A First-in-human Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of Stabilized CH505 TF chTrimer in Healthy, HIV-uninfected Adult Participants.
Phase: PHASE1
Conditions: HIV Infections
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

PROTOCOL 
HVTN 300 
A first-in-human Phase 1 clinical trial to evaluate the 
safety and immunogenicity of stabilized CH505 TF 
chTrimer in healthy, HIV-uninfected adult participants 
DAIDS DOCUMENT ID 38705 
IND 027197 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 
Duke University 
Durham, North Carolina, USA 
DAIDS, NIAID, NIH, DHHS 
Bethesda, Maryland, USA 
Access to Advanced Health Institute (AAHI) 
Seattle, Washington, USA  
International AIDS Vaccine Initiative (IAVI) 
New York, New York, USA 
September 26, 2022 
Final 
HVTN 300 
Version 2.0 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 2 of 127 
Protocol Signature Page 
 
A first-in-human Phase 1 clinical trial to evaluate the safety and immunogenicity 
of stabilized CH505 TF chTrimer in healthy, HIV-uninfected adult participants 
I will conduct the study in accordance with the provisions of this protocol and all 
applicable protocol-related documents. I agree to conduct this study in 
compliance with United States (U.S.) Health and Human Service regulations (45 
CFR 46); applicable U.S. Food and Drug Administration regulations; standards of 
the International Conference on Harmonization Guideline for Good Clinical 
Practice (E6); Institutional Review Board/Ethics Committee determinations; all 
applicable in-country, state, and local laws and regulations; and other applicable 
requirements (eg, U.S. National Institutes of Health, Division of AIDS) and 
institutional policies 
 
 
 
 
 
 
 
 
 
Investigator of Record Name (print) 
 
Investigator of Record Signature 
 
Date 
 
 
 
DAIDS Protocol Number: HVTN 300 
DAIDS Protocol Version: Version 2.0 
Protocol Date: September 26, 2022 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 3 of 127 
Acronyms and abbreviations 
AAHI 
 
Access to Advanced Health Institute 
Ab 
 
antibody 
AESI 
 
adverse event of special interest 
AF 
 
aqueous formulation 
AoU 
 
assessment of understanding 
ALT 
 
alanine transaminase 
BAMA 
 
binding antibody multiplex assay 
BCR 
 
B cell receptor 
β-HCG 
 
beta human chorionic gonadotropin 
BMI 
 
body mass index 
bnAb 
 
broadly neutralizing antibody 
cGMP 
 
current Good Manufacturing Practice 
CRS 
 
clinical research site 
DAIDS 
 
Division of AIDS 
EC 
 
ethics committee 
EIA 
 
enzyme immunoassay 
FDA 
 
(US) Food and Drug Administration 
GCP 
 
Good Clinical Practice 
HLA 
 
human leukocyte antigen 
IB 
 
Investigator’s Brochure 
ICS 
 
intracellular cytokine staining 
IM 
 
intramuscular 
IND 
 
investigational new drug (application) 
IRB 
 
institutional review board 
IRM 
 
immune response modifier 
KI 
 
knock-in 
LABA 
 
long-acting beta agonist 
MO 
 
medical officer 
nAb 
 
neutralizing antibody 
NSAID 
 
non-steroidal anti-inflammatory drug 
PCR 
 
polymerase chain reaction 
PI 
 
principal investigator 
PSRT 
 
Protocol Safety Review Team 
RE 
 
regulatory entity 
SAE 
 
serious adverse event 
SAP 
 
statistical analysis plan 
SDMC 
 
statistics and data management center 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 4 of 127 
SICF 
 
sample informed consent form 
SMB 
 
Safety Monitoring Board 
SSP 
 
Study Specific Procedures 
SUSAR 
 
suspected unexpected serious adverse reaction 
TB 
 
tuberculosis 
TBS 
 
Tris-NaCl buffer 
TLR 
 
toll-like receptor 
UCA 
 
unmutated common ancestor 
ULN 
 
upper limit of normal 
USP 
 
United States pharmacopeia 
VISP 
 
vaccine-induced seropositivity 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 5 of 127 
Contents 
1 Executive summary ........................................................................................................7 
1.1 
Title ................................................................................................................7 
1.2 
Design .............................................................................................................7 
1.3 
Study products ................................................................................................7 
1.4 
Study population ............................................................................................7 
1.5 
Study plan and schema table ..........................................................................8 
1.6 
Duration per participant .................................................................................9 
1.7 
Estimated total study duration ........................................................................9 
1.8 
Study sites ....................................................................................................10 
2 Introduction ..................................................................................................................11 
2.1 
Rationale for evaluation of CH505 TF chTrimer .........................................12 
2.2 
Clinical Experience with Recombinant Env Vaccinations ..........................16 
2.3 
Rationale for Schedule .................................................................................23 
2.4 
Rationale for Dose of Protein .......................................................................23 
2.5 
Rationale for Dose of Adjuvant .................................................................24 
2.6 
Rationale for Fine Needle Aspiration ...........................................................24 
2.7 
Rationale for Leukapheresis .........................................................................24 
2.8 
Risks and benefits .........................................................................................25 
2.9 
Assessment of immunogenicity endpoints ...................................................27 
3 Objectives and endpoints for Part A and Part B ..........................................................28 
3.1 
Primary objectives and endpoints ................................................................28 
3.2 
Secondary objectives and endpoints ............................................................29 
3.3 
Exploratory objectives ..................................................................................29 
4 Laboratory strategy ......................................................................................................31 
5 Study design .................................................................................................................32 
5.1 
Study population ..........................................................................................32 
5.2 
Participant departure from vaccination schedule or withdrawal ..................35 
6 Statistical considerations ..............................................................................................39 
6.1 
Sample size justification and accrual ...........................................................39 
6.2 
Statistical analyses ........................................................................................47 
7 Study vaccine preparation, storage, and administration ..............................................49 
7.1 
Vaccine Regimen .........................................................................................49 
7.2 
Study Product Formulation and Storage ......................................................49 
7.3 
Product Preparation ......................................................................................50 
7.4 
Study Vaccine Administration .....................................................................54 
7.5 
Acquisition of study products ......................................................................55 
7.6 
Study Vaccine Accountability ......................................................................55 
7.7 
Final Disposition of study product ...............................................................55 
8 Clinical procedures ......................................................................................................56 
8.1 
Screening ......................................................................................................56 
8.2 
Definition of Study Day and Study Visit .....................................................56 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 6 of 127 
8.3 
Reactogenicity Assessments ........................................................................56 
8.4 
Lymph node FNA .........................................................................................57 
8.5 
Leukapheresis ...............................................................................................58 
8.6 
Visit windows and missed visits ..................................................................58 
8.7 
Monitoring for HIV infection .......................................................................59 
8.8 
Early termination visit ..................................................................................59 
8.9 
AESI contact ................................................................................................60 
9 Safety and adverse events ............................................................................................61 
9.1 
Adverse events .............................................................................................61 
9.2 
Serious adverse events .................................................................................62 
9.3 
Safety monitoring .........................................................................................63 
9.4 
Total blood volume ......................................................................................64 
9.5 
Initial safety review for Part A .....................................................................64 
9.6 
Interim Safety Review for Part A .................................................................64 
9.7 
Initial safety review for Part B .....................................................................64 
9.8 
Safety pause and prompt PSRT AE review..................................................65 
9.9 
Study termination .........................................................................................66 
9.10 Pregnancy .....................................................................................................67 
10 Protocol conduct and informed consent .......................................................................68 
10.1 Protocol conduct ...........................................................................................68 
10.2 Informed consent ..........................................................................................68 
11 Exploratory studies ......................................................................................................70 
11.1 Specimen storage and other use of specimens .............................................70 
12 Literature cited .............................................................................................................71 
Appendix A Schedule of procedures for Part A ...............................................................74 
Appendix B Schedule of procedures for Part B ................................................................76 
Appendix C Visit windows for Part A and Part B ............................................................78 
Appendix D Sample informed consent form for Part A ...................................................79 
Appendix E Sample informed consent form for Part B ...................................................99 
Appendix F Low risk guidelines (for U.S. studies) ........................................................118 
Appendix G Approved birth control methods ................................................................121 
Appendix H Adverse events of special interest ..............................................................123 
Appendix I Protocol team ..............................................................................................124 
Appendix J Version history ...........................................................................................125 
 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 7 of 127 
1 
Executive summary 
1.1 
Title  
A first-in-human Phase 1 clinical trial to evaluate the safety and immunogenicity 
of stabilized CH505 TF chTrimer in healthy, HIV-uninfected adult participants 
1.2 
Design 
This is an open-label Phase 1 study to evaluate the safety and immunogenicity of 
CH505 TF chTrimer admixed with 3M-052-AF + Alum or 3M-052-AF alone. 
The primary hypothesis is that the CH505 TF chTrimer vaccine will expand B 
cell precursor lineages capable of ultimately producing autologous and 
heterologous Tier 2 broadly neutralizing antibodies (bnAbs). 
1.3 
Study products 
• Vaccine product: CH505 TF chTrimer: a stabilized chimeric SOSIP Env 
trimer protein with the N-terminal sequence of CH505 TF gp120 Env 
transplanted into the BG505 SOSIP sequence. To be administered as 300 mcg 
admixed with 3M-052-AF  ±  Alum adjuvant. 
• Adjuvant 1: 3M-052-AF is an aqueous formulation (AF) of the small 
molecule imidazoquinoline, that works as a toll-like receptor (TLR)7/8 
agonist. To be administered as 5 mcg admixed with CH505 TF chTrimer, with 
or without Alum  
• Adjuvant 2: Aluminum hydroxide suspension (Alum) to be administered as 
500 mcg (aluminum content) admixed with 3M-052-AF and CH505 TF 
chTrimer. 
• Vaccine/adjuvant combination: administered as two separate intramuscular 
(IM) injections into the deltoid muscle of each arm. 
• Tris-NaCl buffer (TBS): diluent for Part A 
• Sodium Chloride for injection, 0.9% Unites States pharmacopeia (USP): 
diluent for Part B 
1.4 
Study population 
Healthy adults ages 18 through 55 years. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 8 of 127 
1.5 
Study plan and schema table 
Participants will receive CH505 TF chTrimer at doses of 300 mcg, administered 
via intramuscular injections into the deltoid muscle. Participants will be evaluated 
for safety and immune responses through blood collection at specified timepoints 
throughout the study. The study schema is below: 
Table 1-1 Schema 
Part A 
Study 
arms 
N 
Protein 
antigen 
Adjuvant 
Route 
Month 0 
 (Day 0) 
Month 
2 
(Day 
56) 
Month 4 
(Day 
112) 
Month 8 
(Day 
224) 
Month 
12 (Day 
364) 
Group 
1 
12
* 
CH505 
TF 
chTrimer 
(300 mcg) 
3M-052-AF 
(5 mcg) +  
Alum (500 
mcg) 
 
IM 
✓ 
✓ 
✓ 
✓ 
✓ 
Part B 
Study 
arms 
N 
Protein 
antigen 
Adjuvant 
Route 
Month 0 
 (Day 0) 
Month 2 
(Day 56) 
Month 4 
(Day 
112) 
Month 8 
(Day 
224) 
Month 
12 (Day 
364) 
Group 
2 
12 
CH505 
TF 
chTrimer 
(300 mcg) 
3M-052-AF 
(3 mcg) 
IM 
✓ 
✓ 
✓ 
✓ 
✓ 
Group 
3 
12 
CH505 
TF 
chTrimer 
(300 mcg) 
3M-052-AF 
(3 mcg) + 
Alum (500 
mcg) 
IM 
✓ 
✓ 
✓ 
✓ 
✓ 
Group 
4 
12 
CH505 
TF 
chTrimer 
(300 mcg) 
3M-052-AF 
(5 mcg) 
IM 
✓ 
✓ 
✓ 
✓ 
✓ 
Total  
48 
Notes: 
*In Part A, up to 18 participants could have been enrolled, if needed, to have at 
least 12 participants contribute to the immunogenicity analyses. 
Study product is 1 mL in volume injected as half of the total volume (0.5 mL) 
intramuscularly into each deltoid muscle (both left and right) by needle and 
syringe. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 9 of 127 
Part A: Enrollment was restricted to one participant per day for the first five 
participants and enrollment was paused after the first five participants are 
enrolled. The Protocol Safety Review Team (PSRT) reviewed cumulative safety 
information for all participants recorded through the visit scheduled 2 weeks post 
first vaccination for the first five participants and determined it was safe to 
proceed with full enrollment. 
There was a pre-planned safety review after the 5th participant received their third 
vaccination. No participants received the 4th and 5th vaccination until PSRT 
evaluation of cumulative safety data 2 weeks following the Month 4 (3rd) study 
injection for the first five participants enrolled in the study, after it was 
determined it was safe to proceed with the remaining vaccinations.  
The protocol team convened after the 12th participant received their third 
vaccination to determine if further participants should be enrolled. Specific 
scenarios which could have necessitated enrollment of additional participants in 
order to prevent loss of statistical power of the study include (but are not limited 
to) the following: loss-of-participants due to moving, withdrawal of consent, 
inability to complete fine needle aspiration, or variations in the clinical care due to 
unpredictable events. Because of the early discontinuation of a participant due to 
a panic attack after vaccination 1, an additional participant was enrolled as a 
replacement, for a total of 13 enrolled in Part A. No additional participants were 
enrolled beyond that.  
Part B: Enrollment in Part B will be stepwise by group. Enrollment in Group 2 
will be restricted to one participant per day for the first five participants and then 
enrollment will be held. The Protocol Safety Review Team (PSRT) will review 
cumulative safety information recorded through the visit scheduled 2 weeks post-
first vaccination for the first five participants and will determine whether it is safe 
to proceed with full enrollment in Group 2, then Group 3 and then Group 4.  
Participants will be followed for safety through the date of a contact to assess for 
adverse events of special interest (AESI) 12 months after the last vaccination 
received.  
1.6 
Duration per participant 
Up to 24 months. Participants will have up to 18 months of scheduled clinic visits. 
There will be a contact for AESI assessment at 12 months after their final 
vaccination. 
1.7 
Estimated total study duration 
Anticipate up to around 48 months if the study enrolls a total of 48 participants, 
and up to 56 months if the study enrolls more than 48 participants (eg, if 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 10 of 127 
participants dropout at a rate higher than anticipated, or miss key visits due to 
unforeseen circumstances). The estimate of the study duration includes 
enrollment, planned safety holds, enrollment of additional participants beyond 48, 
if this occurs, and follow-up. 
1.8 
Study sites 
HVTN Clinical Research Sites (HVTN CRSs) to be specified in the Site 
Announcement Memo. 
 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 11 of 127 
2 
Introduction 
One of the major obstacles to developing an efficacious preventive HIV-1 vaccine 
is the challenge of inducing broadly neutralizing antibodies (bnAbs). The 
approach in this study involves recreating the Env immunogens that induced a 
CD4 binding site (CD4bs) bnAb in an HIV-infected individual by making 
sequential recombinant Envs from the HIV strain that infected the individual and 
using these Envs for vaccination (1, 2). A candidate vaccine could use 
transmitted/founder virus envelopes to, at first, stimulate the beginning stages of a 
bnAb lineage, and subsequently boost with evolved Env variants to recapitulate 
the high level of somatic mutation needed for affinity maturation and bnAb 
activity. The B-cell lineage vaccine strategy thus includes designing immunogens 
based on unmutated ancestors as well as intermediate ancestors of known bnAb 
lineages. The goal of such a strategy is to selectively drive desired bnAb lineages 
by giving a survival advantage to specific bnAb clones that are typically 
subdominant in HIV-infected persons. 
To this end, Haynes et al have defined the natural sequence of Envs that induced 
bnAb lineages in select HIV-infected individuals who make bnAbs. From an 
HIV-infected African individual designated CH505, sequential Envs and bnAbs 
were isolated over time and the co-evolution of the CH103 CD4bs bnAb lineage 
was mapped (1). Among CH505 Env mutants, candidate Env antigens were 
selected for optimal affinity with different steps of the CH103 lineage. The 
CH505 TF (transmitter-founder) Env was found to react optimally with the 
unmutated common ancestor (UCA) of the CH103 lineage. 
This study will test a next generation immunogen in the CH505 TF family, a 
stabilized chimeric SOSIP trimer (CH505 TF chTrimer) that elicited neutralizing 
antibody (nAb) and B cell responses in preclinical testing superior to the CH505 
TF monomer currently being tested in HVTN 115 (B Haynes, personal 
communication). Specifically, when combined with 3M-052-AF 5 mcg in alum, 
the CH505 TF chTrimer induced tier 2 autologous CH505 neutralizing antibodies 
with antibodies targeted to both the CD4 binding site and to the V3-glycan (base 
of the V3 loop) bnAb site. Structural studies of the V3-glycan antibodies 
suggested they were similar to PGT124 type of V3-glycan bnAb precursors. In 
addition, this study will help determine if the preclinical metrics used for this 
immunogen should be applied to future HIV vaccine candidates. Specifically, if 
CH505 TF chTrimer elicits a high frequency of CD4bs-directed B cells, elicits 
high binding and autologous tier 2 neutralization titers, and/or expands pools of 
B cells targeting either the CD4 binding site and the base of the V3 loop bnAb 
site, this will suggest that the preclinical testing models are correct and can be 
applied more generally across the HIV vaccine development pipeline.  

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 12 of 127 
2.1 
Rationale for evaluation of CH505 TF chTrimer 
The stabilized chimeric SOSIP envelope (Env) trimer protein is derived from the 
CH505 TF protein sequence. This immunogen, hereafter referred to as CH505 TF 
chTrimer, is a new generation of CH505 immunogen designed to elicit the 
CH103-class of CD4bs bnAbs. This class of bnAbs is an excellent target for 
vaccine development because of the lower degree of somatic hypermutation in the 
CH103 bnAb lineage (1) and the lower number of improbable mutations required 
to achieve neutralization breadth (3). Moreover, when formulated in the TLR7/8 
agonist 3M-052-AF, CH505 TF chTrimer also induced autologous nAbs to other 
epitopes in rhesus macaques, including the V3-glycan bnAb site similar to PGT 
124 bnAbs. This study follows on the HVTN 115 trial that is testing the ability of 
CH505 TF gp120 Env to initiate the CH103-type of bnAb lineage in vaccinees. 
Preliminary data from HVTN 115 Part A showed that most vaccinees expanded 
populations of B cells that bound to the CH505 TF Env protein but not to a 
variant at amino acid position 371 that eliminates the binding of the CH103 UCA 
(unpublished data), suggesting that the correct lineage may have been engaged by 
the CH505 TF gp120, as demonstrated in non-human primates (4). 
CH505 TF chTrimer was developed using BG505 SOSIP as the starting point. 
The portion of CH505 TF gp120 Env N-terminal to the α5 helix was transplanted 
onto the BG505 SOSIP gp41 sequence, resulting in a chimeric protein that formed 
trimers. CH505 TF chTrimer is antigenic for V2 apex, base of the V3 loop bnAb 
site CD4bs, and gp120-gp41 interface bnAbs, and lacks binding to non-
neutralizing antibodies against the C1, V2, co-receptor binding site, and V3 
regions. The addition of E64K and A316W mutations eliminated antibody 
recognition of V3 and the co-receptor binding site. CH505 TF chTrimer protein 
bound to the CH103 UCA at Kd = 171 nM apparent affinity (5). 
Binding affinity of CH103 lineage members to CH505 TF chTrimer correlated 
with the neutralization titer of the same antibodies against CH505.TF 
pseudovirus. 
Preclinical data: rabbits 
Rabbits immunized six times, 4 weeks apart, with unstabilized (E64 / A316) or 
stabilized (E64K / A316W) CH505 TF chTrimer demonstrated the utility of the 
stabilizing mutations. No rabbits immunized with unstabilized CH505 TF 
chTrimer developed autologous tier 2 neutralizing antibodies. Critically, 6 of 8 
(75%) immunized with stabilized CH505 TF chTrimer neutralized autologous 
tier 2 CH505.TF pseudovirus (6). Two rabbits developed autologous neutralizing 
antibodies after only two immunizations. Importantly, elicited antibodies were 
sensitive to mutation of both the CD4bs and to the N160 glycosylation site 
suggesting that if the evolution of these B cell lineages follows the same course as 
in natural human infection, this immunogen may initiate separate B cell lineages 
capable of giving rise to different bnAbs. The rabbit sera from these studies were 
tested against a panel of heterologous tier 2 viruses showing that two rabbits 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 13 of 127 
developed heterologous tier 2 neutralizing antibodies; one rabbit serum 
neutralized 11 of 12 isolates. These antibodies from rabbit S402 mapped to the 
CD4bs and base of the V3 loop site, again suggesting that induction of multiple 
bnAbs is an important goal of a vaccination strategy (6). 
Preclinical data: rhesus macaques 
Immunogenicity of CH505 TF chTrimer was evaluated in a series of rhesus 
macaque studies designed to evaluate different adjuvants and different doses of 
CH505 TF chTrimer. 
3M-052-SE Improves Tier 2 neutralizing antibodies in rhesus macaques: Eight 
rhesus macaques were immunized with CH505 TF chTrimer in combination with 
either GLA-SE (NHP 133) or 3M-052-SE (NHP 125) as an adjuvant. All 
macaques immunized using the 3M-052-SE formulation generated autologous 
tier 2 neutralizing antibodies after 4 immunizations, while only 3 of 4 macaques 
in the GLA-SE group developed autologous tier 2 neutralizing antibodies and 
only after 6 immunizations. After six immunizations, antibody titers were higher 
in the 3M-052 group (Mann-Whitney, p < 0.05) (Figure 2-1). 
After five immunizations, 3 of 4 macaques immunized with CH505 TF chTrimer 
formulated with 3M-052-SE weakly neutralized 4-6 heterologous tier 2 
pseudoviruses in the HIV pseudovirus global panel (7), and the sixth 
immunization increased heterologous neutralization breadth in two macaques. 
3M-052-SE + CH505 TF chTrimer Generates Multiple bnAb lineages: The 
autologous neutralizing antibodies were mapped using CH505.TF pseudoviruses 
with knockout mutations in bnAb sites. Removal of the V1V2 glycan site reduced 
or knocked out neutralization in several macaques, a phenomenon also seen in 
CH103 VH knock-in mice and in other macaque studies (6). One macaque 
showed an increase in neutralization with the removal of glycans that block access 
0
10
20
30
40
Study week
GLA-SE
38072
T883
CA41
38479
stabilized CH505 TF SOSIP
0 4 8 12 16 20 24 28 32
10
100
1000
10000
Study week
ID50 reciprocal
 serum dilution
3M-052
7068
7069
7070
7089
stabilized CH505 TF SOSIP
Figure 2-1 CH505 TF chTrimer induced autologous tier 2 neutralizing antibodies in 
rhesus macaques. Each line represents the ID50 for an individual macaque. Arrows 
indicate immunization timepoints. Titers against murine leukemia virus were <20.  

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 14 of 127 
to the CD4bs which is an indication of the presence of CD4bs antibodies. 
Neutralization of CH505.TF was also reduced by the introduction of a N280D 
mutation within the CD4bs. In 3 of 4 macaque sera, neutralization was reduced by 
N160 virus Env mutations. Thus, CH505 TF chTrimer induced both CD4bs and 
N160 dependent (indicating binding at or near the Env apex glycan supersite) 
tier 2 neutralizing antibodies in macaques (6). 
Tier 2 neutralizing antibodies in rhesus macaques:An alternative aqueous 
formulation (AF) of the 3M-052 adjuvant similar to the proposed product in this 
trial was evaluated with CH505 TF chTrimer in rhesus macaques (in study NHP 
161). Across three different doses of CH505 TF chTrimer (33, 100 and 300 mcg), 
this regimen elicited tier 2 autologous neutralizing antibodies in 16 of 16 
immunized animals (Figure 2-2). Figure 2-2 also provides a comparison of the 
300 mcg CH505 TF chTrimer dose with 30 mcg 3M-052-SE (Group 2 in NHP 
125). 
 
Figure 2-2  NHP 125 and NHP 161 Plasma Neutralization Post 5th Immunization 
NHP 161 Group 1:  33 mcg in 5 mcg 3M-052-AF + 500 mcg Alum 
NHP 161 Group 2:  100 mcg in 5 mcg 3M-052-AF + 500 mcg Alum 
NHP 161 Group 3:  300 mcg in 5 mcg 3M-052-AF + 500 mcg Alum 
NHP 161 Group 4:  300 mcg in 5 mcg 3M-052-SE 
NHP 125 Group 2:  300 mcg in 30 mcg 3M-052-SE 
Yellow:  ID50>20; Orange:  ID50>200; Red:  ID50>1000 
Structural studies of antibodies induced in NHP 125 showed antibodies binding 
either to the CD4 binding site or to the V3-glycan bnAb site, the latter of which 
are similar to human PGT124 bnAbs in angle of approach. The CD4bs autologous 
neutralizing antibodies were somewhat different from CH103-like antibodies with 
regard to interactions with the V5 loop. Thus, immunogenicity information was 
derived from structural studies, which showed the CH505 chTrimer induced 
PGT124-like V3-glycan antibodies that also were dependent on N160 (as was the 
original human PGT124) (8), and CD4 bs antibodies that interact with the V5 
loop. 
Protection against intrarectal SHIV Challenge: After the immunization regimens 
were complete, protection against intrarectal (IR) SHIV challenge was evaluated 
in animals combined from studies NHP 125, NHP 161 and NHP 161.1. These 
animals received weekly IR SHIV challenges for 9 weeks (weeks 0-8). After a 
four-week rest (week 9-12), weekly challenges were resumed at weeks 13-16 for 
NHP 161
NHP 125
Group 1
Group 2
Group 3
Group 4
Group 2
Virus Name
7349 7358 7359 7365 7348 7350 7354
7360
7355
7361
7357 7351 7338 7340 7352 7364
7068 7069 7070 7089
CH0505.w4.3
5583 4880 2784 2863 32088 9216 16355 8366 26621 43740 29989 4435 1678 13886 4606 14952 26412 3779 1719 36374
CH0505TF
162
51
185
49
122
112
57
168
125
396
1247
144
55
176
170
972
5833
122
106
331
CH0505TF.gly4
4381
52
747 9985
602
189
51
39388 6172 43740 43740 757
658
97
145
2951
6584
381
96
43740

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 15 of 127 
an additional four challenges. For evaluation of results animals immunized with 
CH505 TF chTrimer (all doses) and 3M-052 adjuvant (either formulation) were 
combined and grouped as either high or low bnAb responders based on pre-
challenge neutralizing titers against SHIV CH505.375H (Figure 2-3). After nine 
challenges all 9 control monkeys had developed viral titers, whereas six of seven 
high bnAb responders and two of 15 low responders were protected from 
infection. After all thirteen challenges were complete, one additional macaque in 
the high neutralizing antibody responder group became infected (Figure 2-3).  
 
Figure 2-3 Protection from SHIV challenge. CH505 TF chTrimer-immunized animals 
from studies NHP 125, NHP 161, and NHP 161.1 received intrarectal SHIV challenges 
every week for nine weeks, followed by a three-week rest, and then four more weekly 
challenges. Nine negative control animals also received SHIV challenges. (A) Animals 
from all groups were divided into high and low responders based on pre-challenge titers. 
(B) After 9 challenges, 5 of 7 high-responders were protected from infection, and 2 of the 
15 low responders remained protected. 
Preclinical data: knock-in mice 
CH505 TF chTrimer has been evaluated in over 100 mice at 25 mcg doses. In one 
of these studies (VMU108), seven CH103 VH + VL UCA knock-in (KI) mice 
were immunized with 25 mcg CH505 TF chTrimer + poly I:C adjuvant. An 
adjuvant-only group did not neutralize CH505TF.gly4 variant virus (ie, CH505TF 
lacking glycans at 462, 460, and 276 that are known to impede CD4bs bnAbs). 
After five immunizations, no sera from the adjuvant-only- immunized mice 
neutralized CH505.TF, while 5 of 7 immunized with CH505 TF chTrimer plus 
adjuvant neutralized CH505TF.gly4 virus. Thus, CH505 TF chTrimer induced 
candidate precursors of CD4bs bnAbs in CH103 UCA KI mice. 
For additional information, see the Investigator’s Brochure (IB). 
A.
B. Challenge
Week

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 16 of 127 
2.2 
Clinical Experience with Recombinant Env Vaccinations 
Vaccine mixtures of gp140 Env oligomers, including trimeric forms, have been 
evaluated in healthy, HIV-uninfected participants in previous DAIDS-sponsored 
studies. Table 2-1 summarizes completed Phase 1 clinical trials with gp140 
subtype C and subtype B Env proteins. Overall, almost 240 participants received 
these protein vaccines either co-administered with a DNA or MVA vaccine prime 
or as a protein boost. The safety profile of these products was similar to that 
observed for gp120 Env products. The vaccines were generally well tolerated, 
with no vaccine related SAEs (9-11).  
Table 2-1 Completed studies with HIV Env oligomers and trimers 
Protocol 
Immunogen 
Dose (N) 
Adjuvant 
Schedule 
Safety data 
available 
HVTN 049 
 
gp140  
(oligomeric, clade B) 
100 mcg (80) 
MF59C.1 
Month 0, 3, 9 
(2 protein boosts, IM) 
YES 
HVTN 073E 
gp140  
(oligomeric, clade C) 
100 mcg (17) 
MF59C.1 
Month 0, 3 
(2 protein boosts, IM) 
YES (9)  
HVTN 086 
gp140  
(oligomeric, clade C) 
100 mcg (124) 
MF59C.1 
Month 3, 6 
(2 protein boosts, IM) 
YES (10) 
HVTN 088 
gp140  
(oligomeric, clade C) 
100 mcg (16) 
MF59C.1 
Month 0, 6 
YES (11)  
Note: IM: intramuscular 
Recent progress in the design, selection, and preclinical evaluation of stabilized 
soluble native-like Env trimers have led to development of new immunogens 
capable of maintaining multimeric configurations. Table 2-2 and the following 
paragraphs summarize ongoing clinical trials with this new generation of Env 
proteins. Safety data from these studies are anticipated and we aim to incorporate 
updates in the IND submission. See below for summaries of safety information; 
for more details of these studies please consult the Investigator’s Brochures. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 17 of 127 
Table 2-2 Ongoing studies with HIV Env trimers 
Protocol 
Immunogen 
Dose (N), 
route 
Adjuvant 
Schedule 
Safety data 
(related) 
HVTN 122 
gp145 C.6980 
(oligomers, > 50% 
trimer) 
300 mcg (25) 
100 mcg (15) 
IM 
Alum (500 
mcg) 
Month 0, 2, 
6 
No SAEs 
One Grade 3 
induration 
No product-
associated early 
terminations 
IAVI W001 
(NCT03699241) 
BG505 SOSIP.664 
30 mcg (20) 
100 mcg (20) 
300 mcg (10) 
IM 
AS01B 
Month 0, 2, 
6 
No SAEs 
No Grade 3 or 4 
AEs 
No Early 
Terminations 
HVTN 137 (Part 
A) 
BG505 SOSIP.664 
100 mcg + 1 
mcg 3M-052-
AF+Alum (5), 
IM 
100 mcg + 5 
mcg 3M-052-
AF+Alum (10), 
IM 
3M-052-AF 
(1 or 5 mcg) + 
Alum (500 
mcg) 
Month 0, 2, 
6 (optional) 
 
No related SAEs or 
AESIsTwo Grade 3 
Local 
Reactogenicity 
Erythema/Induration 
Two early 
terminations 
HVTN 137 (Part 
B, Group 4) 
BG505 SOSIP.664 
100 mcg (20), 
IM 
5 mcg 3M-
052-AF + 
500 mcg 
Alum 
Month 0, 2, 
6 
No related SAEs or 
AESIs 
 
HVTN 300 (Part 
A) 
CH505 TF 
chTrimer 
300 mcg (12), 
IM 
3M-052-AF 
(5 mcg) + 
Alum (500 
mcg) 
Month 0, 2, 
4, 8, 12 
No related SAEs, 
AESIs 
HVTN 122: The gp145 C.6980 immunogen is an HIV Env trimer developed by 
the United States Military HIV Research Program (MHRP), constructed with 
modifications to facilitate trimer assembly. The safety and immunogenicity of the 
predominantly trimeric gp145 C.6980 was evaluated in HVTN 122 at 100 mcg 
and 300 mcg protein dose admixed intramuscularly with aluminum hydroxide 
adjuvant (months 0, 2, 6). While analysis of the trial data is still ongoing, no 
serious adverse events related to study product administration were reported. 
HVTN 122 is closed and no early terminations associated with an adverse event 
deemed related to study product have been reported. There has been one report of 
Grade 3 induration. No related SAEs have been reported. 60% (n=27) of 
participants experienced one or more AEs, of which only one AE (mild injection 
site pruritis) was deemed related to study product.  
IAVI W001: BG505 SOSIP.664 gp140, the native-like stabilized SOSIP trimer 
sharing the gp41 sequence and highly similar biophysical and antigenicity 
properties with the CH505 TF chTrimer (12, 13). This immunogen is currently 
being evaluated in IAVI W001 (NCT03699241), a randomized double-blinded, 
placebo-controlled, dose-escalation Phase 1 clinical trial evaluating safety and 
immunogenicity of recombinant HIV BG505 SOSIP.664 gp140 vaccine 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 18 of 127 
formulated with AS01B (GlaxoSmithKline [GSK]) administered intramuscularly. 
Blinded safety data as of May 25, 2020 includes information for 12 volunteers in 
Group 1 (30 mcg in the US), 1 volunteer in Group 2 (100 mcg in the US), 12 
volunteers in Group 4 (30 mcg in Kenya) and 12 volunteers in Group 5 (100 mcg 
in Kenya). The trial is ongoing and remains blinded to investigational product 
administration. As of May 25, 2020, there have been three reported serious 
adverse events, with one volunteer suffering multiple fractures following a road 
accident, another suffering a soft tissue injury while working at a construction site 
and a third volunteer requiring surgery for acute appendicitis. These events were 
all deemed unrelated to the investigational product. One potential immune-
mediated disease has been reported; this was judged to be unrelated to the 
investigational product as signs of the illness were recorded prior to enrollment. 
No incident HIV infections, deaths, or pregnancies have been reported. Six 
volunteers have reported grade 3 reactogenicity events that resolved without 
sequelae. No grade 3 or higher hematology, chemistry or urine laboratory values 
have been reported. No volunteers have been discontinued from the trial due to 
adverse events. Two scheduled interim Safety Monitoring Committee (SMC) 
meetings have occurred, during which the SMC has reviewed all the available 
safety data and recommended continuation of the study, with dose escalation in 
both the US and Kenyan sites.  
HVTN 137 Part A: Part A is a first-in-human, double-blinded dose escalation 
study testing the combination of 100 mcg BG505 SOSIP.664 gp140 with 3M-
052-AF at two doses (1 mcg and 5 mcg) and 500 mcg Alum. The study is ongoing 
and remains blinded to within-group treatment assignment. As of April, 2022, 
both the 1 mcg 3M-052-AF group (6 participants total, 5 receiving 
protein/adjuvant, 1 receiving placebo) and the 5 mcg 3M-052-AF group (11 
participants total, 10 receiving protein/adjuvant, 1 receiving placebo) completed 
enrollment. Part A of the protocol specified that participants would receive two 
total doses, one at month zero and the other at month two. Five out of six 
participants received two doses of the 1 mcg dose (one participant discontinued 
for reasons unrelated to vaccination) and 10 out of 11 participants received two 
doses of the 5 mcg dose. One participant in the 5 mcg dose group (Group 2) 
decided to discontinue vaccination due to Grade 3 induration/erythema first noted 
on Day 8 post-vaccination. The maximum size of both the induration and 
erythema was measured at 17 x 17 cm on Day 8 (Grade 3). The erythema resolved 
over three days and the induration subsided to less than 5 cm on Day 11 (Grade 
1). The induration was measured at 2 x 2 cm on Day 14 but did not completely 
resolve until 41 days post-injection. At no point was the pain/tenderness greater 
than mild and the participant continued to work. It is unknown at present whether 
this participant received placebo or study product. Another participant in Group 2 
experienced two days of Grade 3 induration and erythema from Days 6-7 post-
vaccination that resolved completely by Day 8. In consultation with the Protocol 
Safety Review Team, the participant did receive the second dose, which was 
uneventful. In addition, 4 participants reported Grade 3 systemic reactogenicity 
events. All 4 participants experienced severe fatigue and myalgia which lasted for 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 19 of 127 
1-2 days. Additionally, 2 participants experienced severe myalgia, arthralgia, 
chills and headache that lasted for a day.  
The protocol was later amended and participants in Groups 1 and 2 were given the 
option to receive a third dose for 3 total doses. Nine out of 17 participants elected 
to receive a third dose. There were no unsolicited Grade-3 or -4 AEs and no 
related serious adverse events (SAEs), AESIs, or deaths in either group after this 
third dose. Both local and systemic reactogenicity were similar between all 3 
doses in participants who received 3 doses. 
HVTN 137 Part B is evaluating the safety and immunogenicity of 100 mcg 
BG505 SOSIP.664 gp140 in combination with 3 TLR agonists, including 5 mcg 
3M-052-AF + 500 mcg Alum, and Alum alone. Enrollment is now complete with 
88 participants enrolled. Given that the trial remains blinded across 4 treatment 
arms, interpretation of the blinded safety data from HVTN 137 Part B is 
challenging, but there have been no related SAEs, AESIs, deaths, or unplanned 
study pauses. 
Overall, the BG505 SOSIP.664 with 3M-052-AF was generally well tolerated, 
with no unsolicited Grade 3 or 4 adverse events, no related SAEs, AESIs, or 
deaths, and no unplanned study pauses. Other than the persistent erythema in one 
of the Group 2 participants described above, all reactogenicity symptoms resolved 
within 14 days and generally within seven days. For more detailed information, 
please see the Investigator’s Brochure.  
HVTN 300 (Part A): As of September 7, 2022, the study is ongoing and all 13 
participants have received the first vaccination, 10 participants have received the 
second vaccination, 9 participants have received the third vaccination, 9 
participants have received the fourth vaccination, and 6 participants have received 
the fifth vaccination. Five participants have discontinued further vaccinations (1 
due to a panic attack after the first injection (this participant had a history of panic 
attacks before being part of the study), 3 due to reactogenicity events, and 1 was 
lost to follow-up); Out of these 5 participants, 2 terminated from the study early 
(panic attack and lost to follow-up) and 3 have remained in the study for follow-
up. 
All participants experienced at least some local reactogenicity during the trial, 
mostly mild to moderate. One (1) participant experienced severe pain/tenderness 
in both the right and left injection sites 3 days following the fourth vaccination, 
though it lasted only one day. 
All participants reported some systemic reactogenicity during the course of the 
trial to date, mostly mild to moderate. For example, 11 of 13 participants 
experienced systemic reactogenicity after the first dose. Five (5) participants 
reported Grade 3 (severe) systemic reactogenicity during the trial through 
September 7, 2022. One (1) of these 5 participants received a subsequent 
vaccination without any Grade 3 reactogenicity, one (1) experienced an additional 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 20 of 127 
Grade 3 systemic reactogenicity symptom, one (1) has not yet received a 
subsequent vaccination, and two (2) declined to receive additional vaccinations 
after their first Grade 3 systemic reactogenicity event. All Grade 3 events resolved 
within the 7-day reactogenicity period; the longest duration for severe 
reactogenicity was 2 days.  
There have been no related SAEs, AESIs, or deaths as of September 7, 2022. 
In conclusion, multiple variants of the HIV Env protein including trimeric 
formulations have been evaluated in clinical trials with an acceptable safety 
profile. The Env protein is relatively well conserved functionally albeit with 
amino acid sequence variability associated with strain variants. This characteristic 
is predicted to result in a similar safety profile for different Env antigens, 
including novel stabilized SOSIP trimers. Although two grade 3 local 
erythema/induration events occurred on days 6 and 8 in the 10 participants in the 
HVTN137—Part A who received the 5mcg dose of 3M-052-AF plus alum, no 
grade 3 local reactogenicity was observed in 18 participants in Part B or the 
participants in HVTN300--- Part A. Additionally, the bilateral administration of a 
split dose HVTN300 is different from the unilateral administration in HVTN137. 
We therefore believe that the reactogenicity profile of the regimen in Part B will 
be adequately captured with a standard 7 day reactogenicity monitoring period 
(see Section 8.3 below). 
2.2.1 
Evaluation of 3M-052-AF + Alum  
3M-052-AF contains 3M-052 and an emulsifier in an aqueous formulation. 3M-
052 is a TLR7 and TLR8 agonist (TLR7/8 agonist) that induces production of 
cytokines in vitro from immune cells, such as dendritic cells, macrophages, and 
monocytes (14-17).  
Nonclinical studies in guinea pigs, rats, rabbits, and rhesus macaques comparing 
the immunogenicity of the related SOSIP protein BG505 SOSIP.664 formulated 
with a diverse range of adjuvants have consistently shown that the protein 
adjuvanted with 3M-052-AF + Alum elicits neutralizing and binding antibodies 
more quickly, to higher peak magnitudes, and with greater durability than any of 
the other protein-adjuvant combinations tested. 
In rhesus macaques, among eight adjuvants combined with an Env gp140 
immunogen, the alum/TLR7 were the most potent in assays characterizing both 
Ab and cellular responses. This hierarchy of potency was sustained throughout the 
longitudinal follow up. The overall effect of the alum/TLR combination was to 
boost Env binding Ab titers 3-10-fold compared to alum alone (18). Data 
presented in Figure 2-1 also confirm that the qualitative antibody response 
induced by 3M-052-AF is different as higher levels of autologous tier 2 
neutralizing antibodies were induced when compared with GLA-SE. 
For additional information, see the Investigator’s Brochure (IB). 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 21 of 127 
2.2.2 
Rationale for evaluation of 3M-052-AF alone (addition of Part B) 
3M-052-AF adjuvant was evaluated in a cynomolgus macaque study with and 
without Alum in a study of a coronavirus vaccine candidate. This receptor-
binding domain (RBD) sortase A-conjugated ferritin nanoparticle (RBD-scNP) 
vaccine consists of a 24-mer SARS-CoV-2 RBD nanoparticle conjugated to a 
ferritin scaffold (19).  
 
Figure 2-4 Neutralizing antibodies and in vivo protection elicited by RBD-scNP vaccine 
formulated with three different adjuvants. 
(A) Schematic of the vaccination and challenge study. Cynomolgus macaques (n=5 per group) 
were immunized intramuscularly 3 times with 100 μg of RBD-scNP adjuvanted with 3M-052-AF-
Alum, Alum, 3M052-AF, or PBS control. Animals injected with adjuvant alone or PBS were set 
as control groups. Monkeys were then challenged with SARS-CoV-2 WA-1, collected for blood, 
Bronchoalveolar lavage (BAL) and nasal swab samples, and necropsied for pathologic analysis. 
(B) Neutralization titers of plasma antibodies (post-3rd immunization) against pseudovirus of 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 22 of 127 
SARS-CoV-2 variants in 293T-ACE2-TMPRSS2. (C) Reduction of ID50 titers against variants 
shown as fold reduction compared to the titers against WA-1. (D-E) Neutralization titers of 
plasma antibodies (post-3rd immunization) against pseudoviruses of the SARS-CoV-2 Omicron 
(BA.1 and BA.2) variants, SARS-CoV-2 PMS20 variant, and SARS-CoV in 293T-ACE2 cells. 
For SARS-CoV-2 variants, the geometric mean titers and the fold reduction compared to D614G 
are shown. (F) SARS-CoV-2 N gene sgRNA in BAL and nasal swab samples collected on day 2 
and 4 post-challenge. Dashed line indicates limit of the detection. (G) Histopathological analysis. 
Lung sections from each animal were scored for lung inflammation by haematoxylin and eosin 
(H&E) staining, and for SARS-CoV-2 nucleocapsid antigen (Ag) expression by 
immunohistochemistry (IHC) staining.ns, not significant, *P<0.05, Wilcoxon rank sum exact test. 
The RBD-scNP (100 μg) was administered intramuscularly in the right and left 
quadriceps at 3 timepoints with or without adjuvant as defined in Figure 2-4, 
Panel A. Surprisingly we found that 3M-052-AF in each assay out-performed or 
was not inferior to the other formulations (Figure 2-4). In the cynomolgus 
monkey study (Figure 2-4 Panel A), the antibodies induced by 3M-052-AF 
adjuvant with the RBD-sortase conjugated ferritin nanoparticle (scNP) induced 
higher neutralizing antibodies for many SARS-CoV-2 variants (Figure 2-4 Panel 
B). Of great interest is the finding that 3M-052-AF alone induced higher titers to 
Omicron compared to 3M-052/Alum or Alum alone (Figure 2-4). After 2 or 3 
immunizations, the combination of 3M-052/Alum was the lower value for 
Omicron neutralization and 3M-052-AF alone was the higher titer. Panels F and 
G of Figure 2-4 demonstrate the results of challenge of the monkeys after three 
immunizations and show protection with all adjuvant formulations with the least 
complete protection in the Alum alone group. All adjuvant combinations were 
well tolerated in this study. There were no deaths. Animals were monitored for 
safety and serum chemistry, and hematology parameters were measured routinely. 
Mild eosinophilia was observed in 6 of the 35 monkeys, which did not correlate 
with a particular adjuvant regimen and was not observed in the group receiving 
RBD-scNP + 3M-052-AF. No other vaccine or adjuvant related serum chemistry 
or hematology changes were observed. No weight loss or adverse effects were 
observed. 
The above data provide the rationale for evaluating 3M-052-AF alone as an 
alternative to the combination of 3M-052-AF and Alum for use in HIV-1 vaccine 
trials. While these data were generated with a SARS-CoV-2 RBD immunogen, 
both RBD and HIV-1 Env are highly glycosylated trimers, and effective 
elicitation of neutralizing antibodies to these viruses may therefore be supported 
by similar adjuvant regimens. Additionally, the monoclonal antibodies with the 
most potent neutralization isolated from the memory B cells of SARS-CoV-2 
vaccine recipients have substantial somatic hypermutation, further supporting the 
concept that the underlying immunologic mechanisms that lead to improved 
quality of the neutralizing antibody response are likely to apply to both SARS-
CoV-2 and HIV (20).  
3M-052-AF is a lipid-modified synthetic imidazoquinoline that is a TLR7/8 
agonist. The lipid tail of 3M-052-AF was designed to minimize systemic 
distribution, and this tail associates with a phospholipid excipient, 1,2-Distearoyl-

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 23 of 127 
sn-glycero-3-phosphoglycerol (DSPG) to create an aqueous nanosuspension 
formulation (14). In a mouse study of 3M-052 formulated with 
phosphatidylcholine (a similar phospholipid) instead of DSPG, subcutaneous 
administration of 25 mcg of 3M-052 in mice did not induce circulating TNFα, 
indicating an absence of a systemic proinflammatory effect (15). Additionally, in 
a study performed by Charles River for 3M, localization of radiolabeled 3M-052 
(350 mcg) formulated in sesame oil was measured after subcutaneous 
administration in Sprague Dawley Rats. In this study, concentrations of total 
radioactivity at the dose site were more than 100-fold higher than the 
concentrations of radioactivity observed in the sampled tissues at all times, up to 
14 days. Notably, clinical safety of the DSPG component of 3M-052-AF has been 
demonstrated in the liposomal formulation of amphotericin B (Ambisome) which 
contains DSPG. Ambisome has reduced incidence of adverse events compared to 
amphotericin B deoxycholate upon i.v. administration (19, 21). Even though the 
evaluation of 3M-052-AF biodistribution (without Alum) is not yet available, data 
with other formulations of 3M-052 without Alum, as mentioned above, indicate 
that the activity of this adjuvant is predominantly localized. 
2.3 
Rationale for Schedule 
To match the schedule used in other comparable trials (HVTN 115) and pre-
clinical studies, the CH505 TF chTrimer protein will be administered IM into 
both deltoids in a volume of 1 mL divided into two 0.5 mL injections 
administered in the left and right deltoid at a dose of 150 mcg per deltoid (total 
dose 300 mcg) at months 0, 2, 4, 8, and 12. The rationale for splitting the dose 
between deltoids is based upon both theoretical and practical considerations. 
Theoretically, having more lymph nodes engaged in the germinal center process 
should allow for more clonal selection and competition, leading to additional 
somatic hypermutation necessary for bnAb maturation. Practically, splitting the 
dose should decrease the potential for localized reactogenicity in this first in 
human trial and facilitate sampling of lymph nodes via Fine Needle Aspiration in 
HVTN 300 Part A (see Section 2.6). Additionally, in pre-clinical studies in rhesus 
macaques, antibody titers rose with each subsequent injection up to five boosts. 
This is in contrast to previous experience with other adjuvants.  
2.4 
Rationale for Dose of Protein 
The 300 mcg dose of protein has been selected on the basis of promising 
preclinical data generated from rhesus macaques (see Section 2.1, Figure 2-2 and 
Figure 2-3) and reassuring safety data generated from analogous studies of 
recombinant trimers used in clinical trials. These studies include IAVI W001 (300 
mcg) and HVTN122 (300 mcg) (see Section 2.2).  

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 24 of 127 
Clinical Data: We anticipate summaries of preliminary clinical safety data from 
the HVTN 122 and IAVI W001 studies to support the protein trimer dose selected 
for this study and the IND application. 
For additional information, see the Investigator’s Brochure (IB). 
2.5 
Rationale for Dose of Adjuvant 
The 5 mcg dose of 3M-052-AF adjuvant has been selected based on previous 
preclinical experience (see Section 2.1, Figure 2-2 and Figure 2-3) and dose 
selection in HVTN 137 (see Table 2-2). The 500 mcg dose of alum (ie, aluminum 
content by weight) adjuvant also matches the regimen in HVTN 137. 
The 3 mcg dose of 3M-052-AF was selected for use in HVTN 300 Part B in order 
to compare 3 mcg and 5 mcg doses to determine if the reactogenicity profile seen 
with 5 mcg of 3M-052-AF/Alum can be reduced with 3 mcg 3M-052-AF (± 
Alum) while maintaining similar adjuvant activity. Results from this trial will be 
compared to data from Part A of the HVTN 300 trial. 
2.6 
Rationale for Fine Needle Aspiration 
To improve assessment of the effects of CH505 TF on B cell lineage 
development, this protocol will employ fine needle aspiration (FNA) of an 
axillary lymph node proximal to the site of vaccine administration in study 
participants enrolled in Part A (Appendix A). FNA will be performed after the 3rd 
dose of CH505 TF chTrimer has been administered. The germinal center 
response, which occurs exclusively in the lymphatic tissue, is critical for directing 
B cell lineage development. Havenar-Daughton and colleagues have employed 
repeated direct probing of germinal center responses by fine needle lymph node 
aspirates in nonhuman primate (NHP) studies and found that induction of 
neutralizing antibodies against Tier 2 autologous HIV strains best correlated with 
germinal center B cell magnitude and Env-specific CD4+ Tfh cells (22). Similar 
sampling strategies are under evaluation in licensed vaccine and early phase 
human HIV vaccine studies and are planned in this protocol (23).  
2.7 
Rationale for Leukapheresis 
To assess the expansion of rare precursor B cell populations that occur at a 
frequency of approximately ~1/20 million cells, large numbers of peripheral 
blood mononuclear cells (PBMCs) are required. Leukapheresis can provide 6-10 
billion PBMCs without depleting red blood cells or other blood components. 
There are approximately 1 million PBMCs per milliliter of blood and therefore 
peripheral blood sampling at volumes associated with typical blood donation 
(~500 mL) would not provide sufficient PBMC numbers. Furthermore, 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 25 of 127 
leukapheresis is associated with fewer adverse events when compared to blood 
donation. Hence this protocol will employ leukapheresis in study participants 
enrolled in Part A (Appendix A) to ensure adequate specimens for analysis of rare 
precursors. Leukapheresis will be performed at screening and after the 4th dose of 
CH505 TF chTrimer has been administered. The rationale for performing 
leukapheresis three weeks after the 4th dose is based upon detailed preclinical 
investigations into the kinetics of the germinal center response in rhesus 
macaques (see Section 2.1 and (24)). 
2.8 
Risks and benefits 
2.8.1 
Potential risks  
In addition to risks associated with 3M-052-AF + Alum adjuvants (see Section 
2.2), frequent potential side effects resulting from other intramuscular (vaccines) 
and subcutaneous (local anesthetic prior to FNA) injections include stinging, 
discomfort, redness of skin, or mild bruising at injection site. 
Frequent potential side effects resulting from other intramuscular (vaccines) and 
subcutaneous (local anesthetic prior to FNA) injections include stinging, 
discomfort, redness of skin, or mild bruising at injection site. 
Less frequent side effects from other intramuscular vaccines include: fever, chills, 
rash, aches and pains, nausea, dizziness and fatigue. If these occur, they will be 
monitored, but with other vaccines, these effects are generally short term, mild to 
moderate in severity, and usually do not require treatment.  
Rare risks with any injection procedure include infection at the site of injection. 
Signs of infection at the injection site include severe pain, erythema, induration, 
warmth or drainage. There are rare reports of anaphylaxis with many vaccines. 
There may be side effects from the study products which may be serious or life 
threatening that we do not know about yet. 
If antibodies elicited by the study vaccine result in a positive or indeterminate 
HIV test (ie, vaccine-induced seropositivity or VISP), this may have a negative 
impact on employment, health care, insurance, travel, and personal relationships. 
HIV PCR will be used to exclude or confirm HIV infection.  
Alum adjuvant: For more than 90 years, Alum has been used as an adjuvant in 
commercial vaccines. Hundreds of millions of people have gotten vaccines 
containing Alum. Side effects are generally limited to minor local reactions at the 
injection site. 
Blood drawing may cause pain, bruising, fainting, and, rarely, infection at the site 
where the blood is taken. Leukapheresis can also cause pain, bruising, and, rarely 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 26 of 127 
infection. Additional risks may depend on local leukapheresis procedures. 
Fainting can also occur, but occurs less frequently than with blood drawing. 
Fine needle aspiration of lymph nodes can uncommonly cause pain, bruising, 
and/or bleeding at the site where the needle is inserted. Similar to any procedure 
where a needle is inserted into the skin (such as vaccination, as described above), 
there is a rare risk of localized infection. The local anesthetic rarely can cause arm 
numbness or weakness. 
Risks during Pregnancy: Because possible effects of the study vaccine on a fetus 
or nursing infant are unknown, persons assigned female sex at birth who have 
reproductive potential will be tested for pregnancy at screening and prior to 
administration of each dose of study vaccine. Such persons will be asked to notify 
the site immediately if they suspect or learn they are pregnant during this study. In 
case of pregnancy, participants will continue to be followed for safety and the 
participant will not receive any additional vaccinations. The participant will be 
contacted about the outcome of a pregnancy that begins during the study.  
Other Risks: The medical tests performed as part of this research protocol may 
result in new diagnoses or abnormal values without clinical significance (“false 
positives”). Depending on the medical findings and consequences of being 
provided with the results of these tests, the study participant may view this as 
either a risk or a benefit. Any such information will be shared and discussed with 
the participant and, if requested by the participant, may be forwarded to the 
primary health care provider for further workup and management. 
Participants in this study risk experiencing discrimination or other personal 
problems that may result from study participation itself: these are known 
collectively as negative social impacts. The HVTN clinical research site (CRS) is 
obliged to provide advocacy for and assistance to participants regarding these 
negative social impacts associated with the vaccine trial. If HVTN CRS staff have 
questions regarding ways to assist a participant dealing with a negative social 
impact, a designated HVTN Core representative can be contacted. 
2.8.2 
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. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 27 of 127 
2.9 
Assessment of immunogenicity endpoints 
The primary immunogenicity endpoint assay will measure the frequency of 
CH505TF- and epitope-specific memory B cells after vaccination). Evaluation of 
cellular responses will be performed on all samples after vaccination and 
compared to each participant’s baseline. Multiparameter flow cytometry will be 
used to assess the frequency of CH505TF- and epitope-specific IgG+ B cells. The 
antigen-specific B cell phenotyping assays will be performed at the Fred Hutch 
HVTN laboratory.  
Lymphocytes from an axillary lymph node obtained by fine needle aspiration 
(FNA) of the node will be examined for a germinal center phenotype (germinal 
center B cell) via flow cytometry three weeks after the 3rd vaccination.  
Additional assays may be performed on selected responders and at additional 
timepoints at the discretion of Protocol Team leadership based on its evaluation of 
primary results following the third vaccination (see Section 3.1).  

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 28 of 127 
3 
Objectives and endpoints for Part A and Part B 
3.1 
Primary objectives and endpoints 
Primary objective 1: 
To evaluate the ability of the vaccine regimen to elicit CD4 binding-site, V2 apex 
and V3 glycan (bnAb region at the base of the V3 loop), and CH505TF-specific 
memory B cells  
Primary endpoint 1: 
Flow cytometry analysis of the frequency of the CD4 binding-site, V2 apex and 
V3 glycan (bnAb region at the base of the V3 loop), and CH505TF-specific IgG+ 
B cells  
Primary objective 2 
To evaluate the ability of the vaccine regimen to elicit autologous tier 2 virus 
neutralizing antibodies 
Primary endpoint 2: 
Response rate and magnitude of serum antibody neutralization of vaccine-
matched tier 2 HIV-1 strains as measured by TZM-bl assay  
Primary objective 3: 
To evaluate the safety and tolerability of a 300 mg dose of CH505 TF chTrimer 
admixed with different adjuvant regimens 
Primary endpoint 3: 
Local and systemic reactogenicity signs and symptoms will be collected for a 
minimum of seven days following receipt of any study vaccine. 
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 twelve months following any receipt of study product. Additionally, 
all adverse events will be collected for 30 days after any receipt of study 
vaccination.  

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 29 of 127 
3.2 
Secondary objectives and endpoints 
Secondary objective 1: 
To evaluate HIV-1 binding antibody responses elicited by CH505 TF chTrimer 
admixed in 3M-052-AF + Alum or 3M-052-AF (without alum)  
Secondary endpoint 1: 
Response rate and magnitude of serum IgG binding antibodies as assessed by 
binding Ab multiplex assay (BAMA)  
Secondary objective 2: 
To evaluate the ability of the vaccine regimen to elicit HIV-1 specific 
heterologous tier 2 neutralizing antibodies 
Secondary endpoints 2: 
Response rate and magnitude of serum antibody neutralization of heterologous 
HIV-1 strains as measured by TZM-bl assay 
3.3 
Exploratory objectives 
Exploratory objective 1: 
To map the epitope specificity of autologous and heterologous tier 2 virus 
neutralizing activity 
Exploratory endpoints 1: 
Response rate and magnitude of serum antibody neutralization of epitope knock-
out mutants of CH505 TF and heterologous tier 2 viruses 
Exploratory objective 2: 
Determine the B cell repertoire of peripheral blood B cells in each group of 
vaccinees 
Exploratory endpoints 2: 
Detection of induced V3 glycan and CD4 binding site epitope binding antibodies. 
Exploratory objective 3: 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 30 of 127 
Determine the transcriptome of vaccine and adjuvant induced peripheral blood 
immune cells in each group of vaccinees 
Exploratory endpoints 3: 
Detection of origin of V3-glycan and CD4 binding site antibodies from either 
extrafollicular B cells or follicular B cells. 
Additional exploratory objectives: 
To conduct analyses related to furthering the understanding of HIV, immunology, 
vaccines, and clinical trial conduct, including but not exclusive to B cell repertoire 
analysis (including analysis of rare B cell lineages associated with bnAb 
precursors), and assessment of lymph node aspirate for germinal center activity, 
including cellular phenotyping and mutational frequency analysis suggestive of 
somatic hypermutation and affinity maturation following immunization. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 31 of 127 
4 
Laboratory strategy  
The primary goal of HVTN 300 is to determine whether the CH505 TF chTrimer 
immunogen combined with a 3M-052-AF adjuvant can drive the expansion of B 
cell lineages similar to those known to be associated with broadly neutralizing 
antibodies induced during natural HIV-1 infection. To this end, HVTN 
immunogenicity assays will be used to evaluate induction of vaccine and epitope-
specific B cells and binding antibodies as well as serum neutralization. These data 
will also be used to identify and prioritize samples for in-depth immunogenicity 
analyses, including B cell receptor sequencing of epitope-specific B cells, 
epitope-mapping of neutralizing antibody responses, and characterization of 
isolated mAbs. Specifically, flow cytometry will be used to characterize the 
vaccine-specific B cells using fluorescently-labeled Env probes in both the 
periphery and the regional lymph node. Furthermore, by using different 
fluorescently-labeled Env probes with minimal mutations in epitopes of interest, 
CD4-binding site and epitope-specific lineages of B cells will be identified for 
downstream analysis. These rare epitope-specific populations of B cells will be 
enumerated, characterized by surface expression markers, and sorted for BCR 
sequencing. In addition, the sera from participants will be tested for neutralization 
not only against the autologous CH505TF pseudovirus, but also a panel of 
pseudoviruses with engineered mutations specifically designed to identify 
antibodies that are able to neutralize UCA-sensitive pseudoviruses in an epitope-
specific manner. The pace of the development of both B cell isolation techniques 
and the generation of specific pseudoviruses intended to identify specific antibody 
lineages is rapid. The 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/en/science.html.  
 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 32 of 127 
5 
Study design 
This is an open-label Phase 1 study to examine the safety and immunogenicity of 
the CH505 TF chTrimer vaccine with 3M-052-AF +/- Alum adjuvant in healthy 
adults. The primary hypothesis is that the CH505 TF chTrimer will expand 
CH103-like B-cell precursors. 
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: 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. 18-55 years old, inclusive, on day of enrollment. 
3. Available for clinic follow-up through the last clinic visit, willing to undergo 
lymph node fine needle aspiration and leukapheresis, and willing to be contacted 
12 months after the last vaccine administration. 
4. Agrees not to enroll in another study of an investigational agent during 
participation in the trial. 
5. In good general health according to the clinical judgement of the site investigator. 
6. Physical examination and laboratory results without clinically significant findings 
that would interfere with assessment of safety or reactogenicity in the clinical 
judgement of the site investigator. 
7. Assessed as low risk for HIV acquisition per low risk guidelines (see Appendix 
E), 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 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 33 of 127 
final study visit. Low risk may include persons stably taking PrEP as prescribed 
for 6 months or longer. 
8. Hemoglobin >12.5 mg/dL to 18 mg/dL 
9. White blood cell (WBC) count > 3,500/mm3 
10. Platelets ≥125,000 /mm3 
11. Alanine aminotransferase (ALT) < 2.5 x ULN based on the institutional normal 
range 
12. Serum creatinine ≤1.1 x ULN based on the institutional normal range 
13. Blood pressure in the range of 90 to < 160 mmHg systolic and 50 to < 100 mmHg 
diastolic. 
14. Negative results for HIV infection by an FDA-approved enzyme immunoassay 
(EIA) or chemiluminescent microparticle immunoassay (CMIA). 
15. Negative for anti-Hepatitis C antibodies (anti-HCV) or negative HCV nucleic acid 
test (NAT) if anti-HCV antibodies are detected. 
16. Negative for Hepatitis B surface antigen. 
17. For a volunteer capable of becoming pregnant: 
• Volunteers who were assigned female sex at birth and are of reproductive 
potential must agree to use effective means of birth control from at least 21 
days prior to enrollment through 8 weeks after their fifth vaccination 
timepoint (see Appendix G).  
• Has negative β-HCG (human chorionic gonadotropin) pregnancy test (urine or 
serum) on day of enrollment.  
5.1.2 
Exclusion criteria 
1. Volunteer who is breast-feeding or pregnant. 
2. Previous or current recipient of an investigational HIV vaccine (previous placebo 
recipients are not excluded). 
3. Systemic glucocorticoid use equal to or greater than prednisone 10 mg/day within 
3 months prior to enrollment, congenital or acquired immunodeficiency or other 
systemic medication use likely to impair immune response to vaccine in the 
opinion of the site investigator. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 34 of 127 
4. Blood products or immunoglobulin within 16 weeks prior to enrollment; receipt 
of immunoglobulin within 16 weeks prior to enrollment requires PSRT approval. 
5. Receipt of any live attenuated vaccine within 4 weeks prior to enrollment. 
6. Receipt of any vaccines that are not live attenuated within 14 days prior to 
enrollment; replication incompetent vaccines such as the Jynneos vaccine for the 
prevention of monkeypox disease are not considered to be live vaccines.  
7. ACAM2000 vaccine for Monkeypox received within 30 days prior to enrollment 
or receipt of study product, or if ACAM2000 received greater than 30 days prior 
to enrollment or receipt of study product, vaccination scab still present; or 
planned administration within 30 days after enrollment or receipt of study 
product. 
8. Initiation of antigen-based immunotherapy for allergies within the previous year 
(stable immunotherapy is not exclusionary); inclusion of participants who 
initiated immunotherapy within the previous year requires PSRT approval. 
9. Receipt of 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. 
10. Serious reactions to vaccines that preclude receipt of study injections as 
determined by the principal investigator or designee. History of serious reaction 
(eg. hypersensitivity, anaphylaxis) to any vaccine or any component of the study 
vaccine, including imidazoquinolone (eg, imiquimod). 
11. Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema. 
12. Idiopathic urticaria within the past year. 
13. Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or 
platelet disorder requiring special precautions). 
14. Seizure disorder; febrile seizures as a child or seizures secondary to alcohol 
withdrawal more than 5 years ago are not exclusionary.  
15. Asplenia or functional asplenia. 
16. Active duty and reserve US military personnel. 
17. 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, 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 35 of 127 
serious psychiatric disorders, or cancer that, in the clinical judgement of the site 
investigator, has a potential for recurrence (excluding basal cell carcinoma). 
18. Asthma is excluded if the participant has ANY of the following: 
1. Required either oral or parenteral corticosteroids for an exacerbation two 
or more times within the past year; OR 
2. 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 
3. 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 
4. 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]); 
5. 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. 
19. A participant with a history of an immune-mediated disease, either active or 
remote. Specific examples are listed in Appendix H (AESI index). Not 
exclusionary: 1) remote history of Bell’s palsy (>2 years ago) not associated with 
other neurologic symptoms, 2) mild psoriasis that does not require ongoing 
systemic treatment 
20. History of allergy to local anesthetic (Novocaine, Lidocaine). 
21. Investigator concern for difficulty with venous access based upon clinical history 
and physical examination. For example, history of IV drug abuse or substantial 
difficulty with previous blood draws. 
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: 
• Intercurrent illness or pre-vaccination abnormal vital signs or clinical 
symptoms that may mask assessment of vaccine reaction 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 36 of 127 
• Treatment with systemic glucocorticoids (eg, prednisone or other 
glucocorticoid), immune targeting monoclonal antibodies or other 
immunomodulators (other than nonsteroidal anti-inflammatory drugs 
[NSAIDs]), with the exception that study injection may continue per 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; (Note: ACAM2000 vaccine for Monkeypox received within 
30 days prior to enrollment or receipt of study vaccine; or if ACAM2000 
received greater than 30 days prior to enrollment or receipt of study vaccine 
and vaccination scab still present; or planned administration within 30 days 
after enrollment or receipt of study vaccine). 
• Receipt of any vaccines that are not live attenuated vaccines within 2 weeks 
prior to study vaccine administration. Replication incompetent vaccines such 
as the Jynneos vaccine for the prevention of monkeypox disease are not 
considered to be live vaccines. 
Vaccinations should not be administered outside the visit window period specified 
in Appendix C without PSRT approval.  
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 exception of fever 
and subjective local and systemic symptoms. For grade 3 injection site 
erythema and/or induration, upon review, the PSRT may allow continuation of 
vaccination (except with review by the PSRT) 
• 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 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 37 of 127 
Infectious Disease/Food Allergy and Anaphylaxis Network symposium 
criteria for anaphylaxis (25), is provided below:  
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 PEF, hypoxemia)  
b. Reduced 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): 
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. 
• Newly disclosed AESI (see Appendix H) 
• 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 300 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 for up to 12 months following their last study vaccine administration. At 
the discretion of the CRS clinician and the PSRT (for composition of PSRT see 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 38 of 127 
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 or until the final scheduled clinic visit, whichever comes 
first. 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.  
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 IND 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, CBC with differential, serum chemistry, 
physical examination, and if indicated, a pregnancy test (see Appendix A and 
Appendix B). 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.  

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 39 of 127 
6 
Statistical considerations 
6.1 
Sample size justification and accrual 
Recruitment will target enrolling a total of 48 healthy, HIV-uninfected adult 
participants in 4 groups. 
In Part A, recruitment will target enrolling 12 healthy, HIV-uninfected adult 
participants in Group 1. The protocol team will convene after the 12th participant 
has received their third vaccination to determine if further participants should be 
enrolled to evaluate immunogenicity. Examples of reasons that might necessitate 
enrollment of additional participants are provided in Section 1.5. If some 
participants from the original number of 12 enrolled will not contribute data to 
some of the immunogenicity analyses, the protocol team may enroll additional 
fully evaluable participants, up to 6 additional participants, or a total of 18 
participants enrolled, with the goal of at least 12 contributing to the final 
immunogenicity analyses. 
In Part B, recruitment will target enrolling a total of 36 healthy, HIV-uninfected 
adult participants in Groups 2, 3, and 4 (n = 12 participants per group). 
Enrollment in Groups 2, 3, and 4 will be stepwise by group, starting with Group 
2, continuing with Group 3, and finishing with Group 4.  
Every study participant will be followed for an AESI contact 12 months after the 
last vaccination received (for example, following participants until Month 16 if 
they receive 3 vaccinations, or Month 24 if they receive 5 vaccinations). 
Detail about the pace of enrollment can be found in Section 1.5. 
Since enrollment is concurrent with receiving the first vaccination, all participants 
will provide some safety data. However, for immunogenicity analyses, data may 
be missing for a variety of reasons, including participants terminating from the 
study early, problems in shipping specimens, or high assay background. 
Immunogenicity data from 17 Phase 1 and 2 Phase 2a HVTN vaccine trials, 
which began enrolling after June 2005 (data as of September 2014), indicate that 
17% is a reasonable estimate for the rate of missing data. 
6.1.1 
Power calculations for immunogenicity for Part A 
One primary goal of the statistical analysis for Part A is to assess whether the 
vaccine regimen evaluated in Group 1 elicits CD4 binding-site, V2 apex and V3 
glycan epitope (bnAb region at the base of the V3 loop), and CH505TF-specific 
memory B cells. The primary endpoint will be the frequencies of CD4 binding-
site, V2 apex and V3 glycan epitope (bnAb region at the base of the V3 loop), and 
CH505TF-specific IgG+ B cells at baseline and after vaccination, as measured by 
flow cytometry. Another primary goal is to evaluate the ability of the vaccine 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 40 of 127 
regimen to elicit autologous tier 2 virus neutralizing antibodies, as measured using 
the TZM-bl assay.  
The statistical analysis will first compare the frequencies of CD4 binding-site, V2 
apex and V3 glycan epitope, and CH505TF-specific IgG+ B cells at baseline with 
those observed after vaccination. These comparisons will use Wilcoxon signed-
rank tests. Should the vaccine regimen elicit a desired immune response, we 
expect the frequencies of CD4 binding-site or V2 apex or V3 glycan epitope or 
CH505TF-specific IgG+ B cells to increase after vaccinations, and the tests will 
be one-sided. An additional analysis will compare the frequencies of CD4 
binding-site, V2 apex and V3 glycan epitope, and CH505TF-specific IgG+ B cells 
at different time points after vaccination using two-sided Wilcoxon signed-rank 
tests. 
The statistical analysis will also perform response positivity calls for each study 
participant by comparing B cells frequencies at baseline to B cells frequencies 
post-vaccination using Fisher’s exact tests. The statistical analysis will next assess 
whether the frequencies of CD4 binding-site, V2 apex and V3 glycan epitope, and 
CH505TF-specific IgG+ B cells differ between time points post-vaccination. 
These comparisons will be performed using two-sided Fisher’s exact tests.  
We will next estimate the response rate at each post-vaccination time point by the 
empirical proportion of positive calls among study participants and build an 
associated 95% confidence interval.  
We computed the power of a one-sided Wilcoxon signed-rank to detect a 
significant difference between the frequencies of CD4 binding-site, or V2 apex or 
V3 glycan epitope (bnAb site at the base of the V3 loop), or CH505TF-specific 
IgG+ B cells observed at baseline with that observed at one time point post-
vaccination. The power was evaluated as a function of (1) the effect size, defined 
here as the average change (increase) in the frequencies of (eg) CD4 binding-site 
or V3 glycan (base of the V3 loop) binding-IgG+ B cells after vaccination relative 
to baseline, and (2) the standard deviation (SD) of the difference between pre- and 
post-vaccination frequencies. The calculations made the following assumptions: 
• The average increase in the frequency of CD4 binding-site IgG+ B cells post-
vaccination relative to baseline in study participants ranges between 0 and 5%.  
 
• The standard deviation of the frequency of CD4 binding-site IgG+ B cells 
post-vaccination relative to baseline in study participants ranges between 
0.5% and 4%.  
 
• The increase in the frequency of CD4 binding-site IgG+ B cells after 
vaccination relative to baseline is normally distributed. Departure from this 
assumption is not expected to impact the power of the study because the 
Wilcoxon signed-rank test is nonparametric.  

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 41 of 127 
The calculations considered samples of size n = 12 and n = 10 to assess power 
when the data set is complete (n = 12) and when 2 out of the 12 participants (or, 
equivalently, an attrition rate of approximately 17%; n = 10) are lost to follow up 
before the post-vaccination time point.  
The power function of the test under these different scenarios is presented in 
Figure 6-1. For example, if the standard deviation of the change in the frequency 
of binding IgG+ B cells is SD = 2%, the calculation indicates that a sample of size 
n = 10 achieves almost 80% power to detect a significant increase at the 5% 
significance level if the average increase in the proportion of binding IgG+ B cells 
is 1.5%. With a sample of size n = 12 (no loss to follow-up), the test has more 
than 80% power to detect a significant difference under the same scenario.  
 
Figure 6-1 Power of a one-sided Wilcoxon signed-rank test comparing the frequency of CD4 
binding-site or V2 apex or V3 glycan epitope (bnAb site at the base of the V3 loop) CH505TF-
specific IgG+ B cells post-vaccination relative to baseline. The power was calculated as a 
function of (1) the effect size, defined as the average difference between the frequencies of 
B cells pre- and post-vaccination; (2) the standard deviation (SD) of the difference between 
the pre- and post-vaccination B cell frequencies; and (3) the sample size (n = 10 and n = 12).  
6.1.2 
Power calculations for immunogenicity for Part B 
The goal of Part B is to evaluate whether the three vaccine regimens tested in 
Groups 2, 3, and 4 elicit CD4 binding-site, V2 apex and V3 glycan epitope (bnAb 
region at the base of the V3 loop), and CH505TF-specific memory B cells. The 
primary endpoint will be the frequencies of CD4 binding-site, V2 apex and V3 
glycan epitope (bnAb region at the base of the V3 loop), and CH505TF-specific 
IgG+ B cells at baseline and after vaccination, as measured by flow cytometry. 
Part B will also evaluate whether the vaccine regimens elicit autologous tier 2 
virus neutralizing antibodies using the TZM-bl assay.  
The statistical analysis will first compare the frequencies of CD4 binding-site, V2 
apex and V3 glycan epitope, and CH505TF-specific IgG+ B cells at baseline with 
those observed after vaccination. These comparisons may be performed within 
each treatment group (ie, Group 2, 3, and 4) using Wilcoxon signed-rank tests. 
Should the vaccine regimens elicit a desired immune response, we expect the 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 42 of 127 
frequencies of CD4 binding-site or V2 apex or V3 glycan epitope or CH505TF-
specific IgG+ B cells to increase after vaccinations, and the tests will be one-
sided. Additional analyses will compare the frequencies of CD4 binding-site, V2 
apex and V3 glycan epitope, and CH505TF-specific IgG+ B cells at other time 
points following vaccination; these tests will be two-sided because the direction 
of the effect may not be known. 
The statistical analysis will also perform response positivity calls for each study 
participant by comparing B cells frequencies at baseline to B cells frequencies 
post-vaccination using Fisher’s exact tests. The statistical analysis will next assess 
whether the frequencies of CD4 binding-site, V2 apex and V3 glycan epitope, and 
CH505TF-specific IgG+ B cells differ between time points post-vaccination. 
These comparisons will be performed using two-sided Fisher’s exact tests. We 
will next estimate the response rate at each post-vaccination time point within 
each group by the empirical proportion of positive calls among study participants. 
Associated 95% confidence intervals will also be built.  
We evaluated the power of a one-sided Wilcoxon signed-rank to detect a 
significant difference between the frequencies of CD4 binding-site, or V2 apex or 
V3 glycan epitope (bnAb site at the base of the V3 loop), or CH505TF-specific 
IgG+ B cells observed at baseline with that observed at one time point post-
vaccination in one of the treatment group (ie, either Group 2, 3, or 4; see Section 
6.1.1) and when two groups are combined (eg, Groups 2 and 4; see results below). 
The power was evaluated as a function of (1) the effect size, defined here as the 
average change (increase) in the frequencies of (eg) CD4 binding-site or V3 
glycan (base of the V3 loop) binding-IgG+ B cells after vaccination relative to 
baseline, and (2) the standard deviation (SD) of the difference between pre- and 
post-vaccination frequencies. The calculations made the following assumptions: 
• The average increase in the frequency of CD4 binding-site IgG+ B cells post-
vaccination relative to baseline in study participants ranges between 0 and 5%.  
• The standard deviation of the frequency of CD4 binding-site IgG+ B cells 
post-vaccination relative to baseline in study participants ranges between 
0.5% and 4%.  
• The increase in the frequency of CD4 binding-site IgG+ B cells after 
vaccination relative to baseline is normally distributed. Departure from this 
assumption is not expected to impact the power of the study because the 
Wilcoxon signed-rank test is nonparametric.  
The calculations considered samples of size n = 12 and n = 10 to assess power 
when the data set is complete (n = 12) and when 2 out of the 12 participants (or, 
equivalently, an attrition rate of approximately 17%; n = 10) are lost to follow up 
before the post-vaccination time point. The power function of the test under these 
different scenarios when carried with each group separately (i.e., within either 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 43 of 127 
Group 2, or 3, or 4) is discussed in Section 6.1.1 in the context of Group 1 (Part 
A); see also Figure 6-1. 
The statistical power of statistical tests for the comparison of immunogenicity 
data measured at two time points within participants could be increased by 
combining relevant treatment groups together. For example, we could combine 
Groups 2 and 4 together to assess whether vaccination with 3M-052-AF induced 
any immune responses, regardless of dose. The power of the Wilcoxon signed-
rank test for sample sizes of n = 20 (eg, Groups 2 and 4 combined when 4 out of 
the 24 participants (or, equivalently, an attrition rate of approximately 17% per 
group) are lost to follow up) and n = 24 (eg, Groups 2 and 4 combined when no 
participant is lost to follow-up) are presented in Figure 6-2. 
 
 
Figure 6-2 Power of a one-sided Wilcoxon signed-rank test comparing the frequency of CD4 
binding-site or V2 apex or V3 glycan epitope (bnAb site at the base of the V3 loop) CH505TF-
specific IgG+ B cells post-vaccination relative to baseline. The power was calculated as a 
function of (1) the effect size, defined as the average difference between the frequencies of 
B cells pre- and post-vaccination; (2) the standard deviation (SD) of the difference between 
the pre- and post-vaccination B cell frequencies; and (3) the sample size in the combined 
two groups (n = 20 and n = 24). 
The statistical analysis of immunogenicity data measured in Part B will also 
include the following group comparisons; some of these comparisons may include 
data from Group 1 (Part A): 
 
o Group 2 versus Group 3 post baseline to assess the effect of Alum (at a 
dose of 500 mcg) on immune responses in participants vaccinated with 
3M-052-AF at a dose of 3 mg/kg. 
o Group 1 versus Group 4 post baseline to assess the effect of Alum (at a 
dose of 500 mcg) on immune responses in participants vaccinated with 
3M-052-AF at a dose of 5 mg/kg. 
o Group 1 versus Group 3 post baseline to assess whether vaccination with a 
dose of 3 mcg versus 5 mcg of 3M-052-AF induces different immune 
responses in participants vaccinated with Alum (at a dose of 500 mcg). 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 44 of 127 
o Group 2 versus Group 4 post baseline to assess whether vaccination with a 
dose of 3 mcg versus 5 mcg of 3M-052-AF induces different immune 
responses in participants who were not vaccinated with Alum. 
The effect of vaccination with Alum as well as that of the dose of 3M-052-AF on 
immune responses may be performed using nonparametric one-way analysis of 
variance (ANOVA) (eg, Wilcoxon rank sum tests). To increase the power of 
statistical tests, these comparisons may be carried out by combining all four 
groups together and using nonparametric two-way ANOVA (eg, Friedman-type or 
Skillings-Mack tests) that include vaccination with Alum and vaccination with 
3M-052-AF as factors. 
Since participants will not be randomized between Groups 1, 2, 3, and 4 at 
enrollment, comparisons of immunogenicity endpoints between treatment groups 
will be cautiously interpreted. Differences in baseline characteristics may be 
examined to determine whether differences between groups could have been 
induced by (eg) differences in the demographics of study participants between 
treatment groups.  
6.1.3 
Power calculations for safety for Part A 
The goal of the safety evaluation for Part A is to identify safety concerns 
associated with vaccine administration in Group 1. The ability of the study to 
detect serious adverse events (SAEs) (see Section 9.2) 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 this 
single-arm study (n = 12), there is at least a 90% chance of observing at least 1 
event if the true rate of such an event is 17.5% or more; and there is at least a 90% 
chance of observing no events if the true rate is 0.87% or less. Safety data will be 
evaluated using historical controls. As a reference, in HVTN vaccine trials 
conducted in the US from April 2008 through March 2018, about 1% of 
participants who received placebos experienced an SAE.  
Binomial probabilities of observing 0, 1 or more, and 2 or more events among 12 
participants receiving study vaccine are presented in Table 6-1 for a range of 
possible true adverse event rates. These calculations provide a more complete 
picture of the sensitivity of this study design to identify potential safety problems 
with the vaccine. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 45 of 127 
Table 6-1 Probability of observing 0 events, 1 or more events, and 2 or more events, among 
a group of 12 study participants for different true event rates 
True event rate (%) 
arm size 
0 events 
1+ events 
2+ events 
1 
12 
0.89 
0.11 
0.01 
4 
12 
0.61 
0.39 
0.08 
10 
12 
0.28 
0.72 
0.34 
20 
12 
0.07 
0.93 
0.73 
30 
12 
0.01 
0.99 
0.91 
An alternative way of describing the statistical properties of the study design is in 
terms of the 95% confidence interval for the true rate of an adverse event based 
on the observed data. Table 6-2 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 for CI described in Agresti and Coull formula 2 
(26). If none of the 12 participants receiving the study vaccine experience a safety 
event, the 95% 2-sided upper confidence bound for the true rate of such events in 
the total vaccinated population is 24.2%. 
Table 6-2 Two-sided 95% confidence intervals for the probability of observing a safety event 
based on observing a particular rate of safety endpoints in a group of 12 study participants 
 
Observed event rate 
95% Confidence interval (%) 
0/12 
[0 ; 24.2] 
1/12 
[1.5 ; 35.4] 
2/12 
[4.7 ; 44.8] 
6.1.4 
Power calculations for safety for Part B 
The goal of the safety evaluation for Part B is to identify safety concerns 
associated with vaccine administration in Groups 2, 3, and 4. The ability of the 
study to detect serious adverse events (SAEs) 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 group in 
Part B (n = 12), there is at least a 90% chance of observing at least 1 event if the 
true rate of such an event is 17.5% or more; and there is at least a 90% chance of 
observing no events if the true rate is 0.87% or less. For two vaccine groups of 
Part B combined (eg, Groups 2 and 3; n = 24), there is a 90% chance of observing 
at least 1 event if the true rate of such an event is 9.2% or more; and there is a 
90% chance of observing no events if the true rate is 0.43% or less. For all three 
vaccine groups of Part B combined (n = 36), there is a 90% chance of observing 
at least 1 event if the true rate of such an event is 6.2% or more; and there is a 
90% chance of observing no events if the true rate is 0.29% or less. For the four 
vaccine groups of Parts A and B combined (n = 48), there is a 90% chance of 
observing at least 1 event if the true rate of such an event is 4.7% or more; and 
there is a 90% chance of observing no events if the true rate is 0.21% or less. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 46 of 127 
Binomial probabilities of observing 0, 1 or more, and 2 or more events among the 
12 participants of each group (Groups 2, 3, or 4) are presented in Table 6-1 for a 
range of possible true adverse event rates. Binomial probabilities of observing 0, 1 
or more, and 2 or more events among the 36 participants of Groups 2, 3, and 4 
combined are presented in Table 6-3 for a range of possible true adverse event 
rates. These calculations provide a more complete picture of the sensitivity of this 
study design to identify potential safety problems with the vaccine. 
Table 6-3 Probability of observing 0 events, 1 or more events, and 2 or more events, among 
groups of 12, 24, 36, and 48 study participants for different true event rates 
True event rate (%) 
group size 
0 events 
1+ events 
2+ events 
1 
12 
0.89 
0.11 
0.01 
4 
12 
0.61 
0.39 
0.08 
10 
12 
0.28 
0.72 
0.34 
20 
12 
0.07 
0.93 
0.73 
30 
12 
0.01 
0.99 
0.91 
1 
24 
0.79 
0.21 
0.02 
4 
24 
0.38 
0.62 
0.25 
10 
24 
0.08 
0.92 
0.71 
20 
24 
0.005 
1.00 
0.97 
30 
24 
0.000 
1.00 
1.00 
1 
36 
0.70 
0.30 
0.05 
4 
36 
0.23 
0.77 
0.43 
10 
36 
0.02 
0.98 
0.89 
20 
36 
0.00 
1.00 
1.00 
30 
36 
0.00 
1.00 
1.00 
1 
48 
0.62 
0.38 
0.08 
4 
48 
0.14 
0.86 
0.58 
10 
48 
0.01 
0.99 
0.96 
20 
48 
0.00 
1.00 
1.00 
30 
48 
0.00 
1.00 
1.00 
An alternative way of describing the statistical properties of the study design is in 
terms of the 95% confidence interval for the true rate of an adverse event based 
on the observed data. Table 6-4 shows the 2-sided 95% confidence intervals for 
the probability of an event based on a particular observed rate in one group (eg, 
Group 2, or 3, or 4; n = 12), or 2 groups (eg, Groups 2 and 3; n = 24), or 3 groups 
(Groups 2, 3, and 4; n = 36), or 4 groups (Groups 1through 4; n = 48). 
Calculations are done using the score test method for CI described in Agresti and 
Coull formula 2 (26). If none of the 48 participants receiving any the study 
vaccines experience a safety event, the 95% 2-sided upper confidence bound for 
the true rate of such events in the total vaccinated population is 7.4%. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 47 of 127 
Table 6-4 Two-sided 95% confidence intervals for the probability of observing a safety event 
based on observing a particular rate of safety endpoints in n = 12, or n = 24, or n = 36, or n = 
48 study participants 
Observed event rate 
95% Confidence interval (%) 
0/12 
[0.0 ; 24.2] 
1/12 
[1.5 ; 35.4] 
2/12 
[4.7 ; 44.8] 
0/24 
[0.0 ; 13.8] 
1/24 
[0.7 ; 20.2] 
2/24 
[2.3 ; 25.8] 
0/36 
[0.0 ; 9.6] 
1/36 
[0.5 ; 14.2] 
2/36 
[1.5 ; 18.1] 
0/48 
[0.0 ; 7.4] 
1/48 
[0.4 ; 10.9] 
2/48 
[1.2 ; 14.0] 
6.2 
Statistical analyses 
This section describes the final study analysis, unblinded as to treatment arm 
assignment. All data from enrolled participants will be analyzed regardless of how 
many vaccinations they received. All analyses will be performed using SAS and 
R. 
No formal multiple-comparison adjustments will be employed for multiple safety 
endpoints, multiple primary immunogenicity endpoints, or secondary endpoints. 
Statistical tests for comparisons of primary and secondary endpoints, including 
two- and one-sided tests, will use a significance level (alpha) of 5%. 
6.2.1 
Baseline demographics 
Participants’ baseline characteristics will be summarized using descriptive 
statistics.  
6.2.2 
Immunogenicity analyses 
The frequencies of CD4 binding-site, V2 apex and V3 glycan epitope (bnAb 
region at the base of the V3 loop), and CH505TF-specific IgG+ B cells elicited by 
the vaccine measured by flow cytometry, the response rate and magnitude of 
binding measured by the BAMA assay, and the area-under-the-magnitude-breadth 
curve (AUC) (27) to panels of viral isolates measured by the HIV-1 neutralization 
TZM-bl assay, will be summarized using descriptive statistics. Data will be 
tabulated and graphically displayed by visit number and by number of doses 
received. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 48 of 127 
Discrete categorical assay endpoints (eg, response rates) will be analyzed by 
tabulating the frequency of positive response. Crude response rates will be 
presented with their corresponding 95% confidence interval estimated based on 
the score test method (26). The Barnard’s exact tests may be employed to 
compare the response rates of certain immune responses between the test vaccine 
and other candidates in the CH505 family.  
Quantitative assay endpoints (eg, frequencies of memory B-cells) will be 
summarized by time point. Nonparametric paired comparisons will be performed 
using Wilcoxon signed-rank tests, and the Wilcoxon rank sum test will be used to 
compare independent samples. More details of the analyses of each assay will be 
provided in the statistical analyses plan (SAP). 
6.2.3 
Safety Analyses 
Reactogenicity: The number and percentage of subjects experiencing each type 
of reactogenicity sign or symptom will be tabulated by severity. For a given sign 
or symptom, each subject’s reactogenicity will be counted once under the 
maximum severity for all assessments. 
Adverse Events: AEs will be coded into Medical Dictionary for Regulatory 
Activities (MedDRA) preferred terms. The number and percentage of subjects 
experiencing each specific AE will be tabulated by severity and relationship to 
study vaccine. For the calculations in these tables, each subject’s AE will be 
counted once under the maximum severity or strongest recorded causal 
relationship to treatment. A complete listing of AEs for each subject will provide 
details including severity, relationship to treatment, onset, duration and outcome.  

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 49 of 127 
7 
Study vaccine preparation, storage, and 
administration 
7.1 
Vaccine Regimen 
The schedule of vaccination is shown in Section 1 and additional information is 
given below. 
Part A: 
Group 1  
Treatment 1 (T1)- (300mcg) CH505TF chTrimer admixed with (5mcg) 3M-052-
AF + (500 mcg) Aluminum Hydroxide Suspension (Alum), to be administered as 
two 0.5 mL doses intramuscularly (IM) at months 0, 2, 4, 8 and 12. 
Part B: 
Group 2  
Treatment 2 (T2) - 300 mcg CH505TF chTrimer admixed with (3mcg) 3M-052-
AF to be administered as two 0.5 mL doses intramuscularly (IM) at months 0, 2, 
4, 8, and 12. 
 
Group 3 
Treatment 3 (T3) – 300 mcg CH505TF chTrimer admixed with (3mcg) 3M-052-
AF + (500 mcg) Aluminum Hydroxide Suspension (Alum) to be administered as 
two 0.5 mL doses intramuscularly (IM) at months 0, 2, 4, 8, and 12. 
 
Group 4 
Treatment 4 (T4) - 300mcg CH505TF chTrimer admixed with (5mcg) 3M-052-
AF to be administered as two 0.5 mL doses intramuscularly (IM) at months 0, 2, 
4, 8, and 12. 
7.2 
Study Product Formulation and Storage 
7.2.1 
CH505 TF chTrimer 
CH505 TF chTrimer drug product is formulated in 20 mM Tris, 100mM NaCl, 
pH 7.5. The visual appearance of the formulated product is clear to slightly 
opalescent, colorless to slightly yellow, and essentially free from visible particles. 
The drug product is supplied as a frozen liquid in 2 mL Type 1 glass vials. Each 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 50 of 127 
vial contains 0.75 mL of formulated CH505 TF chTrimer at a concentration of 0.8 
mg/mL and is stored at ≤ -65°C. 
7.2.2 
3M-052-AF (Labeled as AP 60-702) 
3M-052-AF will be provided in 2 mL Type 1 glass vials with a rubber stopper and 
flip-off aluminum seal. Each vial contains a fill volume of 0.4 mL at a 
concentration of 50 mcg/mL. 3M-052-AF is a clear to slightly hazy, colorless 
liquid. The product is stored at 2-8° C. Do not freeze.  
7.2.3 
Aluminum Hydroxide Suspension (Alhydrogel®) 
The Aluminum Hydroxide Suspension (Alum) will be provided in 3 mL Type 1 
glass vials. Each vial contains 0.7 mL fill volume at a concentration of 5 mg/mL 
aluminum. Alum appears as an opaque, white gelatinous precipitate in aqueous 
suspension. The product is stored refrigerated at 2-8° C. Do not freeze.  
7.2.4 
Tris-NaCl buffer (TBS) (Diluent) for Part A 
The Tris-NaCl buffer will be used as a diluent for mixing with adjuvants. The 
sterile buffer will be provided in 2 mL Type 1 glass vials. Each vial contains a fill 
volume of 1.1 ± 0.1 mL. Tris-NaCl buffer is a clear to opalescent, colorless to 
slightly yellow liquid, without any visible particulates. The product is stored at 2-
8° C. 
7.2.5 
Sodium Chloride for injection, 0.9% USP (Diluent) for Part B 
Sodium Chloride for injection, 0.9% USP must be stored as recommended by the 
manufacturer. 
7.3 
Product Preparation 
Pharmacists must follow appropriate aseptic technique and sterile preparation 
procedures/guidance as outlined in USP <797> [medium risk], utilizing a 
pharmacy biosafety cabinet/isolator or better. Local regulations and site 
institutional policies and procedures for use of personal protective equipment, 
such as gloves, gowns, masks, and safety glasses, must be followed. Pharmacists 
should follow the requirements of their country, their institution, and their 
pharmacy regulatory authority regarding these procedures.  
Any unused portion of study product will not be used for another participant. 
Empty vials, unused portion of entered vials, or unused prepared study product 
should be discarded in a biohazard container and disposed of in accordance with 
institutional or pharmacy policy. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 51 of 127 
7.3.1 
Group 1: CH505 TF chTrimer 300 mcg admixed with (5 mcg) 3M-052-AF + 
(500 mcg) Aluminum Hydroxide Suspension (Alum) 
For all preparation steps, use a 1 mL Luer-Lok syringe with 0.01 mL graduations 
and a 22-27 gauge Luer-Lok needle. 
▪ 
Remove one vial of 3M-052-AF, one vial of TBS, and one vial of 
Alum from the refrigerator. Resuspend Alum by inverting the vial 
for 30-60 seconds.  
▪ 
Remove one vial of CH505 TF chTrimer from the freezer and 
allow to thaw at room temperature. Resuspend the protein by 
inverting the vial for 30-60 seconds. 
Preparation of Adjuvants:  
▪ 
Withdraw 0.4 mL of Alum and inject into the 3M-052-AF vial. 
Mix by gently swirling and inverting the vial about 5 times. Do 
not shake vigorously. Allow formulation to incubate at room 
temperature for 30 minutes.  
Preparation of CH505 TF chTrimer: 
▪ 
Withdraw 0.64 mL TBS and inject into the empty sterile vial 
(mixing vial).  
▪ 
Withdraw 0.56 mL of CH505 TF chTrimer and inject into mixing 
vial. Mix by gently swirling and inverting the vial about 5 times. 
Do not shake vigorously. 
▪ 
Withdraw 0.3 mL of the adjuvant mixture and inject into the 
mixing vial. 
▪ 
Mix by gently inverting the vial about 5 times. Do not shake 
vigorously. 
▪ 
Withdraw 0.5 mL of the mixed preparation into two separate 
syringes, for study participant administration. Prior to 
administration, gently invert the syringe to resuspend admixed 
product. 
▪ 
The admixed product is stable for 8 hours at room temperature. 
7.3.2 
Group 2: CH505 TF chTrimer 300 mcg admixed with (3 mcg) 3M-052-
AF 
For all preparation steps, use a 1 mL Luer-Lok syringe with 0.01 mL graduations 
and a 22–27-gauge Luer-Lok needle. 
▪ Remove one vial of 3M-052-AF and an adequate volume of Sodium 
Chloride for injection, 0.9% USP (Diluent)  
▪ Remove one vial of CH505 TF chTrimer from the freezer and allow 
to thaw at room temperature. Resuspend the protein by inverting the 
vial for 30-60 seconds. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 52 of 127 
Preparation of Adjuvants 
▪ Withdraw 0.4 mL of of Sodium Chloride and inject into the vial with 
3M-052-AF. 
▪ Mix by gently swirling and inverting the vial about 5 times. Do not 
shake vigorously. Allow formulation to incubate at room 
temperature for 30 minutes. 
 
Preparation of CH505 TF chTrimer: 
▪ Withdraw 0.76 mL of Sodium Chloride and inject into the empty 
sterile vial (mixing vial).  
▪ Withdraw 0.56 mL of CH505 TF chTrimer and inject into mixing 
vial. Mix by gently swirling and inverting the vial about 5 times. Do 
not shake vigorously. 
▪ Withdraw 0.18 mL of the 3M-052-AF admixture and inject into the 
mixing vial. 
▪ Mix by gently inverting the vial about 5 times. Do not shake 
vigorously. 
▪ Withdraw 0.5 mL of the mixed preparation into two separate 
syringes, for study participant administration. Prior to 
administration, gently invert the syringe to resuspend admixed 
product. 
▪ The admixed product is stable for 8 hours at room temperature. 
7.3.3 
Group 3: CH505 cTrimer 300 mcg admixed with (3 mcg) 3M-052-AF + 
(500 mcg) Aluminum Hydroxide Suspension (Alum) 
For all preparation steps, use a 1 mL Luer-Lok syringe with 0.01 mL graduations 
and a 22–27-gauge Luer-Lok needle. 
▪ Remove one vial of 3M-052-AF, an adequate volume of Sodium 
Chloride , and one vial of Alum from the refrigerator. Resuspend 
Alum by inverting the vial for 30-60 seconds. 
▪ Remove one vial of CH505 TF chTrimer from the freezer and allow 
to thaw at room temperature. Resuspend the protein by inverting the 
vial for 30-60 seconds. 
 
Preparation of Adjuvants: 
▪ Withdraw 0.16 mL of 3M-052-AF and inject into the empty sterile 
vial. 
▪ Withdraw 0.16 mL of of Sodium Chloride and inject into vial with 
3M-052-AF. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 53 of 127 
▪ Withdraw 0.4 mL of Alum and inject into the 3M-052-AF vial. Mix 
by gently swirling and inverting the vial about 5 times. Do not shake 
vigorously. Allow formulation to incubate at room temperature for 
30 minutes. 
 
Preparation of CH505 TF chTrimer: 
▪ Withdraw 0.64 mL of Sodium Chloride and inject into the empty 
sterile vial (mixing vial).  
▪ Withdraw 0.56 mL of CH505 TF chTrimer and inject into mixing 
vial. Mix by gently swirling and inverting the vial about 5 times. Do 
not shake vigorously. 
▪ Withdraw 0.3 mL 3M-052-AF admixture and inject into the mixing 
vial. 
▪ Mix by gently inverting the vial about 5 times. Do not shake 
vigorously. 
▪ Withdraw 0.5 mL of the mixed preparation into two separate 
syringes, for study participant administration. Prior to 
administration, gently invert the syringe to resuspend admixed 
product.  
▪ The admixed product is stable for 8 hours at room temperature. 
7.3.4 
Group 4: CH505 chTrimer 300 mcg admixed with (5 mcg) 3M-052-AF 
For all preparation steps, use a 1 mL Luer-Lok syringe with 0.01 mL graduations 
and a 22–27-gauge Luer-Lok needle. 
▪ Remove one vial of 3M-052-AF and an adequate volume of Sodium 
Chloride 
▪ Remove one vial of CH505 TF chTrimer from the freezer and allow 
to thaw at room temperature. Resuspend the protein by inverting the 
vial for 30-60 seconds. 
 
Preparation of Adjuvants: 
▪ Withdraw 0.4 mL of Sodium Chloride and inject into the 3M-052-
AF vial. 
▪ Mix by gently swirling and inverting the vial about 5 times. Do not 
shake vigorously. Allow formulation to incubate at room 
temperature for 30 minutes. 
 
Preparation of CH505 TF chTrimer: 
▪ Withdraw 0.64 mL of Sodium Chloride and inject into the empty 
sterile vial (mixing vial).  

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 54 of 127 
▪ Withdraw 0.56 mL of CH505 TF chTrimer and inject into mixing 
vial. Mix by gently swirling and inverting the vial about 5 times. Do 
not shake vigorously. 
▪ Withdraw 0.3 mL of the 3M-052-AF admixture and inject into the 
mixing vial. 
▪ Mix by gently inverting the vial about 5 times. Do not shake 
vigorously.  
▪ Withdraw 0.5 mL of the mixed preparation into two separate 
syringes, for study participant administration. Prior to 
administration, gently invert the syringe to resuspend admixed 
product. 
▪ The admixed product is stable for 8 hours at room temperature. 
7.3.5 
Labeling  
Label the study product as follows: 
• Participant identifier(s)  
• CH505 TF chTrimer + Adjuvant(s)  
• Final volume (mL)  
• Route (IM)  
• Beyond use date and time  
• “Syringe 1 of 2” and “Syringe 2 of 2” 
• Any additional information required by jurisdiction  
7.4 
Study Vaccine Administration 
Study product will be administered as two separate 0.5 mL injections 
intramuscularly into both deltoid muscles (both left and right) by needle and 
syringe. 
If an injection needs to be administered in an alternate body site (eg, lateral thigh) 
due to a medical contraindication, it should not be administered in the same 
deltoid as the other injection. If no injection can be administered in either deltoid 
muscle, the injections should be administered in separate alternate body sites. The 
appropriate study staff should document this clearly. Under this circumstance, this 
is NOT a protocol violation. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 55 of 127 
When preparing a dose in a syringe and administering the dose, consideration 
should be given to the volume of solution in the needle before and after the dose 
is administered. Particularly if the needle used to withdraw the product is replaced 
prior to vaccine administration, consideration should be given to conserving the 
full dose of product. The pharmacy and clinic staff members are encouraged to 
work together to administer the dose specified in the protocol. 
7.5 
Acquisition of study products 
CH505 TF chTrimer was CGMP manufactured by Vetter Development Services 
in Skokie, IL and will be provided by Duke University (Durham, NC, USA). 
The 3M-052-AF adjuvant was CGMP manufactured and will be provided by 
AAHI (Seattle, WA, USA).  
Alum (labeled as Aluminum Hydroxide Suspension) was manufactured by Leidos 
Biomed (Vaccine Research Center, Frederick, MD, USA) and will be provided by 
DAIDS, NIAID, NIH (Rockville, MD, USA). 
Tris-NaCl buffer (TBS) was manufactured by Ajinomoto Althea, Inc (San Diego, 
CA, USA) and will be provided by the International AIDS Vaccine Initiative 
(IAVI, New York, NY, USA). 
Sodium Chloride (NaCl) will be locally sourced by the CRSs. 
Once an HVTN CRS is protocol registered, the pharmacist can obtain study 
products from the NIAID Clinical Research Products Management Center 
(CRPMC) by following the ordering procedures given in Pharmacy Guidelines 
and Instructions for DAIDS Clinical Trials Networks. 
7.6 
Study Vaccine Accountability 
The HVTN CRS pharmacist is required to maintain complete records of all study 
products.  
7.7 
Final Disposition of study product 
For US clinical research sites, all unused study products must be returned to the 
CRPMC after the study is completed or terminated unless otherwise instructed by 
the study sponsor. For non-US clinical research sites, all unused study products 
must be destroyed after the study is completed or terminated unless otherwise 
instructed by the study sponsor. The procedures are included in the Pharmacy 
Guidelines and Instructions for DAIDS Clinical Trials Networks. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 56 of 127 
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 and 
Appendix B) 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.  
Leukapheresis specimens for baseline comparison will be drawn during the 
screening period if participant meets all additional eligibility criteria and wishes 
to join the study (Section 5.1.1 and 8.5). 
An Assessment of Understanding (AoU) will be completed prior to enrollment. 
Records will be kept documenting the reason that screened participants did not 
enroll. 
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 C), procedures for a study visit 
can be completed over multiple days. 
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. 
Guidance for participants scheduling licensed vaccines or allergy 
immunotherapy: In order to prevent interference with reactogenicity assessment, 
participants who plan to receive licensed vaccines or allergy immunotherapy 
should be counseled to avoid scheduling receipt of these substances, when 
possible, within the 2-week interval after study-product administration. To avoid 
unnecessary delays in study-product administration, participants should be 
counseled to avoid scheduling receipt of these substances before study-product 
administration (see Section 5.2.1). 
 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 57 of 127 
Post-Vaccine Administration Follow-Up in Clinic: Following each vaccine 
administration, participants will be observed for a minimum of 60 minutes post-
injection, vital signs will be recorded, the injection site will be inspected for 
evidence of local reaction, and any evidence of systemic symptoms will be 
assessed.  
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 and erythema. Participant diaries will be reviewed by a clinician and 
reconciled for accuracy and completeness. No attribution assessment will be 
performed for systemic reactogenicity events reported in the participant diary 
without additional evaluation of the participant by clinician. 
Participants will be given a thermometer for oral temperature measurement, a 
ruler, and provided access to the electronic diary. The participant will use the 
diary to record daily their highest temperature as well as local and systemic signs 
and symptoms for 7 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 at least once on the third- or fourth-day following vaccination. The 
reactogenicity assessment period is seven days following vaccine administration. 
Clinicians will follow and collect resolution information for any reactogenicity 
signs and symptoms that have not resolved within 7 days. 
Any postvaccination 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. 
8.4 
Lymph node FNA 
Tissue sampling of an axillary lymph node will be carried out percutaneously by 
fine needle aspiration (FNA). This procedure will be performed in accordance 
with the standard practices of the participating provider and/or facility. The 
procedure involves tissue retrieval with a needle via a small skin incision under 
sonographic guidance. Approximately 2-4 passes will be made to retrieve 
cytologic material. 
Post-procedural safety assessments will be performed in accordance with the 
standard practices of the participating provider and/or facility. The participant will 
be advised to contact the study site if they experience severe pain, fever (post-

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 58 of 127 
procedural body temperature ≥ 38.0°C or 100.4°F) or other evidence of infection 
(inflammation and/or pus) at the aspiration site, or arm numbness or weakness. 
Eligibility for lymph node FNA: 
• Participant may not be taking warfarin, oral antithrombin equivalents 
(including, but not limited to, apixiban, rivaroxiban, dabigatran), 
enoxaparin injections, or other medications that would increase the risk of 
bleeding as assessed by the clinician performing the procedure. 
• No evidence of localized infection directly superior to aspiration site 
• No other contraindication to procedure as assessed by the clinician 
performing the procedure 
• Participants who can become pregnant must have a negative pregnancy 
test within 48 hours prior to the procedure. 
8.5 
Leukapheresis 
Collection of PBMC via leukapheresis will be performed in accordance with the 
standard practices of the participating apheresis center. Typically, in this 
procedure, approximately 6 liters of blood will be processed over about 1.5 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 adverse 
events following the procedure. 
Eligibility for leukapheresis: 
• Prior to leukapheresis, participant must meet all apheresis center requirements 
for this procedure. 
• Participants who can become pregnant must have a negative pregnancy test 
within 48 hours prior to the procedure. 
8.6 
Visit windows and missed visits 
The schedule of visits and evaluations performed at each visit are shown in 
Appendix A and Appendix B. Visit windows are shown in Appendix C. The 
procedures for documenting missed visits and out of window visits are described 
in the HVTN 300 SSP. If the missed visit is one that required safety assessments 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 59 of 127 
or local safety labs, HVTN CRS staff should attempt to bring the participant in for 
an interim visit as soon as possible. 
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 and Appendix B. The 
Laboratory Program (or approved diagnostic laboratory) will follow the HVTN 
HIV testing algorithm (see Study Specific Procedures [SSP]), 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 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 
vaccine induced seropositivity (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 offered poststudy HIV diagnostic testing (per 
the HVTN poststudy HIV testing algorithm) periodically free of charge as 
medically/socially indicated (approximately every 6 months) unless or until 
HIV antibody testing is no longer standard in clinical settings. 
• Unless they 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 
principal investigator should consider if the following assessments are 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 60 of 127 
appropriate: end-of-study HIV test, CBC with differential, serum chemistry, 
physical examination, and if indicated, a pregnancy test (see Appendix A and 
Appendix B). For participants with HIV infection, please see Section 5.2.2. If the 
site principal investigator has questions regarding a termination visit they should 
consult with the PSRT. 
8.9 
AESI contact 
CRS staff will contact study participants 12 months after the last vaccination to 
collect the information listed below. If indicated, the participant may be asked to 
come in for a clinical assessment which may also include referrals for AESI 
assessment. AESIs are described further in Appendix H. 
• Confirmation of vital status; if deceased, attempt to learn cause and date of 
death 
• If participant is alive, record the participant’s responses to the following: 
• SAEs 
• AESI (a sample list of AESIs is provided in Appendix H). AESIs are reported 
regardless of relationship to study product(s); 
• MAAEs, defined as any adverse events leading to an unscheduled visit to a 
healthcare professional which are reported regardless of relationship to study 
product(s); 
• New diagnosis of HIV infection; and 
• Pregnancies and outcomes, including congenital anomalies/birth defects. 
• All such events will be recorded and adverse events will be assessed for 
relationship to study vaccines.  
 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 61 of 127 
9 
Safety and adverse events 
9.1 
Adverse events 
Unsolicited AEs will be collected over a period of 30 days after each vaccination. 
All collected AEs are captured in the clinical database on the appropriate 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 9.7), (3) if the AE meets 
the criteria for an MAAE, and (4) if the AE is a potential immune-mediated 
disease that may be listed as an AE of special interest (AESI). A sample list of 
AESIs is provided in Appendix H. 
In addition, a limited set of AEs will be collected and reported for 12 months 
following the any vaccine administration 
• SAEs/EAEs, 
• AESIs, 
• MAAEs (defined as any adverse events leading to an unscheduled visit to a 
healthcare professional) 
• AEs leading to early participant withdrawal or early discontinuation of study 
vaccine(s) administration.  
Adverse events (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 
300 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 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.  

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 62 of 127 
• 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:  
o Grade 1 is: 2.5 to < 5 cm in diameter; 
o Grade 2 is: ≥ 5 to < 10 cm in diameter; 
o Grade 3 is: ≥ 10 cm in diameter OR Ulceration OR Secondary 
infection OR Phlebitis OR Sterile abscess OR Drainage; 
o Grade 4 is: Potentially life-threatening consequences (eg, abscess, 
exfoliative dermatitis, necrosis involving dermis or deeper tissue); 
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 subject and may require 
medical or surgical intervention to prevent one of the outcomes listed in this 
definition. Examples of such medical events include allergic bronchospasm 
requiring intensive treatment in an emergency room or at home, blood dyscrasias 
or convulsions that do not result in inpatient hospitalization, or the development 
of drug dependency or drug abuse.” 
“Life-threatening” refers to an adverse event that at occurrence represents an 
immediate risk of death to the subject. Similarly, a hospital admission for an 
elective procedure is not considered an SAE.  

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 63 of 127 
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 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 expedited AE (EAE) reporting to DAIDS. In the event of system 
outages or technical difficulties, expedited AEs may be submitted via the DAIDS 
EAE form https://rsc.niaid.nih.gov/clinical-research-sites/paper-eae-reporting. 
The SAE Reporting Category will be used throughout the study. After completion 
of the study the 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: CH505 TF 
chTrimer, administered in combination with 3M-052-AF (aqueous formulation), 
and Aluminum hydroxide suspension (Alum). There is no placebo product 
administered in this protocol. 
9.3 
Safety monitoring 
9.3.1 
Protocol Safety Review Team (PSRT)  
The PSRT comprises the Study Chairs, participating CRS PI(s), HVTN Protocol 
Team Leader, DAIDS Medical Officer, HVTN Clinical Safety Specialist (CSS), 
and other Study Clinicians. The PSRT will review study safety information on a 
weekly basis through 2 weeks after the last participant receives the final study 
injection. Because participants can be enrolled in the study with a Grade 1 ALT 
value (up to <2.5 x ULN), the PSRT will monitor all ALT values on all study 
participants throughout the trial. 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 
300 PSRT. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 64 of 127 
Study sites will receive SMB summary minutes and are responsible for 
forwarding them to their IRB/EC and any applicable Regulatory Entity. 
9.4 
Total blood volume 
Required blood volumes per visit are shown in Appendix A and Appendix B. 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 as 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. Alternate tube types may be used under certain circumstances (eg, ACD 
tube shortages) upon approval of the HVTN Laboratory Center. Refer to the HVTN 
300 Specimen Collection SSP for more information. 
9.5 
Initial safety review for Part A 
Enrollment was restricted to one participant per day for the first 5 participants and 
then enrollments were held. The PSRT reviewed cumulative safety information 
recorded through the visit scheduled 2 weeks post first vaccination and 
determined it was safe to proceed with full enrollment. 
9.6 
Interim Safety Review for Part A 
There was a pre-planned safety review after the 5th participant in Part A received 
their third vaccination. The PSRT reviewed cumulative safety information 
recorded through the visit scheduled 2 weeks post third vaccination and decided it 
was safe to proceed with the remaining vaccinations. No participant received the 
fourth or fifth vaccination until the PSRT gave express permission. 
9.7 
Initial safety review for Part B 
Enrollment in Part B will be stepwise by group. Enrollment in Group 2 will be 
restricted to one participant per day for the first 5 participants and then enrollment 
will be held. The PSRT will review cumulative safety information recorded 
through the visit scheduled 2 weeks post first vaccination for the first 5 
participants and determine whether it is safe to proceed to full enrollment in 
Group 2 and then followed by enrollment in Group 3 and then Group 4.  

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 65 of 127 
 
9.8 
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 300 PSRT AE review are 
summarized in Table 9-1. Vaccinations may be suspended for safety concerns 
other than those described in the table, or before pause rules are met, if, in the 
judgment of the HVTN 300 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. 
Table 9-1 Pause Rules Table 
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)  

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 66 of 127 
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 you need 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). 
9.8.1 
Plan for review of pause rules  
For all safety pauses, HVTN Core notifies the HVTN 300 PSRT, HVTN 
Regulatory Affairs, DAIDS Pharmaceutical Affairs Branch (PAB), DAIDS 
Regulatory Affairs Branch (RAB), DAIDS Safety and Pharmacovigilance Team 
(SPT), and participating HVTN CRSs. When an immediate safety pause is 
triggered, HVTN Core notifies the SMB.  
Once a trial is paused, the HVTN 300 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 300 PSRT assessment, DAIDS RAB 
notifies the FDA as needed. 
If an immediate HVTN 300 PSRT notification or prompt HVTN 300 PSRT AE 
review is triggered, HVTN Core notifies the HVTN 300 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 300 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. 
9.9 
Study termination 
This study may be terminated early by the determination of the HVTN 300 PSRT, 
the NIH, the United States Department of Health and Human Services Office for 
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. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 67 of 127 
9.10 
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 in persons who 
are confirmed pregnant, pregnancy testing is not required, unless clinically 
indicated. If the participant terminates from the study prior to the pregnancy 
outcome, the site should make every effort to keep in touch with the participant in 
order to ascertain the pregnancy outcome. Pregnancies and pregnancy outcomes 
will be reported as described in the HVTN 300 SSP section on Pregnancy 
Management and Reporting. If the participant is no longer pregnant, refer to 
Section 5.2.2. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 68 of 127 
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) (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 300 Study Specific Procedures. Regarding 
protocol registration, sites should follow procedures outlined in the current 
version of the DAIDS Protocol Registration Manual. 
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 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 (SICF) in Appendix D and Appendix E 
describes the investigational vaccine 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 level of understandability. 
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 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 69 of 127 
to determine eligibility. HVTN CRSs must submit recruitment and prescreening 
materials to their IRB/EC and any applicable RE for human subjects 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. 
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. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 70 of 127 
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 accord with the language in the sample informed 
consent forms (Appendix D and Appendix E) 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 forms for the main study (see Appendix D and Appendix E). 
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. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 71 of 127 
12 
Literature cited 
1. Liao HX, Lynch R, Zhou T, Gao F, Alam SM, Boyd SD, et al. Co-evolution 
of a broadly neutralizing HIV-1 antibody and founder virus. Nature. 
2013;496(7446):469-76. 
2. Haynes BF, Bradley T. Broadly Neutralizing Antibodies and the 
Development of Vaccines. JAMA. 2015;313(24):2419-20. 
3. Wiehe K, Bradley T, Meyerhoff RR, Hart C, Williams WB, Easterhoff D, et 
al. Functional Relevance of Improbable Antibody Mutations for HIV Broadly 
Neutralizing Antibody Development. Cell Host Microbe. 2018;23(6):759-65 
e6. 
4. Williams WB, Zhang J, Jiang C, Nicely NI, Fera D, Luo K, et al. Initiation of 
HIV neutralizing B cell lineages with sequential envelope immunizations. 
Nat Commun. 2017;8(1):1732. 
5. Abbott RK, Lee JH, Menis S, Skog P, Rossi M, Ota T, et al. Precursor 
Frequency and Affinity Determine B Cell Competitive Fitness in Germinal 
Centers, Tested with Germline-Targeting HIV Vaccine Immunogens. 
Immunity. 2018;48(1):133-46 e6. 
6. Saunders KO, Verkoczy LK, Jiang C, Zhang J, Parks R, Chen H, et al. 
Vaccine Induction of Heterologous Tier 2 HIV-1 Neutralizing Antibodies in 
Animal Models. Cell Rep. 2017;21(13):3681-90. 
7. 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. 
8. Sok D, Doores KJ, Briney B, Le KM, Saye-Francisco KL, Ramos A, et al. 
Promiscuous glycan site recognition by antibodies to the high-mannose patch 
of gp120 broadens neutralization of HIV. Sci Transl Med. 
2014;6(236):236ra63. 
9. Gray GE, Mayer KH, Elizaga ML, Bekker LG, Allen M, Morris L, et al. 
Subtype C gp140 Vaccine Boosts Immune Responses Primed by the South 
African AIDS Vaccine Initiative DNA-C2 and MVA-C HIV Vaccines after 
More than a 2-Year Gap. Clin Vaccine Immunol. 2016;23(6):496-506. 
10. Churchyard G, Mlisana K, Karuna S, Williamson AL, Williamson C, Morris 
L, et al. Sequential Immunization with gp140 Boosts Immune Responses 
Primed by Modified Vaccinia Ankara or DNA in HIV-Uninfected South 
African Participants. PLoS One. 2016;11(9):e0161753. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 72 of 127 
11. Spearman P, Tomaras GD, Montefiori DC, Huang Y, Elizaga ML, Ferrari G, 
et al. Rapid Boosting of HIV-1 Neutralizing Antibody Responses in Humans 
Following a Prolonged Immunologic Rest. J Infect Dis. 2019. 
12. Sanders RW, Derking R, Cupo A, Julien JP, Yasmeen A, de Val N, et al. A 
next-generation cleaved, soluble HIV-1 Env trimer, BG505 SOSIP.664 
gp140, expresses multiple epitopes for broadly neutralizing but not non-
neutralizing antibodies. PLoS Pathog. 2013;9(9):e1003618. 
13. Dey AK, Cupo A, Ozorowski G, Sharma VK, Behrens AJ, Go EP, et al. 
cGMP production and analysis of BG505 SOSIP.664, an extensively 
glycosylated, trimeric HIV-1 envelope glycoprotein vaccine candidate. 
Biotechnol Bioeng. 2018;115(4):885-99. 
14. Fox CB, Orr MT, Van Hoeven N, Parker SC, Mikasa TJ, Phan T, et al. 
Adsorption of a synthetic TLR7/8 ligand to aluminum oxyhydroxide for 
enhanced vaccine adjuvant activity: A formulation approach. J Control 
Release. 2016;244(Pt A):98-107. 
15. Smirnov D, Schmidt JJ, Capecchi JT, Wightman PD. Vaccine adjuvant 
activity of 3M-052: an imidazoquinoline designed for local activity without 
systemic cytokine induction. Vaccine. 2011;29(33):5434-42. 
16. Van Hoeven N, Fox CB, Granger B, Evers T, Joshi SW, Nana GI, et al. A 
Formulated TLR7/8 Agonist is a Flexible, Highly Potent and Effective 
Adjuvant for Pandemic Influenza Vaccines. Sci Rep. 2017;7:46426. 
17. Gupta SG-O, J; Hong, D; Marabelle, A; Munster, P; Aggarwal, R; Aspeslagh, 
S; G. Dixon, R; Patel, M; Subbiah, V; Morehouse, C; Wu, Y; Zha, J; Tseng, 
L; Cooper, Z; Morris, S; Brody, J. Abstract CT091: Safety and 
pharamcodynammic activity of MEDI9197, a TLR 7/8 agonist, administered 
intratumorally in subjects with solid tumors (Proceedings: AACR Annual 
Meeting 2017; April 1-5, 2017; Washington, DC). Cancer Research 
[Internet]. 2017; 77 
(13):[http://cancerres.aacrjournals.org/content/77/13_Supplement/CT091 p.]. 
Available from: 
http://cancerres.aacrjournals.org/content/77/13_Supplement/CT091. 
18. Francica JR, Zak DE, Linde C, Siena E, Johnson C, Juraska M, et al. Innate 
transcriptional effects by adjuvants on the magnitude, quality, and durability 
of HIV envelope responses in NHPs. Blood Adv. 2017;1(25):2329-42. 
19. FDA. AmBisome (amphotericin B) liposome for injection 2021 [updated 
2021. Available from: 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/050740Orig1s03
3lbl.pdf. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 73 of 127 
20. Saunders KO, Lee E, Parks R, Martinez DR, Li D, Chen H, et al. 
Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses. 
Nature. 2021;594(7864):553-9. 
21. Adler-Moore J, Proffitt RT. AmBisome: liposomal formulation, structure, 
mechanism of action and pre-clinical experience. J Antimicrob Chemother. 
2002;49 Suppl 1:21-30. 
22. Havenar-Daughton C, Carnathan DG, Torrents de la Pena A, Pauthner M, 
Briney B, Reiss SM, et al. Direct Probing of Germinal Center Responses 
Reveals Immunological Features and Bottlenecks for Neutralizing Antibody 
Responses to HIV Env Trimer. Cell Rep. 2016;17(9):2195-209. 
23. Patricia D'Souza M, Allen MA, Baumblatt JAG, Boggiano C, Crotty S, 
Grady C, et al. Innovative approaches to track lymph node germinal center 
responses to evaluate development of broadly neutralizing antibodies in 
human HIV vaccine trials. Vaccine. 2018;36(38):5671-7. 
24. Cirelli KM, Carnathan DG, Nogal B, Martin JT, Rodriguez OL, Upadhyay 
AA, et al. Slow Delivery Immunization Enhances HIV Neutralizing Antibody 
and Germinal Center Responses via Modulation of Immunodominance. Cell. 
2019;177(5):1153-71 e28. 
25. Sampson HA, Munoz-Furlong A, Campbell RL, Adkinson NF, Jr., Bock SA, 
Branum A, et al. Second symposium on the definition and management of 
anaphylaxis: summary report--Second National Institute of Allergy and 
Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J 
Allergy Clin Immunol. 2006;117(2):391-7. 
26. Agresti A, Coull BA. Approximate is better than "exact" for interval 
estimation of binomial proportions. Am Stat. 1998;52(2):119-26. 
27. Huang Y, Gilbert P, Montefiori D, Self S. Simultaneous evaluation of the 
magnitude and breadth of a left- and right-censored multivariate response, 
with application to HIV vaccine development. Statistics in Biopharmaceutical 
Research. 2009;1:81-91. 
 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 74 of 127 
Appendix A 
Schedule of procedures for Part A 
 
Visit Number 
01 
02 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
AESI15 
Study Week 
 
0 
2 
8 
10 
16 
18 
32 
34 
52 
54 
80 
104 
Study Month 
 
0 
0.5 
2 
2.5 
4 
4.5 
8 
8.5 
12 
12.5 
18 
24 
Study Day 
-56 to 0 
0 
14 
56 
70 
112 
126 
224 
238 
364 
378 
560 
728 
Procedure 
Screen1 
Vac 1 
 
Vac 2 
 
Vac 3 
 
Vac 4 
 
Vac 5 
 
 
 
Study procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assessment of Understanding 
 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history2 
 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
Physical exam3 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Contraception status assessment4 
 
√ 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
 
 
Risk reduction counseling5 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Concomitant medications6 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Adverse Events (AEs) 
 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
 
AESIs/MAAEs/SAEs 
 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Vaccination7 
 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
 
 
Reactogenicity assessment8 
 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
 
 
Clinical labs 
Tube 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test (urine or serum)9, 10 
 
√ 
√ 
 
√ 
 
√ 
√ 
√ 
√ 
√ 
 
√ 
 
HBsAg/anti-HCV10  
SST 
5 
 
 
 
 
 
 
 
 
 
 
 
 
HIV screening test10, 11 
SST 
5 
 
 
 
 
 
 
 
 
 
 
 
 
CBC/Differential10 
EDTA 
5 
 
5 
 
5 
 
5 
 
5 
 
5 
 
 
ALT & Creatinine10 
SST 
5 
 
5 
 
5 
 
5 
 
5 
 
5 
 
 
HIV diagnostic test 
EDTA 
 
 
 
 
 
10 
 
10 
 
10 
 
20 
 
Research samples12 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PBMC for assays & storage 
ACD 
 
 
136 
 
136 
 
136 
 
 
 
178.5 
178.5 
 
Serum for assays and storage 
SST 
 
34 
34 
 
34 
 
34 
 
34 
 
34 
34 
 
Leukapheresis 
 
 
√13 
 
 
 
 
 
 
√ 
 
 
 
 
Fine Needle Aspiration14 
 
 
 
 
 
 
 
√ 
 
 
 
 
 
 
Daily volume (mL) 
20 
34 
180 
0 
180 
10 
180 
10 
44 
10 
222.5 
232.5 
 
56-day total volume (mL) 
20 
54 
234 
234 
360 
190 
370 
10 
54 
10 
232.5 
232.5 
 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 75 of 127 
Green shading = Vaccination Visit; Blue shading = FNA visit 
1 Screening evaluations at Visit 01 are performed no more than 56 days before Day 0.  
2 Medical history: A complete medical history is performed during screening. At enrollment and at subsequent visits, an interim medical history may be 
performed. 
3 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. 
4 Contraception status assessment is required only for participants who were assigned female sex at birth and are capable of becoming pregnant. 
5 Risk reduction counseling per CRS Standard Operating Procedures. 
6 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. 
7 Vaccination (in clinic assessments): At least 60 minutes after each vaccination and prior to clinic discharge, participants will have vital signs taken, the injection 
site will be assessed, and systemic symptoms will be assessed.  
8 Reactogenicity: Clinic staff will follow new or unresolved reactogenicity symptoms present at day 7 until resolution. 
9 Pregnancy test: For participants assigned female sex at birth. Pregnancy test may be performed on 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. Persons who are confirmed pregnant, pregnancy testing is not required, unless clinically indicated. 
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 Leukapheresis: May be performed prior to enrollment visit once the participant has been found to have met all protocol enrollment criteria (see Section 5.1.1 
and 5.1.2) and leukapheresis eligibility criteria (see Section 8.5). A pregnancy test (see also footnote 9) must be performed and confirmed negative within 48 
hours prior to leukapheresis. 
14 Fine Needle Aspiration: Target for FNA is three weeks post 3rd vaccination. A pregnancy test (see also footnote 9) must be performed and confirmed negative 
within 48 hours prior to lymph node cell collection. 
15 AESI contact: CRS staff will contact study participants 12 months after the last vaccination received to collect the information listed in Section 8.9. 
 
 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 76 of 127 
Appendix B 
Schedule of procedures for Part B 
Visit Number 
01 
02 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
AESI13 
Study Week 
 
0 
2 
8 
10 
16 
18 
32 
34 
52 
54 
80 
104 
Study Month 
 
0 
0.5 
2 
2.5 
4 
4.5 
8 
8.5 
12 
12.5 
18 
24 
Study Day 
-56 to 0 
0 
14 
56 
70 
112 
126 
224 
238 
364 
378 
560 
728 
Procedure 
Screen1 
Vac 1 
 
Vac 2 
 
Vac 3 
 
Vac 4 
 
Vac 5 
 
 
 
Study procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assessment of Understanding 
 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history2 
 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
Physical exam3 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Contraception status assessment4 
 
√ 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
 
 
Risk reduction counseling5 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Concomitant medications6 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Adverse Events (AEs) 
 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
 
AESIs/MAAEs/SAEs 
 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Vaccination7 
 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
 
 
Reactogenicity assessment8 
 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
 
 
Clinical labs 
Tube 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test (urine or serum)9, 10 
 
√ 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
HBsAg/anti-HCV10  
SST 
5 
 
 
 
 
 
 
 
 
 
 
 
 
HIV screening test10, 11 
SST 
5 
 
 
 
 
 
 
 
 
 
 
 
 
CBC/Differential10 
EDTA 
5 
 
5 
 
5 
 
5 
 
5 
 
5 
 
 
ALT & Creatinine10 
SST 
5 
 
5 
 
5 
 
5 
 
5 
 
5 
 
 
HIV diagnostic test 
EDTA 
 
 
 
 
 
10 
 
10 
 
10 
 
20 
 
Research samples12 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PBMC for assays & storage 
ACD 
 
136 
136 
 
136 
 
136 
 
136 
 
178.5 
178.5 
 
Serum for assays and storage 
SST 
 
34 
34 
 
34 
 
34 
 
34 
 
34 
34 
 
Daily volume (mL) 
20 
170 
180 
0 
180 
10 
180 
10 
180 
10 
222.5 
232.5 
 
56-day total volume (mL) 
20 
190 
370 
370 
360 
190 
370 
10 
190 
10 
232.5 
232.5 
 
 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 77 of 127 
1 Screening evaluations at Visit 01 are performed no more than 56 days before Day 0.  
2 Medical history: A complete medical history is performed during screening. At enrollment and at subsequent visits, an interim medical history may be 
performed. 
3 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. 
4 Contraception status assessment is required only for participants who were assigned female sex at birth and are capable of becoming pregnant. 
5 Risk reduction counseling per CRS Standard Operating Procedures. 
6 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. 
7 Vaccination (in clinic assessments): At least 60 minutes after each vaccination and prior to clinic discharge, participants will have vital signs taken, the injection 
site will be assessed, and systemic symptoms will be assessed.  
8 Reactogenicity: Clinic staff will follow new or unresolved reactogenicity symptoms present at day 7 until resolution. 
9 Pregnancy test: For participants assigned female sex at birth. Pregnancy test may be performed on 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. Persons who are confirmed pregnant, pregnancy testing is not required, unless clinically indicated. 
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 AESI contact: CRS staff will contact study participants 12 months after the last vaccination received to collect the information listed in Section 8.9. 
 
 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 78 of 127 
Appendix C 
Visit windows for Part A and Part B 
 
Visit 
Number 
Visit Type 
Lower 
Allowable 
Window  
(-) 
Lower 
Target 
Window  
(-) 
Target 
Day* 
Upper 
Target 
Window 
(+) 
Upper 
Allowable 
Window  
(+) 
01.0 
Screening 
-56 
- 
0 
- 
+0 
02.0 
Enrollment/Vaccination 1 
- 
- 
0 
- 
- 
03.0 
2 weeks post-vaccination 1 
 
-4 
14 
+4 
+7 
04.0 
Vaccination 2 
 
-7 
56 
+9 
+14 
05.0 
2 weeks post-vaccination 2 
 
-4 
70 
+4 
+7 
06.0 
Vaccination 3 
-21 
-14 
112 
+14 
+21 
07.0** 
2 weeks post-vaccination 3 
Primary Immunogenicity 
- 
-4 
126 
+4 
+21 
08.0 
Vaccination 4 
-28 
-14 
224 
+14 
+28 
09.0 
2 weeks post-vaccination 4 
- 
-4 
238 
+4 
+7 
10.0 
Vaccination 5 
 
-28 
364 
+28 
 
11.0 
2 weeks post-vaccination 5 
 
-4 
378 
+4 
+7 
12.0 
Final Visit 
-28 
-14 
560 
+14 
+28 
AESI 
AESI Contact 
-28 
-14 
728 
+14 
+28 
* All target dates are relative to Day 0, with the exception of the post-vaccination visits, visits 3.0, 5.0, 
7.0, 9.0, and 11.0 which are relative to the vaccination immediately preceding the visit. 
** Target date for FNA is three weeks post 3rd vaccination, see HVTN 300 Study Specific Procedures (SSP) 
for more details. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 79 of 127 
Appendix D 
Sample informed consent form for Part A 
Title: A first-in-human Phase 1 clinical trial to evaluate the safety and 
immunogenicity of stabilized CH505 TF chTrimer in healthy, HIV-uninfected adult 
participants 
HVTN protocol number: HVTN 300 
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 18-55, HIV 
negative and healthy. 
• The purpose of this study is to see how a person’s immune system responds to the 
study vaccine. 
• The study will also see if the study vaccine is safe to give to people and does not 
make people too uncomfortable. 
• You will be in this study for up to 18 months of clinic visits, with a follow up 
contact 1 year after your last vaccination to check on your health. 
• Procedures will include blood draws and injections of study vaccine, as well as 
the collection of white blood cells and cells from your lymph nodes. White blood 
cells will be collected by a procedure called leukapheresis. Lymph node cells will 
be collected by a doctor using a very thin needle guided by ultrasound. We will 
tell you more about these procedures later in this consent form. 
• There are risks from participating. The most common risks are: 
▪ Because this vaccine has not been given to people yet, we do not know 
what all of the risks may be. 
▪ Taking blood and giving injections can cause bruising, pain, fainting, 
soreness, redness, swelling, itching, a sore and bleeding.  
▪ Leukapheresis and collecting cells from your lymph node can cause pain, 
bruising, and rarely an infection. 
▪ We will tell you more information about risks later in this consent form. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 80 of 127 
• We do not expect the study vaccine 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 an HIV vaccine. HIV is the virus that causes AIDS. 
Up to 18 people will take part in this study. 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. 
1. We are doing this study to answer several questions. 
• Is the study vaccine safe to give to people? 
• Are people able to take the study vaccine without becoming too 
uncomfortable? 
• How do people’s immune systems respond to the study vaccine? (Your 
immune system protects you from infections and disease.)  
2. The study vaccine cannot give you HIV. 
The study vaccine is not made from HIV. It is impossible for the study vaccine to 
give you HIV. Also, it cannot cause you to give HIV to someone else. 
We do not know if the study vaccine will decrease, increase, or not change your risk 
of getting HIV if you are exposed to the virus.  
3. This study vaccine is experimental. 
We are testing an experimental vaccine called CH505 TF chTrimer. It is a man-made 
piece of protein that looks like a protein found on the outside of HIV. This protein is 
mixed with an adjuvant called 3M-052-AF + Alum. An adjuvant is something added 
to a vaccine to help the immune system respond better. From here on, we will call the 
protein-adjuvant combination “the study vaccine”. We do not know if the study 
vaccine will be safe to use in people, or if it will work to prevent HIV infection. This 
study vaccine is used only in research studies. 
The protein part of the study vaccine was developed by the Duke Human Vaccine 
Institute and is being provided by Duke University in Durham, North Carolina, USA. 
3M-052 was developed by 3M Corporation, headquartered in St. Paul, Minnesota, 
USA. In this study, 3M-052-AF is being provided by the Infectious Disease Research 
Institute (IDRI) in Seattle, Washington. Alum is being provided by the Division of 
AIDS (DAIDS) at the US National Institutes of Health in Rockville, Maryland, USA. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 81 of 127 
The study vaccine has not been given to people before. The protein part of the 
vaccine has been engineered to stay in a shape much like natural HIV. In this way it is 
different from proteins used in some other HIV study vaccines. 
3M-052 is one of many similar products developed by 3M Corporation to treat skin 
conditions, tumors, and to make vaccines more effective. It is an experimental 
product. It is designed to stimulate parts of the immune system that recognize 
invaders like viruses. In this study, 3M-052-AF is dissolved in water and is mixed 
with Alum. Alum is an approved adjuvant that has been used in commercial vaccines 
for more than 90 years.  
A protein-adjuvant combination very similar to this study vaccine is being tested for 
the first time in humans in another HVTN study called HVTN 137. That study gives 
some people the study vaccine and some people a placebo which does not contain the 
study vaccine. As of November 4, 2020, 17 people have had 2 injections (15 people 
were given the study vaccine and 2 people were given a placebo). These injections 
have not caused any serious health problems. 
In HVTN 137, two people had redness and swelling over a large area on their arm 
where they got the injection that started about 1 week after the injection. The redness 
lasted for about 2 to 3 days. For one of these people, the swelling went away within 2 
to 3 days. The second person had significant swelling for about 3 days. The swelling 
went down but it took about 5 weeks to completely go away. They had mild pain 
which did not prevent them from going to work. Four other people had symptoms that 
did prevent them from going to work. Because the study is ongoing and is blinded, 
we do not know if these people got the study vaccine or placebo. 
Risks of vaccines: 
All vaccines can cause fever, chills, rash, aches and pains, nausea, dizziness, and 
feeling tired. Vaccines can also cause redness or itching where you got the injection. 
Most side effects do not interfere with daily activities or make a person visit the 
doctor. 
Rarely, a vaccine can cause an allergic reaction, including a rash, hives, or trouble 
breathing. Allergic reactions can be life-threatening. Tell us if you ever had a bad 
reaction to an injection or vaccine. 
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. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 82 of 127 
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, that will not affect your other care at this clinic and the 
benefits or rights you would normally have. 
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. 
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 also test you for Hepatitis B and Hepatitis C. 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.  
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. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 83 of 127 
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 G, Approved birth control methods (for sample 
informed consent form), in this consent form, paste it below and delete paragraph 
below. 
You should not become pregnant during the study because we do not know how the 
study vaccine could affect a developing baby. For this reason, you must agree to use 
effective birth control from 21 days before your first injection until 8 weeks after the 
time of your fifth study injection (14 months). 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 up to [#] times over 18 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. 
A study visit can be done in person at the clinic. They may also be done using tools 
such as phone calls, text messages, web platforms (sometimes called “telemedicine”) 
or email. A combination of these types of visits might also be used. 
You may have 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 
two of the study procedures. We will tell you more about that below. 
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). 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 84 of 127 
10. We will give you the study vaccine on a schedule. 
The study is designed to give participants injections of the study vaccine at 5 visits, 
according to the schedule in the table below. At these 5 visits, you will get 2 
injections, 1 into the deltoid muscle of both upper arms. We will give the injections 
with a needle and syringe.  
Because this is the first time the study vaccine is being given to people, the study also 
has planned pauses when safety information will be reviewed to decide if it is safe to 
continue the study. The first pause will be after the first 5 participants have their first 
injection visit, to determine if the rest of the participants should be enrolled. The 
second pause will be after the 5th participant has their third injection visit. At this 
second pause, a decision will be made about whether it is safe for participants to 
continue with the 4th and 5th injection visits.  
 
 
First 
injection 
visit 
2 months 
later 
4 months 
later 
8 months 
later 
12 months 
later 
Study 
vaccine 
✓ 
✓ 
✓ 
✓ 
✓ 
You will have to wait in the clinic for about an hour after getting injections to see if 
there are any problems. We will measure your temperature, blood pressure, heart and 
breathing rates. We will also look at your injection sites and ask how you feel. Then 
for that night and for 7 more days, you will use a secure online symptom log to keep 
track of how you are feeling. If you are unable or unwilling to use the online 
symptom log, please talk with us about other options that may be available. Within 4 
days after each injection visit, we will contact you 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 the study vaccine, we will do the procedures shown in 
the following table. 
 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 85 of 127 
 
 
 
Time after first injection visit 
 
 
 
 
 
Procedure 
Screening 
visit(s) 
First 
injection 
visit  
2 weeks 
2 months 
2½ months 
4 months 
4½ months 
8 months  
8½ months  
12 months 
12½ months 
18 months 
 2 years 
Injection 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
 
 
Medical history 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical 
√ 
 
 
 
 
 
 
 
 
 
 
√ 
 
Brief physical 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
 
Blood drawn 
√ 
√ 
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Lymph node cell collection 
 
 
 
 
 
 
√ 
 
 
 
 
 
 
Leukapheresis* 
 
√ 
 
 
 
 
 
 
√ 
 
 
 
 
Pregnancy test** 
√ 
√ 
 
√ 
 
√ 
√ 
√ 
√ 
√ 
 
√ 
 
HIV testing  
√ 
 
 
 
 
√ 
 
√ 
 
√ 
 
√ 
 
Risk reduction counseling 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Interview/questionnaire 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
* Leukapheresis may be done at the First injection visit or before enrollment if a person wishes to join the study and is 
eligible.  
** For persons who were assigned female sex at birth and who are capable of becoming pregnant. A negative 
pregnancy test is required within 48 hours before lymph node cell collection and leukapheresis. Persons who have 
had a hysterectomy (removal of the uterus) or removal of both ovaries (verified by medical records), do not have to 
have pregnancy tests. 
When we take blood, the amount will depend on the lab tests we need to do. It will be 
some amount between 10 mL and 233 mL (about 1 tablespoon to a little less than one 
cup). Your body will make new blood to replace the blood we take out. 
We will review test results with you at your next visit, or sooner if necessary. We will 
tell you about any results that are important to your health. 
Leukapheresis procedure: 
This procedure collects large amounts of white blood cells. Blood is made up of red 
cells that carry oxygen, white cells that fight infection, platelets that help form clots, 
and plasma, which is the fluid left over when all the cells are removed. During 
leukapheresis, white blood cells are removed and the rest of the blood is put back into 
the body.  
The leukapheresis procedure will be done at [site: insert location]. Your eligibility to 
have this procedure will be assessed 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. When the white blood cells are taken out, the rest of the blood will go back into 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 86 of 127 
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. 
It is normal to feel tired for up to 24 hours after having leukapheresis.  
The leukapheresis procedure will be done before your first injection visit and again 
about 2 weeks after your 4th injection visit. It will take about [Site: Insert timeframe] 
for the procedure. 
We will give you [Site: Insert compensation] for having leukapheresis. This amount 
is to cover the costs of [Site: Insert text]. 
Risks of leukapheresis 
Generally, the risks of leukapheresis include pain, bruising and rarely, infection. A 
less common risk is fainting. 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.  
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.  
Lymph node cell collection procedure 
The formal name for this procedure is a Fine Needle Aspiration. This procedure 
collects cells from lymph nodes. Lymph nodes are one of the key places where 
immune responses develop and they are located in several places on the human body. 
In this procedure, a doctor will use a very thin needle guided by ultrasound to collect 
cells from a lymph node on your arm or in your arm pit.  
The lymph node cell collection procedure will be done at [site: insert location]. Your 
eligibility to have this procedure will be assessed by the staff at our clinic during 
screening, and again 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. 
To do the procedure, a clinician will find the appropriate lymph node by applying a 
cold gel to your skin and then pressing a hand-held ultrasound device against your 
skin. If necessary, a small area near the lymph node may be shaved. Once the node is 
found, a cleaning solution will be applied to the skin in that area. The area will be 
numbed by an injection of a local anesthetic, such as Lidocaine, which is like 
Novocaine that is used for dental procedures. The doctor will insert a very thin needle 
and use the images from the ultrasound to guide it into the lymph node. The needle 
may be moved up and down to collect cells from the lymph node. Fluid may also be 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 87 of 127 
collected through the needle into a syringe or bottle. Each cell collection lasts about 
10-15 seconds. It usually takes about 4 separate cell collections to get enough cells. 
After the procedure is done, the area will be cleaned with warm water. You will be 
given a band-aid to cover the site where the needle was inserted. 
Lymph node cell collection will happen about 3 weeks after your third injection visit. 
It will take about [site insert timeframe] for the procedure. 
We will give you [Site: Insert compensation] for having a lymph node cell collection. 
This amount is to cover the costs of [Site: Insert text]. 
Risks of lymph node cell collection 
The main risks of this procedure include pain, bruising, bleeding and infection where 
the needle is inserted. The cleaning solution or shaving the area may cause skin 
irritation. Injecting the local anesthetic may sting or burn for a little while until the 
numbing takes effect. Examining the lymph node area may be uncomfortable. 
If discomfort, problems, or side effects happen during or after lymph node cell 
collection, the staff will use the appropriate medical procedures to treat you. 
12. 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. 
13. 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 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 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). It will involve 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 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 88 of 127 
approved for use in making health care decisions. These labs are only approved to do 
research tests.  
14. When your samples are no longer needed for this study, the HVTN will continue 
to store them. 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. [Site: choose one of the following two sentences. African sites 
should choose the sentence referencing the repository in South Africa. All other sites 
should choose the sentence referencing the repository in the United States.] Your 
samples will be stored in the HVTN repository in South Africa. 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 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. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 89 of 127 
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 
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. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 90 of 127 
15. 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 online symptom log after the injection visits, that information only 
has your code number. Your data goes directly from the online symptom log 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, 
• Any regulatory agency that reviews clinical trials, 
• US sites may, but are not required to include: [Insert name of local IRB/EC] , 
• US Sites include if this sIRB will be used: Fred Hutchinson Cancer Research 
Center Institutional Review Board 
• [Insert name of local and/or national regulatory authority as appropriate] 
• The Duke Human Vaccines Institute, IDRI, DAIDS and people who work for 
them, 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 91 of 127 
• 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] 
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 website will not include information that can identify you. The website may 
include a summary of the study results. You can search this website at any time. 
16. 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 but it will be your choice. 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. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 92 of 127 
We will stop your injections if you get HIV. We will also take fewer samples, and we 
will help you get care and support. We will encourage you to stay in the study for up 
to 12 months if you choose. 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 stop your injections if you enroll in a different research study where you get 
another study product. 
17. 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 
18. There are other risks to being in this study. 
In addition to the risks of the study vaccine 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 abnormal laboratory results  
Minor changes in laboratory test results occasionally happen. This means that the test 
results can show something to be abnormal when it is not. If this happens, we will ask 
you to come back to the clinic to be retested. This may cause you to worry, and it may 
be inconvenient to come back to the clinic. If retesting confirms something to be 
abnormal, we will provide care or help you get the care you need. 
Risks of routine medical procedures: 
Routine medical procedures such as taking blood and giving injections 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. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 93 of 127 
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 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 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 someone who should not may see 
your personal information. If that happens, you could face discrimination, stress, and 
embarrassment. We can tell you more about how we will protect your personal 
information. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 94 of 127 
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: 
We do not know if the study vaccine will increase, decrease, or not change your risk 
of getting HIV if exposed. If you get HIV, we do not know how the study vaccine 
might affect your HIV infection or how long it takes to develop AIDS. 
We do not know if getting this study vaccine will affect how you respond to any 
future approved HIV vaccine. Currently, no HIV vaccine has been approved for use. 
We do not know how the study vaccine will affect a pregnant participant or a 
developing baby. 
Benefits 
19. 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 
vaccine later becomes approved for sale, there are no plans to share any money with 
you. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 95 of 127 
Your rights and responsibilities 
20. 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 
21. 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. 
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, and we may 
ask to take some blood samples. Whether you come for this last visit is up to you. 
Injuries 
22. 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 vaccine and/or procedures. If it is, we call it a study-related 
injury. There are funds to pay for treatment of study-related injuries if certain 
conditions are met. 
Some of the study product providers have agreed to pay medical costs for study-
related injuries that are determined to be caused by their own study products. If 
provider funds are not available or are not enough, or if the injury is determined to be 
caused by study procedures, the HVTN has limited funds to pay medical costs that it 
determines are reasonable. (Sites: insert locale-appropriate medical insurance 
language in the following sentence) If the injury is not study related, then you and/or 
your health insurance will be responsible for treatment costs. 
Some injuries are not physical. For example, you might be harmed emotionally by 
being in an HIV vaccine study. Or you might lose wages because you cannot go to 
work. However, there are no funds to pay for these kinds of injuries, even if they are 
study related. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 96 of 127 
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  
23. 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]. 
US sites include this paragraph if this sIRB will be used: This study has been 
reviewed and approved by a committee called the Fred Hutchinson Cancer Research 
Center Institutional Review Board. If you have questions about your rights as a 
research participant, or problems with or concerns about how you are being treated in 
this study, contact the Director at 206-667-5900 or irodirector@fredhutch.org. 
You may also contact the [name of local IRB/EC] at [insert contact information].If 
you want to leave this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
Your permissions and signature  
24. In Section 14 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. 
 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 97 of 127 
 
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.  
 
 
25. 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 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 98 of 127 
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. 
 
 
 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 99 of 127 
Appendix E 
Sample informed consent form for Part B 
Title: A first-in-human Phase 1 clinical trial to evaluate the safety and 
immunogenicity of stabilized CH505 TF chTrimer in healthy, HIV-uninfected adult 
participants 
HVTN protocol number: HVTN 300 
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 18-55, HIV 
negative and healthy. 
• The purpose of this study is to see how a person’s immune system responds to the 
study vaccine. 
• The study will also see if the study vaccine is safe to give to people and does not 
make people too uncomfortable. 
• You will be in this study for up to 18 months of clinic visits, with a follow up 
contact 1 year after your last vaccination to check on your health. 
• Procedures will include blood draws and injections of study vaccine. We will tell 
you more about these procedures later in this consent form. 
• There are risks from participating. The most common risks are: 
▪ Because this vaccine has only been given to 13 people in Part A of this 
study, we do not know what all of the risks may be  
▪ Taking blood and giving injections can cause bruising, pain, fainting, 
soreness, redness, swelling, itching, a sore and bleeding.  
▪ We will tell you more information about risks later in this consent form. 
• We do not expect the study vaccine to benefit you in any way.  

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 100 of 127 
About the study 
The HIV Vaccine Trials Network (HVTN) and [Insert site name]  are doing a study to 
test an HIV vaccine. HIV is the virus that causes AIDS. 
This study originally planned to give the study vaccine to 13 participants. Those 
participants have been enrolled. The researchers have now decided to make changes 
to the dose of the study products and to test these new doses alone and together in 
more participants. We will now call the first part of the study that enrolled 13 
participants Part A, and the part that will enroll more participants will be Part B. Part 
B of this study will enroll about 36 people. You are being invited to participate in Part 
B. 
1. We are doing this study to answer several questions. 
• Are the study products safe to give to people? 
• Are people able to take the study products without becoming too 
uncomfortable? 
• How do people’s immune systems respond to the study products? (Your 
immune system protects you from infections and disease.)  
2. The study vaccine cannot give you HIV. 
The study vaccine is not made from HIV. It is impossible for the study vaccine to 
give you HIV. Also, it cannot cause you to give HIV to someone else. 
We do not know if the study vaccine will decrease, increase, or not change your risk 
of getting HIV if you are exposed to the virus.  
3. This study vaccine is experimental. 
We are testing an experimental vaccine called CH505 TF chTrimer. We will call it 
the protein vaccine. It is a man-made piece of protein that looks like a protein found 
on the outside of HIV. This protein is being mixed with an adjuvant. An adjuvant is 
something added to a vaccine to help the immune system respond better. In Part A, 
the adjuvant was 3M-052-AF + Alum. In Part B, the adjuvant will be either 3M-052-
AF + Alum or just 3M-052-AF alone. From here on, we will call the protein-adjuvant 
combinations “the study products”. We do not know if the study products will be safe 
to use in people, or if they will work to prevent HIV infection. These study products 
are used only in research studies. 
The protein part of the study vaccine was developed by the Duke Human Vaccine 
Institute and is being provided by Duke University in Durham, North Carolina, USA. 
3M-052 was developed by 3M Corporation, headquartered in St. Paul, Minnesota, 
USA. In this study, 3M-052-AF is being provided by the Access to Advanced Health 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 101 of 127 
Institute in Seattle, Washington. Alum is being provided by the Division of AIDS at 
the US National Institutes of Health in Rockville, Maryland, USA. 
The protein part of the vaccine has been engineered to stay in a shape much like 
natural HIV. In this way it is different from proteins used in some other HIV study 
vaccines. 
3M-052 is one of many similar products developed by 3M Corporation to treat skin 
conditions, tumors, and to make vaccines more effective. It is an experimental 
product. It is designed to stimulate parts of the immune system that recognize 
invaders like viruses. In this study, 3M-052-AF is dissolved in water. Alum is an 
approved adjuvant that has been used in commercial vaccines for more than 90 years.  
The protein and 3M-052-AF + Alum were given together to people for the first time 
in Part A of this study. As of September 7, 2022, all 13 people in Part A have gotten 
at least 1 injection, 10 have gotten at least 2 injections, 9 have gotten at least 3 
injections, 9 have gotten 4 injections and 6 have gotten all 5 injections. These 
injections have not caused any serious health problems.  
All people had some side effects that they described as mild to moderate. One (1) 
person had severe pain/tenderness in both the right and left injection sites 3 days 
following the fourth vaccination, though it lasted only one day. Five (5) people had 
severe side effects related to the vaccinations, including chills, headache, muscle 
aches, and generally feeling unwell. These severe side effects went away within 2 
days. Of the 5 people who had severe side effects, 2 decided to stop getting study 
injections because they felt generally unwell after them and it was affecting their 
daily lives. Another 2 of the 5 people who had severe side effects got more injections; 
one of them had more severe side effects while the other did not. And one (1) of the 5 
people who had severe side effects has not yet received another injection. 
Two more people also decided to stop getting the study injections and dropped out of 
the study. One stopped because they experienced a panic attack after the first 
injection. However, this person had a history of panic attacks before being part of this 
study. The other did not return for their next injection visit and is no longer in the 
study. We do not know the reason for this. 
A protein-adjuvant combination very similar to the combination in this study is being 
given to people for the first time in another study called HVTN 137. That study gives 
some people a study vaccine and some people a placebo which does not contain any 
study vaccine. The study has two parts, Part A and Part B. As of April 2022, 17 
people in Part A have had 2 injections (15 people got the study vaccine and 2 people 
got a placebo). These injections have not caused any serious health problems. 
In HVTN 137 Part A, two people had redness and swelling over a large area on their 
arm where they got the injection. The swelling started about 1 week after the 
injection. The redness lasted for about 2 to 3 days. For 1 of these people, the swelling 
went away within 2 to 3 days. The second person had significant swelling for about 3 
days. The swelling went down but it took about 5 weeks to completely go away. They 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 102 of 127 
had mild pain which did not prevent them from going to work. Four other people had 
symptoms that did prevent them from going to work. All 4 felt severely tired and 
generally unwell. Two of them also had severe muscle and joint pain and 1 had severe 
headache and chills. For these 4 people, all of these symptoms lasted 1-2 days. 
Because the study is ongoing and is blinded, we do not know if these people got the 
study vaccine or placebo. 
HVTN 137 was later updated to offer people in Part A a third injection and 9 out of 
the 17 people agreed to it. The third injection has not caused any serious health 
problems. 
In Part B of HVTN 137, 88 people have gotten either the study vaccine and adjuvant 
combinations or placebo injections. These injections have not caused any serious 
health problems. 
Given the side effects experienced to date in HVTN 300 and HVTN 137 and in Part 
A of this study, we expect that many people in Part B of this study will have some 
side effects. The side effects we expect would be similar to those listed in the Risks of 
vaccines section below. 
Risks of vaccines: 
All vaccines can cause fever, chills, rash, aches and pains, nausea, dizziness, and 
feeling tired. Vaccines can also cause redness or itching where you got the injection. 
Most side effects do not interfere with daily activities or make a person visit the 
doctor. 
Rarely, a vaccine can cause an allergic reaction, including a rash, hives, or trouble 
breathing. Allergic reactions can be life-threatening. Tell us if you ever had a bad 
reaction to an injection or vaccine. 
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, that will not affect your other care at this clinic and the 
benefits or rights you would normally have. 
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. 
During the study, you should not donate blood or tissue. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 103 of 127 
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 also test you for Hepatitis B and Hepatitis C. 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.  
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 G, 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. For this reason, you must agree to use 
effective birth control from 21 days before your first injection until 8 weeks after the 
time of your fifth study injection (14 months). We will talk to you about effective 
birth control methods. They are listed on a handout that we will give to you. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 104 of 127 
Being in the study 
If you join the study, here is what will happen: 
8. You will come to the clinic for scheduled visits up to [#] times over 18 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. 
A study visit can be done in person at the clinic. They may also be done using tools 
such as phone calls, text messages, web platforms (sometimes called “telemedicine”) 
or email. A combination of these types of visits might also be used. 
You may have 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 
two of the study procedures. We will tell you more about that below. 
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 products on a schedule. 
When you join the study, you will be assigned to 1 of 3 groups. Each group will get a 
different combination of the study products as shown in the table below. Each 
combination will have the same protein vaccine at the same dose that was given in 
Part A. Group 2’s combination will have a lower dose of the adjuvant 3M-052-AF 
than was given in Part A and will not include Alum. Group 3’s combination will also 
have a lower dose of 3M-052-AF than was given in Part A and will also have the 
same dose of Alum that was given in Part A. Group 4’s combination will have the 
same dose of 3M-052-AF that was given in Part A, but will not include Alum.  
All groups will get injections of their study products at 5 visits, according to the 
schedule in the table below. At these 5 visits, you will get 2 injections, 1 into the 
deltoid muscle of both upper arms. We will give the injections with a needle and 
syringe.  

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 105 of 127 
In Part A of this study there were two pauses when safety information was reviewed 
to decide if it was safe to continue the study. There have been no serious health 
problems in Part A participants, so it was determined to be safe to continue. 
Similarly, in Part B of the study, there will be a pause after the first 5 people in Group 
2 have their first injection visit, to determine if the rest of the people in Part B should 
be enrolled. 
Group 
Study products 
First 
injection 
visit 
2 months 
later 
4 months 
later 
8 months 
later 
12 
months 
later 
2 
Study vaccine + 
lower dose study 
adjuvant 
✓ 
✓ 
✓ 
✓ 
✓ 
3 
Study vaccine + 
lower dose study 
adjuvant combined 
with Alum  
✓ 
✓ 
✓ 
✓ 
✓ 
4 
Study vaccine + 
higher dose study 
adjuvant 
✓ 
✓ 
✓ 
✓ 
✓ 
You will have to wait in the clinic for about an hour after getting injections to see if 
there are any problems. We will measure your temperature, blood pressure, heart and 
breathing rates. We will also look at your injection sites and ask how you feel. Then 
for that night and for 7 more days, you will use a secure online symptom log to keep 
track of how you are feeling. If you are unable or unwilling to use the online 
symptom log, please talk with us about other options that may be available. Within 4 
days after each injection visit, we will contact you 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 the study vaccine, we will do the procedures shown in 
the following table. 
 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 106 of 127 
 
 
 
Time after first injection visit 
 
 
 
 
 
Procedure 
Screening 
visit(s) 
First 
injection 
visit  
2 weeks 
2 months 
2½ months 
4 months 
4½ months 
8 months  
8½ months  
12 months 
12½ months 
18 months 
 2 years 
Injection 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
 
 
Medical history 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical 
√ 
 
 
 
 
 
 
 
 
 
 
√ 
 
Brief physical 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
 
Blood drawn 
√ 
√ 
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Pregnancy test* 
√ 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
HIV testing  
√ 
 
 
 
 
√ 
 
√ 
 
√ 
 
√ 
 
Risk reduction counseling 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Interview/questionnaire 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
* For persons who are capable of becoming pregnant. Persons who have had a hysterectomy (removal of the uterus), 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. It will be 
some amount between 10 mL and 250 mL (about 1 tablespoon to a little more than 
one cup). Your body will make new blood to replace the blood we take out. 
We will review test 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. 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. 
13. 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 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 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). It will involve 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. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 107 of 127 
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. 
14. 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. [Site: choose one of the following two sentences. African sites 
should choose the sentence referencing the repository in South Africa. All other sites 
should choose the sentence referencing the repository in the United States.] Your 
samples will be stored in the HVTN repository in South Africa. 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 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 108 of 127 
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? 
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 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 109 of 127 
• 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. 
15. 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 online symptom log after the injection visits, that information only 
has your code number. Your data goes directly from the online symptom log 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, 
• Any regulatory agency that reviews clinical trials, 
• US sites may, but are not required to include: [Insert name of local IRB/EC] , 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 110 of 127 
• US Sites include if this sIRB will be used: Fred Hutchinson Cancer Research 
Center Institutional Review Board 
• [Insert name of local and/or national regulatory authority as appropriate] 
• The Duke Human Vaccines Institute, AAHI, DAIDS and people who work for 
them, 
• 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] 
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. The Web site may 
include a summary of the study results. You can search this Web site at any time. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 111 of 127 
16. 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 but it will be your choice. 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 also take fewer samples, and we 
will help you get care and support. We will encourage you to stay in the study for up 
to 12 months if you choose. 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 stop your injections if you enroll in a different research study where you get 
another study product. 
17. 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 
18. There are other risks to being in this study. 
In addition to the risks of the study vaccine 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 abnormal laboratory results  
Minor changes in laboratory test results occasionally happen. This means that the test 
results can show something to be abnormal when it is not. If this happens, we will ask 
you to come back to the clinic to be retested. This may cause you to worry, and it may 
be inconvenient to come back to the clinic. If retesting confirms something to be 
abnormal, we will provide care or help you get the care you need. 
Risks of routine medical procedures: 
Routine medical procedures such as taking blood and giving injections can cause 
bruising, pain, fainting, soreness, redness, stinging, swelling, itching, a sore, bleeding, 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 112 of 127 
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 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 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. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 113 of 127 
Risks of disclosure of your personal information: 
Although the risk is very low, it is possible that someone who should not may see 
your personal information. 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: 
We do not know if the study vaccine will increase, decrease, or not change your risk 
of getting HIV if exposed. If you get HIV, we do not know how the study vaccine 
might affect your HIV infection or how long it takes to develop AIDS. 
We do not know if getting this study vaccine will affect how you respond to any 
future approved HIV vaccine. Currently, no HIV vaccine has been approved for use. 
We do not know how the study vaccine will affect a pregnant participant or a 
developing baby. 
Benefits 
19. 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. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 114 of 127 
This study may help in the search for a vaccine to prevent HIV. However, if the study 
vaccine later becomes approved for sale, there are no plans to share any money with 
you. 
Your rights and responsibilities 
20. 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 
21. 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. 
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, and we may 
ask to take some blood samples. Whether you come for this last visit is up to you. 
Injuries 
22. 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 vaccine and/or procedures. If it is, we call it a study-related 
injury. There are funds to pay for treatment of study-related injuries if certain 
conditions are met. 
Some of the study product providers have agreed to pay medical costs for study-
related injuries that are determined to be caused by their own study products. If 
provider funds are not available or are not enough, or if the injury is determined to be 
caused by study procedures, the HVTN has limited funds to pay medical costs that it 
determines are reasonable. (Sites: insert locale-appropriate medical insurance 
language in the following sentence) If the injury is not study related, then you and/or 
your health insurance will be responsible for treatment costs. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 115 of 127 
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  
23. 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]. 
US sites include this paragraph if this sIRB will be used: This study has been 
reviewed and approved by a committee called the Fred Hutchinson Cancer Research 
Center Institutional Review Board. If you have questions about your rights as a 
research participant, or problems with or concerns about how you are being treated in 
this study, contact the Director at 206-667-5900 or irodirector@fredhutch.org. 
You may also contact the [name of local IRB/EC] at [insert contact information].If 
you want to leave this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
Your permissions and signature  
24. In Section 14 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. 
 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 116 of 127 
 
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.  
 
 
25. 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 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 117 of 127 
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. 
 
 
 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 118 of 127 
Appendix F 
Low risk guidelines (for U.S. studies) 
 
 
 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 119 of 127 
 
 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 120 of 127 
For US volunteers on Pre-exposure prophylaxis (PrEP) 
1. PrEP ASSESSMENT 
• Reports equal to or greater than six consecutive months of protective PrEP use 
• Commits to maintaining protective PrEP use throughout trial 
• Participant 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?” 
2. SEXUAL BEHAVIORS 
• Persons stably taking PrEP as prescribed above for 6 months or longer are 
considered low risk of HIV infection, regardless of any sexual behavior that might 
otherwise be associated with high risk of HIV exposure. 
3. NON-SEXUAL BEHAVIORS 
In the last 12 months did not: 
• Inject drugs or other substances without a prescription 
• Use cocaine, methamphetamine, or excessive alcohol, which in the investigator’s 
judgment, rendered the participant at greater than low risk for acquiring HIV 
infection. 
The investigator’s judgment should consider local epidemiologic information 
about HIV prevalence in the area and community networks. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 121 of 127 
Appendix G 
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 vaccine could affect the developing baby. 
You must agree to use effective birth control from 21 days before your first injection 
until 8 weeks after the time of your fifth study injection (14 months).  
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). 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 122 of 127 
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. 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 123 of 127 
Appendix H 
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 300 Study Specific Procedures. 
Neuroinflammatory disorders 
Musculoskeletal disorders 
Skin disorders 
• 
Cranial nerve disorders, including 
paralyses/paresis (eg Bell’s palsy)  
• 
Optic neuritis 
• 
Multiple sclerosis 
• 
Transverse myelitis 
• 
Guillain-Barré syndrome, including 
Miller Fisher syndrome and other variants 
• 
Acute disseminated encephalomyelitis, 
including site specific variants: eg non-
infectious encephalitis, 
encephalomyelitis, myelitis, 
myeloradiculoneuritis 
• 
Myasthenia gravis, including Lambert-
Eaton myasthenic syndrome  
• 
Immune-mediated peripheral 
neuropathies and plexopathies, (including 
chronic inflammatory demyelinating 
polyneuropathy, multifocal motor 
neuropathy and polyneuropathies 
associated with monoclonal 
gammopathy). 
• 
Narcolepsy 
• 
Systemic lupus erythematosus and 
associated conditions 
• 
Systemic scleroderma (Systemic 
sclerosis), including diffuse systemic 
form and CREST syndrome 
• 
Idiopathic inflammatory myopathies, 
including dermatomyositis  
• 
Polymyositis  
• 
Antisynthetase syndrome 
• 
Rheumatoid arthritis, and associated 
conditions including juvenile chronic 
arthritis and Still’s disease 
• 
Polymyalgia rheumatica 
• 
Spondyloarthritis, including ankylosing 
spondylitis, reactive arthritis (Reiter's 
Syndrome) and undifferentiated 
spondyloarthritis  
• 
Psoriatic arthropathy 
• 
Relapsing polychondritis 
• 
Mixed connective tissue disorder 
• 
Psoriasis 
• 
Vitiligo 
• 
Erythema nodosum 
• 
Autoimmune bullous skin 
diseases (including pemphigus, 
pemphigoid and dermatitis 
herpetiformis) 
• 
Alopecia areata 
• 
Lichen planus 
• 
Sweet’s syndrome 
• 
Localized Scleroderma 
(Morphea)  
• 
Cutaneous lupus erythematosus 
 
Metabolic disorders 
• 
Addison’s disease 
• 
Autoimmune thyroiditis 
(including Hashimoto thyroiditis) 
• 
Diabetes mellitus type I 
• 
Grave's or Basedow’s disease 
Vasculitides 
Blood disorders 
Others 
• 
Large vessels vasculitis including: giant 
cell arteritis such as Takayasu’s arteritis 
and temporal arteritis.  
• 
Medium sized and/or small vessels 
vasculitis including: polyarteritis nodosa, 
Kawasaki's disease, microscopic 
polyangiitis, Wegener’s granulomatosis, 
Churg-Strauss syndrome (allergic 
granulomatous angiitis), Buerger’s 
disease (thromboangiitis obliterans), 
necrotizing vasculitis and anti-neutrophil 
cytoplasmic antibody (ANCA) positive 
vasculitis (type unspecified), Henoch-
Schonlein purpura, Behcet’s syndrome, 
leukocytoclastic vasculitis. 
• 
Autoimmune hemolytic anemia 
• 
Autoimmune thrombocytopenia 
• 
Antiphospholipid syndrome 
• 
Pernicious anemia 
• 
Autoimmune aplastic anemia 
• 
Autoimmune neutropenia  
• 
Autoimmune pancytopenia 
 
Gastrointestinal disorders 
• 
Celiac disease 
• 
Crohn’s disease 
• 
Ulcerative colitis 
• 
Ulcerative proctitis 
 
Liver disorders 
• 
Autoimmune cholangitis 
• 
Autoimmune hepatitis 
• 
Primary biliary cirrhosis 
• 
Primary sclerosing cholangitis 
• 
Autoimmune glomerulonephritis 
(including IgA nephropathy, 
glomerulonephritis rapidly 
progressive, membranous 
glomerulonephritis, 
membranoproliferative 
glomerulonephritis, and 
mesangioproliferative 
glomerulonephritis) 
• 
Ocular autoimmune diseases 
(including autoimmune uveitis 
and autoimmune retinopathy) 
• 
Autoimmune 
myocarditis/cardiomyopathy 
• 
Sarcoidosis 
• 
Stevens-Johnson syndrome 
• 
Sjögren’s syndrome 
• 
Idiopathic pulmonary fibrosis 
• 
Goodpasture syndrome 
• 
Raynaud’s phenomenon 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 124 of 127 
Appendix I 
Protocol team 
Protocol leadership 
Chair 
Lindsey Baden 
Brigham & Women’s Hospital 
617-732-6801 
lbaden@bwh.harvard.edu 
Medical officer 
Laura Polakowski 
DAIDS, NIAID 
240-627-3040 
laura.polakowski@nih.gov 
Chair 
Ken Mayer 
Fenway Institute 
617-927-6087 
KMayer@fenwayhealth.org 
Laboratory lead 
John Hural 
HVTN Laboratory Program 
206-667-1683 
jhural@fredhutch.org 
Protocol Team leader 
Will Hahn 
HVTN Core, Fred Hutch 
206-667-3431 
whahn@fredhutch.org 
Statistician 
Ollivier Hyrien 
HVTN SDMC 
206-667-2809 
ohyrien@fredhutch.org 
Other contributors to the original protocol 
Core medical monitor 
Will Hahn 
HVTN Core, Fred Hutch 
DAIDS protocol 
pharmacists 
Oladapo Alli, 
DAIDS, NIAID 
240-627-3593 
Azizza Davis, 
DAIDS, NIAID 
240-669-5248 
Study product developer 
representative 
Bart Haynes 
Duke Human Vaccine Institute 
Clinical safety specialist 
Megan Jones 
HVTN Core, Fred Hutch 
 
Daniel Tonkin  
Duke Human Vaccine Institute 
Clinical trials managers 
Shelly Ramirez 
Taylor Jones 
HVTN Core, Fred Hutch 
 
Emmanuel Walter  
Duke Human Vaccine Institute 
SDMC Associate director 
Jessica Andriesen 
HVTN SDMC, Fred Hutch 
 
Zachary Sagawa  
Access to Advanced Health 
Institute  
Statistical research 
associate 
Abby Isaacs 
HVTN SDMC, Fred Hutch 
 
Antu Dey 
International AIDS Vaccine 
Initiative 
Clinical data managers 
Melissa Peda, 
Jessica Andriessen 
HVTN SDMC, Fred Hutch 
Laboratory center 
representative 
Jen Hanke 
HVTN Laboratory Program, 
Fred Hutch 
SDMC Associate director 
of lab science 
April Randhawa 
HVTN SDMC, Fred Hutch 
Regulatory affairs 
associate 
Liz Briesemeister 
HVTN Core, Fred Hutch 
DAIDS Product Lead 
Michael Pensiero 
DAIDS, NIAID 
Clinic coordinator 
Rossi Fish 
Fenway Health 
Protocol development 
managers 
Daciana Margineantu, 
Smitha Sripathy 
HVTN Core, Fred Hutch 
Community Advisory 
Board (CAB) members 
Harrison Knowlton 
Boston HIV Research CAB 
Community engagement 
unit representative 
Gail Broder  
HVTN Core, Fred Hutch 
 
John Isaac 
Boston HIV Research CAB 
Community 
educator/recruiter 
Adrianna Boulin 
Fenway Health 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 125 of 127 
Appendix J 
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 300 are described below. 
Protocol history and modifications 
Date: September 26, 2022 
Protocol version: Version 2.0 
Protocol modification: Full protocol amendment 1 
Item 1 
Updated in Section 1, Executive summary; Section 2.2, Clinical experience with 
recombinant Env vaccines; Section 2.5, Rationale for Dose of Adjuvant; Section 
3, Objectives and Endpoints for Part A and Part B; Section 5, Study design; 
Section 6, Statistical considerations; Section 7, Study vaccine preparation, 
storage, and administration; Section 9.7, Initial safety review for Part B, Group 
2; A new Appendix B, Schedule of procedures for Part B and a new Appendix 
E, Sample informed consent (SICF) for Part B: Information related to the 
addition of Part B and recruitment of additional participants 
Item 2 
Updated in Section 2.2, Clinical experience with recombinant Env vaccines: 
Updated safety data for HVTN 137 and HVTN 300 Part A 
Item 3 
Added in Section 2.2, Clinical experience with recombinant Env vaccines: 
Rationale for 7-day reactogenicity monitoring period 
Item 4 
Revised in Section 5.1.2, Exclusion criteria: Exclude volunteers with congenital 
or acquired immunodeficiency 
Item 5 
Updated in Section 1.3, Study products; Section 7.2.4, Tris-NaCl buffer (TBS) 
(Diluent) for Part A; new Section 7.2.5, Sodium Chloride for injection, 0.9% 
USP (Diluent) for Part B and Section 7.3, Product preparation: Sodium 
Chloride diluent for Part B 
Item 6 
Clarified in Section 5.2.2, Discontinuation of study vaccine administration: 
Assessment of grade 3 adverse event (AE) 
Item 7 
Clarified in Section 8.7, Monitoring for HIV infection: Included reference to 
HVTN HIV testing algorithm 
Item 8 
Added in Section 10.1, Protocol conduct: Stipulation for Protocol monitoring 
Item 9 
Revised in Section 1.5, Study plan and schema table; Section 9.5, Initial safety 
review for Part A and Section 9.6, Interim safety review for Part A: Updated 
safety reviews 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 126 of 127 
Item 10 Added in Section 5.1.2, Exclusion criteria; Section 5.2.1, Delaying vaccinations 
for a participant and in Section 8.3, Reactogenicity assessments: considerations 
for timing of receipt of vaccines for Monkeypox 
Item 11 Corrected in Appendix A, Schedule of procedures for Part A: corrected errors in 
blood volume. 
Item 12 Revised in Section 7.6, Study vaccine accountability: Deleted language related 
to randomization 
Item 13 Revised in Section 2.8.1, Potential Risks: Included reference to risks associated 
with 3M-052-AF + Alum 
Item 14 Updated Appendix I, Protocol Team: Included new team members 
Item 15 Updated in Title page; Appendix J, Version history; Acronyms and 
abbreviations and Section 12, Literature cited: Contents of this amendment 
Item 16 Updated throughout the Protocol: Name of the study product provider 
Item 17 Updated throughout the Protocol: Formulation of the adjuvant 3M-052-AF 
Item 18 Corrected throughout the Protocol: Minor errors in grammar, typography, 
formatting 
Item 19 Updated throughout the Protocol: Section headers, Section sub- headers, Section 
numbering and cross-references 
Item 20 Updated per Protocol Version 1.0, Letter of Amendment 1, dated Feb 09, 2021 
Item 21 Updated per Protocol Version 1.0, Clarification Memo 1, dated Aug 16, 2022 
 
Date: August 16, 2022 
Protocol version: Version 1.0 
Protocol modification: Clarification Memo 1 
Item 1 
Added in Section 9.4, Total blood volume: alternate laboratory specimen tube 
types allowed for research samples upon HVTN laboratory center approval 
Date: February 09, 2021 
Protocol version: Version 1.0 
Protocol modification: Letter of Amendment 1 
Item 1 
Updated the Protocol Title page: added IND number 027197 for this protocol 
Item 2 
Clarified in Section 5.1.2, Exclusion criteria: criterion 8 referring to serious 
reactions to vaccines or any component of the study vaccine 
Item 3 
Added in Section 5.2.2, Discontinuation of study vaccine administration: 
definition of clinically significant type 1 hypersensitivity 

HVTN 300 Version 2.0 / September 26, 2022 
HVTN300_v2.0_Final_26Sep2022 / Page 127 of 127 
Date: December 16, 2020 
Protocol version: 1.0  
Protocol modification: Original protocol