 15°C to 27°C 
for a maximum of 4 hours, including administration time. The prepared study 
product may not be stored in direct sunlight 
7.3.6 
Trimer 4571 (100 mcg) + Timer 6931 (100 mcg): 
The pharmacy will need to prepare a dose containing 100 mcg Trimer 4571 + 100 
mcg Trimer 6931 + adjuvant for the following participants at the listed study 
weeks: 
• Group 6; Weeks 36 and 48 
• Group 7; Week 48 
• Group 8; Weeks 32 and 44 

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Preparation of 100-mcg Trimer 4571 Vaccine + 100-mcg Trimer 6931 with 
Adjuvant: 
When preparing doses, glass or polypropylene containers are preferred for 
compounding; avoid polystyrene and polytetrafluoroethylene (PTFE) materials. 
Pipettors with plastic disposable tips may be used in place of syringes for 
compounding. 
1. Remove 1 vial of HIV-1 Trimer 4571 Vaccine (VRC-HIVRGP096-00-VP), 1 
vial of HIV-1 Trimer 6931 Vaccine (VRC-HIVRGP0106-00-VP) and 1 vial of 
Phosphate Buffered Saline (PBS; VRC-PBSPLA043-00-VP) from frozen storage. 
Thaw and equilibrate vials at ambient temperature (15°C to 27°C) for a minimum 
of 30 minutes. Vials should NOT be moved directly from the freezer to a 
refrigerator to thaw. 
2. Remove 1 vial of Adjuplex adjuvant (VRC-GENADJ0110-AP-NV) from 2°C 
to 8°C storage and equilibrate vial at ambient temperature (15°C to 27°C) for a 
minimum of 30 minutes. 
3. Gently swirl the equilibrated HIV-1 Trimer 4571, HIV-1 Trimer 6931 and 
PBS vials until the contents look homogenous. DO NOT SHAKE THE VIALS. 
If some white to translucent particles are observed, vials may be used for the 
preparation of the IM administration. 
4. Gently swirl the equilibrated vial of Adjuplex until the contents look 
homogenous. The Adjuplex adjuvant emulsion will retain some opacity. 
5. Transfer 0.51 mL of PBS into a new sterile container using 1-mL syringe and 
a large-bore needle (eg, 18G, 16G). 
6. Transfer 0.3 mL of HIV-1 Trimer 4571 into the same sterile container using a 
new 1-mL syringe and a new large-bore needle (eg, 18G, 16G). 
7. Transfer 0.15 mL of HIV-1 Trimer 6931 into the same sterile container using 
a new 1-mL syringe and a new large-bore needle (eg, 18G, 16G). 
8. Transfer 0.24 mL of Aduplex into the same sterile container using a new 1-mL 
syringe and a new large-bore needle (eg, 18G, 16G). 
9. Close and invert the container gently 10 times to mix the compounded dose. 
10. Withdraw 0.4 mL of the compounded dose twice into 2 separate 1-mL 
syringes using 2 new large-bore needles (eg, 18G, 16G). Each syringe will be 
administered IM to one of the deltoids for a total dose volume of 0.8 mL. 

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11. Remove the needles used in Step 10 to withdraw compounded vaccine and 
attach appropriately sized needles for administration on the prepared syringes 
before dispensing. 
12. Place a participant-specific label on each prepared syringe for administration. 
NOTE: after preparation into a syringe for administration, the adjuvanted Trimer 
4571 + Trimer 6931 vaccine may be stored at 2°C to 8°C for up to 8 hours and/or 
at 15°C to 27°C for a maximum of 4 hours, including administration time. The 
prepared study product may not be stored in direct sunlight. 
7.3.7 
FP Conjugate Vaccine (200 mcg) + Timer 4571 (200 mcg): 
The pharmacy will need to prepare a dose containing 200 mcg FP Conjugate 
Vaccine + 200 mcg Trimer 4571 + adjuvant for the following participants at the 
listed study weeks: 
• Group 8; Weeks 0, 4 and 8 
Preparation of 200-mcg FP Conjugate Vaccine + 200-mcg Trimer 4571 with 
Adjuvant: 
When preparing doses, glass or polypropylene containers are preferred for 
compounding; avoid polystyrene and polytetrafluoroethylene (PTFE) materials. 
Pipettors with plastic disposable tips may be used in place of syringes for 
compounding. 
1. Remove 1 vial of FP8v1-rTTHC Vaccine (VRC-HIVVCP0108-00-VP), 1 vial 
of HIV-1 Trimer 4571 Vaccine (VRC-HIVRGP096-00-VP) and 1 vial of 
Phosphate Buffered Saline (PBS; VRC-PBSPLA043-00-VP) from frozen storage. 
Thaw and equilibrate vials at ambient temperature (15°C to 27°C) for a minimum 
of 30 minutes. Vials should NOT be moved directly from the freezer to a 
refrigerator to thaw. 
2. Remove 1 vial of Adjuplex adjuvant (VRC-GENADJ0110-AP-NV) from 2°C 
to 8°C storage and equilibrate vial at ambient temperature (15°C to 27°C) for a 
minimum of 30 minutes. 
3. Gently swirl the equilibrated FP Conjugate Vaccine, HIV-1 Trimer 4571 and 
PBS vials until the contents look homogenous. DO NOT SHAKE THE VIALS. 
If some white to translucent particles are observed, vials may be used for the 
preparation of the IM administration. 
4. Gently swirl the equilibrated vial of Adjuplex until the contents look 
homogenous. The Adjuplex adjuvant emulsion will retain some opacity. 

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5. Transfer 0.06 mL of PBS into a new sterile container using a new 1-mL 
syringe and a large-bore needle (eg, 18G, 16G). 
6. Transfer 0.3 mL of FP Conjugate Vaccine into the same sterile container 
using a new 1-mL syringe and a new large-bore needle (eg, 18G, 16G). 
7. Transfer 0.6 mL of HIV-1 Trimer 4571 into the same sterile container using a 
new 1-mL syringe and a new large-bore needle (eg, 18G, 16G). 
8. Transfer 0.24 mL of Adluplex into the same sterile container using a new 1-
mL syringe and a new large-bore needle (eg, 18G, 16G). 
9. Close and invert the container gently 10 times to mix the compounded dose. 
10. Withdraw 0.4 mL of the compounded dose twice into 2 separate 1-mL 
syringes using 2 new large-bore needles (eg, 18G, 16G). Each syringe will be 
administered IM to one of the deltoids for a total dose volume of 0.8 mL. 
11. Remove the needles used in Step 10 to withdraw compounded vaccine and 
attach appropriately sized needles on the prepared syringe before dispensing. 
12. Place a participant-specific label on each prepared syringe for administration. 
NOTE: after preparation into a syringe for administration, the adjuvanted FP 
Conjugate + Trimer 4571 vaccine may be stored at 2°C to 8°C for up to 8 hours 
and/or at 15°C to 27°C for a maximum of 4 hours, including administration time. 
The prepared study product may not be stored in direct sunlight. 
7.4 
Labeling of Study Products 
Label the prepared study product in a syringe as follows: 
• Participant identifier(s) 
• Study product name 
• Total dose or dosages 
• Volume in mL 
• Route of administration (IM) 
• Instructions to “Invert syringe 5 times prior to administration” 
• Beyond-use date and time 

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• Any additional information required by jurisdiction 
7.5 
Study Product Administration 
The prepared dose will be administered as two IM injections in a deltoid muscle, 
0.4 mL in volume for each arm. The prepared syringe must be inverted 5 times 
prior to administration to the participant. 
If an injection needs to be administered in the same deltoid as the other injection 
due to a medical contraindication, the appropriate study staff should document 
this clearly. Under this circumstance, this is NOT a protocol violation. Two 
injections administered into the same deltoid should be at least 2.4 cm apart and 
should be documented on the participant’s study record. 
7.6 
Acquisition of study products 
FP Conjugate Vaccine, Trimer 4571, Trimer 6931, PBS diluent and Adjuplex 
adjuvant are provided by the VRC, NIAID, DAIDS. Once a 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. 
7.7 
Study Product Accountability 
The 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.  
7.8 
Final Disposition of study product 
For US clinical research sites, all unused study products must be returned to the 
clinical research products management center (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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8 
Clinical procedures 
8.1 
Screening 
Screening for eligibility will be performed after informed consent has been 
obtained and properly documented before enrollment. Screening evaluations and 
sample collection include medical history review, physical exam, and any clinical 
laboratory tests as detailed in the Schedule of procedures (Appendix A, Appendix 
B, Appendix C and Appendix D) needed to confirm eligibility. Persons assigned 
female sex at birth who are of reproductive potential will be given a pregnancy 
test. Additional assessments of health may be conducted at screening based on 
clinical judgment. 
If screening evaluations suggest a current concerning health condition or 
infection, then appropriate laboratory tests may be conducted to evaluate these 
conditions. Additional assessments of health may be conducted at screening based 
on clinical judgment. Screening evaluations for specific eligibility criteria 
(Section 5) must be completed within the time interval specified prior to 
enrollment for the given parameter and may be repeated, as needed, to confirm 
eligibility. 
An Assessment of Understanding (AoU) will be completed prior to enrollment. 
Records will be kept documenting the reasons that screened participants did not 
enroll or were ineligible. 
8.2 
Definition of Study Day and Study Visit  
Study Day 0 is defined as the day of the first vaccination. A study visit may be 
conducted remotely, such as via phone, text message, email, or other electronic 
means, in lieu of, or in combination with, in-person visits. As long as they are 
completed within the visit window (see Appendix E and Appendix F), procedures 
for a study visit can be completed over multiple days. The procedures for 
documenting remote visits and out of window visits are described in the HVTN 
303 SSP. 
8.3 
Reactogenicity Assessments 
Pre-Vaccine Administration: Medical history and evaluations including vital 
signs and planned injection site evaluation are performed prior to each vaccine 
administration. 
Post-Vaccine Administration Follow-Up in Clinic: Following each vaccine 
administration, participants will be observed for a minimum of 30 minutes post 
injection, vital signs will be recorded, the injection site will be inspected for 

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evidence of local reaction, and any evidence of systemic symptoms will be 
assessed. Participants will be contacted on the day after each study injection as 
indicated on the Schedule of Procedures (Appendix A, Appendix B, Appendix C 
and Appendix D). 
Post-Clinic Follow-Up: Participants are asked to record symptoms on a daily 
basis using an electronic participant diary. Signs and symptoms considered to 
represent reactogenicity from the vaccine include systemic events of increased 
body temperature, fatigue, generalized myalgia, generalized arthralgia, headache, 
chills, nausea, and local events at the injection site, including pain/tenderness, 
induration, erythema, and bruising. Participant diaries will be reviewed by a 
clinician and reconciled for accuracy and completeness. 
Participants will be given a thermometer for oral temperature measurement, a 
ruler, and provided access to the electronic diary. Participants will be encouraged 
to use the preferred electronic diary but will have the option to use a paper diary. 
The paper diary, if used, will be transcribed into the study database and stored in 
the participant file for monitoring purposes. The participant will use the diary to 
record daily their highest temperature as well as local and systemic signs and 
symptoms for 10 full days following each study vaccination. Participants will be 
provided training on diary completion, proper thermometer usage, and the use of 
the measuring device to measure any injection site induration and/or erythema. 
 
Remote or in-person contact between the participant and the site staff should take 
place on the day after each study injection. The reactogenicity assessment period 
is 10 days following vaccine administration. Clinicians will follow and collect 
resolution information for any reactogenicity signs and symptoms that have not 
resolved within 10 days. 
Any post vaccination reaction grade 2 or higher will be assessed by a clinician 
within 48 hours after onset, unless the reaction is improving and/or has 
completely resolved. Additionally, other clinical concerns may prompt a study 
visit based on the judgment of a study clinician. 
Given the first-in-human use of the various adjuvanted study products alone or in 
prime-boost regimens, the HVTN 303 PSRT may recommend that skin biopsies 
be obtained if unusual skin reactions following vaccinations are reported. Sites are 
In LOA #3 for protocol version 1.0 (distributed to the sites on Dec 14, 2022) 
the reactogenicity assessment period was increased from 7 days to 10 days. 
However, as vaccinations were permanently discontinued on January 13, 2023, 
the change in post-vaccine reactogenicity assessment period was no longer 
applicable and was not implemented. The reactogenicity assessment period of 
the previously vaccinated participants remained 7 days following vaccine 
administration.  

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encouraged to have a process in place for this optional study procedure. Refer to 
the HVTN 303 SSP for further details. 
Clinicians or site staff may photograph the skin reactions to document unusual 
skin findings. 
8.4 
Leukapheresis for Part B participants 
Part B (groups 6-8) participants who consented to leukapheresis (see Sections 2.7 
and 5.1.3) will undergo leukapheresis at 2 weeks post–last vaccination in order to 
collect blood cells of special interest for research. This procedure requires 
participants meeting additional eligibility criteria (see Section 5.1.3). Collection 
of PBMC via leukapheresis will be performed in accordance with the standard 
practices of the participating apheresis center. Ideally, in this procedure, 
approximately 1 to 4 liters of blood will be processed over 1 to 2 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 AEs 
following the procedure. 
8.5 
Visit windows and missed visits 
The schedule of visits and evaluations performed at each visit are shown in 
Appendix A, Appendix B, Appendix C and Appendix D. Visit windows are 
shown in Appendix E and Appendix F. The procedures for documenting missed 
visits and out of window visits are described in the HVTN 303 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. 
8.6 
Monitoring for COVID-19 symptoms  
Participants will be monitored for symptoms of COVID-19 at each study visit (see 
Appendix A, Appendix B, Appendix C and Appendix D). 
Only participants who received two vaccinations in Part B (Groups 7-8) and 
who consent to leukapheresis will undergo leukapheresis at 10 months +/- 2 
months post–last vaccination in order to collect blood cells for research. 

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8.7 
Monitoring for HIV infection 
Study participants will be tested for HIV infection periodically throughout the 
study, as indicated in the schedules included in Appendix A, Appendix B, 
Appendix C and Appendix D. The Laboratory Program (or approved diagnostic 
laboratory) will follow the HVTN HIV testing algorithm (see HVTN Laboratory 
Center MOP), which is able to distinguish vaccine-induced antibody responses 
from actual HIV infections. Participants will be promptly informed and counseled 
if they become HIV-infected during the study and will be referred for treatment 
(see Section 5.2.2). 
Study participants will receive regularly scheduled counseling regarding 
avoidance of HIV infection in accordance with the most recent Centers for 
Disease Control and Prevention HIV counseling guidelines. 
Although the study vaccine will not cause HIV infection, it may induce antibodies 
detectable by standard HIV infection screening techniques. This is referred to as 
VISP. The following steps will be taken to protect participants from adverse 
consequences associated with VISP: 
• Participants will be counseled to avoid HIV antibody testing outside of the 
HVTN CRS during study participation. 
• Participants can receive HIV diagnostic testing from the CRS following their 
last scheduled visit until they are told they do not have VISP. 
• Participants with VISP will be periodically offered free-of-charge poststudy 
HIV diagnostic testing (per the HVTN poststudy HIV testing algorithm) as 
medically/socially indicated (approximately every 6 months) unless or until 
HIV antibody testing is no longer standard in clinical settings. 
• Unless participants request that their names be removed, the names of all 
participants in HVTN studies are entered into a secure VISP registry in order 
to verify that an individual received an HIV vaccine (and therefore has the 
potential for VISP) and to qualify former participants for post study HIV 
testing to distinguish between VISP and HIV infection. Information in the 
VISP registry is not used for research. 
8.8 
Early termination visit 
If a participant terminates participation in the study early for any reason, the site 
PI should consider if the following assessments are appropriate: end-of-study HIV 
test, CBC with differential, serum chemistry, physical examination, social impact 
assessment and, if indicated, a pregnancy test (see Appendix A, Appendix B, 
Appendix C and Appendix D). For participants with HIV infection, please see 

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Section 5.2.2. If the site PI has questions regarding a termination visit, they 
should consult with the PSRT. 

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9 
Safety and adverse events 
9.1 
Adverse events 
Unsolicited AEs will be collected over a period of 28 days after each vaccination. 
All collected AEs are captured in the clinical database on the appropriate case 
report form (CRF). Clinic staff should evaluate every AE to determine if (1) the 
AE meets the requirements for expedited reporting (see Section 9.2.1), (2) if the 
AE meets the criteria for a safety pause/prompt AE review (see Section 9.5), (3) if 
the AE meets the criteria for an MAAE, and (4) if the AE is a potential immune-
mediated medical condition (PIMMC) or an AESI. A sample list of AESIs and 
PIMMCs is provided in Appendix M. 
In addition, a limited set of AEs will be collected and reported for 12 months 
following any vaccine administration. 
• SAEs/EAEs, 
• AESIs, 
• MAAEs (defined as any AEs leading to an unscheduled visit to a healthcare 
professional), 
• Safety lab-related AEs, 
• AEs leading to early participant withdrawal or early discontinuation of study 
vaccine(s) administration. 
AEs will be graded according to the Division of AIDS (DAIDS) Table for 
Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 
2.1 (https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-
tables), with the following exceptions: 
• 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 
303 SSP). 
• 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. 
• Do not grade creatinine clearance or estimated glomerular filtration rate 
(eGFR) based on the change from the baseline parameter. Do not grade on the 
basis of eGFR if there is clinical concern for kidney injury. 

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• 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) 
• For severity grading of the solicited bruising parameter at the product 
administration site, the definitions based on size of the largest diameter and 
listed for the “Injection Site Erythema or Redness” will be used. The severity 
grade definition for “Bruising” provided under the Dermatologic Clinical 
Conditions will be used only for unsolicited AEs involving bruising at other 
body locations. 
9.2 
Serious adverse events 
The term “Serious Adverse Event” (SAE) is defined in 21 CFR 312.32 as follows: 
“An adverse event or suspected adverse reaction is considered serious if, in the 
view of either the investigator or the sponsor, it results in any of the following 
outcomes: 
• death, 
• a life-threatening adverse event, 
• inpatient hospitalization or prolongation of existing hospitalization, 
• a persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions, 
• congenital anomaly/birth defect, 
• Important medical events that may not result in death, be life-threatening, or 
require hospitalization may be considered serious when, based upon 
appropriate medical judgment, they may jeopardize the patient or participant 
and may require medical or surgical intervention to prevent one of the 
outcomes listed in this definition. Examples of such medical events include 
allergic bronchospasm requiring intensive treatment in an emergency room or 

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at home, blood dyscrasias or convulsions that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse.” 
“Life-threatening” refers to an AE that, at occurrence, represents an immediate 
risk of death to the participant. Similarly, a hospital admission for an elective 
procedure is not considered an SAE. 
9.2.1 
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 Expedited Adverse Event [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 internet-based DAIDS Adverse Experience Reporting System (DAERS) must 
be used for EAE reporting to DAIDS. In the event of system outages or technical 
difficulties, EAEs may be submitted using 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 NIAID CRMS Support at 
CRMSSupport@niaid.nih.gov. Please note that site queries may also be sent from 
within the DAERS application itself. 
The SAE Reporting Category will be used throughout the study. All SAEs 
observed in this clinical trial (including PIMMCs) that are unexpected, and judged 
to be related to the study products, will be reported by the NIAID/DAIDS to the 
FDA in accordance with 21 CFR 312.32 (IND Safety Reports). After completion 
of the study, the suspected unexpected serious adverse reaction (SUSAR) 
reporting category will be used if clinical staff becomes aware of an event on a 
passive basis. 
The study products for which expedited reporting are required are: 
• VRC-HIVVCP0108-00-VP (FP8v1-rTTHC; FP conjugate vaccine) with 
Adjuplex 
• VRC-HIVRGP096-00-VP (Trimer 4571) with Adjuplex 
• VRC-HIVRGP0106-00-VP (Trimer 6931) with Adjuplex 
There is no placebo product administered in this protocol. 
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). 

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9.3 
Safety monitoring 
9.3.1 
Protocol Safety Review Team (PSRT) 
The PSRT comprises the Study Chairs, HVTN Protocol Team Leader, DAIDS 
Medical Officer, HVTN Clinical Safety Specialist (CSS), and CRS Clinic 
Coordinator. The Protocol Team clinic coordinator, clinical data manager, vaccine 
developer representative, clinical trial manager, and others may also be included 
in HVTN 303 PSRT meetings. The clinician members of HVTN 303 PSRT are 
responsible for decisions related to participant safety. The PSRT will review study 
safety information on a weekly basis through 4 weeks after the last participant 
receives the final study injection. Less frequent safety reviews will be conducted 
at the discretion of the PSRT. 
9.3.2 
HVTN Safety Monitoring Board (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 (including cumulative reactogenicity events, AEs, 
laboratory safety data, and individual SAE reports) approximately every 4 
months. The SMB conducts additional special reviews at the request of the HVTN 
303 PSRT. 
Study sites will receive SMB summary minutes and are responsible for 
forwarding them to their Institutional Review Board (IRB)/Ethics Committee 
(EC) and any applicable Regulatory Entity (RE). 
9.4 
Safety reviews 
There are 2 planned safety holds in this study: the first to determine dose 
escalations between groups 1 and 2 and between groups 3 and 4, and the second 
to review safety data for the higher-dose groups prior to proceeding to Part B. The 
PSRT must assess the accumulated product-specific data as showing no 
significant safety concerns before proceeding with activation of additional groups. 
9.4.1 
Safety considerations for Part A: Initial Safety reviews 
Part A of the study may begin with direct enrollment of participants into the 
following groups simultaneously: 
• Group 1 with no more than 1 participant enrolled per day for the 3 participants 
• Group 3 with no more than 1 participant enrolled per day for the 3 participants 

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After Groups 1 and 3 have been fully enrolled, the study will be placed on a 
safety hold. No additional enrollments will proceed until the PSRT has 
determined it is safe to do so. Once all of the reactogenicity and 2-week safety 
data from at least 6 participants have been submitted to the database, the PSRT 
must assess the accumulated product-specific data as showing no significant 
safety concerns before proceeding with enrollment of Groups 2, 4 and 5. 
If the PSRT has determined it is safe to proceed after reviewing data from 
Groups 1 and 3, the following groups may begin simultaneously: 
• Group 2 with no more than 1 participant enrolled per day for the 3 participants 
• Group 4 with no more than 1 participant enrolled per day for the 3 participants 
• Group 5 with no more than 1 participant enrolled per day for the 3 participants 
Once Groups 2, 4 and 5 have been fully enrolled, the study will be placed on a 
safety hold before proceeding with Part B. Once all of the reactogenicity and 2-
week safety data from at least 9 participants has been submitted to the database, 
the PSRT must assess the accumulated product-specific data as showing no 
significant safety concerns before proceeding with enrollment of Part B. Please 
see Table 9-1 for more details. 
9.4.2 
Safety evaluations for opening enrollment in Part B 
Once all of the cumulative safety data from all Part A participants have been 
reviewed and the PSRT determines there are no safety concerns, Part B may 
proceed with enrollment into Groups 6, 7, and 8 simultaneously. 

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Table 9-1 Summary of planned safety reviews 
Planned Safety 
Review 
Timepoint/Data Reviewed 
Actions 
Planned Safety 
Hold #1: Groups 
1 and 3 
 
Enrollment is on 
hold 
Reactogenicity and safety data from the 
“Week 2” post vaccination visit will be 
reviewed for the following: 
• 
At least 3 recipients of the FP 
conjugate vaccine (with Adjuplex) 
at a dose of 25 mcg (Group 1) 
• 
At least 3 recipients of the Trimer 
6931 (with Adjuplex) at a dose of 
100 mcg (Group 3) 
An interim safety review by the PSRT 
will determine:  
• 
If the FP conjugate vaccine plus 
Adjuplex (Group 1) is safe for further 
evaluation at a dose of 200 mcg 
(Group 2) 
• 
If the Trimer 6931 plus Adjuplex 
(Group 3) is safe for further 
evaluation at a dose of 200 mcg 
(Group 4) 
 
If the PSRT determines it is safe to 
proceed, enrollments into Groups 2, 4 and 
5 may begin with no more than 1 
participant enrolled per day for the 3 
participants in each of these groups 
Planned Safety 
Hold #2: Groups 
2, 4 and 5 
 
Enrollment is on 
hold 
 
Reactogenicity and safety data from the 
“Week 2” post vaccination visit will be 
reviewed for the following: 
1. At least 3 recipients of FP conjugate 
vaccine plus Adjuplex at a dose of 200 
mcg (Group 2) 
2. At least 3 recipients of Trimer 6931 
plus Adjuplex at a dose of 200 mcg 
(Group 4) 
3. At least 3 recipients Trimer 4571 plus 
Adjuplex at a dose of 200 mcg (Group 
5) 
An interim safety review by the PSRT 
will determine if it is safe to proceed with 
all groups in Part B. 
 
If the PSRT determines it is safe to 
proceed, enrollments into Groups 6, 7, 
and 8 may begin and is unrestricted to the 
number of participants enrolled per day. 
 
9.5 
Safety pause and prompt PSRT AE review 
The PSRT (see Section 9.3) will closely monitor participant safety. The trial can 
be paused at any time for any reason by the PSRT. When a trial is placed on 
safety pause, all enrollment and vaccination will be held until further notice. The 
AEs that will lead to a safety pause or prompt HVTN 303 PSRT AE review are 
summarized in Table 9-2.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 303 PSRT, participant safety may be threatened. Criteria 
for an individual participant’s departure from the schedule of vaccinations are 
listed in Section 5.2.3. 
 

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Table 9-2 Pause rules 
Event and relationship 
to study vaccine 
Severity 
Grade 
HVTN Site Actions 
HVTN Core action 
SAE, related 
5 or 4 
Phone 24/7 Safety Phone immediately 
Email vtn.clin.safety.spec@hvtn.org 
Submit CRFs immediately 
Immediate pause 
SAE, related 
3, 2, or 1 Email clinical safety specialist 
Submit CRFs immediately 
Prompt PSRT AE review  
AE, related 
(see grade 3 
exceptions) 
4 or 3 
Email clinical safety specialist 
Submit CRFs immediately 
Prompt PSRT AE review  
Exceptions to the related Grade 3 AEs (for Grade 3 subjective reactogenicity 
events): 
• injection site pain/tenderness 
• fatigue 
• generalized myalgia 
• generalized arthralgia 
• chills 
• headache 
• nausea (unless IV rehydration required) 
Unrelated Participant Death: Sites will call the CSS office phone upon learning 
of any unrelated participant deaths. The site will also email the CSS and 
immediately submit CRFs. The PSRT will then be immediately notified. 
If the site needs to contact the CSS, refer to phone numbers and email addresses 
found on the Protocol home page on the HVTN Members’ site 
(https://members.hvtn.org/protocols/hvtn300). 
9.5.1 
Plan for review of pause rules  
For all safety pauses, HVTN Core notifies the HVTN 303 PSRT, HVTN 
Regulatory Affairs, DAIDS Pharmaceutical Affairs Branch (PAB), DAIDS 
Regulatory Affairs Branch (RAB), DAIDS Safety and Pharmacovigilance Team 

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(SPT), and participating HVTN CRSs. When an immediate safety pause is 
triggered, HVTN Core notifies the SMB. 
Once a trial is paused, the HVTN 303 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 303 PSRT assessment, DAIDS RAB 
notifies the FDA as needed. 
If an immediate HVTN 303 PSRT notification or prompt HVTN 303 PSRT AE 
review is triggered, HVTN Core notifies the HVTN 303 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 303 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. 
9.6 
Total blood volume 
Required blood volumes per visit are shown in Appendix A, Appendix B, 
Appendix C and Appendix D. 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, per American Red Cross guidelines for blood donation 
(https://www.redcrossblood.org/donate-blood/how-to-donate/eligibility-
requirements.html). 
The preferred laboratory specimen tube types for research samples are shown in 
Appendix A, Appendix B, Appendix C and Appendix D. Alternate tube types 
may be used under certain circumstances (eg, ACD tube shortages) upon approval 
of the HVTN Laboratory Center. Refer to the HVTN 303 Specimen Collection 
SSP for more information. 
9.7 
Study termination 
This study may be terminated early by the determination of the HVTN 303 PSRT, 
the NIH, the United States Department of Health and Human Services Office for 

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Human Research Protections (OHRP), the FDA, or study product developers. 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. 
9.8 
Pregnancy 
If a participant becomes pregnant during the course of the study, no more 
injections of study product will be given, but remaining visits and study 
procedures should be completed unless medically contraindicated or applicable 
regulations require termination from the study. During follow-up for 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 303 SSP. If the participant is no longer 
pregnant, refer to Section 5.2.2. 

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10 
Protocol conduct and informed consent 
10.1 
Protocol conduct 
This research study will be conducted in compliance with the protocol, Good 
Clinical Practice (GCP) (the international council for harmonization of technical 
requirements for pharmaceuticals for human use (ICH) E6 [R2]), HVTN and 
DAIDS policies and procedures as specified in the HVTN Manual of Operations 
and DAIDS Clinical Research Policies and Standard Procedures Documents, and 
all applicable regulatory requirements. These policies and procedures include 
protocol monitoring (on-site and remote) and compliance. DAIDS and HVTN 
policies and procedures are available for review by any IRB/EC/RE upon request. 
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 303 Study Specific Procedures. 
HVTN scientists and operational staff are committed to substantive community 
input into the planning, conduct, and follow-up of its research, ensuring that 
locally appropriate cultural and linguistic needs of study populations are met. 
Community Advisory Boards (CAB) are required by DAIDS and are supported at 
all HVTN research sites to ensure community input in accordance with Good 
Participatory Practices (GPP) and all local and national guidelines. 
10.2 
Informed consent 
The sample informed consent forms (SICFs) describe the investigational vaccines 
and all aspects involved in study participation. Documentation of appropriate 
informed consent must be in place prior to conducting study procedures with 
participants. Periodic assessment of participants’ continued understanding of key 
study concepts and informed consent must also be documented. Study sites are 
strongly encouraged to have their local CABs review their site-specific consent 
forms. This review should include, but should not be limited to, issues of cultural 
competence, local language considerations, and the SICF’s level of 
comprehensibility. 
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 

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materials to their IRB/EC and any applicable RE for human participants 
protection review and approval. 
10.2.1 
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. Sites should follow procedures outlined in the current version 
of the DAIDS Protocol Registration Manual. 
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. 

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11 
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. 
Only genetic testing that is in accordance with the language in the sample 
informed consent forms (see Appendix G, Appendix H, Appendix I and Appendix 
J) may be performed on samples. 
11.1 
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 destruction or a time limit 
for storage is 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 G, Appendix H, 
Appendix I and Appendix J). 
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 IRBs/ECs/REs of 
the CRSs, 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. 

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HIV-1 Neutralization Breadth When Used To Boost Fusion Peptide-Directed 
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38. Ou L, Kong WP, Chuang GY, Ghosh M, Gulla K, O'Dell S, et al. Preclinical 
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39. Rutten L, Lai YT, Blokland S, Truan D, Bisschop IJM, Strokappe NM, et al. 
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40. Guenaga J, Garces F, de Val N, Stanfield RL, Dubrovskaya V, Higgins B, et 
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41. Julien JP, Cupo A, Sok D, Stanfield RL, Lyumkis D, Deller MC, et al. 
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42. Kuroda E, Coban C, Ishii KJ. Particulate adjuvant and innate immunity: past 
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44. Gasper DJ, Neldner B, Plisch EH, Rustom H, Carrow E, Imai H, et al. 
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46. Chakrabarti BK, Feng Y, Sharma SK, McKee K, Karlsson Hedestam GB, 
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49. Cheng C, Xu K, Kong R, Chuang GY, Corrigan AR, Geng H, et al. 
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55. Brookes ST, Whitely E, Egger M, Smith GD, Mulheran PA, Peters TJ. 
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56. Lachenbruch PA. Comparisons of two-part models with competitors. Stat 
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57. Hu Z, Proschan M. Two-part test of vaccine effect. Stat Med. 
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58. Hughes JP. Mixed effects models with censored data with application to HIV 
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59. Rotnitzky A, Robins J. Analysis of semi-parametric regression models with 
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61. DeCamp A, Hraber P, Bailer RT, Seaman MS, Ochsenbauer C, Kappes J, et 
al. Global panel of HIV-1 Env reference strains for standardized assessments 
of vaccine-elicited neutralizing antibodies. J Virol. 2014;88(5):2489-507. 
62. Huang Y, Gilbert P, Montefiori D, Self S. Simultaneous evaluation of the 
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with application to HIV vaccine development. Statistics in Biopharmaceutical 
Research. 2009;1:81-91. 
63. Liu W. On sample size determination of Dunnett's procedure for comparing 
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Inference. 1997;62(2):255-61. 
64. Finak G, McDavid A, Chattopadhyay P, Dominguez M, De RS, Roederer M, 
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65. Lin L, Finak G, Ushey K, Seshadri C, Hawn TR, Frahm N, et al. COMPASS 
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2015;33(6):610-6. 
 
 

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Schedule of procedures for Part A (Groups 1-5) 
See updated procedure for Part A (Groups 1-5) post termination of vaccination in Appendix B. 
 

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Green shaded columns represent vaccination visits. 
1 Screening evaluations at Visit 01 are performed no more than 56 days before Day 0.  
2 A complete physical exam is performed at screening and last clinic visit, to include height, weight, vital signs, and clinical assessments of head, ears, eyes, nose, 
and throat; neck, lymph nodes; heart; chest; abdomen; extremities; neurological function; and skin. At other visits, a targeted physical exam will be performed as 
needed, based on participant report or indications of illness. 
3 Medical history: A complete history is performed during screening. At enrollment and subsequently, an interim medical history may be performed. 
4 Concomitant medications, including prescription and non-prescription drugs, vitamins, topical products, alternative/complementary medicines, recreational 
drugs, vaccinations, and allergy shots are recorded during screening, at enrolment, and at each subsequent clinic visit.  
5 Vaccination (in clinic assessments): At least 30 minutes after each study injection and prior to clinic discharge, participants will have vital signs taken and the 
injection site will be assessed, and systemic symptoms will be assessed.  
6 Reactogenicity diary: Participants will complete a 10-day diary as noted in Section 8.3. If any solicited reactogenicity is unresolved by Day 10, it will continue to 
be reviewed with the participant at each visit until resolved. 
7 Follow-Up Contact: Participants will be contacted the day after vaccination which might not necessarily be within the visit window for vaccination. 
8 Contraception status assessment and pregnancy test are required only for participants who were assigned female sex at birth and are capable of becoming 
pregnant. Pregnancy test may be performed on urine or blood specimens. Persons who are NOT capable of becoming pregnant due to total hysterectomy or 
bilateral oophorectomy (verified by medical records), or menopause (no menses for ≥ 1 year) are not required to undergo pregnancy testing. For persons who are 
confirmed pregnant, pregnancy testing is not required, unless clinically indicated. 
9 HIV risk reduction and post-test counseling, including potential for VISP will be conducted as indicated above and at other visits if deemed clinically 
appropriate. A wallet card and letter regarding VISP will be provided to volunteers as noted in Section 8.6. 
10 Local labs may assign appropriate alternative tube types for locally performed tests. 
11 HIV screening test: see Section 5.1.1. 
12 Research Samples: Blood draw volumes for each tube type shown. 
13 Skin biopsies will be obtained if unusual skin reactions following vaccinations are reported (see Section 8.3) 
 

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Appendix B 
Follow-up schedule of procedures for Part A (Groups 1-5) post termination of 
vaccinations 
 
 

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Green shaded columns represent vaccination visits. 
1 Screening evaluations at Visit 01 are performed no more than 56 days before Day 0.  
2 A complete physical exam is performed at screening and last clinic visit, to include height, weight, vital signs, and clinical assessments of head, ears, eyes, nose, 
and throat; neck, lymph nodes; heart; chest; abdomen; extremities; neurological function; and skin. At other visits, a targeted physical exam will be performed as 
needed, based on participant report or indications of illness. 
3 Medical history: A complete history is performed during screening. At enrollment and subsequently, an interim medical history may be performed. 
4 Concomitant medications, including prescription and non-prescription drugs, vitamins, topical products, alternative/complementary medicines, recreational drugs, 
vaccinations, and allergy shots are recorded during screening, at enrolment, and at each subsequent clinic visit.  
5 Vaccination (in clinic assessments): At least 30 minutes after each study injection and prior to clinic discharge, participants will have vital signs taken and the 
injection site will be assessed, and systemic symptoms will be assessed.  
6 Reactogenicity diary: Participants will complete a 7-day diary as noted in Section 8.3. If any solicited reactogenicity is unresolved by Day 10, it will continue to be 
reviewed with the participant at each visit until resolved. 
7 Follow-Up Contact: Participants will be contacted the day after vaccination which might not necessarily be within the visit window for vaccination. 
8 Contraception status assessment and pregnancy test are required only for participants who were assigned female sex at birth and are capable of becoming pregnant. 
Pregnancy test may be performed on urine or blood specimens. Persons who are NOT capable of becoming pregnant due to total hysterectomy or bilateral 
oophorectomy (verified by medical records), or menopause (no menses for ≥ 1 year) are not required to undergo pregnancy testing. For persons who are confirmed 
pregnant, pregnancy testing is not required, unless clinically indicated. 
9 HIV risk reduction and post-test counseling, including potential for VISP will be conducted as indicated above and at other visits if deemed clinically appropriate. 
A wallet card and letter regarding VISP will be provided to volunteers as noted in Section 8.6. 
10 Local labs may assign appropriate alternative tube types for locally performed tests. 
11 HIV screening test: see Section 5.1.1. 
12 Research Samples: Blood draw volumes for each tube type shown. 
13 Skin biopsies will be obtained if unusual skin reactions following vaccinations are reported (see Section 8.3) 

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Appendix C 
Schedules of procedures for Part B (Tables for Group 6, Group 7, and Group 8) 
See updated schedule of procedures for Part B (Tables for Groups 6-8) post termination of vaccination in Appendix D 
Part B, Group 6 
 

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Part B, Group 7 
 

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Part B, Group 8 
 
 

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Green shaded columns represent vaccination visits  
^If a participant discontinues study injections, the schedule of evaluations should be followed for Visits 28-44, starting from a visit for the last completed injection. 
1 Screening evaluations at Visit 100 are performed no more than 56 days before Day 0.  
2 A complete physical exam is performed at screening and last clinic visit, to include height, weight, vital signs, and clinical assessments of head, ears, eyes, nose, and throat; neck, 
lymph nodes; heart; chest; abdomen; extremities; neurological function; and skin. At other visits, a targeted physical exam will be performed as needed, based on participant report 
or indications of illness. 
3 Medical history: A complete history is performed during screening. At enrollment and subsequently, an interim medical history may be performed. 
4 Concomitant medications, including prescription and non-prescription drugs, vitamins, topical products, alternative/complementary medicines, recreational drugs, vaccinations, 
and allergy shots are recorded during screening, at enrolment, and at each subsequent clinic visit.  
5 Vaccination (in clinic assessments): At least 30 minutes after each study injection and prior to clinic discharge, participants will have vital signs taken and the injection site will 
be assessed, and systemic symptoms will be assessed.  
6 Reactogenicity diary: Participants will complete a 10-day diary as noted in Section 8.3. If any solicited reactogenicity is unresolved by Day 7, it will continue to be reviewed with 
the participant at each visit until resolved. 
7 Follow-Up Contact: Participants will be contacted by telephone the day after each vaccination which might not necessarily be within the visit window for vaccination. 
8 Contraception status assessment and pregnancy test are required only for participants who were assigned female sex at birth and are capable of becoming pregnant. Pregnancy test 
may be performed on urine or blood specimens. Persons who are NOT capable of becoming pregnant due to total hysterectomy or bilateral oophorectomy (verified by medical 
records), or menopause (no menses for ≥ 1 year) are not required to undergo pregnancy testing. For persons who are confirmed pregnant, pregnancy testing is not required, unless 
clinically indicated. 
9 HIV risk reduction and post-test counseling, including potential for VISP will be conducted as indicated above and at other visits if deemed clinically appropriate. A wallet card 
and letter regarding VISP will be provided to volunteers as noted in Section 8.6. 
10 Local labs may assign appropriate alternative tube types for locally performed tests. 
11 HIV screening test: see Section 5.1.1. 
12 Research Samples: Blood draw volumes for each tube type shown. 
13 PBMC for assays & storage: To be collected only from participants who will not undergo leukapheresis. 
14 Leukapheresis: Will only be collected from participants who agreed to provide this sample type and who have met leukapheresis eligibility criteria (see Section 8.4). A 
pregnancy test must be performed and confirmed negative within 72 hours prior to leukapheresis (see also: footnote 8). For participants who decide not to provide leukapheresis 
samples, 119 mL of ACD blood will be collected instead of leukapheresis.  
15 Skin biopsies will be obtained if unusual skin reactions following vaccinations are reported (see Section 8.3) 
16 Collection of research samples has been discontinued since March 13, 2023 
17 Vaccinations have been permanently discontinued since January 13, 2023 

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Appendix D 
Follow-up schedule of procedures for Part B (Tables for Group 6, Group 7, and 
Group 8) post termination of vaccinations 
Part B, Group 6 
 
 

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Part B, Group 7 
 
 
 

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Part B, Group 8 
 
 
 

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Green shaded columns represent vaccination visits  
Yellow shaded columns represent visits without any sample collection. If these visits have already happened, please collect data in the CRFs. Otherwise, please skip 
these visits.  
1 Screening evaluations at Visit 100 are performed no more than 56 days before Day 0.  
2 A complete physical exam is performed at screening and last clinic visit, to include height, weight, vital signs, and clinical assessments of head, ears, eyes, nose, 
and throat; neck, lymph nodes; heart; chest; abdomen; extremities; neurological function; and skin. At other visits, a targeted physical exam will be performed as 
needed, based on participant report or indications of illness. 
3 Medical history: A complete history is performed during screening. At enrollment and subsequently, an interim medical history may be performed. 
4 Concomitant medications, including prescription and non-prescription drugs, vitamins, topical products, alternative/complementary medicines, recreational drugs, 
vaccinations, and allergy shots are recorded during screening, at enrolment, and at each subsequent clinic visit.  
5 Vaccination (in clinic assessments): At least 30 minutes after each study injection and prior to clinic discharge, participants will have vital signs taken and the 
injection site will be assessed, and systemic symptoms will be assessed.  
6 Reactogenicity diary: Participants will complete a 7-day diary as noted in Section 8.3. If any solicited reactogenicity is unresolved by Day 10, it will continue to be 
reviewed with the participant at each visit until resolved. 
7 Follow-Up Contact: Participants will be contacted by telephone the day after each vaccination which might not necessarily be within the visit window for 
vaccination.  
8 Contraception status assessment and pregnancy test are required only for participants who were assigned female sex at birth and are capable of becoming pregnant. 
Pregnancy test may be performed on urine or blood specimens. Persons who are NOT capable of becoming pregnant due to total hysterectomy or bilateral 
oophorectomy (verified by medical records), or menopause (no menses for ≥ 1 year) are not required to undergo pregnancy testing. For persons who are confirmed 
pregnant, pregnancy testing is not required, unless clinically indicated. 
9 HIV risk reduction and post-test counseling, including potential for VISP will be conducted as indicated above and at other visits if deemed clinically appropriate. 
A wallet card and letter regarding VISP will be provided to volunteers as noted in Section 8.6. 
10 Local labs may assign appropriate alternative tube types for locally performed tests. 
11 HIV screening test: see Section 5.1.1. 
12 Research Samples: Blood draw volumes for each tube type shown. 
13 PBMC for assays & storage: To be collected only from participants who received two vaccinations and who will not undergo leukapheresis. There is a wide visit 
window for this collection (see Appendix F). 
14 Leukapheresis: Will only be collected from participants who received two vaccinations and have agreed to provide this sample type and who have met 
leukapheresis eligibility criteria (see Section 8.4). A pregnancy test must be performed and confirmed negative within 72 hours prior to leukapheresis (see also: 
footnote 8). For participants who received two vaccinations and decide not to provide leukapheresis samples, 204 mL of ACD blood will be collected instead of 
leukapheresis. There is a wide visit window for this collection (see Appendix F).  
15 Skin biopsies will be obtained if unusual skin reactions following vaccinations are reported (see Section 8.3) 
16 Collection of research samples has been discontinued since March 13, 2023 
17 Vaccinations have been permanently discontinued since January 13, 2023 

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Appendix E 
Visit windows 
See updated visit windows post termination of vaccination in Appendix F 
Visit windows for Part A (Groups 1-5) 
Visit 
Number 
Visit Type 
Lower 
Allowable 
Window  
(-) 
Lower 
Target 
Window  
(-) 
Target 
Day* 
Upper 
Target 
Window 
(+) 
Upper Allowable 
Window  
(+) 
01 
Screening 
-56 
- 
0 
- 
+0 
02 
Enrollment/Vaccination 1 
- 
- 
0 
- 
- 
03 
1-week post-vaccination 1 
-2 
-1 
7 
+1 
+3 
04 
2 weeks post-vaccination 1 
Primary Immunogenicity 
-4 
-2 
14 
+2 
+7 
05 
Follow-up 
-7 
-2 
28 
+2 
+7 
06 
Follow-up 
-7 
-3 
56 
+3 
+7 
07 
Follow-up 
-7 
-3 
84 
+3 
+7 
08 
Follow-up 
-14 
-3 
112 
+3 
+14 
09 
Follow-up 
-14 
-7 
168 
+7 
+14 
10 
Follow-up 
-14 
-7 
224 
+7 
+14 
11 
Follow-up 
-14 
-7 
280 
+7 
+14 
12 
Final Visit 
-21 
-14 
364 
+14 
+21 
* All target dates are relative to Day 0. 
 

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Visit windows for Part B (Group 6) 
Visit 
Number 
Visit Type 
Lower 
Allowable 
Window  
(-) 
Lower 
Target 
Window  
(-) 
Target 
Day* 
Upper 
Target 
Window 
(+) 
Upper 
Allowable 
Window  
(+) 
100 
Screening 
-56 
- 
0 
- 
+0 
101 
Enrollment/Vaccination 1 
- 
- 
0 
- 
- 
102 
1-week post-vaccination 1 
-2 
-1 
7 
+1 
+3 
103 
2 weeks post-vaccination 1 
-4 
-2 
14 
+2 
+14 
110 
Vaccination 2 
-14 
-3 
84 
+3 
+14 
111 
1-week post-vaccination 2 
-2 
-1 
91 
+1 
+3 
112 
2 weeks post-vaccination 2 
-4 
-2 
98 
+2 
+14 
116 
Vaccination 3 
-21 
-3 
168 
+3 
+21 
117 
1-week post-vaccination 3 
-2 
-1 
175 
+1 
+3 
118 
2 weeks post-vaccination 3 
-4 
-2 
182 
+2 
+14 
122 
Vaccination 4 
-21 
-3 
252 
+3 
+21 
123 
1-week post-vaccination 4 
-2 
-1 
259 
+1 
+3 
124 
2 weeks post-vaccination 4 
-4 
-2 
266 
+2 
+14 
129 
Vaccination 5 
-21 
-3 
336 
+3 
+21 
130 
1-week post-vaccination 5 
-2 
-1 
343 
+1 
+3 
131 
2 weeks post-vaccination 5 
Primary Immunogenicity 
Leukapheresis 
-4 
-2 
350 
+2 
+14 
133 
Follow-up 
-28 
-3 
420 
+3 
+28 
135 
Follow-up 
-28 
-3 
504 
+3 
+28 
137 
Final Visit 
-28 
-7 
700 
+7 
+28 
 
*Target dates are relative to Day 0 (Enrollment), with the exception of post-vaccination visits, which are relative to 
the prior vaccination visit. 

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Visit windows for Part B (Group 7) 
Visit 
Number 
Visit Type 
Lower 
Allowable 
Window (-) 
Lower 
Target 
Window (-) 
Target 
Day* 
Upper 
Target 
Window (+) 
Upper 
Allowable 
Window (+) 
100 
Screening 
-56 
- 
0 
- 
+0 
101 
Enrollment/Vaccination 1 
- 
- 
0 
- 
- 
102 
1-week post-vaccination 1 
-2 
-1 
7 
+1 
+3 
103 
2 weeks post-vaccination 1 
-4 
-2 
14 
+2 
+7 
104 
Vaccination 2 
-6 
-3 
28 
+3 
+7 
105 
1-week post-vaccination 2 
-2 
-1 
35 
+1 
+3 
106 
2 weeks post-vaccination 2 
- 
-2 
42 
+2 
- 
107 
Vaccination 3 
-6 
-3 
56 
+3 
+7 
108 
1-week post-vaccination 3 
-2 
-1 
63 
+1 
+3 
109 
2 weeks post-vaccination 3 
- 
-2 
70 
+2 
- 
110 
Vaccination 4 
-6 
-3 
84 
+3 
+14 
111 
1-week post-vaccination 4 
-2 
-1 
91 
+1 
+3 
112 
2 weeks post-vaccination 4 
-4 
-2 
98 
+2 
+14 
116 
Vaccination 5 
-21 
-3 
168 
+3 
+21 
117 
1-week post-vaccination 5 
-2 
-1 
175 
+1 
+3 
118 
2 weeks post-vaccination 5 
-4 
-2 
182 
+2 
+14 
122 
Vaccination 6 
-21 
-3 
252 
+3 
+21 
123 
1-week post-vaccination 6 
-2 
-1 
259 
+1 
+3 
124 
2 weeks post-vaccination 6 
-4 
-2 
266 
+2 
+14 
129 
Vaccination 7 
-21 
-3 
336 
+3 
+21 
130 
1-week post-vaccination 7 
-2 
-1 
343 
+1 
+3 
131 
2 weeks post-vaccination 7  
Primary Immunogenicity 
Leukapheresis 
-4 
-2 
350 
+2 
+14 
133 
Follow-up 
-28 
-3 
420 
+3 
+28 
135 
Follow-up 
-28 
-7 
504 
+7 
+28 
137 
Final Visit 
-28 
-7 
700 
+7 
+28 
*Target dates are relative to Day 0 (Enrollment), with the exception of post-vaccination visits, which are 
relative to the prior vaccination visit. 

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Visit windows for Part B (Group 8) 
Visit 
Number 
Visit Type 
Lower 
Allowable 
Window  
(-) 
Lower 
Target 
Window  
(-) 
Target 
Day* 
Upper 
Target 
Window 
(+) 
Upper 
Allowable 
Window  
(+) 
100 
Screening 
-56 
- 
0 
- 
+0 
101 
Enrollment/Vaccination 1 
- 
- 
0 
- 
- 
102 
1-week post-vaccination 1 
-2 
-1 
7 
+1 
+3 
103 
2 weeks post-vaccination 1 
-4 
-2 
14 
+2 
+7 
104 
Vaccination 2 
-6 
-3 
28 
+3 
+7 
105 
1-week post-vaccination 2 
-2 
-1 
35 
+1 
+3 
106 
2 weeks post-vaccination 2 
- 
-2 
42 
+2 
- 
107 
Vaccination 3 
-6 
-3 
56 
+3 
+7 
108 
1-week post-vaccination 3 
-2 
-1 
63 
+1 
+3 
109 
2 weeks post-vaccination 3 
-4 
-2 
70 
+2 
+14 
113 
Vaccination 4 
-14 
-3 
140 
+3 
+14 
114 
1-week post-vaccination 4 
-2 
-1 
147 
+1 
+3 
115 
2 weeks post-vaccination 4 
-4 
-2 
154 
+2 
+14 
119 
Vaccination 5 
-21 
-3 
224 
+3 
+21 
120 
1-week post-vaccination 5 
-2 
-1 
231 
+1 
+3 
121 
2 weeks post-vaccination 5 
-4 
-2 
238 
+2 
+14 
122 
4 weeks post-vaccination 5 
-7 
-2 
252 
+2 
+7 
125 
8 weeks post-vaccination 5 
-7 
-3 
280 
+3 
+7 
126 
Vaccination 6 
-21 
-3 
308 
+3 
+21 
127 
1-week post-vaccination 6 
-2 
-1 
315 
+1 
+3 
128 
2 weeks post-vaccination 6 
Primary Immunogenicity 
Leukapheresis 
-4 
-2 
322 
+2 
+14 
132 
Follow-up 
-28 
-4 
392 
+4 
+28 
134 
Follow-up 
-28 
-7 
476 
+7 
+28 
136 
Final Visit 
-28 
-7 
672 
+7 
+28 
*Target dates are relative to Day 0 (Enrollment), with the exception of post-vaccination visits, which are 
relative to the prior vaccination visit. 

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Appendix F 
Follow up visit windows post termination of 
vaccination 
 
Visit windows for Part A (Groups 1-5) 
Visit 
Number 
Visit Type 
Lower 
Allowable 
Window  
(-) 
Lower 
Target 
Window  
(-) 
Target 
Day* 
Upper 
Target 
Window 
(+) 
Upper Allowable 
Window  
(+) 
01 
Screening 
-56 
- 
0 
- 
+0 
02 
Enrollment/Vaccination 1 
- 
- 
0 
- 
- 
03 
1-week post-vaccination 1 
-2 
-1 
7 
+1 
+3 
04 
2 weeks post-vaccination 1 
Primary Immunogenicity 
-4 
-2 
14 
+2 
+7 
05 
Follow-up 
-7 
-2 
28 
+2 
+7 
06 
Follow-up 
-7 
-3 
56 
+3 
+7 
07 
Follow-up 
-7 
-3 
84 
+3 
+7 
08 
Follow-up 
-14 
-3 
112 
+3 
+14 
09 
Follow-up 
-14 
-7 
168 
+7 
+14 
10 
Follow-up 
-14 
-7 
224 
+7 
+14 
11 
Follow-up 
-14 
-7 
280 
+7 
+14 
12 
Final Visit 
-21 
-14 
364 
+14 
+21 
* All target dates are relative to Day 0. 
 
 
 
 

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Visit windows for Part B (Group 6) 
Visit 
Number 
Visit Type 
Lower 
Allowable 
Window 
(-) 
Lower 
Target 
Window 
(-) 
Target 
Day* 
Upper 
Target 
Window 
(+) 
Upper 
Allowable 
Window 
(+) 
100 
Screening 
-56 
- 
0 
- 
+0 
101 
Enrollment/Vaccination 1 
- 
- 
0 
- 
- 
102 
1-week post-vaccination 1 
-2 
-1 
7 
+1 
+3 
103 
2 weeks post-vaccination 1 
-4 
-2 
14 
+2 
+14 
110 
Follow-up visit  
-14 
-3 
84 
+3 
+14 
111 
Follow-up visit  
-2 
-1 
91 
+1 
+3 
112 
Follow-up visit  
-4 
-2 
98 
+2 
+14 
116 
Follow-up visit  
-21 
-3 
168 
+3 
+21 
117 
Follow-up visit  
-2 
-1 
175 
+1 
+3 
118 
Follow-up visit  
-4 
-2 
182 
+2 
+14 
122 
Follow-up visit  
-21 
-3 
252 
+3 
+21 
123 
Follow-up visit  
-2 
-1 
259 
+1 
+3 
124 
Follow-up visit  
-4 
-2 
266 
+2 
+14 
129 
Follow-up visit  
-21 
-3 
336 
+3 
+21 
130 
Follow-up visit  
-2 
-1 
343 
+1 
+3 
131 
Follow-up visit  
-4 
-2 
350 
+2 
+14 
132 
Follow-up visit 
-28 
-3 
392 
+3 
+28 
 
*Target dates are relative to Day 0 (Enrollment), with the exception of post-vaccination visits, which are relative to 
the prior vaccination visit. 

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Visit windows for Part B (Group 7) 
Visit 
Number 
Visit Type 
Lower 
Allowable 
Window 
(-) 
Lower 
Target 
Window 
(-) 
Target 
Day* 
Upper 
Target 
Window 
(+) 
Upper 
Allowable 
Window 
(+) 
100 
Screening 
-56 
- 
0 
- 
+0 
101 
Enrollment/Vaccination 1 
- 
- 
0 
- 
- 
102 
1-week post-vaccination 1 
-2 
-1 
7 
+1 
+3 
103 
2 weeks post-vaccination 1 
-4 
-2 
14 
+2 
+7 
104 
Vaccination 2 
-6 
-3 
28 
+3 
+7 
105 
1-week post-vaccination 2 
-2 
-1 
35 
+1 
+3 
106 
2 weeks post-vaccination 2 
- 
-2 
42 
+2 
- 
107 
Follow-up visit  
-6 
-3 
56 
+3 
+7 
108 
Follow-up visit  
-2 
-1 
63 
+1 
+3 
109 
Follow-up visit  
- 
-2 
70 
+2 
- 
110 
Follow-up visit  
-6 
-3 
84 
+3 
+14 
111 
Follow-up visit  
-2 
-1 
91 
+1 
+3 
112 
Follow-up visit  
-4 
-2 
98 
+2 
+14 
116 
Follow-up visit  
-21 
-3 
168 
+3 
+21 
117 
Follow-up visit  
-2 
-1 
175 
+1 
+3 
118 
Follow-up visit  
-4 
-2 
182 
+2 
+14 
122 
Follow-up visit  
-21 
-3 
252 
+3 
+21 
123 
Follow-up visit  
-2 
-1 
259 
+1 
+3 
124 
Follow-up visit  
-4 
-2 
266 
+2 
+14 
129 
Follow-up visit  
-21 
-3 
336 
+3 
+21 
 
Leukapheresis 
Leukapheresis (or large blood draw) must be completed at 
only one of the following visits (130, 131, or 132) but 
NOT at all 3 visits for the subset of participants who 
received two vaccinations (see Section 8.4).  
130 
Follow-up visit  
-2 
-1 
343 
+1 
+3 
131 
Follow-up visit  
-4 
-2 
350 
+2 
+14 
132 
Follow-up visit  
-28 
-3 
392 
+3 
+28 
*Target dates are relative to Day 0 (Enrollment), with the exception of post-vaccination visits, which are relative to the prior 
vaccination. 
 

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Visit windows for Part B (Group 8) 
Visit 
Number 
Visit Type 
Lower 
Allowable 
Window 
(-) 
Lower 
Target 
Window 
(-) 
Target 
Day* 
Upper 
Target 
Window 
(+) 
Upper 
Allowable 
Window 
(+) 
100 
Screening 
-56 
- 
0 
- 
+0 
101 
Enrollment/Vaccination 1 
- 
- 
0 
- 
- 
102 
1-week post-vaccination 1 
-2 
-1 
7 
+1 
+3 
103 
2 weeks post-vaccination 1 
-4 
-2 
14 
+2 
+7 
104 
Vaccination 2 
-6 
-3 
28 
+3 
+7 
105 
1-week post-vaccination 2 
-2 
-1 
35 
+1 
+3 
106 
2 weeks post-vaccination 2 
- 
-2 
42 
+2 
- 
107 
Follow-up visit  
-6 
-3 
56 
+3 
+7 
108 
Follow-up visit  
-2 
-1 
63 
+1 
+3 
109 
Follow-up visit  
-4 
-2 
70 
+2 
+14 
113 
Follow-up visit  
-14 
-3 
140 
+3 
+14 
114 
Follow-up visit  
-2 
-1 
147 
+1 
+3 
115 
Follow-up visit  
-4 
-2 
154 
+2 
+14 
119 
Follow-up visit  
-21 
-3 
224 
+3 
+21 
120 
Follow-up visit  
-2 
-1 
231 
+1 
+3 
121 
Follow-up visit  
-4 
-2 
238 
+2 
+14 
122 
Follow-up visit  
-7 
-2 
252 
+2 
+7 
125 
Follow-up visit  
-7 
-3 
280 
+3 
+7 
126 
Follow-up visit  
-21 
-3 
308 
+3 
+21 
127 
Follow-up visit  
-2 
-1 
315 
+1 
+3 
 
Leukapheresis 
Leukapheresis (or large blood draw) must be completed at 
only one of these 2 visits (128 or 132) but NOT both visits 
for the subset of participants who received two 
vaccinations (see Section 8.4).  
128 
Follow-up visit  
-4 
-2 
322 
+2 
+14 
132 
Follow-up visit  
-28 
-4 
392 
+4 
+28 
*Target dates are relative to Day 0 (Enrollment), with the exception of post-vaccination visits, which are 
relative to the prior vaccination visit. 
 

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Appendix G 
Sample informed consent form for Part A 
(Groups 1-5) 
Title: A Phase 1, Open-Label Clinical Trial to Evaluate Safety, Tolerability, and 
Immunogenicity of Adjuvanted HIV-1 Fusion Peptide Conjugate Vaccine (VRC- 
HIVVCP0108-00-VP) Alone or in Prime-Boost Regimens with Adjuvanted HIV-
1 Envelope Trimer 4571 (VRC-HIVRGP096-00-VP) and HIV-1 Trimer 6931 
(VRC-HIVRGP0106-00-VP) Vaccines in Healthy Adults 
HVTN protocol number: HVTN 303 
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. 
Key information 
• 
Being in this research study is voluntary. It is your choice. 
• 
You are being asked to take part in this study because you are age 18-50, HIV 
negative and healthy. 
• 
The purpose of the study is to see if the study vaccines are safe to give to 
people and do not make people too uncomfortable. 
• 
Another purpose of the study is to see how a person’s immune system 
responds to the study vaccines. (Your immune system protects you from 
infections and disease.) 
• 
You will be in this study for up to 12 months of clinic visits.  
• 
Procedures will include blood draws and injections of study vaccine. There is 
also an optional procedure of a skin biopsy that we may ask you to have done. 
We will tell you more about this procedure later in this consent form. 
• 
There are risks from participating. 
▪ The vaccine you receive has not been given to people before or has only 
been given to a small number of people. We do not know all the risks of 
the vaccines in this study. A few known risks are pain and itching at the 
injection site, muscle pain, swelling, skin redness, soreness, tenderness, 
headache, nausea, fatigue and fever. 
▪ Taking blood and giving injections can cause bruising, pain, fainting, 
soreness, redness, swelling, itching, a sore and bleeding. A skin biopsy can 
cause bleeding, pain, bruising, and scarring, and rarely an infection. 

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▪ We will tell you more information about risks later in this consent form. 
• 
We do not expect the study vaccines to benefit you in any way.  
About the study 
The HIV Vaccine Trials Network (HVTN) and [Insert site name] are doing a 
study to test 3 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 3 different proteins with 1 
adjuvant. 
Up to 70 people will take part in this study at multiple sites in the United States. 
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. 
The study is divided into 2 parts, Part A and Part B. In Part A, participants will 
get 1 of the 3 study vaccines. Up to 20 people will be in Part A. If there are no 
safety concerns in Part A, we will do Part B. Up to 50 people will be in Part B. 
Part B will test the study vaccines in different combinations. You are being 
invited to join Part A of the study.  
1. We are doing this study to answer several questions. 
• 
Are the study vaccines safe to give to people? 
• 
Are people able to take the vaccines without becoming too uncomfortable? 
• 
How do people’s immune systems respond to the study vaccines? (Your 
immune system protects you from infections and disease.)  
2. The study vaccines cannot give you HIV. 
The study vaccines are not made from HIV. It is impossible for the study vaccines 
to give you HIV. Also, they cannot cause you to give HIV to someone else. 
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.  
3. These study vaccines are experimental. 
The study vaccines include two parts. One part is a lab-made piece of protein that 
looks like a protein found on the outside of HIV. The second part is an adjuvant 
called Adjuplex. (An adjuvant is something that helps the immune system respond 
better.) From here on, we will call it “the adjuvant”.  

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We are testing 3 different proteins in this study and each of these will be mixed 
with the adjuvant. We will use the term “vaccine” or “study vaccine” to refer to 
the combination of a protein and the adjuvant. The 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. 
The 3 proteins being tested are called Fusion Peptide (FP conjugate), Trimer 4571 
and Trimer 6931. They are all lab-made small pieces of proteins that look like 
parts of proteins found in the HIV virus. The immune system will be able to see 
the pieces that look like parts of HIV and learn how to recognize them. 
Researchers hope that the immune system will respond by making antibodies that 
could fight HIV. (The body makes antibodies to fight germs after it is exposed to 
them. The antibodies attack germs and keep them from infecting the body’s cells.) 
Each of the 3 proteins in the study is made slightly differently to see how the 
immune system will respond to these different structures. The proteins were 
developed by the Vaccine Research Center (VRC) at the US National Institutes of 
Health.  
The FP conjugate protein and the Trimer 6931 protein have not been given to 
people before. The Trimer 4571 protein mixed with a different adjuvant has been 
given to a small number of people in several other studies. 
The Adjuplex adjuvant is being provided for this study by the VRC. The adjuvant 
is made of a fatty substance called lecithin and a suspending agent called 
carbomer mixed together in a saline solution. It has been given to 20 people in a 
different study.  
These combinations of protein and adjuvant have been tested in mice, guinea pigs 
and rabbits. The adjuvant has also been tested in studies using mice and rabbits. In 
these studies, animals that got these products had symptoms consistent with the 
general risks of other vaccines (as described below). 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, dizziness, and 
feeling tired. Vaccines can also cause stinging, discomfort, redness, mild bruising 
or an infection where you got the injection. Signs of infection at the injection site 
include severe pain, redness, swelling, warmth or drainage. Rarely, people have 
side effects that limit their normal activities or make them go to the doctor. 
Risks of the study vaccines: 
FP conjugate vaccine and Trimer 6931 vaccine  
The FP conjugate vaccine and the Trimer 6931 vaccine have not been given to 
people before so we do not know what the risks may be. However, we expect they 

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will be similar to the general risks of vaccines described above. There may be 
other side effects, even serious or life-threatening ones, which we do not know 
about yet. 
Trimer 4571 vaccine 
This vaccine mixed with a different adjuvant was given to people for the first time 
in a study called VRC 018 that ended in June 2020. The 16 participants in it each 
got 3 injections at doses higher and lower than the dose we will give in this study. 
The injections did not cause any serious health problems. 14 people had mild pain 
where they got the injection and 6 people had muscle pain, which went away 
within 7 days. 6 people had mild itching where they got the injection that lasted 
between 1 and 9 days. One person had swelling after their second injection and 
skin redness after their third. Both of these went away within 7 days. Another 
person had moderate swelling and severe skin redness where they got the 
injection. Both of these disappeared at 8 days after the injection. 4 people had 
mild headaches and 3 people felt nauseous after injection. These symptoms went 
away within 7 days. One person had a decrease in neutrophils which is a type of 
white blood cell. This went away after 8 days.  
As of January 2022, there are 2 other studies giving the Trimer 4571 vaccine to 
people. NIH-19-I-0069 will enroll 200 participants and give them a different 
study vaccine followed by a booster injection of a higher dose of the Trimer 4571 
vaccine than we will give in this study with a different adjuvant 6 months later. 
As of January 5, 2022, 12 participants have gotten their booster injection. The 
injections have not caused serious health problems. The common side effects are 
mild pain at the injection site, mild headache and mild fatigue. The other study, 
called NETI, will give participants with HIV infection multiple injections of 
either placebo or lower and higher doses of Trimer 4571 than we will use in this 
study with a different adjuvant. As of January 1, 2022, 5 participants have 
received a total of 7 injections. The common side effects are mild to moderate 
injection site pain and tenderness, fatigue, joint stiffness and headache. 
Because this protein has only been given to a small number of people, we do not 
know all the side effects. There may be side effects, which may be serious or life 
threatening, that we do not know about yet.  
Risks of the Adjuplex adjuvant: 
The 20 people who got a different vaccine with this adjuvant in a different study 
have not had serious health problems from it. Some people have had injection site 
pain, soreness, tenderness and occasional fever after getting this adjuvant. 
Because this adjuvant with a different vaccine has only been given to a small 
number of people, we do not know all the side effects.  
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. 

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Joining the study 
4. It is up to you whether or not to join the study. 
Take your time. Talk to people you trust. If you decide not to join this study or if 
you leave after you have joined, your other care at this clinic and the benefits or 
rights you would normally have will not be affected. 
You cannot be in this study while you are in another study where you get a study 
product. If you do not join this study, you may be able to join another study. 
If you join this study, you may not be allowed to join other HIV vaccine or HIV 
prevention trials now or in the future.  
During the study, you should not donate blood or tissue. 
Site: Remove item 5 if you use a separate screening consent that covers these 
procedures. 
5. 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 run blood tests. These tell us about the health of your kidneys and 
liver. We will ask you about medicines 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 test results with you. They may show you are not eligible for 
the study, even if you want to join.  
Site: adapt the following section per the care available at your site 
6. 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 help you get care elsewhere. For health 
problems unrelated to the study, we will not pay for care. 

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7. If you were assigned female sex at birth and could become pregnant, you 
must use birth control to join this study. 
Site: If you want to include Appendix L, 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 a developing baby. You must agree to use 
effective birth control from at least 3 weeks before your study injection through 
12 weeks later. We will talk to you about effective birth control methods. They are 
listed on a handout that we will give to you. 
Being in the study 
If you join the study, here is what will happen: 
8. You will come to the clinic for scheduled visits about [#] times over 12 
months. 
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 study ends (for example, to tell you about the study results). 
We may also contact you about other studies you may want to join. 
9. We will give you [Site: Insert compensation] for each study visit you 
complete. 
This amount is to cover the costs of [Site: Insert text].  
There is also compensation for the optional skin biopsy study procedure we may 
ask you to have done. We will tell you more about the procedure below. If you 
have the skin biopsy procedure, we will give you [Site: Insert amount]. 
Site: Insert any costs to participants (eg, birth control costs for female 
participants who could become pregnant). 
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. 

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You do not have to pay anything to be in this study. Site: Insert any costs to 
participants (eg, birth control costs for female participants who could become 
pregnant). 
10. We will give you one of the study vaccines.  
When you join the study, you will get one of the study vaccines, split into 2 
injections. We will give the injections with a needle and syringe into the muscle 
of both upper arms. If there is a reason we cannot give an injection into one of 
your arms, then we will give both injections into the other arm. 
You will be in 1 of 5 groups. Which group you are in will depend on when you 
join the study. The table below shows the groups and what study vaccine and dose 
each will get. Groups 1-4 will get the 2 study vaccines that have not been given to 
people before. These are the FP conjugate vaccine and the Trimer 6931 vaccine. 
We will start by giving a low dose of each of these vaccines. Group 1 will get a 
low dose of the FP conjugate vaccine and Group 3 will get a low dose of the 
Trimer 6931 vaccine.  
Because this is the first time these study vaccines are being given to people, we 
want to be very careful. Only 1 participant in each group will get the study 
vaccine each day. Once 3 people in Group 1 and 3 people in Group 3 have gotten 
the study vaccine, we will pause the study for a review by a team that is watching 
the study closely to ensure it is safe for participants. They will look at how these 6 
participants responded to their study vaccines and decide if it is safe to give a 
higher dose of these 2 study vaccines. If this team allows us to continue with the 
study, we will then begin enrolling Groups 2, 4 and 5.  
Group 2 will get a higher dose of the FP conjugate vaccine and Group 4 will get a 
higher dose of the Trimer 6931 vaccine. Group 5 will get the study vaccine that 
has been given to people before, the Trimer 4571 vaccine. In these groups, just 
like with Groups 1 and 3, only 1 participant in each group will get the study 
vaccine each day.  
Once 3 people in each group (Group 2, Group 4 and Group 5) have gotten the 
study vaccine, we will again pause the study for a review by the same team 
watching the safety of participants. They will look at how these 9 participants 
responded to their study vaccines and decide if it is safe to start Part B of the 
study, which will give multiple injections of the study vaccines to participants. It 
is possible they may ask us at any time to enroll up to 5 more participants in Part 
A to provide more information to help them with their decision. 

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Group  
Number of 
participants 
Study vaccine and dose  
1 
3 
25 mcg FP conjugate vaccine 
2 
3 
200 mcg FP conjugate vaccine 
3 
3 
100 mcg Trimer 6931 vaccine 
4 
3 
200 mcg Trimer 6931 vaccine 
5 
3 
200 mcg Trimer 4571 vaccine 
You will have to wait in the clinic for at least 30 minutes after your injections to 
see if there are any reactions or health concerns. Then for that night and for 10 
more days, you will use an electronic participant diary to record how you are 
feeling, including your highest daily temperature. We will give you a 
thermometer to help you do this. We will also give you a ruler to measure any 
swelling at the injection site. If you are unable or unwilling to use the electronic 
participant diary, please talk with us about other options that may be available. 
We will contact you the day after your injection to ask how you are doing. 
Contact the clinic staff if you have any issues or concerns after getting an 
injection.  
11. In addition to giving you a study vaccine, we will do the procedures shown in 
the following table. 
 
 
 
Time after first injection visit 
Procedure 
Screening 
visit(s) 
Injection 
visit 
1 week 
2 weeks 
4 weeks 
8 weeks 
12 weeks 
16 weeks 
24 weeks 
32 weeks 
40 weeks 
52 weeks 
Injection 
 
√ 
 
 
 
 
 
 
 
 
 
 
Medical history 
√ 
 
 
 
 
 
 
 
 
 
 
 
COVID-19 
symptom check 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Complete 
physical 
√ 
 
 
 
 
 
 
 
 
 
 
√ 
Brief physical 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Blood drawn 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Pregnancy test* 
√ 
√ 
 
 
 
 
√ 
 
 
 
 
 
HIV testing  
√ 
 
 
 
 
 
√ 
 
√ 
 
√ 
√ 
Risk reduction 
counseling 
√ 
√ 
 
√ 
 
 
√ 
 
√ 
 
√ 
√ 
Interview/ 
questionnaire 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
* For persons who were assigned female sex at birth and who are capable of becoming pregnant. Persons who 
have had a hysterectomy (removal of the uterus) or removal of both ovaries (verified by medical records) or are 
in menopause, do not have to have pregnancy tests. 
When we take blood, the amount will depend on the lab tests we need to do at a 
certain visit. It will be some amount between 8.5 mL and 101 mL (about ½ 

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tablespoon to 7 tablespoons). Your body will make new blood to replace the 
blood we take out. 
When we do tests, we will review the results with you at your next visit, or sooner 
if necessary. We will tell you about any results that are important to your health. 
12. If you have an unusual reaction on your skin due to a study injection, we 
may want to photograph it. 
Taking photographs may help researchers learn more about reactions to the study 
products. We will not take photos of your face. Your name and other identifying 
information will not be included on the photos. The photos will only be used to 
research the safety of the study products. 
13. If you have an unusual reaction on your skin to a study injection, we may 
want to do a skin biopsy. 
A skin biopsy collects a small sample of skin cells so they can be examined in a 
lab. This may help researchers better understand your skin reaction and learn 
more about the study products.  
We will ask you at the end of this consent form if you agree to the skin biopsy 
procedure. You can change your mind at any time. It is possible that you may not 
be asked to have a skin biopsy, even if you agree to it. 
If we ask you to have a skin biopsy, this procedure will be done at [site: insert 
location].  
Sites referring out to another facility for the skin biopsy:  
• must obtain copies of the informed consent form and any other educational 
materials that are available from the facility where it will be done so that they 
can be reviewed with potential participants during the study informed consent 
process.  
• include these sentences: There will be another consent form for you to review 
and sign at the facility. As part of the consent process, you will be able to 
discuss the procedure in more detail with the clinician who will do the 
procedure. The discussion will include the location, size, depth and risks of 
the skin biopsy.  
Sites doing the skin biopsy in the clinic and that have their own separate ICF for 
the procedure:  
• must review it and any other educational materials they have about it with the 
potential participant during the study informed consent process. 

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• Include these sentences: We will give you a separate consent form to review 
and sign. As part of the consent process, you will be able to discuss the 
procedure in more detail with the clinician who will do the procedure. The 
discussion will include the location, size, depth and risks of the skin biopsy.  
Sites doing the skin biopsy in the clinic and that do not have their own separate 
ICF for the procedure must modify the general information below about skin 
biopsies to provide the details of the procedure & its risks at their clinic.  
There are several different tools that can be used to do a skin biopsy. The clinician 
doing the procedure will examine the reaction on your skin to determine which 
one to use. They will tell you how the tool works and the general size of the 
sample they will take from your skin. They will apply a cleaning solution to your 
skin in the area where the biopsy will be done and numb the area with an injection 
of a local anesthetic. Once the area is numb, the clinician will take a small sample 
of skin. This procedure may require a few stitches to close the wound. A skin 
biopsy may cause a scar. This scar will likely fade over time. A skin biopsy 
typically takes about 15 minutes total, including the preparation time, dressing the 
wound, and instructions for at-home care.  
14. We will counsel you about protecting yourself from HIV. 
We will ask you 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 body, including your 
immune system, responds to the study vaccine. 
We will send your samples (without your name or other identifying information) 
to labs in the United States approved by the HVTN for this study. In rare cases, 
some of your samples may be sent to labs 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. This genetic testing will involve only 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. 
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 how the virus is impacted by the study vaccine. 
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. 

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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. 
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, the HVTN will destroy all extra samples 
that it has. 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 the HVTN shares your 
samples and information, it 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 

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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 the HVTN shares may be personal, 
such as your race, ethnicity, sex, health information from the study, and HIV 
status. The HVTN 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 

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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. 
Site: Check HIPAA authorization for conflicts with this section. 
All of your samples and most of your study records will be labeled with a code 
number. Samples and study records are kept in secure locations. When you 
provide information in the electronic participant diary after the injection visits, 
that information only has your code number. Your information goes directly from 
the electronic participant diary into your study record. 
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 vaccines(s) you received 
No HIV test results are 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 can see your study records. Your records may also be reviewed by 
groups that 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 (FDA), 
• 
Any regulatory agency that reviews clinical trials, 
• 
US sites may, but are not required to include: [Insert name of local IRB/EC] , 
• 
Advarra Institutional Review Board (IRB) 
• 
Site: [Insert name of local and/or national regulatory authority as appropriate] 

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• 
The HVTN and people who work for them, 
• 
The HVTN Safety Monitoring Board, and 
• 
The US Office for Human Research Protections. 
All reviewers will keep your records private. 
We cannot guarantee absolute privacy. If you 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] 
Site: Include the following boxed text. You can remove the box around the text. 
To help protect your privacy, we have a Certificate of Confidentiality from the US 
government. 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. 
However, we cannot withhold information from the US government because it 
funds this research. You can still give 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 Web site will not include information that can 
identify you. At most, the Web site will include a summary of the results. You can 
search this Web site at any time. 
18. If you become pregnant or get HIV during the study, we will encourage you 
to stay in the study until your final scheduled clinic visit if you choose. 
If you leave the study while you are pregnant, we will contact you after your due 
date to ask some questions about your pregnancy and delivery. If you stay in the 

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study, we may take fewer samples from you. If you get HIV, we will help you get 
care and support. 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 your HIV care. If you stay in the study, we will take fewer 
samples from you. 
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. 
In addition to the risks of the study vaccines and the procedures that were 
described above, this section describes the other risks we know about. There may 
be other risks, even serious ones. We will tell you if we learn anything new that 
may affect your decision 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, stinging, swelling, itching, a sore, bleeding, and rarely infection 
where you got the injection. Taking blood can cause a low blood cell count 
(anemia), making you feel tired. 
Risks of skin biopsy: 
A skin biopsy can cause bleeding, pain, bruising, and scarring, and rarely, an 
infection. The injection of a local anesthetic can cause brief stinging or burning in 
the area of the injection. 
Personal problems/discrimination/testing HIV antibody positive: 
Some people report personal problems or discrimination because they joined an 
HIV vaccine study. Family or friends may worry, get upset, or assume that you 
have HIV. Rarely, someone has lost a job because the study took too much time 
away from work, or because their employer thought they had HIV. 
Most vaccines cause the body to make antibodies to prevent infection. Your body 
may make antibodies to HIV because you received an HIV study vaccine. Those 

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antibodies could cause you to test positive on some types of HIV tests, even if you 
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 is likely to say you have HIV, even if you don’t. For this reason, you should 
get HIV tests only at this clinic. Our tests can tell the difference between true HIV 
infection and a positive result caused by the study vaccine. If you have VISP, we 
can arrange free HIV testing for as long as you need it.  
It is unlikely, but you could test antibody negative at the end of the study and then 
test positive sometime later, even though you don’t have HIV.  
Site: Modify the following paragraph if applicable. If someone believes you have 
HIV, you could face discrimination and other problems. In some countries, you 
could be denied medical or dental care, employment, insurance, a visa, or entry 
into the military. If you have VISP, 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 VISP, and how you can avoid some of these 
problems. 
If you become pregnant during or after the study and have VISP, the antibodies 
might be passed to your baby. We know that this happens with some other 
vaccines. The antibodies are not a danger to the baby and they go away, usually in 
about 6 months. 
You should 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, 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 tests that can 
distinguish true HIV infection from VISP. 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 questions about HIV risks, such as 
having sex and using drugs. Also, waiting for HIV test results could make you 
feel anxious. You could feel worried if 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: 
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 happens, you could face 
discrimination, stress, and embarrassment. We can tell you more about how we 
will protect your personal information. 
Risks of genetic testing: 

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It is possible that genetic tests could show you may be at risk for certain diseases. 
If others found out, it could lead to discrimination or other problems. However, 
genetic test results are not part of your study record, so it is almost impossible for 
anyone to connect them to you personally. 
Even if your genetic information somehow gets 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 this 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. 
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 
might detect health problems you don’t yet know about. 
When asked, most study participants say that participating in a study made them 
feel good about helping others, increased their knowledge about HIV, and 
improved their self-esteem. 
This study may help in the search for a vaccine to prevent HIV. However, if the 
study vaccines later become approved for sale, 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. 
We list these in the Bill of Rights and Responsibilities (BRR) for HIV Research. 
We will give you a copy of it. 

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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. This will not affect 
your care at this clinic and your legal rights, but it is important for you to let us 
know. 
Previously collected information about you will remain in the study records and 
will be included in the analysis of results. Your information cannot be removed 
from the study records. 
We will ask you to come to the clinic one last time for a physical exam. We may 
ask to take some blood samples from you and ask you to answer some questions. 
If you were assigned female sex at birth, we may test you for pregnancy. Whether 
you come for this last visit is up to you. 
Injuries 
Sites: Approval from HVTN Regulatory Affairs (at vtn.core.reg@fredhutch.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 care that we 
can give here. For 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 
this is related to the study vaccines 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. 
The HVTN has limited funds to pay medical costs that it determines are 
reasonable. 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. 

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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]. 
 
An institutional review board (IRB) is an independent committee established to 
help protect the rights of research subjects. If you have any questions about your 
rights as a research participant, and/or concerns or complaints regarding this 
research study, contact: 
• 
By mail: 
Study Subject Adviser 
Advarra IRB 
6100 Merriweather Dr, Suite 600 
Columbia, MD 21044 
• 
or call toll free:    877-992-4724 
• 
or by email:          adviser@advarra.com 
 
Please reference the following number when contacting the Study 
Subject Adviser: #######. 
US sites may include, but are not required to: You may also contact the [name of 
local IRB/EC] at [insert contact information]. 
Your permissions and signature  
26. In Section 13 of this form, we told you about the skin biopsy procedure we 
may ask you to have done. If you agree to the skin biopsy, please write your 
initials or make your mark in the box below. If you do not agree to the skin 
biopsy, leave the box blank. You can change your mind after signing this 
form.  
 
 
I agree to the skin biopsy. 

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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. 
 
 
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 

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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 
Sample addendum to informed consent form 
for Part A (Groups 1-5) post termination of 
vaccinations 
Title: A Phase 1, Open-Label Clinical Trial to Evaluate Safety, Tolerability, and 
Immunogenicity of Adjuvanted HIV-1 Fusion Peptide Conjugate Vaccine (VRC- 
HIVVCP0108-00-VP) Alone or in Prime-Boost Regimens with Adjuvanted HIV-
1 Envelope Trimer 4571 (VRC-HIVRGP096-00-VP) and HIV-1 Trimer 6931 
(VRC-HIVRGP0106-00-VP) Vaccines in Healthy Adults 
HVTN protocol number: HVTN 303 
Site: [Insert site name] 
Key information 
• 
Being in this research study is voluntary. It is your choice. 
• 
Study injections have been stopped for all participants.  
• 
If you stay in this study, you will be in it until one year after you completed 
your study injection visit. 
• 
Procedures will still include blood draws. 
• 
There are risks from participating. 
▪ Taking blood can cause bruising, pain, fainting, soreness, redness, 
swelling, itching, a sore and bleeding. 
1. Review of study information  
This study started in August 2022 and planned to enroll 60 participants. All study 
injections were stopped on January 13, 2023 because of reactions in some 
participants. There were 44 participants in the study at that time and we have not 
enrolled any more. Part A is fully enrolled with 15 participants, all of whom 
completed their 1 planned study injection visit. Part B enrolled 29 participants 
across Groups 6-8. Group 6 participants were planned to have only 1 study 
injection visit. There are 10 participants enrolled in Group 6 and all completed 
their 1 study injection visit. Groups 7 and 8 were planned to have 3 study 
injection visits. No participant completed 3 study injection visits. There are 10 
participants enrolled in Group 7 and 5 of them completed their second study 
injection visit. There are 9 participants in Group 8 and 6 of them completed their 
second study injection visit.  
We sent you a letter to tell you that study injections had been stopped and to give 
you more information about the reactions participants experienced. We also asked 

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you to continue to come for scheduled clinic visits and blood draws so we could 
monitor your safety. The letter noted that study leadership and experts monitoring 
participant safety in this study would be discussing changes to the study to help 
determine the cause of the reactions.  
In a more recent, second letter, we told you that the symptoms experienced by all 
participants who had reactions went away and these participants have not had any 
more problems. We noted that 7 months of safety monitoring of all participants 
showed no problems in any participants and so we were stopping the blood draws 
for safety.  
In order to help determine the cause of the reactions, changes are being made to 
this study. We will tell you about these below. We will also ask you if you agree 
to stay in the study. 
2. You are free to continue or leave the study. 
If you choose to leave, your other care at this clinic and the benefits or rights you 
would normally have will not be affected. We will ask you to come to the clinic 
one last time for a physical exam. We may ask to take some blood samples from 
you and ask you to answer some questions. If you were assigned female sex at 
birth, we may test you for pregnancy. Whether you come for this last visit is up to 
you. 
3. If you stay in the study, this will change: 
In the consent form you signed when you joined the study, we said that if you had 
an unusual reaction on your skin after a study injection, we may want to do a skin 
biopsy. We did do a skin biopsy on 2 Part B participants who had unusual 
reactions after their study injections. We will not do any more skin biopsies in this 
study. 
4. Many things described in the informed consent form you signed when you 
joined the study remain the same. 
These include: 
• 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; 

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• Reasons we might take you out of the study; 
• 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. We will give you 
[Site: Insert compensation] for each study visit you complete.  
• In the consent form you signed when you joined the study, we told you about 
possible use of your samples and information in other studies. At the end of 
that consent form, 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. 
The schedule of visits will stay the same. The procedures we do at each visit will 
also remain the same, except that we will not take blood from you at the visit 
scheduled 32 weeks after your first injection. You will still be in the study for 1 
year after you completed your study injection visit.  
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]. 
 
An institutional review board (IRB) is an independent committee established to 
help protect the rights of research subjects. If you have any questions about your 
rights as a research participant, and/or concerns or complaints regarding this 
research study, contact: 
• 
By mail: 
Study Subject Adviser 
Advarra IRB 
6100 Merriweather Dr, Suite 600 
Columbia, MD 21044 
• 
or call toll free:    877-992-4724 
• 
or by email:          adviser@advarra.com 
 

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Please reference the following number when contacting the Study Subject 
Adviser: #######. 
US sites may include, but are not required to: You may also contact the [name of 
local IRB/EC] at [insert contact information]. 
5. If you agree to continue in 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 stay in 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 stay in 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 I 
Sample informed consent form for Part B 
(Groups 6-8) 
Title: A Phase 1, Open-Label Clinical Trial to Evaluate Safety, Tolerability, and 
Immunogenicity of Adjuvanted HIV-1 Fusion Peptide Conjugate Vaccine (VRC- 
HIVVCP0108-00-VP) Alone or in Prime-Boost Regimens with Adjuvanted HIV-
1 Envelope Trimer 4571 (VRC-HIVRGP096-00-VP) and HIV-1 Trimer 6931 
(VRC-HIVRGP0106-00-VP) Vaccines in Healthy Adults 
HVTN protocol number: HVTN 303 
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. 
Key information 
• 
Being in this research study is voluntary. It is your choice. 
• 
You are being asked to take part in this study because you are age 18-50, HIV 
negative and healthy. 
• 
The purpose of the study is to see if the study vaccines are safe to give to 
people and do not make people too uncomfortable. 
• 
Another purpose of the study is to see how a person’s immune system 
responds to the study vaccines. (Your immune system protects you from 
infections and disease.) 
• 
You will be in this study for up to 25 months of clinic visits.  
• 
Procedures will include blood draws and injections of study vaccine. If you 
agree, we may collect white blood cells by a procedure called leukapheresis. 
There is also an optional procedure of a skin biopsy that we may ask you to 
have done. We will tell you more about these procedures later in this consent 
form. 
• 
There are risks from participating. 
▪ The vaccines you receive have only been given to a small number of 
people. We do not know all the risks of the vaccines in this study. A few 
known risks are pain and itching at the injection site, muscle pain, 
swelling, skin redness, soreness, tenderness, headache, nausea, fatigue and 
fever. 

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▪ Taking blood and giving injections can cause bruising, pain, fainting, 
soreness, redness, swelling, itching, a sore and bleeding. 
▪ Leukapheresis can cause pain, bruising, and rarely an infection. A skin 
biopsy can cause bleeding, pain, bruising, and scarring, and rarely an 
infection. 
▪ We will tell you more information about risks later in this consent form. 
• 
We do not expect the study vaccines to benefit you in any way.  
About the study 
The HIV Vaccine Trials Network (HVTN) and [Insert site name] are doing a 
study to test 3 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 3 different proteins with 1 
adjuvant. 
Up to 70 people will take part in this study at multiple sites in the United States. 
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. 
The study is divided into 2 parts, Part A and Part B. Up to 20 people are currently 
in Part A. In Part A, participants got just 1 of the 3 study vaccines. Because there 
have been no safety concerns to date in Part A, we are now starting Part B. It will 
test the 3 study vaccines in different combinations. Up to 50 people will be in Part 
B. You are being invited to join Part B of the study.  
1. We are doing this study to answer several questions. 
• 
Are the study vaccines safe to give to people? 
• 
Are people able to take the vaccines without becoming too uncomfortable? 
• 
How do people’s immune systems respond to the study vaccines? (Your 
immune system protects you from infections and disease.)  
2. The study vaccines cannot give you HIV. 
The study vaccines are not made from HIV. It is impossible for the study vaccines 
to give you HIV. Also, they cannot cause you to give HIV to someone else. 
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.  

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3. These study vaccines are experimental. 
The study vaccines include two parts. One part is a lab-made piece of protein that 
looks like a protein found on the outside of HIV. The second part is an adjuvant 
called Adjuplex. (An adjuvant is something that helps the immune system respond 
better.) From here on, we will call it “the adjuvant”.  
We are testing 3 different proteins in this study and each of these will be mixed 
with the adjuvant. We will use the term “vaccine” or “study vaccine” to refer to 
the combination of a protein and the adjuvant. The 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. 
The 3 proteins being tested are called Fusion Peptide (FP conjugate), Trimer 4571 
and Trimer 6931. They are all lab-made small pieces of proteins that look like 
parts of proteins found in the HIV virus. The immune system will be able to see 
the pieces that look like parts of HIV and learn how to recognize them. 
Researchers hope that the immune system will respond by making antibodies that 
could fight HIV. (The body makes antibodies to fight germs after it is exposed to 
them. The antibodies attack germs and keep them from infecting the body’s cells.) 
Each of the 3 proteins in the study is made slightly differently to see how the 
immune system will respond to these different structures. The proteins were 
developed by the Vaccine Research Center (VRC) at the US National Institutes of 
Health.  
The FP conjugate protein and the Trimer 6931 protein were given to people for 
the first time in Part A of this study. The Trimer 4571 protein mixed with a 
different adjuvant has been given to a small number of people in several other 
studies. The Trimer 4571 protein was also given to people in Part A of this study.  
The Adjuplex adjuvant is being provided for this study by the VRC. The adjuvant 
is made of a fatty substance called lecithin and a suspending agent called 
carbomer mixed together in a saline solution. It has been given to 20 people in a 
different study and to the participants in Part A of this study 
There have been no safety concerns to date in the participants who got these study 
vaccines in Part A of this study so we will now give them to participants in Part 
B. 
General risks of vaccines: 
All vaccines can cause fever, chills, rash, aches and pains, nausea, dizziness, and 
feeling tired. Vaccines can also cause stinging, discomfort, redness, mild bruising 
or an infection where you got the injection. Signs of infection at the injection site 
include severe pain, redness, swelling, warmth or drainage. Rarely, people have 
side effects that limit their normal activities or make them go to the doctor. 

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Risks of the study vaccines: 
FP conjugate vaccine and Trimer 6931 vaccine 
The FP conjugate vaccine and the Trimer 6931 vaccine were given to a small 
number of people for the first time in Part A of this study so we do not know what 
all the risks may be. However, we expect they will be similar to the general risks 
of vaccines described above. There may be other side effects, even serious or life-
threatening ones, which we do not know about yet. 
Trimer 4571 vaccine 
This vaccine mixed with a different adjuvant was given to people for the first time 
in a study called VRC 018 that ended in June 2020. The 16 participants in iteach 
got 3 injections at doses higher and lower than the dose we will give in this study. 
The injections did not cause any serious health problems. 14 people had mild pain 
where they got the injection and 6 people had muscle pain, which went away 
within 7 days. 6 people had mild itching where they got the injection that lasted 
between 1 and 9 days. One person had swelling after their second injection and 
skin redness after their third. Both of these went away within 7 days. Another 
person had moderate swelling and severe skin redness where they got the 
injection. Both of these disappeared at 8 days after the injection. 4 people had 
mild headaches and 3 people felt nauseous after injection. These symptoms went 
away within 7 days. One person had a decrease in neutrophils which is a type of 
white blood cell. This went away after 8 days.  
As of January 2022, there are 2 other studies giving the Trimer 4571 vaccine to 
people. NIH-19-I-0069 will enroll 200 participants and give them a different 
study vaccine followed by a booster injection of a higher dose of the Trimer 4571 
vaccine than we will give in this study with a different adjuvant 6 months later. 
As of January 5, 2022, 12 participants have gotten their booster injection. The 
injections have not caused serious health problems. The common side effects are 
mild pain at the injection site, mild headache and mild fatigue. The other study, 
called NETI, will give participants with HIV infection multiple injections of 
either placebo or lower and higher doses of Trimer 4571 than we will use in this 
study with a different adjuvant. As of January 1, 2022, 5 participants have 
received a total of 7 injections. The common side effects are mild to moderate 
injection site pain and tenderness, fatigue, joint stiffness and headache. 
The same Trimer 4571 protein vaccine we will give to participants in Part B was 
given to a small number of people for the first time in Part A so, we do not know 
all the side effects. There may be serious or life-threatening side effects that we 
do not know about yet.  
Risks of the Adjuplex adjuvant: 
The 20 people who got a different vaccine with this adjuvant in a different study 
have not had serious health problems from it. Some people have had injection site 

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pain, soreness, tenderness and occasional fever after getting this adjuvant. 
Because this adjuvant with a different vaccine has only been given to a small 
number of people, we do not know all the side effects.  
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. 
Joining the study 
4. It is up to you whether or not to join the study. 
Take your time. Talk to people you trust. If you decide not to join this study or if 
you leave after you have joined, your other care at this clinic and the benefits or 
rights you would normally have will not be affected. 
You cannot be in this study while you are in another study where you get a study 
product. If you do not join this study, you may be able to join another study. 
If you join this study, you may not be allowed to join other HIV vaccine or HIV 
prevention trials now or in the future.  
During the study, you should not donate blood or tissue. 
Site: Remove item 5 if you use a separate screening consent that covers these 
procedures. 
5. 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 tests. These tell us about the health of your kidneys and 
liver. We will ask you about medicines 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 test results with you. They may show you are not eligible for 
the study, even if you want to join.  

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Site: adapt the following section per the care available at your site 
6. 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 help you get care elsewhere. For health 
problems unrelated to the study, we will not pay for care. 
7. If you were assigned female sex at birth and could become pregnant, you 
must use birth control to join this study. 
Site: If you want to include Appendix L, 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 a developing baby. You must agree to use 
effective birth control from at least 3 weeks before your first study injections 
through 12 weeks after your last study injections. We will talk to you about 
effective birth control methods. They are listed on a handout that we will give to 
you. 
Being in the study 
If you join the study, here is what will happen: 
8. You will come to the clinic for scheduled visits over about 25 months. 
The number of visits you will have depends on which group you are assigned to 
when you join the study. It will be between 18 and 24. We will tell you more 
about the groups below.  
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 study ends (for example, to tell you about the study results). 
We may also contact you about other studies you may want to join. 
9. We will give you [Site: Insert compensation] for each study visit you 
complete. 
This amount is to cover the costs of [Site: Insert text].  

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There is also compensation for the leukapheresis study procedure that we will do 
on about half of all study participants and for the skin biopsy study procedure we 
may ask you to have done. We will tell you more about these procedures below. If 
you have the leukapheresis procedure, we will give you [Site: Insert text]. If you 
have the skin biopsy procedure, we will give you [Site: Insert text]. 
Site: Insert any costs to participants (eg, birth control costs for female 
participants who could become pregnant). 
Site: 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. Site: Insert any costs to 
participants (eg, birth control costs for female participants who could become 
pregnant). 
10. We will give you the study vaccines on a schedule.  
You will be in 1 of 3 groups shown in the table below. Which group you are in 
will depend on when you join the study. Each group will get different 
combinations of the study vaccines. The table below shows which study vaccines 
each group will get and at what timepoint. When we give you the study vaccines, 
it will always be in 2 injections. When we give you 2 study vaccines at the same 
time, the pharmacist will mix them together and then split the mixture into 2 
syringes. We will give the injections with a needle and syringe into the muscle of 
both upper arms. If there is a reason we cannot give an injection into one of your 
arms, then we will give both injections into the other arm.  
Group 6 will get injections 5 times. They will get the Trimer 4571 vaccine 2 
times, the Trimer 6931 vaccine once, then a combination of the Trimer 4571 and 
the Trimer 6931 vaccines 2 times. Group 7 will get injections 7 times. They will 
get the FP conjugate vaccine 3 times, then the Trimer 4571 vaccine 2 times, then 
the Trimer 6931 vaccine 1 time, then a combination of the Trimer 4571 and the 
Trimer 6931 vaccines 1 time. Group 8 will get injections 6 times. They will get a 
combination of the FP conjugate vaccine and the Trimer 4571 vaccine 3 times, 
then the Trimer 6931 vaccine once, then a combination of the Trimer 4571 and 
the Trimer 6931 vaccines 2 times. 
We plan to enroll 15 participants in each group, for a total of 45. We may need to 
enroll up to 5 more participants if we need more information on how participants 
are responding to the study vaccines. 
You will have to wait in the clinic for at least 30 minutes after your injections to 
see if there are any problems. Then for that night and for 10 more days, you will 
use an electronic participant diary to record how you are feeling, including your 
highest daily temperature. We will give you a thermometer to help you do this. 

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We will also give you a ruler to measure any swelling at the injection site. If you 
are unable or unwilling to use the electronic participant diary, please talk with us 
about other options that may be available. We will contact you the day after your 
injections to ask how you are doing. Contact the clinic staff if you have any issues 
or concerns after getting injections. 

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Time after first injection visit 
Group
  
Number of 
participants 
First 
injection visit 
4 weeks  
8 weeks 
12 weeks 
20 weeks 24 weeks 32 weeks 36 weeks 
44 weeks 
48 weeks 
6  
15  
200 mcg 
Trimer 4571 
vaccine 
 
 
200 mcg  
Trimer 
4571 
vaccine  
  
200 mcg 
Trimer 
6931 
vaccine 
  
100 mcg  
Trimer 4571 
vaccine 
+  
100 mcg  
Trimer 6931 
vaccine 
 
100 mcg 
Trimer 4571 
vaccine 
+  
100 mcg 
Trimer 6931 
vaccine 
7  
15  
200 mcg 
FP conjugate 
vaccine  
200 mcg  
FP conjugate 
vaccine  
200 mcg  
FP conjugate 
vaccine  
200 mcg  
Trimer 
4571 
vaccine 
  
200 mcg 
Trimer 
4571 
vaccine 
  
200 mcg  
Trimer 6931 
vaccine  
 
100 mcg 
Trimer 4571 
vaccine 
+  
100 mcg  
Trimer 6931 
vaccine 
8  
15  
200 mcg 
FP conjugate 
vaccine  
+ 
200 mcg 
Trimer 4571 
vaccine 
200 mcg 
FP conjugate 
vaccine  
+ 
200 mcg 
Trimer 4571 
vaccine 
200 mcg  
FP conjugate 
vaccine  
+  
200 mcg  
Trimer 4571 
vaccine  
  
200 mcg 
Trimer 
6931 
vaccine  
 
100 mcg 
Trimer 
4571 
vaccine 
+  
100 mcg 
Trimer 
6931 
vaccine 
 
100 mcg  
Trimer 
4571 
vaccine  
+  
100 mcg  
Trimer 
6931 
vaccine  
 

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11. In addition to giving you the study vaccines, we will do the procedures shown in the following tables. 
Group 6 
 
Time after first injection visit 
Procedure 
Screening 
visit(s) 
First 
injection 
visit  
1 week 
2 weeks 
12 weeks 
13 weeks 
14 weeks  
24 weeks  
25 weeks 
26 weeks 
36 weeks 
37 weeks 
38 weeks 
48 weeks 
49 weeks 
50 weeks 
60 weeks 
72 weeks 
100 weeks  
Injection 
 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
 
 
 
Medical history 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COVID-19 
symptom check  
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Complete 
physical 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
√ 
Brief physical 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Blood drawn 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Leukapheresis or 
larger blood 
draw* 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
√ 
 
 
 
Pregnancy test** 
√ 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
√**  
 
 
 
HIV testing  
√ 
 
 
 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
√ 
√ 
√ 
Risk reduction 
counseling 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
√ 
 
 
√ 
 
√ 
 
√ 
Interview/questio
nnaire 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Notes: 
* Leukapheresis will only be collected from participants who agreed to provide this sample type and are eligible. For participants who do not provide leukapheresis samples, a larger blood 
draw will be done instead.  
** For persons who were assigned female sex at birth and who are capable of becoming pregnant. A negative pregnancy test is required within 72 hours before leukapheresis. 
Persons who have had a hysterectomy (removal of the uterus) or removal of both ovaries (verified by medical records) or are in menopause, do not have to have pregnancy tests.  
 
 

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Group 7 
 
Time after first injection visit 
Procedure 
Screening 
visit(s) 
First 
injection 
visit  
1 week 
2 weeks 
4 weeks 
5 weeks  
6 weeks 
8 weeks 
9 weeks 
10 weeks  
12 weeks 
13 weeks 
14 weeks 
24 weeks 
25 weeks 
26 weeks 
36 weeks 
37 weeks 
38 weeks 
48 weeks 
49 weeks 
50 weeks 
60 weeks 
72 weeks 
100 weeks 
Injection 
 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
 
 
 
Medical history 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COVID-19 
symptom check 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Complete 
physical 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
√ 
Brief physical 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Blood drawn 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Leukapheresis 
or larger blood 
draw* 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
√ 
 
 
 
Pregnancy test** 
√ 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
√** 
 
 
 
HIV testing 
√ 
 
 
 
 
 
 
 
 
 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
√ 
√ 
√ 
Risk reduction 
counseling 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
√ 
 
√ 
 
√ 
Interview/quest
ionnaire 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Notes: 
* Leukapheresis will only be collected from participants who agreed to provide this sample type and are eligible. For participants who do not provide leukapheresis samples, a larger 
blood draw will be done instead.  
** For persons who were assigned female sex at birth and who are capable of becoming pregnant. A negative pregnancy test is required within 72 hours before leukapheresis. 
Persons who have had a hysterectomy (removal of the uterus) or removal of both ovaries (verified by medical records) or are in menopause, do not have to have pregnancy tests.  
 
 
 

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Notes: 
* Leukapheresis will only be collected from participants who agreed to provide this sample type and are eligible. For participants who do not provide leukapheresis samples, a larger blood 
draw will be done instead.  
** For persons who were assigned female sex at birth and who are capable of becoming pregnant. A negative pregnancy test is required within 72 hours before leukapheresis. 
Persons who have had a hysterectomy (removal of the uterus) or removal of both ovaries (verified by medical records) or are in menopause, do not have to have pregnancy tests.  
Group 8 
 
Time after first injection visit 
Procedure 
Screening 
visit(s) 
First 
injection 
visit  
1 week 
2 weeks 
4 weeks 
5 weeks 
6 weeks 
8 weeks  
9 weeks 
10 weeks 
20 weeks 
21 weeks 
22 weeks 
32 weeks 
33 weeks 
34 weeks 
36 weeks 
40 weeks 
44 weeks 
45 weeks  
46 weeks  
56 weeks 
68 weeks 
96 weeks 
Injection 
 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
 
 
√ 
 
 
 
 
 
Medical history 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COVID-19 
symptom check  
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Complete 
physical 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
√ 
Brief physical 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Blood drawn 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Leukapheresis or 
larger blood 
draw* 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
√ 
 
 
 
Pregnancy test** 
√ 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
 
 
√ 
 
√** 
 
 
 
HIV testing  
√ 
 
 
 
 
 
 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
 
 
√ 
 
√ 
√ 
Risk reduction 
counseling 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
 
 
√ 
 
√ 
 
√ 
 
√ 
Interview/questio
nnaire 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 

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When we take blood, the amount will depend on the lab tests we need to do at a 
certain visit. It will be some amount between 12 mL and 182 mL (about 1 
tablespoon to 12 tablespoons). Your body will make new blood to replace the 
blood we take out. 
When we do tests, we will review the results with you at your next visit, or sooner 
if necessary. We will tell you about any results that are important to your health. 
12. If you have an unusual reaction on your skin due to a study injection, we 
may want to photograph it. 
Taking photographs may help researchers learn more about reactions to the study 
products. We will not take photos of your face. Your name and other identifying 
information will not be included on the photos. The photos will only be used to 
research the safety of the study products. 
13. If you have an unusual reaction on your skin to a study injection, we may 
want to do a skin biopsy. 
A skin biopsy collects a small sample of skin cells so they can be examined in a 
lab. This may help researchers better understand your skin reaction and learn 
more about the study products.  
We will ask you at the end of this consent form if you agree to the skin biopsy 
procedure. You can change your mind at any time. It is possible that you may not 
be asked to have a skin biopsy, even if you agree to it. 
If we ask you to have a skin biopsy, this procedure will be done at [site: insert 
location].  
Sites referring out to another facility for the skin biopsy:  
• must obtain copies of the informed consent form and any other educational 
materials that are available from the facility where it will be done so that they 
can be reviewed with potential participants during the study informed consent 
process.  
• include these sentences: There will be another consent form for you to review 
and sign at the facility. As part of the consent process, you will be able to 
discuss the procedure in more detail with the clinician who will do the 
procedure. The discussion will include the location, size, depth and risks of 
the skin biopsy.  
Sites doing the skin biopsy in the clinic and that have their own separate ICF for 
the procedure:  

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• must review it and any other educational materials they have about it with the 
potential participant during the study informed consent process. 
• Include these sentences: We will give you a separate consent form to review 
and sign. As part of the consent process, you will be able to discuss the 
procedure in more detail with the clinician who will do the procedure. The 
discussion will include the location, size, depth and risks of the skin biopsy.  
Sites doing the skin biopsy in the clinic and that do not have their own separate 
ICF for the procedure must modify the general information below about skin 
biopsies to provide the details of the procedure & its risks at their clinic.  
There are several different tools that can be used to do a skin biopsy. The clinician 
doing the procedure will examine the reaction on your skin to determine which 
one to use. They will tell you how the tool works and the general size of the 
sample they will take from your skin. They will apply a cleaning solution to your 
skin in the area where the biopsy will be done and numb the area with an injection 
of a local anesthetic. Once the area is numb, the clinician will take a small sample 
of skin. This procedure may require a few stitches to close the wound. A skin 
biopsy may cause a scar. This scar will likely fade over time. A skin biopsy 
typically takes about 15 minutes total, including the preparation time, dressing the 
wound, and instructions for at-home care.  
14. We would like to collect white blood cells from about half of the participants 
in Part B using a procedure called leukapheresis.  
The leukapheresis procedure collects more white blood cells than we can collect 
in an ordinary blood draw. During leukapheresis, the white blood cells are 
removed from the blood and the rest of the components of blood are put back into 
the body. Blood is made up of red cells that carry oxygen, white cells that fight 
infection, platelets that help form clots, and plasma, which is the fluid left over 
when all the cells are removed. Researchers will use white blood cell samples to 
look more deeply at immune responses. They will try to detect any rare cells that 
respond to the study vaccines, and whether these ways of making vaccines can 
stimulate the right kinds of cell responses. This information will guide the ways 
that vaccines are designed in the future. To get the number of white blood cells 
we need for this research, this procedure should take between 1-2 hours. 
We would like to collect these samples from about half of the participants in 
Groups 6, 7 and 8. If more than half of participants agree to the procedure, we 
will collect samples from all who agree. We will ask you at the end of this 
consent form if you agree to the leukapheresis procedure. You can change your 
mind at any time. It is possible that you may not be eligible to do leukapheresis, 
even if you agree to the procedure. We can discuss the eligibility criteria with you 
now if you would like.  
The leukapheresis procedure will be done about 2 weeks after your last injection 
visit. Participants who do not have the leukapheresis procedure will instead have a 

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larger blood draw of around 182 mL (about 12 tablespoons) 2 weeks after their 
last injection visit. Before this point in the study, the largest blood draw was 
around 100 mL (about 7 tablespoons), with most of them being well below that. 
To compare, people who donate blood in the US usually donate 500 mL (1 pint or 
32 tablespoons) at a time.  
Leukapheresis may not be available at every clinic participating in the study. 
Some clinics may send their participants to a different facility in the area to have 
the leukapheresis procedure done. 
Site: Sites must obtain copies of the informed consent form and any other 
educational materials that are available from the facilities where leukapheresis 
will be performed, so that they can be reviewed with potential participants during 
the study informed consent process.  
The leukapheresis procedure will be done at [site: insert location]. Your 
eligibility to have this procedure will be decided by the staff at our clinic and at 
the facility before you have the procedure. There will be another consent form for 
you to review and sign at the facility. It will provide additional details about the 
procedure and any risks involved.  
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. After 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 water 
solution, or a solution containing a protein called albumin. This protein is 
normally found in human blood. An anticoagulant may be added to your blood 
during the procedure. Anticoagulants prevent blood from clotting.  
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 down the procedure. If there are any problems, the staff will use the 
appropriate medical procedures to treat you. It is normal to feel tired for up to 24 
hours after having leukapheresis.  
15.  We will counsel you about protecting yourself from HIV. 
We will ask you 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. 
16. The HVTN will test your samples to see how your body, including your 
immune system, responds to the study vaccines. 
We will send your samples (without your name or other identifying information) 
to labs in the United States approved by the HVTN for this study. In rare cases, 

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some of your samples may be sent to labs 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. This genetic testing will involve only 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. 
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 how the virus is impacted by the study vaccine. 
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. 
17. 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, the HVTN will destroy all extra samples 
that it has. 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. 

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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 the HVTN shares your 
samples and information, it 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 the HVTN shares may be personal, 
such as your race, ethnicity, sex, health information from the study, and HIV 
status. The HVTN 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? 

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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. 
18. We will do our best to protect your private information. 
Site: Check HIPAA authorization for conflicts with this section. 
All of your samples and most of your study records will be labeled with a code 
number. Samples and study records are kept in secure locations. When you 
provide information in the electronic participant diary after the injection visits, 
that information only has your code number. Your information goes directly from 
the electronic participant diary into your study record. 
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 vaccines(s) you received 
No HIV test results are 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. 

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Clinic staff can see your study records. Your records may also be reviewed by 
groups that 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 (FDA), 
• 
Any regulatory agency that reviews clinical trials, 
• 
US sites may, but are not required to include: [Insert name of local IRB/EC] , 
• 
Advarra Institutional Review Board (IRB) 
• 
Site: [Insert name of local and/or national regulatory authority as appropriate] 
• 
The HVTN and people who work for them, 
• 
The HVTN Safety Monitoring Board, and 
• 
The US Office for Human Research Protections. 
All reviewers will keep your records private. 
We cannot guarantee absolute privacy. If you 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] 
Site: Include the following boxed text. You can remove the box around the text. 
To help protect your privacy, we have a Certificate of Confidentiality from the US 
government. 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. 
However, we cannot withhold information from the US government because it 
funds this research. You can still give information about yourself and your study 
participation to others. 

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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 Web site will not include information that can 
identify you. At most, the Web site will include a summary of the results. You can 
search this Web site at any time. 
19. We may stop your injections 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 until your final scheduled clinic visit if you choose. If you stay in 
the study, we may take fewer samples from you. If you leave the study while you 
are 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 help you get care and 
support. 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 
your HIV care. We will encourage you to stay in the study until your final 
scheduled clinic visit if you choose. If you stay in the study, we will take fewer 
samples from you.  
We will stop your injections if you enroll in a different research study where you 
get another study product. We may stop your injections if we think that giving 
you more of them is not in your best interest.  
20. 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 
21. There are other risks to being in this study. 
In addition to the risks of the study vaccines and the procedures that were 
described above, this section describes the other risks we know about. There may 

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be other risks, even serious ones. We will tell you if we learn anything new that 
may affect your decision to stay in the study. 
Risks of skin biopsy: 
A skin biopsy can cause bleeding, pain, bruising, and scarring, and rarely, an 
infection. The injection of a local anesthetic can cause brief stinging or burning in 
the area of the injection. 
Risks of leukapheresis:  
Generally, the risks of leukapheresis include pain, bruising and rarely, infection. 
Rarely, albumin can cause an allergic reaction. If the leukapheresis procedure has 
to be stopped, it could result in the loss of up to 1 cup of blood. Your body makes 
new blood within 2 weeks.  
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, stinging, swelling, itching, a sore, bleeding, and rarely 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: 
Some people report personal problems or discrimination because they joined an 
HIV vaccine study. Family or friends may worry, get upset, or assume that you 
have HIV. Rarely, someone has lost a job because the study took too much time 
away from work, or because their employer thought they had HIV. 
Most vaccines cause the body to make antibodies to prevent infection. Your body 
may make antibodies to HIV because you received an HIV study vaccine. Those 
antibodies could cause you to test positive on some types of HIV tests, even if you 
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 is likely to say you have HIV, even if you don’t. For this reason, you should 
get HIV tests only at this clinic. Our tests can tell the difference between true HIV 
infection and a positive result caused by the study vaccine. If you have VISP, we 
can arrange free HIV testing for as long as you need it.  
It is unlikely, but you could test antibody negative at the end of the study and then 
test positive sometime later, even though you don’t have HIV.  
Site: Modify the following paragraph if applicable. If someone believes you have 
HIV, you could face discrimination and other problems. In some countries, you 
could be denied medical or dental care, employment, insurance, a visa, or entry 
into the military. If you have VISP, you will not be able to donate blood or 

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organs. Your family and friends may treat you differently. We will give you a 
brochure that tells you more about VISP, and how you can avoid some of these 
problems. 
If you become pregnant during or after the study and have VISP, the antibodies 
might be passed to your baby. We know that this happens with some other 
vaccines. The antibodies are not a danger to the baby and they go away, usually in 
about 6 months. 
You should 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, 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 tests that can 
distinguish true HIV infection from VISP. 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 questions about HIV risks, such as 
having sex and using drugs. Also, waiting for HIV test results could make you 
feel anxious. You could feel worried if 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: 
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 happens, you could face 
discrimination, stress, and embarrassment. We can tell you more about how we 
will protect your personal information. 
Risks of genetic testing: 
It is possible that genetic tests could show you may be at risk for certain diseases. 
If others found out, it could lead to discrimination or other problems. However, 
genetic test results are not part of your study record, so it is almost impossible for 
anyone to connect them to you personally. 
Even if your genetic information somehow gets 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: 

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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 this 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. 
Benefits 
22. 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 
might detect health problems you don’t yet know about. 
When asked, most study participants say that participating in a study made them 
feel good about helping others, increased their knowledge about HIV, and 
improved their self-esteem. 
This study may help in the search for a vaccine to prevent HIV. However, if the 
study vaccines later become approved for sale, there are no plans to share any 
money with you. 
Your rights and responsibilities 
23. If you join the study, you have rights and responsibilities. 
We list these in the Bill of Rights and Responsibilities (BRR) for HIV Research. 
We will give you a copy of it. 
Leaving the study 
24. Tell us if you decide to leave the study. 
You are free to leave the study at any time and for any reason. This will not affect 
your care at this clinic and your legal rights, but it is important for you to let us 
know. 
Previously collected information about you will remain in the study records and 
will be included in the analysis of results. Your information cannot be removed 
from the study records. 

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We will ask you to come to the clinic one last time for a physical exam., We may 
ask to take some blood samples from you and ask you to answer some questions. 
If you were assigned female sex at birth, we may test you for pregnancy. Whether 
you come for this last visit is up to you. 
Injuries 
Sites: Approval from HVTN Regulatory Affairs (at vtn.core.reg@fredhutch.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. 
25. 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 care that we 
can give here. For 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 
this is related to the study vaccines 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. 
The HVTN has limited funds to pay medical costs that it determines are 
reasonable. 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  
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]. 
 

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An institutional review board (IRB) is an independent committee established to 
help protect the rights of research subjects. If you have any questions about your 
rights as a research participant, and/or concerns or complaints regarding this 
research study, contact: 
• 
By mail: 
Study Subject Adviser 
Advarra IRB 
6100 Merriweather Dr, Suite 600 
Columbia, MD 21044 
• 
or call toll free:    877-992-4724 
• 
or by email:          adviser@advarra.com 
 
Please reference the following number when contacting the Study Subject 
Adviser: #######. 
US sites may include, but are not required to: You may also contact the [name of 
local IRB/EC] at [insert contact information]. 
Your permissions and signature  
27. In Section 13 of this form, we told you about the skin biopsy procedure we 
may ask you to have done. If you agree to the skin biopsy, please write your 
initials or make your mark in the box below. If you do not agree to the skin 
biopsy, leave the box blank. You can change your mind after signing this 
form.  
 
 
I agree to the skin biopsy. 
 
28. In Section 14 of this form, we told you about the procedure of leukapheresis. 
If you agree to leukapheresis, please write your initials or make your mark in 
the box below. If you do not agree to leukapheresis, leave the box blank. You 
can change your mind after signing this form.  
 
 
I agree to leukapheresis. 
 

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29. In Section 17 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.  
 
 
30. 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 

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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 J 
Sample addendum to informed consent form 
for Part B (Groups 6-8) post termination of 
vaccinations 
Title: A Phase 1, Open-Label Clinical Trial to Evaluate Safety, Tolerability, and 
Immunogenicity of Adjuvanted HIV-1 Fusion Peptide Conjugate Vaccine (VRC- 
HIVVCP0108-00-VP) Alone or in Prime-Boost Regimens with Adjuvanted HIV-
1 Envelope Trimer 4571 (VRC-HIVRGP096-00-VP) and HIV-1 Trimer 6931 
(VRC-HIVRGP0106-00-VP) Vaccines in Healthy Adults 
HVTN protocol number: HVTN 303 
Site: [Insert site name] 
Key information 
• 
Being in this research study is voluntary. It is your choice. 
• 
Study injections have been stopped for all participants. We will not give any 
more injections. 
• 
If you stay in this study, you will be in it until about one year after your last 
study injection. 
• 
Procedures will still include blood draws. If you completed 2 injection visits 
earlier in this study and if you agree, we may collect white blood cells by a 
procedure called leukapheresis. We will tell you more about this procedure 
later in this consent form. 
• 
There are risks from participating. 
▪ Taking blood can cause bruising, pain, fainting, soreness, redness, 
swelling, itching, a sore and bleeding. 
▪ Leukapheresis can cause pain, bruising, and rarely an infection.  
1. Review of study information  
This study started in August 2022 and planned to enroll 60 participants. All study 
injections were stopped on January 13, 2023 because of reactions in some 
participants. There were 44 participants in the study at that time and we have not 
enrolled any more. Part A is fully enrolled with 15 participants, all of whom 
completed their 1 planned study injection visit. Part B enrolled 29 participants 
across Groups 6-8. Group 6 participants were planned to have only 1 study 
injection visit. There are 10 participants enrolled in Group 6 and all completed 
their 1 study injection visit. Groups 7 and 8 were planned to have 3 study 
injection visits. No participant completed 3 study injection visits. There are 10 
participants enrolled in Group 7 and 5 of them completed their second study 

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injection visit. There are 9 participants in Group 8 and 6 of them completed their 
second study injection visit.  
We sent you a letter to tell you that study injections had been stopped and to give 
you more information about the reactions participants experienced. We also asked 
you to continue to come for scheduled clinic visits and blood draws so we could 
monitor your safety. The letter noted that study leadership and experts monitoring 
participant safety in this study would be discussing changes to the study to help 
determine the cause of the reactions.  
In a more recent, second letter, we told you that the symptoms experienced by all 
participants who had reactions went away and these participants have not had any 
more problems. We noted that 7 months of safety monitoring of all participants 
showed no problems in any participants and so we were stopping the future blood 
draws for safety.  
In order to help determine the cause of the reactions, changes are being made to 
this study. We will tell you about these below. We will also ask you if you agree 
to stay in the study. 
2. You are free to continue or leave the study. 
If you choose to leave, your other care at this clinic and the benefits or rights you 
would normally have will not be affected. We will ask you to come to the clinic 
one last time for a physical exam., We may ask to take some blood samples from 
you and ask you to answer some questions. If you were assigned female sex at 
birth, we may test you for pregnancy. Whether you come for this last visit is up to 
you. 
3.  If you stay in the study, these things will change.  
You will be in it until one year after you completed your last study injection visit. 
The schedule of visits and procedures below shows the injections and visits you 
have already completed and some changes to future visits.

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Group 6 
 
Time after first injection visit 
Procedure 
Screening visit(s) 
First injection 
visit  
1 week 
2 weeks 
12 weeks 
13 weeks 
14 weeks  
24 weeks  
25 weeks 
26 weeks 
36 weeks 
37 weeks 
38 weeks 
48 weeks 
49 weeks 
50 weeks 
56 weeks  
Injection 
 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COVID-19 
symptom check  
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Complete physical 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
√ 
Brief physical 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Blood drawn 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
 
√ 
√ 
Pregnancy test** 
√ 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV testing  
√ 
 
 
 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
√ 
Risk reduction 
counseling 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
√ 
 
 
√ 
 
√ 
Interview/question
naire 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Notes: 
** For persons who were assigned female sex at birth and who are capable of becoming pregnant.  
Persons who have had a hysterectomy (removal of the uterus) or removal of both ovaries (verified by medical records) or are in menopause, do not have to have pregnancy tests.  
 
 

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Group 7 
 
Time after first injection visit 
Procedure 
Screening 
visit(s) 
First 
injection 
visit  
1 week 
2 weeks 
4 weeks 
5 weeks  
6 weeks 
8 weeks 
9 weeks 
10 weeks  
12 weeks 
13 weeks 
14 weeks 
24 weeks 
25 weeks 
26 weeks 
36 weeks 
37 weeks 
38 weeks 
48 weeks 
49 weeks 
50 weeks 
56 weeks 
Injection 
 
√ 
 
 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical 
history 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COVID-19 
symptom 
check 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Complete 
physical 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
√ 
Brief physical 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Blood drawn 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
√ 
√ 
√ 
Leukapheresis 
or larger blood 
draw* 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
√ 
 
 
Pregnancy 
test** 
√ 
√ 
 
 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
√** 
 
 
HIV testing 
√ 
 
 
 
 
 
 
 
 
 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
√ 
Risk reduction 
counseling 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
√ 
 
√ 
Interview/ques
tionnaire 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Notes: 
* Leukapheresis will only be collected from participants who completed 2 injection visits and who agreed to provide this sample type and are eligible. For participants who do not 
provide leukapheresis samples, a larger blood draw will be done instead.  
** For persons who were assigned female sex at birth and who are capable of becoming pregnant. A negative pregnancy test is required within 72 hours before leukapheresis. 
Persons who have had a hysterectomy (removal of the uterus) or removal of both ovaries (verified by medical records) or are in menopause, do not have to have pregnancy tests.  

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Notes: 
* Leukapheresis will only be collected from participants who completed 2 injection visits and who agreed to provide this sample type and are eligible. For participants who do not provide 
leukapheresis samples, a larger blood draw will be done instead.  
** For persons who were assigned female sex at birth and who are capable of becoming pregnant. A negative pregnancy test is required within 72 hours before leukapheresis. 
Persons who have had a hysterectomy (removal of the uterus) or removal of both ovaries (verified by medical records) or are in menopause, do not have to have pregnancy tests.  
Group 8 
 
Time after first injection visit 
Procedure 
Screening 
visit(s) 
First 
injection 
visit  
1 week 
2 weeks 
4 weeks 
5 weeks 
6 weeks 
8 weeks  
9 weeks 
10 weeks 
20 weeks 
21 weeks 
22 weeks 
32 weeks 
33 weeks 
34 weeks 
36 weeks 
40 weeks 
44 weeks 
45 weeks  
46 weeks  
56 weeks 
Injection 
 
√ 
 
 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COVID-19 
symptom check  
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Complete 
physical 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
√ 
Brief physical 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Blood drawn 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
 
 
√ 
√ 
Leukapheresis 
or larger blood 
draw* 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
√ 
 
Pregnancy 
test** 
√ 
√ 
 
 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
√** 
 
HIV testing  
√ 
 
 
 
 
 
 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
 
 
√ 
√ 
Risk reduction 
counseling 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
√ 
 
 
 
 
√ 
 
√ 
 
√ 
Interview/quest
ionnaire 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 

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The amount of blood we will take has changed. It will be some amount between 7 
mL and 225 mL (about 1 tablespoon to 15 tablespoons).  
In the consent form you signed when you joined the study, we said that if you had 
an unusual reaction on your skin after a study injection, we may want to do a skin 
biopsy. We did do a skin biopsy on 2 Part B participants who had unusual 
reactions after their study injections. We will not do any more skin biopsies in this 
study. 
4. If you are in Group 7 or 8 and completed 2 injection visits earlier in the 
study, we would like to collect white blood cells from you using a procedure 
called leukapheresis.  
The leukapheresis procedure collects more white blood cells than we can collect 
in an ordinary blood draw. During leukapheresis, the white blood cells are 
removed from the blood and the rest of the components of blood are put back into 
the body. Blood is made up of red cells that carry oxygen, white cells that fight 
infection, platelets that help form clots, and plasma, which is the fluid left over 
when all the cells are removed. Researchers will use white blood cell samples to 
look more deeply at immune responses. They will try to detect any rare cells that 
respond to the study vaccines, and whether these ways of making vaccines can 
stimulate the right kinds of cell responses. This information will guide the ways 
that vaccines are designed in the future. To get the number of white blood cells 
we need for this research, this procedure should take between 1-2 hours. 
We will ask you at the end of this consent form if you agree to the leukapheresis 
procedure. You can change your mind at any time. It is possible that you may not 
be eligible to do leukapheresis, even if you agree to the procedure. We can discuss 
the eligibility criteria with you now if you would like.  
The leukapheresis procedure will be done about 42-44 weeks after your last 
injection visit. Participants who do not have the leukapheresis procedure will 
instead have a larger blood draw of around 200 mL (about 15 tablespoons) 42-44 
weeks after their last injection visit. To compare, people who donate blood in the 
US usually donate 500 mL (1 pint or 32 tablespoons) at a time.  
Some sites may send their participants to a different facility in the area to have the 
leukapheresis procedure done. 
Site: Sites must obtain copies of the informed consent form and any other 
educational materials that are available from the facilities where leukapheresis 
will be performed, so that they can be reviewed with potential participants during 
the study informed consent process.  
The leukapheresis procedure will be done at [site: insert location]. Your 
eligibility to have this procedure will be decided by the staff at our clinic and at 
the facility before you have the procedure. There will be another consent form for 

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you to review and sign at the facility. It will provide additional details about the 
procedure and any risks involved.  
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. After 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 water 
solution, or a solution containing a protein called albumin. This protein is 
normally found in human blood. An anticoagulant may be added to your blood 
during the procedure. Anticoagulants prevent blood from clotting.  
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 down the procedure. If there are any problems, the staff will use the 
appropriate medical procedures to treat you. It is normal to feel tired for up to 24 
hours after having leukapheresis.  
5. Many things described in the informed consent form you signed when you 
joined the study remain the same. 
These include: 
• 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; 
• 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. We will give you 
[Site: Insert compensation] for each study visit you complete. If you have the 
leukapheresis procedure, we will give you [Site: Insert text]. 
• In the consent form you signed when you joined the study, we told you about 
possible use of your samples and information in other studies. At the end of 
that consent form, 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 

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decision will not affect your being in this study or have any negative 
consequences here. 
6. 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]. 
 
An institutional review board (IRB) is an independent committee established to 
help protect the rights of research subjects. If you have any questions about your 
rights as a research participant, and/or concerns or complaints regarding this 
research study, contact: 
• 
By mail: 
Study Subject Adviser 
Advarra IRB 
6100 Merriweather Dr, Suite 600 
Columbia, MD 21044 
• 
or call toll free:    877-992-4724 
• 
or by email:          adviser@advarra.com 
 
Please reference the following number when contacting the Study Subject 
Adviser: #######. 
US sites may include, but are not required to: You may also contact the [name of 
local IRB/EC] at [insert contact information]. 
7. In Section 3 of this form, we told you about the procedure of leukapheresis. If 
you agree to leukapheresis, please write your initials or make your mark in 
the box below. If you do not agree to leukapheresis, leave the box blank. You 
can change your mind after signing this form.  
 
 
I agree to leukapheresis. 
 

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8. If you agree to continue in 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 stay in 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 stay in 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 K 
Low risk guidelines for 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: 
A. Have oral, vaginal or anal intercourse with an HIV-infected partner, or a 
partner who uses injection drugs  
B. 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 a person born male with partner(s) born male (MSM) 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), OR  

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• 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  
• 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  

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• Epididymitis  
• Proctitis  
• Lymphogranuloma venereum  
• Chancroid  
• Hepatitis B 
B. 
For US volunteers on Pre-exposure prophylaxis (PrEP) 
1. PrEP ASSESSMENT 
• Reports 6 months (180 days) or more of protective daily oral PrEP use  
▪ For persons born male at birth who have sex with persons born male at 
birth: 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 intra-vaginal intercourse: reports 
equal to or greater than 90% when asked the following: “Thinking 
about the past 4 weeks, how many days per week were you able to take 
all your PrEP medications?” 
• Commits to maintaining protective PrEP use throughout trial 
Note that some anti-retroviral medications at certain dose levels may potentially 
interfere with pseudoneutralization immunogenicity assays and could be 
exclusionary. Sites should consult the PSRT regarding eligible medications prior to 
enrolling persons on PrEP. The PrEP medication names and doses taken during 
screening and the trial should be recorded. 
2. SEXUAL BEHAVIORS 
Persons stably taking PrEP as described 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 
• 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. 

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Appendix L 
Approved birth control methods 
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 at least 3 weeks before your 
first injection until 12 weeks 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, 
• You are sexually abstinent (no sex at all). 

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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 M 
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 303 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, noninfectious 
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 
• 
Rosacea 
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 

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Appendix N 
Protocol team 
Protocol leadership 
Chair 
Troy Martin 
HVTN LOC, Fred Hutch 
206-667-2764 
tmartin@fredhutch.org 
Statistician 
Sue Li 
HVTN SDMC, Fred Hutch 
206-667-7066 
sli@fredhutch.org 
Co-chair 
Michael Keefer 
University of Rochester Medical 
Center 
585-275-8058 
michael_keefer@urmc.rochester.edu 
DAIDS Medical 
officer 
Mary Allen 
DAIDS, NIAID 
240-627-3036 
mallen@niaid.nih.gov 
Protocol Team leader 
Carmen Paez 
HVTN LOC, Fred Hutch 
206-667-2881 
cpaez@fredhutch.org 
Laboratory leads 
John Hural 
206-667-1683 
jhural@fredhutch.org 
 
David Montefiori 
919-684-5278 
david.montefiori@duke.edu 
HVTN Laboratory Center 
Other contributors to the original protocol 
 
Core medical monitor 
Carmen Paez 
HVTN LOC, Fred Hutch 
Clinical safety 
specialist 
Megan Jones 
HVTN LOC, Fred Hutch 
Study product developer 
representative 
Lucio Gama 
Joseph Casazza 
VRC/NIAID 
Clinical trials 
managers 
Lori Proulx-Burns 
Shelly Ramirez 
HVTN LOC, Fred Hutch 
Laboratory center 
representative 
Jen Hanke  
HVTN Laboratory Center, Fred 
Hutch 
Senior clinical data 
manager 
Eva Hom 
Jana Strakova 
HVTN SDMC, Fred Hutch 
Regulatory affairs 
associate 
Liz Briesemeister  
HVTN LOC, Fred Hutch 
SDMC Associate 
director of lab 
science 
April Randhawa 
HVTN SDMC, Fred Hutch 
Clinic coordinator 
Catherine Bunce 
University of Rochester Medical 
Center 
SDMC Associate 
director of 
operations 
Jessica Andriesen 
HVTN SDMC, Fred Hutch 
Community Advisory 
Board (CAB) members 
Tasia Baldwin 
Seattle Vaccine Trials Unit 
Michael Willoughby 
Rochester Victory Alliance 
Protocol 
development 
managers 
Kajari Mondal 
Smitha Sripathy 
HVTN LOC, Fred Hutch 
DAIDS protocol 
pharmacist 
Cindy Parker 
DAIDS, NIAID 
 
Community 
engagement unit 
representative 
Linda Oseso  
HVTN LOC, Fred Hutch 
Statistical research 
associates 
Kevin Gillespie 
HVTN SDMC, Fred Hutch 
Community 
educator/recruiter 
Christopher Goodwin 
Rochester Victory Alliance 
 
 
Technical editor 
Sydney Strauss 
HVTN LOC, Fred Hutch 

HVTN 303 Version 2.0 / September 21, 2023 
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Appendix O 
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 303 are described 
below. 
Protocol history and modifications 
Date: September 21, 2023 
Protocol version: Version 2.0 
Protocol modification: Full protocol amendment 1 
Item 1 
Added following title page: Boxed text summary of protocol version 2.0 
rationale and design 
Item 2 
Updated in Section 1, Executive summary; Section 2, Introduction; 
Section 3, Objectives and endpoints; Section 5.1.3, Leukapheresis 
Eligibility Criteria; Section 6, Statistical considerations; Section 7, 
Study product preparation, storage, and administration; Section 8; 
Clinical procedures; New Appendix B, Follow-up schedule of 
procedures for Part A (Groups 1-5) post termination of vaccinations; 
New Appendix D, Follow-up schedule of procedures for Part B (Tables 
for Group 6, Group 7, and Group 8) post termination of vaccinations; 
New Appendix F, Follow up visit windows post termination of 
vaccination; New Appendix H, Sample addendum to informed consent 
form for Part A (Group 1-5) post termination of vaccinations and  New 
Appendix J, Sample addendum to informed consent form for Part B 
(Groups 6-8) post termination of vaccinations: Language and content 
related to the updated study design and visit schedule due to vaccination 
termination 
Item 3 
Updated per Protocol Version 1.0, Clarification Memo 1, dated May 19, 
2022 
Item 4 
Updated per Protocol Version 1.0, Letter of Amendment 1, dated July 
12, 2022 
Item 5 
Updated per Protocol Version 1.0, Clarification Memo 2, dated July 29, 
2022 
Item 6 
Updated per Protocol Version 1.0, Clarification Memo 3, dated August 
16, 2022 

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Item 7 
Updated per Protocol Version 1.0, Letter of Amendment 2, dated 
September 28, 2022 
Item 8 
Updated per Protocol Version 1.0, Letter of Amendment 3, dated 
December 1, 2022 
Item 9 
Updated per Protocol Version 1.0, Letter of Amendment 4, dated July 
31, 2023 
Item 10 Corrected throughout the protocol: Minor errors in grammar, 
typography, formatting 
Item 11 Updated throughout the protocol: Section numbering and cross-
references 
Date: July 31, 2023 
Protocol version: Version 1.0 
Protocol modification: Letter of Amendment 4 
 
Removed in Appendix B, Schedule of procedures for Part B (Tables for 
Group 6, Group 7 and Group 8): Blood collection for safety labs for 
any future visits. 
Date: December 1, 2022 
Protocol version: Version 1.0 
Protocol modification: Letter of Amendment 3 
 
Revised in Section 8.3, Reactogenicity Assessments; Appendix A, 
Schedule of procedures for Part A (Groups 1-5); Appendix B, Schedule 
of procedures for Part B (Tables for Group 6, Group 7 and Group 8); 
Appendix D, Sample informed consent form for Part A (Groups 1-5) 
and Appendix F, Sample informed consent form for Part B (Groups 6-
8): reactogenicity assessment period for the study 
Date: September 28, 2022 
Protocol version: Version 1.0 
Protocol modification: Letter of Amendment 2 
 
Added in Section 9.1, Adverse events; Section 9.2.1, Expedited 
reporting of adverse events to DAIDS and Acronyms and abbreviations: 
language in response to comment received from FDA dated July 19, 
2022 

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Deleted in Section 1.5, Study plan and schema table: language from 
Table 1-1 footnotes 
 
Added in Section 3.3, Exploratory objectives: new objectives 
 
Added in Section 5.1.2, Exclusion criteria; and Section 5.2.1, Delaying 
vaccinations for a participant: considerations for timing of receipt of 
Monkeypox vaccines 
 
Added in Section 2.11.1, Risks of the Vaccines; New Section 2.11.3, 
Other risks; Section 8.3, Reactogenicity assessments; Appendix A, 
Schedule of procedures for Part A (Groups 1-5); Appendix B, 
Schedules of procedures for Part B (Tables for Group 6, Group 7, and 
Group 8); Appendix D, Sample informed consent form for Part A 
(Groups 1-5) and Appendix E, Sample informed consent form for Part 
B (Groups 6-8): language to implement a system for optional skin 
biopsies 
Date: August 16, 2022 
Protocol version: Version 1.0 
Protocol modification: Clarification Memo 3 
 
Added in Section 9.6, Total blood volume: alternate laboratory 
specimen tube types allowed for research samples upon HVTN 
Laboratory Center approval 
Date: July 29, 2022 
Protocol version: Version 1.00 
Protocol modification: Clarification Memo 2 
 Revised in Section 8.3, Reactogenicity Assessments; Appendix A, 
Schedule of procedures for Part A (Groups 1-5) and Appendix B, 
Schedule of procedures for Part B (Tables for Group 6, Group 7 and 
Group 8): participant contact on the day after vaccinations. 
 Corrected in Section 8.3, Reactogenicity Assessments: title referring to 
Appendix A and Appendix B. 

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Date: July 12, 2022 
Protocol version: Version 1.0 
Protocol modification: Letter of Amendment 1 
 Updated in Appendix C, Visit Windows: upper and lower allowable and 
target window dates for Part B (Groups 7-8) 
 Updated in Appendix B, Schedules of procedures for Part B (Tables for 
Group 6, Group 7 and Group 8) and in Appendix E, Sample informed 
consent form for Part B (Groups 6-8): footnotes related to pregnancy 
test requirement before leukapheresis 
 Added in Appendix B, Schedule of procedures for Part B (Tables for 
Group 6, Group 7 and Group 8): blood collection for CBC/Differential 
and ALT/Creatinine at visit # 118 in the table for Group 7 
 Deleted in Appendix A, Schedule of procedures for Part A (Groups 1-5) 
and Appendix B, Schedule of procedures for Part B (Tables for Group 
6, Group 7 and Group 8): plasma collection 
 Added in Section 8.2, Definition of Study Day and Study Visit: reference 
to Study Specific procedures to describe remote visits 
 Updated in Appendix F, Low risk guidelines for US: PrEP assessment 
guidelines for US volunteers of PrEP 
 Updated in Appendix I, Protocol team: names of team members 
Date: May 19, 2022 
Protocol version: Version 1.00 
Protocol modification: Clarification Memo 1 
 Added in Appendix A, Schedule of procedures for Part A (Groups 1-5) 
and Appendix B, Schedule of procedures for Part B (Tables for Group 
6, Group 7 and Group 8): blood collection for Hepatitis B and Hepatitis 
C testing at the screening visit (Visit #01 fo Part A groups and visit 
#100 for Part B groups) 
 Updated in Appendix A, Schedule of procedures for Part A (Groups 1-
5) and Appendix B, Schedule of procedures for Part B (Tables for 
Group 6, Group 7 and Group 8): footnote #8 related to the pregnancy 
testing 
 

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Date: April 6, 2022 
Protocol version: 1.0 
Protocol modification: Not applicable  
Original protocol