Characterizing SARS-CoV-2-specific Immunity in Convalescent Individuals
Conditions: SARS-CoV-2, COVID-19
Sponsor: HIV Vaccine Trials Network

 
 
 
PROTOCOL 
HVTN 405/HPTN 1901 
Characterizing SARS-CoV-2-specific immunity in 
convalescent individuals 
DAIDS DOCUMENT ID 38725 
Non IND Study  
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 
June 4, 2020 
FINAL 
HVTN 405/HPTN 1901 
Version 2.0 

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Contents 
1 Overview ........................................................................................................................4 
1.1 
Protocol Team ................................................................................................7 
2 Ethical considerations ....................................................................................................8 
3 IRB/EC review considerations .......................................................................................9 
3.1 
Minimized risks to participants ......................................................................9 
3.2 
Reasonable risk/benefit balance .....................................................................9 
3.3 
Equitable participant selection .....................................................................10 
3.4 
Appropriate informed consent ......................................................................10 
3.5 
Protect privacy/confidentiality .....................................................................10 
4 Background ..................................................................................................................12 
4.1 
Rationale for trial concept ............................................................................12 
4.2 
Potential Risks and Benefits .........................................................................14 
5 Objectives and endpoints .............................................................................................16 
5.1 
Primary objectives and endpoints ................................................................16 
5.2 
Secondary objectives and endpoints ............................................................17 
5.3 
Exploratory objectives ..................................................................................17 
6 Statistical considerations ..............................................................................................19 
6.1 
Accrual and sample size calculations ...........................................................19 
6.2 
Statistical analyses ........................................................................................21 
7 Selection and withdrawal of participants .....................................................................24 
7.1 
Inclusion criteria ...........................................................................................24 
7.2 
Exclusion criteria ..........................................................................................24 
7.3 
Participant termination from the study .........................................................25 
8 Clinical procedures ......................................................................................................26 
8.1 
Informed consent ..........................................................................................26 
8.2 
Enrollment visit ............................................................................................27 
8.3 
Follow-up visits ............................................................................................28 
8.4 
Nasal and nasopharyngeal sampling ............................................................28 
8.5 
Visit windows ...............................................................................................28 
9 Laboratory ....................................................................................................................29 
9.1 
HVTN CRS laboratory procedures ..............................................................29 
9.2 
Total blood volume ......................................................................................29 
9.3 
Endpoint assays ............................................................................................29 
9.4 
Lab assay portfolio .......................................................................................31 
9.5 
Exploratory studies .......................................................................................32 
9.6 
Specimen storage and other use of specimens .............................................32 
9.7 
Biohazard containment .................................................................................32 
10 Protocol conduct ..........................................................................................................34 
10.1 Emergency communication with study participants ....................................34 
10.2 Study termination .........................................................................................35 
11 Version history .............................................................................................................36 

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12 Document references (other than literature citations) ..................................................38 
13 Acronyms and abbreviations........................................................................................40 
14 Literature cited .............................................................................................................42 
Appendix A Sample informed consent form ....................................................................45 
Appendix B Table of procedures (for sample informed consent form) ............................57 
Appendix C Schedule of procedures ................................................................................58 
Appendix D Visit windows ...............................................................................................59 
Appendix E Protocol Signature Page ...............................................................................60 
 

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1 
Overview 
Title  
Characterizing SARS-CoV-2-specific immunity in convalescent individuals 
Primary objectives 
Primary objective 1: 
To identify serologic reactivities that differentiate SARS-CoV-2 infection from 
vaccination. 
Primary objective 2: 
To develop and formally qualify a suite of immunologic assays and reference 
reagents that permit detailed interrogations of the immune response to SARS-
CoV-2 infection in preparation for similar assessments of vaccine-elicited 
immune responses and immunotherapeutics. 
Primary objective 3: 
To measure SARS-CoV-2-specific adaptive immune responses in order to 
identify immune markers of COVID-19 disease severity and duration in different 
demographic groups (eg, age, gender) and in people with different medical 
histories, including pre-existing conditions, new acute or chronic medical 
conditions, and concomitant medications. 
Primary objective 4: 
To characterize presentations of SARS-CoV-2 infection, including the clinical 
course of COVID-19, among convalescent individuals. 

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Table 1-1 Cohorts 
Group 
 
N 
(approximate*)  
1 
Persons not hospitalized for COVID-19, without clinical spectrum or outcomes 
specified in group 3 
 
1A 
Persons with asymptomatic infection, ages 18 through 55, inclusive 
75-125 
1B 
Persons with asymptomatic infection, age > 55 
50-75 
1C 
Persons with symptomatic infection (ie, COVID-19) ages 18 through 55 
175 
1D 
Persons with symptomatic infection (ie, COVID-19), age > 55  
75 
 
 
 
2 
Persons previously hospitalized for COVID-19, without clinical spectrum or outcomes 
specified in group 3 
 
2A 
Persons 18 through 55 years of age 
125 
2B 
Persons > 55 years of age 
75 
 
 
 
3** 
Persons with specific clinical spectrums or outcomes, regardless of hospitalization 
history (eg, persons recovered after intubation, with prolonged viral shedding, with 
myocarditis/pericarditis, with rapid recovery from COVID-19, with a second positive 
SARS-CoV-2 RT-PCR test result after a negative result) 
100-150 
*Actual sample size may be adjusted over time in response to evolving information regarding SARS-CoV-2 infection and 
COVID-19. 
** See HVTN 405/HPTN 1901 Study Specific Procedures (SSP). 
Participants 
Approximately 675-800 volunteers aged 18 or older  
Design 
Observational cohort study 
Duration per participant 
Minimum one visit (1-8 weeks post resolution of COVID-19 OR 2-10 weeks post 
most recent positive SARS-CoV-2 test, if asymptomatic) and optional visits 
approximately 2 months, 4 months, and 1 year later. Additional follow up visit(s) 
may be added over time in response to evolving information regarding SARS-
CoV-2 infection and COVID-19.  
Estimated total study duration 
15 months (includes enrollment) with possible extension in response to evolving 
information regarding SARS-CoV-2 infection and COVID-19. 
Core operations 
HVTN Vaccine Leadership Group/Core Operations Center, Fred Hutchinson 
Cancer Research Center (Fred Hutch) (Seattle, Washington, USA) 

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Statistical and data management center (SDMC) 
Statistical Center for HIV/AIDS Research and Prevention (SCHARP), Fred Hutch 
(Seattle, Washington, USA) 
HVTN Laboratory Center (LC) 
SARS-CoV-2 diagnostic laboratories 
• University of Washington Virology Laboratory (Seattle, Washington, USA) 
• Bio-Analytical Research Corporation – South Africa (BARC-SA) 
(Johannesburg, South Africa) 
Endpoint assay laboratories 
• Duke University Medical Center (Durham, North Carolina, USA) 
• Fred Hutch/University of Washington (Seattle, Washington, USA) 
• University of North Carolina Michael Hooker Research Center (Chapel Hill, 
North Carolina, USA) 
• Cape Town HVTN Immunology Laboratory (Cape Town, South Africa) 
• South Africa Immunology Laboratory and National Institute for 
Communicable Diseases (SAIL-NICD) (Johannesburg, South Africa) 
Study sites 
HIV Vaccine Trials Network (HVTN) and HIV Prevention Trials Network 
(HPTN) Clinical Research Sites (CRSs) in North and South America and in sub-
Saharan Africa participating in this study to be specified in the Site 
Announcement Memo. 

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1.1 
Protocol Team 
Protocol leadership 
Chair 
Larry Corey 
HVTN Core, Fred Hutch 
206-667-6770 
lcorey@fredhtch.org 
Lead Statistician 
Sue Li 
HVTN SDMC, Fred Hutch 
206-667-7066 
sli@fredhutch.org 
Co-chairs 
Shelly Karuna 
HVTN Core, Fred Hutch 
206-667-4355 
mkaruna@fredhutch.org 
Katherine Gill 
Masiphumelele CRS 
0829290991 
katherine.gill@hiv-
research.org.za 
Medical officers 
Laura Polakowski 
DAIDS, NIAID 
240-627-3040 
laura.polakowski@nih.gov 
Julia Hutter 
DAIDS, NIAID 
240-627-3039 
julia.hutter@nih.gov 
Protocol Team 
leader 
Shelly Karuna 
HVTN Core, Fred Hutch 
206-667-4355 
mkaruna@fredhutch.org 
Laboratory leads 
John Hural 
HVTN Laboratory Program 
206-667-1683 
jhural@fredhutch.org 
 
 
 
David Montefiori 
HVTN Laboratory Program 
919-684-5278 
david.montefiori@duke.edu 
Other contributors to the original protocol 
Co-Protocol Team 
Leader 
Will Hahn 
HVTN Core, Fred Hutch 
Statisticians  Ollivier Hyrien 
Leigh Fisher 
HVTN SDMC, Fred Hutch 
Laboratory center 
representatives 
Jen Hanke 
Lisa Sanders 
HVTN Laboratory 
Program, Fred Hutch 
Clinical trials 
manager 
Carissa Karg 
HVTN Core, Fred Hutch 
Regulatory affairs 
associate 
Laurie Rinn 
HVTN Core, Fred Hutch 
Clinical data 
managers 
Alison Ayres 
Vicky Kim 
HVTN SDMC, Fred Hutch 
Clinic coordinator 
Theresa Wagner 
San Francisco Department 
of Public Health 
Clinical safety 
specialist 
Megan Jones 
HVTN Core, Fred Hutch 
Statistical research 
associates 
Doug Grove 
Shannon Grant 
HVTN SDMC, Fred Hutch 
SDMC Associate 
director of lab 
science 
April Randhawa 
HVTN SDMC, Fred Hutch 
Community 
engagement unit 
representative  
Gail Broder 
HVTN Core, Fred Hutch 
Protocol 
development 
manager 
Meg Trahey 
HVTN Core, Fred Hutch 
Community 
educator 
representative  
Ro Yoon 
UW/Fred Hutch CRS 
Community 
Advisory Board 
member 
representative 
Nick Maurice, UW/Fred 
Hutch CRS CAB 
Regional medical 
liaison Peru 
Robert De La Grecca 
HVTN Core, Fred Hutch 
Regional medical 
liaison sub-
Saharan Africa 
Simba Takuva 
HVTN Core, Fred Hutch 

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2 
Ethical considerations 
It is critical that universally accepted ethical guidelines are followed at all sites 
involved in the conduct of clinical trials. The HIV Vaccine Trials Network 
(HVTN) and the HIV Prevention Trials Network (HPTN) have addressed ethical 
concerns in the following ways: 
• HVTN and HPTN (Network) trials are designed and conducted to enhance the 
scientific knowledge base using methods that are scientifically rigorous and 
valid, and in accordance with International Council for Harmonisation of 
Technical Requirements for Pharmaceuticals for Human Use (ICH) and/or 
other Good Clinical Practice (GCP) guidelines. 
• Network scientists and operational staff incorporate the philosophies 
underlying major codes (1-3), declarations, and other guidance documents 
relevant to human subjects research into the design and conduct of clinical 
trials. 
• Network scientists and operational staff are committed to substantive 
community input—into the planning, conduct, and follow-up of its research—
to help ensure that locally appropriate cultural and linguistic needs of study 
populations are met, in keeping with the Good Participatory Practices (GPP) 
for Emerging Pathogens guidance. Community Advisory Boards (CAB) are 
required by DAIDS and supported at all HVTN and HPTN research sites to 
ensure community input, in accordance with GPP and all local and national 
guidelines.  
• The Networks provide training so that all participating sites similarly ensure 
fair participant selection, protect the privacy of research participants, and 
obtain meaningful informed consent. During the study, participants will have 
their wellbeing monitored, and to the fullest extent possible, their privacy 
protected. Participants may withdraw from the study at any time. 
• Prior to implementation, Network trials are rigorously reviewed by scientists 
who are not involved in the conduct of the trials under consideration. 
• Network trials are reviewed by local and national regulatory bodies and are 
conducted in compliance with all applicable national and local regulations. 
• The Networks design their research to minimize risk and maximize benefit to 
both study participants and their local communities.  
• The Networks value the role of in-country Institutional Review Boards 
(IRBs), Ethics Committees (ECs), and other Regulatory Entities (REs) as 
custodians responsible for ensuring the ethical conduct of research in each 
setting. 

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3 
IRB/EC review considerations 
US federal regulations require IRBs/ECs/REs to ensure that certain requirements 
are satisfied on initial and continuing review of research (Title 45, Code of 
Federal Regulations (CFR), Part 46.111(a) 1-7; 21 CFR 56.111(a) 1-7). The 
following section highlights how this protocol addresses each of these research 
requirements. Each Network Investigator welcomes IRB/EC/RE questions or 
concerns regarding these research requirements. 
This trial is being conducted in countries outside of the United States, with 
funding from the US NIH among others. Due to this, the trial is subject to both 
US and local regulations and guidelines on the protection of human research 
subjects and ethical research conduct. Where there is a conflict in regulations or 
guidelines, the Networks strive towards maximum protection of human research 
participants. 
In compliance with international and local (as appropriate) ICH and/or other GCP 
guidelines, each research location has a locally-based Principal Investigator (PI) 
who is qualified to conduct (and supervise the conduct of) the research. The 
investigators take responsibility for the conduct of the study, including obtaining 
all appropriate regulatory and ethical reviews of the research. 
3.1 
Minimized risks to participants 
45 CFR 46.111 (a) 1 and 21 CFR 56.111 (a) 1: Risks to subjects are 
minimized. 
This protocol minimizes risks to participants by (a) correctly and promptly 
informing participants about risks so that they can join in partnership with the 
researcher in recognizing and reporting harms; (b) respecting local/national blood 
draw limits; and (c) having staff properly trained in administering study 
procedures that may cause physical harm or psychological distress, such as blood 
draws. 
3.2 
Reasonable risk/benefit balance 
45 CFR 46.111(a) 2 and 21 CFR 56.111(a) 2: Risks to subjects are 
reasonable in relation to anticipated benefits, if any, to subjects, and 
the importance of the knowledge that may reasonably be expected to 
result. 
In all public health research, the risk-benefit ratio may be difficult to assess 
because the benefits to a healthy participant are not as apparent as they would be 
in treatment protocols, where a study participant may be ill and may have 
exhausted all conventional treatment options. However, this protocol is designed 

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to minimize the risks to participants while maximizing the potential value of the 
knowledge it is designed to generate. 
3.3 
Equitable participant selection  
45 CFR 46.111 (a) 3 and 21 CFR 56.111 (a) 3: Subject selection is 
equitable 
This protocol has specific inclusion and exclusion criteria for investigators to 
follow in admitting participants into the protocol. Participants are selected 
because of these criteria and not because of positions of vulnerability or privilege. 
Investigators are required to maintain screening and enrollment logs to document 
volunteers who screened into and out of the protocol and for what reasons. 
3.4 
Appropriate informed consent 
45 CFR 46.111 (a) 4 and 5 and 21 CFR 56.111 (a) 4 and 5: Informed 
consent is sought from each prospective subject or the subject’s 
legally authorized representative as required by 45 CFR 46.116 and 
21 CFR Part 50; informed consent is appropriately documented as 
required by 45 CFR 46.117 and 21 CFR 50.27 
The protocol specifies that informed consent must be obtained before any study 
procedures are initiated and assessed throughout the trial (see Section 8.1). Each 
site is provided training in informed consent by the Networks as part of its 
entering the Network. The HVTN and HPTN require a signed consent document 
for documentation, in addition to chart notes or a consent checklist. 
3.5 
Protect privacy/confidentiality 
45 CFR 46.111 (a) 7 and 21 CFR 56.111 (a) 7: There are adequate 
provisions to protect the privacy of subjects and maintain the 
confidentiality of data. 
Privacy refers to an individual’s right to be free from unauthorized or 
unreasonable intrusion into his/her private life and the right to control access to 
individually identifiable information about him/her. The term “privacy” concerns 
research participants or potential research participants as individuals whereas the 
term “confidentiality” is used to refer to the treatment of information about those 
individuals. This protocol respects the privacy of participants by informing them 
about who will have access to their personal information and study data (see 
Appendix A). The privacy of participants is protected by assigning unique 
identifiers in place of the participant’s name on study data and specimens. In the 
United States, research participants in HVTN and HPTN protocols are protected 
by a Certificate of Confidentiality from the US NIH, which can prevent disclosure 

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of study participation even when that information is requested by subpoena. 
Participants are told of the use and limits of the certificate in the study consent 
form. In addition, each staff member at each study site in this protocol signs an 
Agreement on Confidentiality and Use of Data and Specimens with the HVTN. In 
some cases, a comparable confidentiality agreement process may be acceptable. 
Each study site participating in the protocol is required to have a standard 
operating procedure on how the staff members will protect the confidentiality of 
study participants. 

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4 
Background 
4.1 
Rationale for trial concept 
The novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is 
one of three related betacoronaviruses that have caused highly pathogenic 
epidemics in humans; the others are Severe Acute Respiratory Syndrome 
Coronavirus (SARS-CoV-1) and Middle East Respiratory Syndrome Coronavirus 
(MERS-CoV). An initial outbreak of SARS-CoV-2, first reported in Wuhan, 
China, quickly became a pandemic and currently presents an unprecedented 
global public health challenge. Given the extent of dissemination, mathematical 
models suggest that SARS-CoV-2 will likely become endemic in human 
populations (4). Therefore, there is a critical need for an improved understanding 
of the immune response following natural infection in order to develop a vaccine 
to prevent transmission and to identify and develop strategies to distinguish 
vaccine-elicited responses from those induced by SARS-CoV-2 natural infection.  
Early epidemiologic data suggest that specific populations are at higher risk for 
developing poor clinical outcomes during acute infection but even within defined 
populations there exist a variety of disease phenotypes (5). The variety of immune 
outcomes following natural infection is not well understood, and there is currently 
no preventive vaccine or effective therapy. The following study proposes to 
illuminate the variety of immune signatures after recovery from natural SARS-
CoV-2 infection across a range of clinical phenotypes, to develop and refine 
immunologic assays and inform efforts to distinguish natural infection from 
vaccine-elicited responses in preparation for future preventive and therapeutic 
vaccine trials, and to explore whether clinical phenotypes are associated with 
particular immune outcomes. 
The published data regarding the immune response following natural coronavirus 
infection are largely drawn from the experience with SARS-CoV-1 (6). SARS-
CoV-1 and SARS-CoV-2 share ~79% sequence identity and use the same cellular 
receptor, however, there are several differences in spike contact sites (7). 
Neutralizing Ab responses to SARS-CoV-1 infection show considerable 
variability, but in general are first observed in the second week after onset of 
fever, peak during week 4, and persist in some cases for >200 days, but often 
wane considerably by 2 years post-infection (8-10). In convalescent sera 12 
months post-infection with SARS-CoV-1, both IgG directed against whole cell 
lysates and neutralizing antibodies were detected in greater than 90% of infected 
patients. However, no correlation was observed between total IgG titers and 
degree of neutralization (11). Data following mild SARS-CoV-1 infection further 
suggest that these responses are likely to persist beyond one year, as CD4+ T cells 
capable of producing IFN-gamma in response to a variety of viral antigens were 
detected 12 years following natural infection (12, 13). This is in contrast to the 
duration of the humoral response following severe SARS-CoV-1 infection, as 
neither SARS-specific IgG nor SARS-specific memory B cells (as assessed via 

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ELISpot) were detected in the periphery of patients who recovered from severe 
SARS (14).  
Rapid and high neutralizing Ab responses that decline early are associated with 
greater disease severity and a higher risk of death from SARS-CoV-1 infection (9, 
15, 16). A similar phenomenon was observed in a nonhuman primate model of 
SARS-CoV-1 infection, where ensuing acute lung injury was attributed to 
inflammatory cytokines and skewed macrophage functions (16). Additional 
variations in the immune response to coronavirus infection are associated with 
clinical disease. More PBMCs capable of producing IFN-gamma and or TNF-
alpha were isolated 6 to 24 months after infection in patients recovered from 
severe MERS-CoV than in asymptomatic seroconverters (17). CD4+ T cells 
isolated from patients convalescing from severe SARS-CoV-1 infection were 
capable of recognizing more epitopes than those in patients with mild disease 
(11). Titers of antibodies directed against the MERS spike protein were also 
higher in patients with severe MERS disease than in those with milder disease 
(18), and higher titers of antibodies directed against the SARS-CoV-2 spike 
protein were recently reported for those with severe SARS-CoV-2 disease 
compared to those with milder disease (19).  
It remains to be seen to what extent lessons learned from SARS-CoV-1 are 
helpful in formulating hypotheses about SARS-CoV-2. Recent neutralizing and 
non-neutralizing monoclonal antibodies (mAbs) from SARS-CoV-2 infected 
individuals provide some of the earliest insights (20). Non-neutralizing but not 
neutralizing mAbs bound SARS-CoV-1 and MERS-CoV Spike proteins. The 
neutralizing mAbs targeted the receptor binding domain (RBD), arose from 
multiple families of heavy and light chains, and possessed few somatic mutations, 
suggesting a relatively low barrier to vaccine elicitation. Many of the non-
neutralizing antibodies targeted regions outside the RBD, which probably 
explains their lack of neutralizing activity. There appears to be limited cross-
neutralization of SARS-CoV-1 and SARS-CoV-2 (20-22), although one group 
identified a monoclonal antibody from a convalescent SARS-CoV-1 subject that 
exhibits substantial neutralizing activity against SARS-CoV-2 (23). 
As SARS-CoV-2 becomes endemic, understanding the immunity generated by 
natural infection will be critical for both public health efforts and rational vaccine 
design. Prior investigations have revealed both protective and harmful roles for 
pre-existing immunity. Human challenge models with endemic coronavirus 
(229E) have suggested that pre-challenge serum neutralizing antibody is 
significantly associated with protection from clinical disease (24). In addition, low 
pre-challenge secretory IgA was associated with the development of disease and 
prolonged viral shedding (defined as greater than 5 days), suggesting that pre-
existing immune memory can ameliorate the clinical course of coronavirus 
disease and reduce transmissibility. Less is known about the specific role of 
CD8+ T cells but vaccines targeting CD8+ T-cell epitopes are capable of inducing 
protective immunity against homologous rechallenge in murine models (25, 26). 
Additional studies in preclinical models have demonstrated that there are cross-
reactive CD4+ T cells between SARS-CoV-1 and MERS-CoV and that these T-

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cells are capable of mediating protection when they are located in the correct 
anatomic compartments (eg, in lung-resident CD4+ T cells) (19). 
A critical unknown is the quality and duration of the adaptive immune response to 
SARS-CoV-2 infection and whether the immune response is associated with the 
underlying disease phenotype. Understanding the dynamics and duration, as well 
as the epitope specificity and other defining signatures, of the natural immune 
response can inform rational design and testing of preventive and therapeutic 
vaccines and monoclonal antibodies. In addition, the data could inform predictive 
models and public health decisions, such as decisions regarding population-
specific return-to-work policies and surveillance practices during future 
epidemics.  
To this end, data generated from this cohort study will facilitate the development 
and formal qualification of a suite of immunologic assays, including 
characterizing the kinetics, magnitude and duration of adaptive immune responses 
to SARS-CoV-2 infection; identifying and producing stable supplies of key 
reference agents; and ultimately establishing GCLP-compliant centralized 
laboratory activities that build upon and advance the Networks’ existing 
laboratory expertise and resources. Furthermore, the study will generate highly 
standardized datasets of SARS-CoV-2-specific adaptive immunity; identify 
immune markers of COVID-19 disease severity and duration and shed light on the 
impact of demographic variables such as age and gender; and, perhaps most 
importantly, identify serologic reactivities that differentiate SARS-CoV-2 
infection from vaccination, all of which will inform future vaccine and 
monoclonal antibody design and testing. 
4.2 
Potential Risks and Benefits 
4.2.1 
Potential Risks 
The potential risks associated with this study are minimal and are primarily 
associated with sample collection and potential loss of confidentiality. The 
potential risks are outlined below. 
Blood Draw by Venipuncture: 
Blood drawing may cause pain and bruising and may, infrequently, cause a 
feeling of lightheadedness or fainting. Rarely, it may cause infection at the site 
where the blood is taken. Risk will be minimized by using sterile technique and 
universal precautions. Blood drawing may also cause anemia. 
Urine sample collection: 
There are no known risks for collection of urine by routine clean catch methods. 
Nasopharyngeal or nasal swab, and nasal wash sample collection: 

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Risks are minimal with a nasopharyngeal or nasal swab or a nasal wash. If a nasal 
or nasopharyngeal swab were misapplied, it could theoretically cause bleeding. 
Previous investigations using a similar washing strategy have been well tolerated 
(27). The major theoretical risk of instilling liquid into the nose (ie, a nasal wash) 
relate to the potential for aspiration into the respiratory tract. We will be using 
sterile solution, so we do not anticipate any risk of infection. 
Maintenance of Confidentiality: 
Participants will be asked to provide personal health information. Every effort 
will be made to protect participant’s privacy and confidentiality (see Section 3.5).  
4.2.2 
Known potential benefits 
There is no direct benefit for subjects who are enrolled in this study. 
A better understanding of the clinical history of SARS-CoV-2 infection, virus 
persistence in different body fluids and the acquisition of samples to study 
infection and immune responses, including, in particular, responses that may 
distinguish natural infection from vaccination, constitutes a great potential benefit 
to society. These samples will assist in the understanding of the immune 
responses to SARS-CoV-2 infection and will help guide the development and 
testing of diagnostics, vaccines, monoclonal antibodies, and treatments for SARS-
CoV-2 infection. 

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5 
Objectives and endpoints 
5.1 
Primary objectives and endpoints 
Primary objective 1: 
To identify serologic reactivities that differentiate SARS-CoV-2 infection from 
vaccination. 
Primary endpoints 1: 
Identification of humoral responses to peptide and protein antigens derived from 
SARS-CoV-2 structural proteins and regions of the spike protein not present in 
vaccines. 
Primary objective 2: 
To develop and formally qualify a suite of immunologic assays and reference 
reagents that permit detailed interrogations of the immune response to SARS-
CoV-2 infection in preparation for similar assessments of vaccine-elicited 
immune responses and immunotherapeutics.  
Primary endpoints 2: 
• SARS-CoV-2-specific antibody responses including binding, neutralization, 
and Antibody-Dependent Cellular Cytotoxicity (ADCC) 
• SARS-CoV-2-specific CD4+ and CD8+ T cell responses 
• SARS-CoV-2-specific memory B cell characterization 
Primary objective 3: 
To measure SARS-CoV-2-specific adaptive immune responses in order to 
identify immune markers of COVID-19 disease severity and duration in different 
demographic groups (eg, age, gender) and in people with different medical 
histories, including pre-existing conditions, new acute or chronic medical 
conditions, and concomitant medications.  
Primary endpoints 3: 
• Response rate, magnitude, and epitope specificity of SARS-CoV-2-specific 
antibody neutralization activity, binding, and antibody-dependent cellular 
cytotoxicity (ADCC) 
• Response rate, magnitude, and functional profiling of SARS-CoV-2-specific 
CD4+ and CD8+ T cells 

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• Phenotypic characterization of SARS-CoV-2-specific memory B cells 
Primary objective 4: 
To characterize presentations of SARS-CoV-2 infection, including the clinical 
course of COVID-19, among convalescent individuals. 
Primary endpoint 4: 
Demographics and medical history, including pre-existing conditions, new acute 
or chronic medical conditions, and concomitant medications 
5.2 
Secondary objectives and endpoints 
Secondary objective 1: 
To determine if participants with a history of SARS-CoV-2 infection have 
detectable levels of virus 
Secondary endpoint 1: 
Detection of viral RNA in nasopharyngeal or nasal swab samples via RT-PCR 
Secondary objective 2: 
To determine if participants with a history of SARS-CoV-2 infection have 
detectable levels of SARS-CoV-2-specific antibodies in nasal cavity 
Secondary endpoint 2: 
Response rate and magnitude of SARS-CoV-2-specific binding antibodies in 
nasal samples 
5.3 
Exploratory objectives 
Exploratory objective 1: 
To evaluate associations of host genetics (eg, HLA, FcR, ACE-2, TMPRSS2 gene 
variants) with immune responses and clinical outcomes  
Exploratory objective 2: 
To investigate immune-mediated enhancement of infection and disease (eg, 
antibody-dependent enhancement of infection in vitro) 
Exploratory objective 3: 

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To assess cross-reactivity of immune responses with other pathogens (eg, other 
circulating coronaviruses) 
Exploratory objective 4: 
To further evaluate immune responses associated with SARS-CoV-2 infection, 
additional assays may be performed including, but not limited to, antibody 
avidity, antibody isolation and mAb production/functional characterization  
Exploratory objective 5: 
To conduct analyses related to furthering the understanding of SARS-CoV-2, 
immunology, vaccines, passive protection, and clinical trial conduct 

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6 
Statistical considerations 
6.1 
Accrual and sample size calculations 
This protocol will enroll persons post report of recent SARS-CoV-2 infection (see 
Section 7). Recruitment will target enrolling 375-450 participants who were not 
hospitalized for COVID-19 (75-125 in Group 1A, 50-75 in Group 1B, 175 in 
Group 1C, and 75 in Group 1D), approximately 200 participants who were 
hospitalized (approximately 125 in Group 2A and 75 in Group 2B), and 100-150 
participants who exhibited specific clinical spectrums or outcomes (Group 3, see 
cohort descriptions in Table 1-1).  
6.1.1 
Sample size calculations  
One primary objective of this study is to characterize immune responses in 
participants with a history of SARS-CoV-2 infection and identify associations 
with the clinical course of COVID-19. The immune responses will be analyzed by 
measuring response rates and magnitudes among all participants. No adjustments 
for multiple comparisons will be made for the use of multiple assays. The 
precision with which the true response rate can be estimated from the observed 
data depends on the true underlying response rate and the sample size. Two-sided 
95% confidence intervals for the response rate based on observing a particular 
rate of responses among all participants (n=675-800) or within a group (n=375-
450, 200, 100-150) or within a subgroup (175, 125, 100, 75, 50) is shown in Table 
6-1. Calculations are done using the score test method (28).  
Table 6-1 Two-sided 95% confidence intervals for the true response rate based on observing 
a particular rate of responses among all participants (n = 675-800) and each group and 
subgroup (n=375-450, 200, 175, 150, 125, 100, 75, 50) 
No. of responses 
Observed response rate (%) 
95% Confidence interval 
400/800 
50 
[46.5, 53.5] 
480/800 
60 
[56.6, 63.3] 
560/800 
70 
[66.7, 73.1] 
640/800 
80 
[77.1, 82.6] 
720/800 
90 
[87.7, 91.9] 
 
 
 
338/675 
50.1 
[46.3, 53.8] 
405/675 
60 
[56.3, 63.6] 
472/675 
69.9 
[66.4, 73.3] 
540/675 
80 
[76.8, 82.8] 
608/675 
90.1 
[87.6, 92.1] 
 
 
 
225/450 
50 
[45.4, 54.6] 
270/450 
60 
[55.4, 64.4] 
315/450 
70 
[65.6, 74.1] 
360/450 
80 
[76.1, 83.4] 
405/450 
90 
[86.9, 92.4] 

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No. of responses 
Observed response rate (%) 
95% Confidence interval 
188/375 
50.1 
[45.1, 55.2] 
225/375 
60 
[55, 64.8] 
262/375 
69.9 
[65, 74.3] 
300/375 
80 
[75.7, 83.7] 
338/375 
90.1 
[86.7, 92.8] 
188/375 
50.1 
[45.1, 55.2] 
 
 
 
125/250 
50 
[43.8, 56.2] 
150/250 
60 
[53.8, 65.9] 
175/250 
70 
[64.1, 75.3] 
200/250 
80 
[74.6, 84.5] 
225/250 
90 
[85.7, 93.1] 
 
 
 
100/200 
50 
[43.1, 56.9] 
120/200 
60 
[53.1, 66.5] 
140/200 
70 
[63.3, 75.9] 
160/200 
80 
[73.9, 85] 
180/200 
90 
[85.1, 93.4] 
 
 
 
88/175 
50.3 
[43, 57.6] 
105/175 
60 
[52.6, 67] 
122/175 
69.7 
[62.5, 76] 
140/175 
80 
[73.5, 85.3] 
158/175 
90.3 
[85, 93.8] 
 
 
 
75/150 
50 
[42.1, 57.9] 
90/150 
60 
[52, 67.5] 
105/150 
70 
[62.2, 76.8] 
120/150 
80 
[72.9, 85.6] 
135/150 
90 
[84.2, 93.8] 
 
 
 
62/125 
49.6 
[41, 58.2] 
75/125 
60 
[51.2, 68.2] 
88/125 
70.4 
[61.9, 77.7] 
100/125 
80 
[72.1, 86.1] 
112/125 
89.6 
[83, 93.8] 
 
 
 
50/100 
50 
[40.4, 59.6] 
60/100 
60 
[50.2, 69.1] 
70/100 
70 
[60.4, 78.1] 
80/100 
80 
[71.1, 86.7] 
90/100 
90 
[82.6, 94.5] 
 
 
 
38/75 
50.7 
[39.6, 61.7] 
45/75 
60 
[48.7, 70.3] 
52/75 
69.3 
[58.2, 78.6] 
60/75 
80 
[69.6, 87.5] 
68/75 
90.7 
[82, 95.4] 
 
 
 

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No. of responses 
Observed response rate (%) 
95% Confidence interval 
25/50 
50 
[36.6, 63.4] 
30/50 
60 
[46.2, 72.4] 
35/50 
70 
[56.2, 80.9] 
40/50 
80 
[67, 88.8] 
The study is adequately powered to evaluate differences in response rates between 
groups. Combinations of true response rates for two groups that can be 
distinguished with statistical power of 80% and 90% are provided in Table 6-2. 
For example, we will have 80% (90%) power to detect the difference between 
Group 1 (n=375-450) and Group 2 (n=200) if the response rate is 63% (64-65%) 
in Group 1 and 50% in Group 2; we will have 80% (90%) power to detect the 
difference between Group 1 (n=375-450) and Group 3 (100-150) if the response 
rate is 64-67% (66-69%) in Group 1 and 50% in Group 3; and we will have 80% 
(90%) power to detect the difference between Group2 (n=200) and Group 3 
(n=100-150) if the response rate is 66-68% (68-71%) in Group 2 and 50% in 
Group 3. These calculations use a Fisher’s exact 2-sided test with a Type I error 
rate of 0.05.  
Table 6-2 Power for comparison of response rates between 2 groups given different sample 
sizes in groups 
True 
response 
rate 
Group 2 
(%) 
Minimum true response rate in Group 1 in order to detect a difference 
80% power 
90% power 
n1=450 
n2=200 
n1=450 
n2=150 
n1=200 
n2=150 
n1=375 
n2=200 
n1=375 
n2=100 
n1=200 
n2=100 
n1=450 
n2=200 
n1=450 
n2=150 
n1=200 
n2=150 
n1=375 
n2=200 
n1=375 
n2=100 
n1=200 
n2=100 
10 
19 
20 
22 
19 
22 
24 
21 
22 
24 
21 
25 
26 
20 
31 
32 
34 
32 
35 
37 
33 
34 
37 
33 
37 
39 
30 
42 
44 
46 
43 
46 
48 
44 
46 
48 
45 
49 
51 
40 
53 
54 
56 
53 
57 
58 
55 
56 
58 
55 
59 
61 
50 
63 
64 
66 
63 
67 
68 
64 
66 
68 
65 
69 
71 
6.2 
Statistical analyses 
All data from enrolled participants will be analyzed. Analyses for primary, 
secondary and exploratory endpoints will be performed using SAS and R 
statistical software. No formal multiple comparison adjustments will be employed 
for multiple primary immunogenicity endpoints, or secondary endpoints across 
assays. However, multiplicity adjustments will be made for certain 
immunogenicity assays when the assay endpoint is viewed as a collection of 

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hypotheses (eg, testing multiple peptide pools to determine a positive response) or 
group comparisons. 
6.2.1 
Analysis variables 
The analysis variables consist of participant characteristics such as demographics 
and medical history (including pre-existing conditions, new acute or chronic 
medical conditions, and concomitant medications), presentations of SARS-CoV-2 
infection (including the clinical course of COVID-19), immunogenicity for 
primary, secondary, and exploratory objective analyses, and host genetics. 
6.2.2 
Primary and Secondary Analysis 
Data from all enrolled participants will be evaluated and compared between 
groups (Group 1- Group 3) and between subgroups within Group 1- Group 2. 
Additional analyses may be performed, limited to participants with confirmed 
SARS-Cov-2 infection. All analyses will be performed for overall and by region 
(Americas and sub-Saharan Africa (SSA)). The comparison between regions 
(Americas vs SSA) may be conducted as well.  
Discrete categorical assay endpoints (eg, response rates) will be analyzed by 
tabulating the frequency of positive response for each assay by antigen and group 
at each timepoint for which an assessment is performed. Crude response rates will 
be presented with their corresponding 95% confidence interval estimates 
calculated using the score test method (28). Fisher’s exact tests will be used to 
compare the response rates of any 2 groups.  
To compare the response rates among more than two groups, an overall test for 
any difference in crude response rate among the groups will be conducted, using a 
Chi-square test. When all pair-wise comparisons between the multiple groups are 
of interest, the Holm-Bonferroni procedure will be used to calculate adjusted p-
values for multiplicity adjustment.  
For quantitative assay data (eg, percentage of positive cells from the intracellular 
cytokine staining (ICS) assay), graphical and tabular summaries of the 
distributions by antigen and group at each time point will be made. Box plots and 
plots of estimated reverse cumulative distribution curves will be used for 
graphical display by antigen and group at each timepoint.  
The difference between groups will be tested with a nonparametric Wilcoxon rank 
sum test if the data are not normally distributed and with a 2-sample t-test if the 
data appear to be normally distributed. To test for differences among more than 
two groups, first a Kruskal-Wallis test or an F-test (depending on the normality 
assumption) will be used to test for overall differences. Secondly, if the overall 
test is significant at the 2-sided 0.05 level, then pair-wide group comparisons will 
be done unless prespecified. When all pair-wise comparisons between the 
multiple groups are of interest, the Holm-Bonferroni procedure will be used to 
calculate adjusted p-values for multiplicity adjustment. An appropriate data 

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transformation (eg, log10 transformation) may be applied to better satisfy 
assumptions of symmetry and homoscedasticity (constant variance).  
In addition, we will perform the comparisons between groups adjusting for some 
relevant covariates (eg, gender, race, hospitalization status, underlying health 
conditions) using regression models. 
Details for calculating a positive response, response magnitude, and additional 
analyses for each assay data will be provided in the statistical analysis plan. 
Categorical variables of participants’ characteristics and medical history etc. at 
the enrollment visit will be tabulated for overall and by group and compared 
between groups using chi-square test. The distribution of continuous variables of 
participants’ characteristics and medical history etc. at the enrollment visit will be 
summarized and compared between groups using t-test.  
6.2.3 
Exploratory Analysis 
Clinical outcomes and immune responses will be compared between host genetics 
(eg, HLA, FcR, ACE-2, and TMPRSS2 gene variants) groups. For a binary 
clinical outcome or immune response rate, we will use Fisher’s Exact test and/or a 
logistic regression to assess the association of host genetic groups with clinical 
outcome and immune response rate after adjusting for participants’ characteristics 
such as age, gender, race, hospitalization status, and underlying health conditions. 
For a continuous clinical outcome or immune response magnitude, we will use 
Wilcoxon rank sum or t-test or a general linear regression adjusting for other 
covariates to assess the association of host genetic group with clinical outcomes 
and immune response. Benjamini-Hochberg procedure (29) will be used to 
calculate q-values adjusting for multiple comparisons involving host genotype 
groups.  
For assessing humoral and cellular responses such as pro-inflammatory cytokine, 
cross-reactivity of immune responses with other pathogens or evaluating immune 
responses measured from additional assays associated with SARS-CoV-2 
infection, we will calculate the Spearman correlation between immune responses 
or use methods described in Section 6.2.2. Additional information about 
immunological outcome analysis methods will be detailed in the Statistical 
Analysis Plan.  

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7 
Selection and withdrawal of participants 
Volunteers determined to be eligible, based on the inclusion and exclusion 
criteria, may be enrolled in the study. Final eligibility determination will depend 
on information available at the time of 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.  
7.1 
Inclusion criteria 
1. Age 18 or older. 
2. Reports having had a positive test for SARS-CoV-2. 
3. Reports resolution of COVID-19 within 1-8 weeks of enrollment OR, if 
asymptomatic infection, reports positive SARS-CoV-2 test within 2-10 weeks of 
enrollment. Not excluded: individuals with symptoms consistent with residual 
sequelae of resolved COVID-19, in the clinical judgement of the investigator. 
4. Access to a participating HVTN or HPTN CRS and willingness to be followed for 
the planned duration of the study. 
5. Ability and willingness to provide informed consent. 
6. Assessment of understanding: volunteer demonstrates understanding of this study. 
7. Volunteers who were assigned female sex at birth: negative urine or serum beta 
human chorionic gonadotropin (β-HCG) pregnancy test within 4 days of 
enrollment visit (ie, prior to enrollment blood draw or nasal collections). Persons 
who are NOT of reproductive potential due to having undergone hysterectomy or 
bilateral oophorectomy (verified by medical records) or having reached 
menopause (no menses for ≥ 1 year ), are not required to undergo pregnancy 
testing. 
7.2 
Exclusion criteria 
1. Reports current COVID-19. 
2. Pregnant. 
3. Receipt of SARS-CoV-2 specific antibodies (eg, convalescent plasma or sera, 
monoclonal antibodies, hyperimmune globulin). Not excluded: antibody therapy 
without SARS-CoV-2 specificity (eg, IL-6 pathway inhibitors for COVID-19). 

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4. SARS-CoV-2 vaccine(s) received in a prior vaccine trial. 
5. Any medical, psychiatric, occupational, or other condition that, in the judgment of 
the investigator, would interfere with, or serve as a contraindication to, protocol 
adherence or a volunteer’s ability to give informed consent. 
7.3 
Participant termination from the study 
Under certain circumstances, an individual participant may be terminated from 
participation in this study. Specific events that will result in early termination 
include: 
• Participant becomes pregnant, 
• Participant refuses further participation, 
• Participant relocates and remote follow-up or transfer to another HVTN or 
HPTN CRS is not possible, 
• HVTN or HPTN CRS determines that the participant is lost to follow-up,  
• Investigator decides, in consultation with Protocol Team leadership, to 
terminate participation (eg, if participant exhibits inappropriate behavior 
toward clinic staff), or 
• Any condition where termination from the study is required by applicable 
regulations. 

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8 
Clinical procedures 
The schedule of clinical and laboratory procedures is shown in Appendix C. 
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. 
Furthermore, some visit procedures may be conducted outside the CRS (eg, home 
nasal sample collection). 
8.1 
Informed consent 
Informed consent is the process of working with participants so that they fully 
understand what will and may happen to them while participating in a research 
study. The protocol-specific informed consent form documents that a participant 
(1) has been informed about the potential risks, benefits, and alternatives to 
participation, and (2) is willing to participate in the study. Informed consent 
encompasses all written, verbal, and electronic study information HVTN and 
HPTN (Network) CRS staff provide to the participant, before and during the trial. 
Network CRS staff will obtain informed consent of participants according to 
HVTN MOP policies and procedures. 
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 provide revised informed consent. 
8.1.1 
Protocol-specific consent forms 
The protocol-specific consent form describes the study and all aspects of protocol 
participation, including study procedures. A sample protocol-specific consent 
form is located in Appendix A.  
Each Network CRS is responsible for developing a protocol-specific consent form 
for local use, based on the sample protocol-specific consent form in Appendix A 
The consent form must be developed in accordance with requirements of the 
following: 
• CRS’s IRB/EC and any applicable REs, 
• CRS’s institution, and 
• Elements of informed consent as described in Title 45, CFR Part 46 and Title 
21 CFR, Part 50, and in ICH E6, Good Clinical Practice: Consolidated 
Guidance 4.8. 
The sample informed consent form includes instructions for developing specific 
content. 

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Regarding protocol registration, sites should follow procedures outlined in the 
current version of the DAIDS Protocol Registration Manual. 
8.1.2 
Assessment of Understanding 
Study staff are responsible for ensuring that participants fully understand the 
study before enrolling them. This process involves reviewing the informed 
consent form with the participant, allowing time for the participant to reflect on 
the procedures and issues presented, and answering all questions completely. 
An Assessment of Understanding is used to document the participant’s 
understanding of key concepts in this study. Participants must verbalize 
understanding of all questions answered incorrectly. This process and the 
participant’s understanding of the key concepts is to be recorded in source 
documentation at the site. 
8.2 
Enrollment visit 
All inclusion and exclusion criteria must be assessed on the day of enrollment (ie, 
no separate screening visit) with the exception of a pregnancy test, which must be 
done within 4 days of enrollment visit. An individual who has signed the study-
specific consent and meets all inclusion and exclusion criteria (see Sections 7.1 
and 7.2) will be considered enrolled.  
After the appropriate informed consent and assessment of understanding have 
been obtained the following procedures are performed: 
• Urine or serum pregnancy test (for participants who were assigned female sex 
at birth). Persons who are NOT of reproductive potential due to having 
undergone hysterectomy or bilateral oophorectomy (verified by medical 
records) or having reached menopause (no menses for ≥ 1 year), are not 
required to undergo pregnancy testing.  
• Medical history (including COVID-19 history), documented in the case 
history record. 
• Obtaining of volunteer demographics in compliance with the NIH Policy on 
Reporting Race and Ethnicity Data: Subjects in Clinical Research, Aug. 8, 
2001 (available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-01-
053.html). 
• Assessment of concomitant medications, including all treatment for COVID-
19, prescription and nonprescription drugs, vitamins, topical products, 
alternative/complementary medicines (eg, herbal and health food 
supplements), recreational drugs, vaccinations, and allergy shots.  
Sample collections are described in Appendix C. 

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8.3 
Follow-up visits 
At all follow-up visits, which are optional, the following procedures are 
performed before blood sample collections: 
• Urine or serum pregnancy test (for participants who were assigned female sex 
at birth). Persons who are NOT of reproductive potential due to having 
undergone hysterectomy or bilateral oophorectomy (verified by medical 
records) or having reached menopause (no menses for ≥ 1 year ), are not 
required to undergo pregnancy testing.  
• Medical history, updated from the enrollment visit and subsequent follow-up 
visits, to include new acute or chronic medical conditions. 
• Assessment of concomitant medications, including prescription and 
nonprescription drugs, vitamins, topical products, alternative/complementary 
medicines (eg, herbal and health food supplements), recreational drugs, 
vaccinations, and allergy shots.  
Sample collections are described in Appendix C.  
8.4 
 Nasal and nasopharyngeal sampling 
An optional nasal or nasopharyngeal swab may be collected at the enrollment visit 
and may also be collected at any follow-up visit at which a participant reports 
symptoms that per CRS clinician judgement are consistent with possible COVID-
19. The swab may be collected by site staff or it may be self-collected (at home or 
in the clinic); both nostrils will be sampled.   
An optional nasal wash (preferred collection method) or nasal swab (if nasal wash 
cannot be collected) may be collected at all visits. For nasal wash, a sterile 
solution (eg, normal saline) will be instilled into the nostril and then removed; this 
process will be repeated until sufficient sample is collected (about 5mL). The 
wash or swab may be collected by site staff or it may be self-collected at home or 
in the clinic. 
8.5 
Visit windows  
Visit windows are included in Appendix D.  

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9 
Laboratory 
9.1 
HVTN CRS laboratory procedures 
The HVTN 405/HPTN 1901 Site Processing Lab Instructions and SSP provide 
further guidelines for operational issues concerning the clinical and processing 
laboratories. These documents include special considerations for phlebotomy and 
guidelines for general specimen collection, specimen labeling and specimen 
processing. 
Tube types for blood collection are specified in Appendix C. For tests performed 
locally, the local lab may assign appropriate tube types. 
In specific situations, the blood collection tubes may be redirected to another 
laboratory or may require study-specific processing techniques. In these cases, 
laboratory special instructions will be posted on the protocol-specific section of 
the HVTN website. 
Of note, all assays described below are performed as research assays to evaluate 
the ability of the SARS-CoV-2 virus to induce immune responses in the context 
of the participants’ genetic background and are not approved for use in medical 
care. Results from these assays are not made available to participants or medical 
professionals to guide treatment decisions. 
9.2 
Total blood volume 
Required blood volumes per visit are shown in Appendix C. Not shown is any 
additional blood volume that would be required 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. 
9.3 
Endpoint assays  
9.3.1 
SARS-CoV-2 PCR 
Real-time reverse transcription polymerase chain reaction (RT-PCR) assays to 
detect SARS-CoV-2 will be run on nasal and/or nasopharyngeal swab samples 
collected from study participants. After RNA extraction, specimens will be 
analyzed by a laboratory developed test using the World Health Organization’s 
E/RdRp primer set, the N1/N2 primer set from the Centers for Disease Control 
and Prevention, or tests from Hologic (Panther Fusion), DiaSorin (Simplexa), or 
Roche (cobas). Novel methods to detect SARS-CoV-2 may also be used if 
applicable. 

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9.3.2 
Neutralizing antibody assay (NAb) 
SARS-CoV-2–specific nAb assays may be performed on serum samples from 
study participants. The assay will test neutralization of S-pseudotyped and/or full-
genome recombinant viruses as measured by a reduction in luciferase (Luc) 
reported gene expression after infection in ACE2-positive cells. 
9.3.3 
Binding antibody multiplex assay (BAMA) 
SARS-CoV-2 specific total IgG binding antibodies may be assessed in serum 
samples and IgA binding antibodies may be measured in nasal samples. In 
addition, SARS-CoV-2–specific serum IgA and IgG subclass (IgG1, IgG2, IgG3, 
and IgG4) antibodies may also be assessed.  
9.3.4 
ACE-2 blocking assay 
The ability of polyclonal sera to block binding of SARS-CoV-2 spike protein to 
the cellular ACE-2 receptor may be determined by biophysical assays utilizing 
Biolayer Interferometry (BLI) or Surface Plasmon Resonance (SPR) and/or cell-
based flow cytometry assay.  
9.3.5 
Peptide microarray  
Linear epitope specificities of purified serum IgG may be examined by peptide 
microarray using a SARS-CoV-2 peptide library, which contains 15-mer peptides 
that overlap by 12 amino acids. 
9.3.6 
Antibody avidity assay 
Antibody avidity may be measured using BAMA with the addition of a 
dissociation step to calculate the antibody avidity index (BAMA-AI). BLI and/or 
SPR technologies may also be used to measure antibody avidity.  
9.3.7 
Antibody-dependent cellular cytotoxicity assay (ADCC)  
ADCC activity may be assessed using serum samples from study participants. For 
the Granzyme B flow-based cytotoxicity assay, participant sera are incubated with 
effector cells sourced from human PBMCs and S protein-transfected 293F cells. 
ADCC is quantified as net percent granzyme B activity which is the percent of 
target cells positive for GranToxiLux (GTL), an indicator of granzyme B uptake, 
minus the percent of mock transfected target cells positive for GTL when 
incubated with effector cells and sera.  
9.3.8 
Antibody dependent enhancement (ADE) assays  
SARS-CoV-2–specific ADE assays may be performed on serum samples from 
study participants. The assays will test enhancement of S-pseudotyped virus 

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infection as measured by an increase in luciferase (Luc) reported gene expression 
after a single round of infection in ACE2+/FcR- and ACE2-/FcR+ cells. 
9.3.9 
T-cell responses by intracellular cytokine staining (ICS) 
Flow cytometry may be used to examine SARS-CoV-2-specific CD4+ and CD8+ 
T-cell responses following stimulation of PBMCs with synthetic peptides that 
span the proteins encoded by the SARS-CoV-2 virus. Data will be reported as 
percentages of CD4+ or CD8+ T cells responding to a specific peptide pool. 
Additional cell surface markers, cytokines, or functional markers may also be 
analyzed. Additional assays may include evaluation of additional cytokines using 
a multiplexed secreted cytokine assay, mapping of individual peptide-level T- cell 
responses, and characterization of viral inhibition. 
9.3.10 
SARS-CoV-2 -specific B cell phenotyping and monoclonal antibody 
isolation 
SARS-CoV-2 -specific memory B cells and plasmablasts induced by infection 
may be identified and characterized using fluorescently labeled recombinant 
proteins in combination with a flow cytometry phenotyping panel. In particular, 
SARS-CoV-2 spike and receptor binding domain-specific B cells and 
plasmablasts will be enumerated and may be further characterized for expression 
of memory, activation, inhibitory or other markers of interest. From a subset of 
individuals, SARS-CoV-2-specific memory B cells or plasmablasts will be 
isolated for B cell receptor sequencing and generation of recombinant monoclonal 
antibodies for in-depth characterization (e.g. function, binding-specificity, etc.). 
9.3.11 
Genotyping 
Molecular human leukocyte antigen (HLA), Fc Receptors, ACE-2, and TMPRSS2 
genotyping may be performed on enrolled participants using cryopreserved whole 
blood. Other genes, including those associated with immune responses (eg, 
immunoglobulin or T cell receptor genes) or SARS-CoV-2 infection may also be 
evaluated. 
9.4 
Lab assay portfolio 
Additional assays may be performed per the HVTN Laboratory Center assay 
portfolio, which includes immune assessments such as those for cellular, humoral, 
and innate immune responses, and host genetics. The assay portfolio will be 
updated periodically to include new assays and adjust qualification levels of 
existing assays. 

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9.5 
Exploratory studies 
Samples may be used for other testing and research related to furthering the 
understanding of SARS-CoV-2 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. 
9.6 
Specimen storage and other use of specimens 
The HVTN stores specimens from all study participants indefinitely, unless a 
participant requests that specimens be destroyed or if required by IRB/EC, or RE. 
Other use of specimens is defined as studies not covered by the protocol or the 
informed consent form for the main study (see Appendix A). 
This research may relate to SARS-CoV-2, vaccines, passive protection, 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. 
9.7 
Biohazard containment 
The transmission of blood-borne pathogens can occur through contact with 
contaminated needles, blood, and blood products, and the transmission of SARS-
CoV-2 and other respiratory pathogens may occur through contact with 
contaminated respiratory droplets and aerosols. Appropriate precautions will be 
employed by all personnel in the collection, shipping and handling of all 
specimens for this study, as currently recommended by the CDC and the NIH or 
other applicable agencies. 

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All dangerous goods materials, including Biological Substances, Category A or 
Category B, must be transported according to instructions detailed in the 
International Air Transport Association Dangerous Goods Regulations. 

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10 
Protocol conduct 
This protocol and all actions and activities connected with it will be conducted in 
compliance with the principles of GCP (ICHe6), and according to DAIDS and 
HVTN policies and procedures as specified in the HVTN Manual of Operations, 
DAIDS Clinical Research Policies and Standard Procedures Documents including 
procedures for the following: 
• Protocol registration, activation, and implementation; 
• Informed consent and enrollment; 
• Study participant reimbursement; 
• Data collection, documentation, transfer, and storage; 
• Participant confidentiality; 
• Study follow-up and close-out; 
• Quality control; 
• Protocol monitoring and compliance; 
• Specimen collection, processing, and analysis; 
• Exploratory and ancillary studies and sub-studies; and 
• Destruction of specimens. 
Any policies or procedures that vary from DAIDS and HVTN standards or require 
additional instructions (eg, instructions specific to this study) will be described in 
the HVTN 405/HPTN 1901 Study Specific Procedures. 
10.1 
Emergency communication with study participants 
As in all clinical research, this study may generate a need to reach participants 
quickly to avoid imminent harm, or to report study findings that may otherwise 
concern their health or welfare. 
When such communication is needed, the CRS will request that its IRB/EC and 
any applicable RE expedite review of the message. If this review cannot be 
completed in a timeframe consistent with the urgency of the required 
communication, the site can contact the participant without IRB/EC approval if 
such communication is necessary to avoid imminent harm to the study participant. 
The CRS must notify the IRB/EC and any applicable RE of the matter as soon as 
possible. 

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10.2 
Study termination 
This study may be terminated early by the determination of a pertinent national 
regulatory authority, NIH, or Office for Human Research Protections (OHRP). In 
addition, the conduct of this study at an individual HVTN or HPTN CRS may be 
terminated by the determination of the IRB/EC and any applicable RE. 
 

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11 
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 405/HPTN 1901 are 
described below. 
Protocol history and modifications 
Date: June 4, 2020 
Protocol version:2.0 
Protocol modification: Full protocol amendment 1 
Item 1 
Added in Section 1, Overview, Section 2, Ethical considerations, 
Section 6, Statistical considerations, Section 13, Acronyms and 
abbreviations, and Appendix A, Sample informed consent form: Clinical 
research sites in sub-Saharan Africa 
Item 2 
Revised in Section 1, Overview, Section 6, Statistical considerations, 
and Appendix A, Sample informed consent form: sample size increased 
from 400 to a target of 800 with a range from 675-800 
Item 3 
Added to Section 7.1, Inclusion criteria #7, Section 8.2, Enrollment visit 
and Appendix C, Schedule of procedures as new footnote 9: pregnancy 
test may be completed within 4 days prior to enrollment. 
Item 4 
Added to Section 1, Overview: new diagnostic and endpoint laboratories 
Item 5 
Added to Appendix A, Sample informed consent form, and Appendix C, 
Schedule of procedures: optional antibody testing for SARS-CoV-2 and 
return of results to participants 
Item 6 
Revised in Section 8.1, Informed consent: requirements for signed form 
Item 7 
Revised in Appendix A, Sample informed consent form, item 13: 
medical emergency and study-related injury language 
Item 8 
Version history updated in Section 11 
Item 9 
Editorial changes: corrected minor formatting issues in Section 1, 
Overview and Appendix A, Sample informed consent form and updated 
date and version number on Title page 
Item 10 
Updated with changes described in Letter of Amendment 1 dated May 
12, 2020 

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Date: May 12, 2020 
Protocol version: Version 1.0 
Protocol modification: Letter of Amendment 1 
Item 1 
Added in Section 7.2, Exclusion criteria: Receipt of passive 
antibodies for SARS-CoV-2 infection (eg, convalescent plasma or 
sera, monoclonal antibody, hyperimmune globulin) 
Item 2 
Added in Section 7.2, Exclusion criteria: SARS-CoV-2 vaccine(s) 
received in a prior vaccine trial 
Item 3 
Clarified Section 8.2, Enrollment visit, and Section 8.3, Follow-up 
visits: pregnancy testing requirements 
Item 4 
Revised in Section 9.3.1, SARS-CoV-2 PCR: description for SARS-
CoV-2 PCR test 
Item 5 
Revised in Section 9.3.2, Neutralizing antibody assay (Nab): 
description of the neutralization assay 
Item 6 
Added in Section 1.1, Protocol Team: Regional medical liaison 
 
Date: April 27, 2020 
Protocol version: 
Protocol modification: 
Original protocol 

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12 
Document references (other than literature 
citations) 
Other documents referred to in this protocol, and containing information relevant 
to the conduct of this study, include: 
• Assessment of Understanding. Accessible through the HVTN protocol-
specific website. 
• Division of AIDS (DAIDS) Clinical Research Policies and Standard 
Procedures Documents. Available at 
https://www.niaid.nih.gov/research/daids-clinical-research-policies-standard-
procedures 
• Division of AIDS Protocol Registration Manual. Available at 
https://www.niaid.nih.gov/sites/default/files/prmanual.pdf  
• HVTN Certificate of Confidentiality. Accessible through the HVTN website. 
• HVTN 405/HPTN 1901 Special Instructions. Accessible through the HVTN 
protocol-specific website. 
• HVTN 405/HPTN 1901 Study Specific Procedures. Accessible through the 
HVTN protocol-specific website. 
• HVTN 405/HPTN 1901 Site Lab Instructions. Accessible through the HVTN 
protocol-specific website. 
• HVTN Manual of Operations. Accessible through the HVTN website. 
• Dangerous Goods Regulations (updated annually), International Air Transport 
Association. Available for purchase at 
https://www.iata.org/publications/dgr/Pages/index.aspx 
• HVTN Lab Center assay portfolio. 
• International Council on Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) E6, Guideline for Good Clinical 
Practice: Section 4.8, Informed consent of trial subjects. Available at 
http://www.ich.org/products/guidelines/efficacy/article/efficacy-
guidelines.html 
• Good Participatory Practice Guidelines for Trials of Emerging (And Re-
emerging) Pathogens that are Likely to Cause Severe Outbreaks in the Near 
Future and for Which Few or No Medical Countermeasures Exist WHO 
December 2016): https://www.avac.org/resource/good-participatory-practice-
guidelines-trials-emerging-and-re-emerging-pathogens%C2%A0-are 

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• Bill of Rights and Responsibilities. Accessible through the HVTN protocol-
specific website. 
• NIH Policy on Reporting Race and Ethnicity Data: Subjects in Clinical 
Research. Available at https://grants.nih.gov/grants/guide/notice-files/NOT-
OD-01-053.html 
• Requirements for Source Documentation in DAIDS Funded and/or Sponsored 
Clinical Trials. Available at 
https://www.niaid.nih.gov/sites/default/files/daids-sourcedocpolicy.pdf  
• Title 21, Code of Federal Regulations, Part 50. Available at 
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFR
Part=50 
• Title 45, Code of Federal Regulations, Part 46. Available at 
https://www.hhs.gov/ohrp/regulations-and-policy/regulations/45-cfr-
46/index.html 
See Section 14 for literature cited in the background and statistics sections of this 
protocol. 

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13 
Acronyms and abbreviations 
Ab 
 
antibody 
ACE2 
 
angiotensin-converting enzyme 2 
ADCC 
 
Antibody-dependent cellular cytotoxicity assay 
AUC-MB  
area-under-the-curve-magnitude-breadth 
BAMA 
 
Binding antibody multiplex assay 
β-HCG 
 
beta human chorionic gonadotropin 
BLI 
 
biolayer interferometry 
CAB 
 
Community Advisory Board 
CDC 
 
US Centers for Disease Control and Prevention 
CFR 
 
Code of Federal Regulations 
COVID-19 
Coronavirus Disease 2019 
CRS 
 
clinical research site 
CTL 
 
cytotoxic T lymphocyte 
DAIDS 
 
Division of AIDS (US NIH) 
DHHS 
 
US Department of Health and Human Services 
EC 
 
Ethics Committee 
EIA 
 
enzyme immunoassay 
ELISA 
 
enzyme-linked immunosorbent assay 
ELISpot 
 
enzyme-linked immunospot 
FcR 
 
Fc receptor 
FDA 
 
US Food and Drug Administration 
Fred Hutch 
Fred Hutchinson Cancer Research Center 
GCP 
 
Good Clinical Practice 
GEE 
 
generalized estimating equation 
GPP-EP 
 
Good Participatory Practices for Emerging Pathogens 
GTL 
 
GranToxiLux 
HLA 
 
human leukocyte antigen 
HPTN 
 
HIV Prevention Trials Network 
HVTN 
 
HIV Vaccine Trials Network 
ICH 
 
International Council on Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use 
ICS 
 
intracellular cytokine staining 
IFN-γ 
 
interferon gamma 
IND 
 
Investigational New Drug 
IRB 
 
Institutional Review Board 
mAb 
 
monoclonal antibody 
MERS-CoV 
Middle East Respiratory Syndrome Coronavirus 
nAb 
 
neutralizing antibody 

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NIAID 
 
National Institute of Allergy and Infectious Diseases (US NIH) 
NIH 
 
US National Institutes of Health 
OHRP 
 
US Office for Human Research Protections 
PBMC 
 
peripheral blood mononuclear cell 
PCR 
 
polymerase chain reaction 
RE 
 
regulatory entity 
RT-PCR  
reverse transcription polymerase chain reaction 
SAHPRA  
South African Healthcare Products Regulatory Authority 
SAP 
 
Statistical Analysis Plan 
SARS-CoV 
Severe Acute Respiratory Syndrome Coronavirus  
SCHARP  
Statistical Center for HIV/AIDS Research and Prevention 
SDMC 
 
statistical and data management center 
SPR 
 
surface plasmon resonance 
SSP 
 
study-specific procedures 
TMPRSS2  
Transmembrane protease serine 2 
UW-VSL  
University of Washington Virology Specialty Laboratory 
 
 

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14 
Literature cited 
1. UNAIDS. Ethical considerations in biomedical HIV prevention trials. 2007 
7/2007. 
2. The National Commission for the Protection of Human Subjects of 
Biomedical and Behavioral Research. The Belmont Report: Ethical Principles 
and Guidelines for the Protection of Human Subjects of Research. 1979 
4/18/1979. 
3. Council for International Organizations of Medical Sciences (CIOMS). 
International ethical guidelines for biomedical research involving human 
subjects. Bull Med Ethics. 2002(182):17-23. 
4. Yang CY, Wang J. A mathematical model for the novel coronavirus epidemic 
in Wuhan, China. Math Biosci Eng. 2020;17(3):2708-24. 
5. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical 
Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020. 
6. Liu WJ, Zhao M, Liu K, Xu K, Wong G, Tan W, et al. T-cell immunity of 
SARS-CoV: Implications for vaccine development against MERS-CoV. 
Antiviral Res. 2017;137:82-92. 
7. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation 
and epidemiology of 2019 novel coronavirus: implications for virus origins 
and receptor binding. Lancet. 2020;395(10224):565-74. 
8. Temperton NJ, Chan PK, Simmons G, Zambon MC, Tedder RS, Takeuchi Y, 
et al. Longitudinally profiling neutralizing antibody response to SARS 
coronavirus with pseudotypes. Emerg Infect Dis. 2005;11(3):411-6. 
9. Zhang L, Zhang F, Yu W, He T, Yu J, Yi CE, et al. Antibody responses 
against SARS coronavirus are correlated with disease outcome of infected 
individuals. J Med Virol. 2006;78(1):1-8. 
10. Liu W, Fontanet A, Zhang PH, Zhan L, Xin ZT, Baril L, et al. Two-year 
prospective study of the humoral immune response of patients with severe 
acute respiratory syndrome. J Infect Dis. 2006;193(6):792-5. 
11. Li CK, Wu H, Yan H, Ma S, Wang L, Zhang M, et al. T cell responses to 
whole SARS coronavirus in humans. J Immunol. 2008;181(8):5490-500. 
12. Fan YY, Huang ZT, Li L, Wu MH, Yu T, Koup RA, et al. Characterization 
of SARS-CoV-specific memory T cells from recovered individuals 4 years 
after infection. Arch Virol. 2009;154(7):1093-9. 

HVTN 405/HPTN 1901 Version 2.0 / June 4, 2020 
HVTN405_HPTN1901_v2.0_FINAL / Page 43 of 60 
13. Ng OW, Chia A, Tan AT, Jadi RS, Leong HN, Bertoletti A, et al. Memory T 
cell responses targeting the SARS coronavirus persist up to 11 years post-
infection. Vaccine. 2016;34(17):2008-14. 
14. Tang F, Quan Y, Xin ZT, Wrammert J, Ma MJ, Lv H, et al. Lack of 
peripheral memory B cell responses in recovered patients with severe acute 
respiratory syndrome: a six-year follow-up study. J Immunol. 
2011;186(12):7264-8. 
15. Ho MS, Chen WJ, Chen HY, Lin SF, Wang MC, Di J, et al. Neutralizing 
antibody response and SARS severity. Emerg Infect Dis. 2005;11(11):1730-
7. 
16. Liu L, Wei Q, Lin Q, Fang J, Wang H, Kwok H, et al. Anti-spike IgG causes 
severe acute lung injury by skewing macrophage responses during acute 
SARS-CoV infection. JCI Insight. 2019;4(4). 
17. Zhao J, Alshukairi AN, Baharoon SA, Ahmed WA, Bokhari AA, Nehdi AM, 
et al. Recovery from the Middle East respiratory syndrome is associated with 
antibody and T-cell responses. Sci Immunol. 2017;2(14). 
18. Choe PG, Perera R, Park WB, Song KH, Bang JH, Kim ES, et al. MERS-
CoV Antibody Responses 1 Year after Symptom Onset, South Korea, 2015. 
Emerg Infect Dis. 2017;23(7):1079-84. 
19. Zhao J, Yuan Q, Wang H, Liu W, Liao X, Su Y, et al. Antibody responses to 
SARS-CoV-2 in patients of novel coronavirus disease 2019. Clin Infect Dis. 
2020. 
20. Ju B, Zhang Q, Ge X, Wang R, Yu J, Shan S, et al. Potent human neutralizing 
antibodies elicited by SARS-CoV-2 infection. bioRxiv preprint doi: 
https://doiorg/101101/20200321990770. 2020. 
21. Ou X, Liu Y, Lei X, Li P, Mi D, Ren L, et al. Characterization of spike 
glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity 
with SARS-CoV. Nat Commun. 2020;11(1):1620. 
22. Wu F, Wang A, Liu M, Wang Q, Chen J, Xia S, et al. Neutralizing antibody 
responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their 
implications. medRxiv preprint doi: 
https://doiorg/101101/2020033020047365. 2020. 
23. Pinto D, Park Y-J, Beltramello M, Walls A, Tortorici MA, Bianchi S, et al. 
Structural and functional analysis of a potent sarbecovirus neutralizing 
antibody. bioRxiv preprint doi: https://doiorg/101101/20200407023903. 
2020. 

HVTN 405/HPTN 1901 Version 2.0 / June 4, 2020 
HVTN405_HPTN1901_v2.0_FINAL / Page 44 of 60 
24. Callow KA. Effect of specific humoral immunity and some non-specific 
factors on resistance of volunteers to respiratory coronavirus infection. J Hyg 
(Lond). 1985;95(1):173-89. 
25. Liu WJ, Lan J, Liu K, Deng Y, Yao Y, Wu S, et al. Protective T Cell 
Responses Featured by Concordant Recognition of Middle East Respiratory 
Syndrome Coronavirus-Derived CD8+ T Cell Epitopes and Host MHC. J 
Immunol. 2017;198(2):873-82. 
26. Channappanavar R, Fett C, Zhao J, Meyerholz DK, Perlman S. Virus-specific 
memory CD8 T cells provide substantial protection from lethal severe acute 
respiratory syndrome coronavirus infection. J Virol. 2014;88(19):11034-44. 
27. Hermelingmeier KE, Weber RK, Hellmich M, Heubach CP, Mosges R. Nasal 
irrigation as an adjunctive treatment in allergic rhinitis: a systematic review 
and meta-analysis. Am J Rhinol Allergy. 2012;26(5):e119-25. 
28. Agresti A, Coull BA. Approximate is better than "exact" for interval 
estimation of binomial proportions. Am Stat. 1998;52(2):119-26. 
29. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical 
and powerful approach to multiple testing. Journal of the Royal Statistical 
Society, Series B. 1995;57(1):125-33. 

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Appendix A 
Sample informed consent form 
Title: Characterizing SARS-CoV-2-specific immunity in convalescent individuals 
HVTN protocol number: HVTN 405/HPTN 1901 
Site: [Insert site name] 
Thank you for your interest in our research study. Please read this consent form or 
ask someone to read it to you. If you decide to join the study, we will ask you to 
sign or make your mark on this form. We will offer you a copy to keep. We will 
ask you questions to see if we have explained everything clearly. You can also 
ask us questions about the study. 
Research is not the same as treatment or medical care. The purpose of a research 
study is to answer scientific questions. 
Key information 
• Being in this research study is voluntary. It is your choice. 
• The purpose of this study is to learn more about infection with and recovery 
from the virus called SARS-CoV-2. Some people know this virus by the name 
“coronavirus.” It can cause the disease called COVID-19. You are being 
asked to take part in this study because you are age 18 or older, had a positive 
test for SARS-CoV-2, and have recovered. 
• Your participation in this study will last for at least 1 visit and may last up to 
about 1 year. Procedures will include blood draws and optional nasal sample 
collections at one required visit and 3 optional visits. 
• The risks associated with this study are minimal and are primarily due to 
collecting certain samples and the potential loss of confidentiality.  
• We do not expect the study to benefit you in any way. 
About the study 
The HIV Vaccine Trials Network (HVTN), HIV Prevention Trials Network 
(HPTN) and [Insert site name]  are doing a study to learn more about SARS-CoV-
2 infection and the COVID-19 disease that it can cause.  
About 800 people will take part in this study at multiple sites across the United 
States, South America and sub-Saharan Africa. 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. 

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1. Why are we doing this study? 
The main purpose of this study is to learn more about SARS CoV-2 infection and 
how our bodies respond to and recover from it. This information can be used to 
help develop better tests for SARS-CoV-2 infection and COVID-19 disease and 
may help in developing future vaccines and treatments.  
Joining the study 
2. It is completely up to you whether or not to join the study. 
Take your time in deciding. If it helps, talk to people you trust, such as your 
doctor, friends or family. If you decide not to join this study, or if you leave it 
after you have joined, your other care at this clinic and the benefits or rights you 
would normally have will not be affected. If you decide not to enroll today and 
want to come back at another time, we may need to repeat some procedures to 
make sure you are still eligible. 
Being in the study 
3. You will have at least 1 scheduled visit, and 3 more optional visits over about 
1 year if you choose. 
At the first visit, we will review your medical history to see if you meet the study 
requirements and want to join. If you are eligible, we will collect more 
information about your health and medications you take. We will also ask you 
about any symptoms you may have had related to COVID-19 disease. We may 
need to review your medical records for additional information. If we do, we will 
ask you to sign a medical release of information so we can get your records from 
your doctor. 
At this visit, we will also: 
• Take urine or blood to do a pregnancy test if you were assigned female sex at 
birth. You will not be able to join the study if you are pregnant. (People who 
are NOT capable of becoming pregnant due to total hysterectomy or bilateral 
oophorectomy (verified by medical records) or who have reached menopause 
(no menses for one year or more) are not required to have pregnancy testing.) 
• Ask if you are willing to provide optional nasal swab and nasal wash samples. 
You may be able to do these procedures yourself at home or in the clinic, or 
the clinic staff can do them for you. This may depend on what the clinic is 
allowed to do, and may change over time. 
• Take blood samples. We will ask if you want to know if you have antibodies 
for SARS-CoV-2. If you do, we will take an additional blood sample. 
The first visit could last from 1 to 2 hours. 

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When we take blood, the amount will depend on the lab tests we need to do. It 
will be some amount between about 62 mL and about 112.5 mL (or about one 
quarter to one half a cup). Your body will make new blood to replace the blood 
we take out. 
Site: You may want to add a sentence to the end of the previous paragraph 
contextualizing the blood volumes described (eg, “To compare, people who donate 
blood in the US can give a total of about 500 mL in an 8-week period.”). Modify the 
example for cultural relevance and alter blood volumes as necessary. 
We would like to have you complete the optional visits so that we can check on 
your health, and so that we can collect samples to see how your immune 
responses develop or change over time. Some parts of these visits could be 
completed over the phone or through electronic communication such as text 
messages and email, in addition to the sample collections done in person. For the 
3 optional follow-up visits scheduled at about 2 months, about 4 months, and 
about 1 year later, we will: 
• Take urine or blood to do a pregnancy test if you were assigned female sex at 
birth. Your participation in the study will end if you are pregnant. 
• Ask if you are willing to provide a nasal swab if you have any new signs or 
symptoms of possible COVID-19. You may be able to do this procedure 
yourself at home or in the clinic, or the clinic staff can do it. 
• Ask if you are willing to provide a nasal wash sample. You may be able to do 
this procedure yourself at home or in the clinic, or the clinic staff can do it. If 
a nasal wash collection is not possible, we may ask you for a second nasal 
swab sample instead. 
• Ask questions about your health and any medications you are taking.  
• Take blood samples. If you haven’t already provided a sample for antibody 
testing, we will ask if you want to know if you have antibodies for SARS-
CoV-2. If you want to know, we will take an additional blood sample. 
These visits could last from ½ hour to 2 hours. 
Site: Insert Appendix B, Table of procedures (for informed consent form) in this 
section or distribute it as a separate sheet if it is helpful to your study participants. 
You are not required to do either. 
Information about SARS-CoV-2 and COVID-19 is changing every day. We may 
ask you to complete additional visits that are not currently scheduled. This may be 
because we would like to obtain additional samples and/or information. We will 
keep you updated about any new information we learn that may change your 
decision to be involved in this study. 

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We may contact you after the study ends (for example, to tell you about the study 
results). 
4. We will give you [Site: Insert compensation] for each study visit you 
complete. 
This amount is to cover the costs of [Site: Insert text] 
US sites: Include the following paragraph. You can remove the box around the text.  
Payments you receive for being in the study may be taxable. We may need to ask 
you for your Social Security number for tax reasons. 
You do not have to pay anything to be in this study. 
5. The HVTN will use your samples for research related to your immune 
system’s response to COVID-19. 
We will send your samples (without your name or other identifying information) 
to labs approved by the HVTN for this study, which are located in the United 
States and South Africa. In rare cases, some of your samples may be sent to labs 
approved by the HVTN in other countries for research related to this study. 
Researchers may also do genetic testing related to this study on your samples. 
Your genes are passed to you from your birth parents. They affect how you look 
and how your body works. The differences in people’s genes can help explain 
why some people get a disease while others do not. The genetic testing will only 
involve some of your genes, not all of your genes (your genome). The researchers 
will study only the genes related to the immune system and COVID-19, and those 
that affect how people get infected with the SARS-CoV-2 virus that causes 
COVID-19. 
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. If you choose to provide a sample for antibody testing for SARS-CoV-2, 
the clinic will provide you the results. For all other lab tests, we will not give the 
results to you or this clinic because those 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. 

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6. When samples are no longer needed for this study, the HVTN wants to use 
them in other studies and share them with other researchers.  
The HVTN calls these samples “extra samples.” The HVTN will only allow your 
extra samples to be used in other studies if you agree to this. You will mark your 
decision at the end of this form. If you have any questions, please ask. 
Do I have to agree? No. You are free to say yes or no, or to change your mind 
after you sign this form. At your request, we will destroy all extra samples that we 
have. Your decision will not affect your being in this study or have any negative 
consequences here. 
Where are the samples stored? Extra samples are stored in a secure central place 
called a repository. [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 we share your samples and 
information, we may not be able to get them back. 
How do other researchers get my samples and information? When a researcher 
wants to use your samples and information, their research plan must be approved 
by the HVTN. Also, the researcher’s institutional review board (IRB) or ethics 
committee (EC) will review their plan. [Site: If review by your institution’s 
IRB/EC/RE is also required, insert a sentence stating this.] IRBs/ECs protect the 
rights and well-being of people in research. If the research plan is approved, the 
HVTN will send your samples to the researcher’s location. 
What information is shared with HVTN or other researchers? The samples and 
information will be labeled with a code number. The key to the code will stay at 
this clinic. It will not be shared with anyone who does not need to know your 

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name. Your name will not be part of the information. However, some information 
that we share may be personal, such as your race, ethnicity, and sex assigned at 
birth.  
What kind of studies might be done with my extra samples and information? The 
studies will be related to COVID-19, vaccines, antibodies, 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. 
7. We will do our best to protect your private information. 
US sites: Check HIPAA authorization for conflicts with this section. 

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Your study records and samples will be kept in a secure location. We will label all 
of your samples and most of your records with a code number, not your name or 
other personal information. However, it is possible to identify you, if necessary. 
We will not share your name with the lab that does the tests on your samples, or 
with anyone else who does not need to know your name. 
Clinic staff will have access to your study records. Your records may also be 
reviewed by groups who watch over this study to see that we are protecting your 
rights, keeping you safe, and following the study plan. These groups include: 
• The US National Institutes of Health and its study monitors, 
• Any regulatory agency that reviews clinical trials, 
• Sites must include: [Insert name of local IRB/EC] , 
• [Insert name of local and/or national regulatory authority as appropriate], 
• The HVTN and people who work for them, 
• The US Office for Human Research Protections. 
All reviewers will take steps to keep your records private. 
US sites: Include the following boxed text. You can remove the box around the text. 
We have a Certificate of Confidentiality from the US government, to help protect 
your privacy. With the certificate, we do not have to release information about 
you to someone who is not connected to the study, such as the courts or police. 
Sometimes we can’t use the certificate. Since the US government funds this 
research, we cannot withhold information from it. Also, you can still release 
information about yourself and your study participation to others. 
The results of this study may be published. No publication will use your name or 
identify you personally. 
We may share information from the study with other researchers. We will not 
share your name or information that can identify you. 
Site: The text below may not be deleted or changed, per FDA requirement. You can 
remove the box. 
A description of this clinical trial will be available on 
http://www.ClinicalTrials.gov. This website will not include information that can 
identify you. At most, the website will include a summary of the results. You can 
search this website at any time. 

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8. 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, 
• you become pregnant, or 
• the study is stopped for any reason. 
Risks 
9. The potential risks associated with this study are minimal. 
This section describes the risks we know about. There may also be unknown 
risks. We will tell you if we learn anything new that may affect your willingness 
to stay in the study. 
Risks of taking blood: 
In this study, we will take blood. This procedure can cause bruising, pain, feeling 
faint or dizzy, soreness, redness, swelling, itching, a sore, or bleeding. Taking 
blood can cause a low blood cell count (anemia), making you feel tired. 
Risks of the nasal swab procedure: 
The feeling of having a small, soft-tipped swab inserted into your nostril and 
twirled around may be a little uncomfortable, but it should not be painful. There is 
a small chance there could be some bleeding, but this is unlikely.  
Risks of the nasal wash procedure: 
The nasal wash may be uncomfortable, but it should not be painful. There is a 
small chance that the sterile salt water could go into your throat, causing you to 
cough or feel like you are choking, but this is unlikely. 
Risks of disclosure of your personal information: 
We will take several steps to protect your personal information. Although the risk 
is very low, it is possible that your personal information could be given to 
someone who should not have it. If that happened, you could face discrimination, 
stress, and embarrassment. We can tell you more about how we will protect your 
personal information if you would like it. 
Risks of genetic testing: 

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It is unlikely, but the genetic tests done on your samples could show you may be 
at risk for certain diseases. If others found out, it could lead to discrimination or 
other problems. However, it is almost impossible for you or others to know your 
test results from the genetic testing. The results are not part of your study records 
and are not given to you. 
US Sites, include the following paragraph. In the very unlikely event that your 
genetic information becomes linked to your name, a federal law called the 
Genetic Information Nondiscrimination Act (GINA) helps protect you. GINA 
keeps health insurance companies and employers from seeing results of genetic 
testing when deciding about giving you health insurance or offering you work. 
GINA does not help or protect you against discrimination by companies that sell 
life, disability or long-term care insurance. 
Benefits 
10. The study may not benefit you. 
We do not expect the study to benefit you in any way. This study may help us 
learn more about SARS-CoV-2 infection and COVID-19 disease. The study 
results may be used to help others in the future. 
Your rights and responsibilities 
11. If you join the study, you have rights and responsibilities. 
You have many rights that we will respect. You also have responsibilities. We list 
these in the Bill of Rights and Responsibilities for Research. We will give you a 
copy of it. 
Leaving the study 
12. Tell us if you decide to leave the study. 
You are free to leave the study at any time and for any reason. Your care at this 
clinic and your legal rights will not be affected, but it is important for you to let us 
know. 
Injuries 
Sites: Approval from HVTN Regulatory Affairs (at vtn.core.reg@hvtn.org) is needed 
for any change to the section below (other than those that the instructions specifically 
request or those previously approved by HVTN Regulatory Affairs). 

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13. If you have a life-threatening emergency, call [insert local-appropriate 
emergency number (e.g. 911)] right away or seek help immediately. 
Contact us when the life-threatening medical emergency is over or as soon as you 
can. For all other medical problems or injuries related to this study, contact us 
immediately. We will treat you or refer you for treatment. (Sites: insert locale- 
appropriate medical insurance language in the following sentence) You and/or 
your health insurance will be responsible for treatment costs.  
There are no funds to pay for a study-related injury, added treatment costs, loss of 
a job, or other costs to you or your family. Local or national law may give you 
rights to seek payment for some of these expenses. You always have the right to 
use the court system if you are not satisfied. 
Questions  
14. If you have questions or problems at any time during your participation in 
this study, use the following important contacts. 
If you have questions about this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
If you have any symptoms that you think may be related to this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
This study has been reviewed and approved by a committee called the 
[name of local IRB/EC]. If you have questions about your rights as a research 
participant, or problems or concerns about how you are being treated in this study, 
contact [name or title and telephone number of person on IRB/EC] , at the 
committee. 
Paragraph for South African sites. The study has been structured in accordance 
with the Declaration of Helsinki (last updated October 2013) which deals with the 
recommendations guiding doctors in biomedical research involving human 
participants, the Ethics in Health Research: Principles, Structures and Processes 
Second Edition 2015, and Guidelines for Good Practice in the Conduct of Clinical 
Trials in Human Participants in South Africa. We can provide you with copies of 
these guidelines if you wish to review them. 
If you want to leave this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
Remainder of section for South African sites only.  
You can reach a study staff member 24 hours a day at [telephone number]. 
If you have questions about this trial you should first discuss them with your 
doctor or the ethics committee (contact details as provided on this form). After 

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you have consulted your doctor or the ethics committee and if they have not 
provided you with answers to your satisfaction, you should write to the South 
African Healthcare Products Regulatory Authority (SAHPRA) at: 
The Chief Executive Officer 
Dr Boitumelo Semete-Makokotlela 
South African Health Products Regulatory Authority Private Bag X828 
PRETORIA 
0001 
Tel: (012) 842 7629/26 
e-mail: Boitumelo.Semete@sahpra.org.za 
 
Your permissions and signature  
15. In Section 6 of this form, we told you about possible other uses of your extra 
samples and information, outside this study. Please choose only one of the 
options below and write your initials or make your mark in the box next to it. 
Whatever you choose, the HVTN keeps track of your decision about how 
your samples and information can be used. You can change your mind after 
signing this form. 
 
 
I allow my extra samples and information to be used for other studies related to 
COVID-19, vaccines, antibodies, 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.  
 
16. 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. 

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• You agree to join this study. 
You will not be giving up any of your rights by signing this consent form. 
 
 
 
 
 
 
 
Participant’s name (print) 
 
Participant’s signature or mark 
 
Date 
 
Time 
 
 
 
 
 
 
 
Clinic staff conducting consent 
discussion (print) 
 
Clinic staff signature 
 
Date 
 
Time 
For participants who are unable to read or write, a witness should complete the 
signature block below: 
 
 
 
 
 
 
 
Witness’s name (print) 
 
Witness’s signature  
 
Date 
 
Time 
*Witness is impartial and was present for the entire discussion of this consent form. 
 
 

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Appendix B 
Table of procedures (for sample informed 
consent form) 
Procedure 
Visit 1 
Month 0 
Optional Visit 2 
Month 2 
Optional Visit 3 
Month 4 
Optional Visit 4 
Month 12 
Medical history 
√ 
√ 
√ 
√ 
Pregnancy test (if appropriate*) 
√ 
√ 
√ 
√ 
Blood drawn 
√ 
√ 
√ 
√ 
Optional nasal swab 
√ 
    √** 
    √** 
    √** 
Optional nasal wash sample 
     √*** 
     √*** 
     √*** 
     √*** 
Interview/questionnaire 
√ 
√ 
√ 
√ 
* For participants assigned female sex at birth. Pregnancy test may be performed on urine or blood samples. 
Persons who are NOT capable of becoming pregnant due to total hysterectomy or bilateral oophorectomy 
(verified by medical records) or who have reached menopause (no menses for one year or more) are not 
required to undergo pregnancy testing. 
**Nasal swab may be collected at these visits if the participant reports new symptoms that are consistent with 
possible COVID-19.  
*** If a nasal wash collection is not possible, participants may be asked to provide a second nasal swab sample 
instead.

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Appendix C 
Schedule of procedures 
 
Visit Number 
01 
021 
031 
041 
Study Month 
0 
2 
4 
12 
Study Day 
0 
56 
112 
364 
Study procedures 
 
 
 
 
 
Assessment of Understanding 
 
√ 
― 
― 
― 
Informed consent 
 
√ 
― 
― 
― 
Eligibility confirmation 
 
√ 
― 
― 
― 
Demographics 
 
√ 
― 
― 
― 
Medical history 
 
√ 
√ 
√ 
√ 
Concomitant medications2 
 
√ 
√ 
√ 
√ 
Clinical labs 
Tube (size) 
 
 
 
 
Pregnancy test (urine or serum) 3 
 
√9 
√ 
√ 
√ 
Optional SARS-CoV-2 IgG assay4 
SST (8.5mL) 
8.5 
― 
― 
― 
Research samples5 
 
 
 
 
 
Cells for assays & storage6 
ACD (8.5mL) 
42.5–85 
42.5–85 
42.5–85 
42.5–85 
Serum for assays and storage 
SST (8.5mL) 
17 
17 
17 
17 
Whole blood for assays and storage 
EDTA (2mL) 
2 
― 
― 
― 
Optional nasal or nasopharyngeal swab  
 
√ 
√7 
√7 
√7 
Optional nasal wash or swab sample  
 
√ 
√ 
√ 
√ 
Daily volume (mL) 
61.5–112.5 
59.5–102 
59.5–
102 
59.5–102 
56-day total volume (mL)8 
112.5 
214.5 
204 
102 
1 These visits are optional. Additional optional visits may be conducted based on evolving 
information regarding SARS-CoV-2 infection and COVID-19.  
2 Concomitant medications (see Section 8.2 and 8.3). 
3 Pregnancy test (see Section 7.1). Pregnant participants will be terminated from the study (see Section 
7.3). 
4 Specimen for optional SARS-CoV-2 IgG assay may be collected at interim or other optional visits if 
not collected at first clinic visit. See Specimen Collection SSP.  
5 Research samples: Blood draw volumes for each tube type shown. 
6 A minimum of 42.5mL up to a maximum 85mL of ACD blood will be collected. Within this range, the 
volume of ACD blood to be drawn should be determined in consideration of the current and planned 
56-day blood draw volume total. See HVTN 405/HPTN 1901 Study Specific Procedures. 
7 An optional nasal or nasopharyngeal swab may be collected at these visits if the participant reports 
onset of new symptoms that in the clinician’s judgment are consistent with possible COVID-19 (see 
Section 8.4).   
8 56-day total based on maximum daily collection volume.  
9 Pregnancy test may be completed within 4 days prior to enrollment. 

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Appendix D 
Visit windows 
 
Visit 
Number 
Visit Type 
Lower 
Allowable 
Window  
Lower 
Target Day 
Target Day 
Upper 
Target Day 
Upper 
Allowable 
Window  
01.0 
Enrollment 
- 
- 
0 
- 
+0 
02.0² 
Follow-up 
- 
-28 
Day 56 
+28 
- 
   03.0¹,² 
Follow-up 
- 
-27 
Day 112  
+56 
- 
04.0² 
Follow-up 
-84 
-28 
Day 364 
+28 
+84 
¹Visit 3 must occur at least 28 days after Visit 2. 
²These visits are optional. Additional optional visits may be conducted based on evolving information 
regarding SARS-CoV-2 infection and COVID-19. 

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Appendix E 
Protocol Signature Page 
 
Characterizing SARS-CoV-2-specific immunity in convalescent individuals 
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 405/HPTN 1901 
DAIDS Protocol Version: Version 2.0 
Protocol Date: June 4, 2020