This proposal outlines the scientific agenda of the Leadership and Operations Center of the HIV Vaccine Trials Network (HVTN), the collaboration of physician scientists at 64 clinical trial sites in 15 countries on 4 continents dedicated to developing a globally effective HIV vaccine. During the current funding period, the HVTN has transformed HIV prevention science by taking two HIV vaccine concepts and the broadly neutralizing monoclonal antibody (mAb) VRC01 from phase 1 to efficacy evaluation. We have added over 35 clinical trial sites in sub- Saharan Africa and now have over 12,500 participants enrolled in randomized controlled efficacy trials. We propose to continue our scientific leadership in HIV vaccines. The scientific pipeline for vaccines with the potential to induce broadly neutralizing antibodies (bnAbs) to HIV has markedly expanded. This proposal describes a novel fast-track phase 1 program to assess, in an iterative fashion, candidate trimers, germline or lineage-based vaccines designed to elicit bnAbs in adults. A phase 1 program to investigate these vaccines in HIV-1?exposed infants is also proposed. The HVTN currently has five HIV efficacy trials in place. Two vaccine trials (HVTN 702 & 705) are in progress; a third (HVTN 706) will start in August 2019; and we are collaborating with the HIV Prevention Trials Network (HPTN) on two antibody-mediated prevention (AMP) trials evaluating the infusion of passively administered mAbs. These efficacy trials will define the potential of neutralizing and/or non- neutralizing antibodies to prevent HIV acquisition. The samples and statistical design of the efficacy trials are developed around correlates of protection; we will continue to develop the robust integrated laboratory, statistical and computational platform needed to define these correlates. We will also continue to expand our behavioral sciences program to enhance our already successful recruitment and retention programs, and to continue to expand the enrollment of persons of color and transgender persons into HVTN trials. Vaccine clinical trials involve a complex interplay between clinical trial sites, HVTN laboratories, computational scientists, and our operational, training, mentoring, and fiscal management teams; these interactions are described in the application. The clinical, laboratory and statistical infrastructure we have built for HIV vaccines will also be used to assist in tuberculosis (TB) vaccine development. Importantly, we will build on our success in the unique community-based programs and integration of community representatives and community advisory boards into HVTN research process and conduct. We will also continue to develop the next generation of vaccine scientists and expand our scientific collaborations to engage the scientific community to utilize the extensive specimen and data repositories we have established. The overall goal of the HVTN in this proposal is to develop a vaccine regimen or combination mAb regimen that will reduce HIV acquisition in adults and infants by more than 60 percent.

Public Health Relevance

Despite the increasing availability and effectiveness of antiretroviral therapy, HIV continues to be the greatest pandemic of the last 50 years ? 70 million infected, 36 million currently living with HIV and over 1.8 million new infections, including over 180,000 new infant infections annually ? so it is imperative to develop an effective population-based approach to reduce transmission. This proposal for the Leadership and Operations Center of the HIV Vaccine Trials Network, the collaboration of scientists at 64 clinical trial sites in 15 countries on 4 continents dedicated to developing a globally effective HIV vaccine, describes the marked advances in candidate vaccines to induce broadly neutralizing antibodies (bnAbs), the advances in bnAbs administered by injection at levels that can prevent infection, and the HVTN?s extensive programs in engaging both local communities and other scientists throughout the world working to stop the spread of HIV. The goal of the HVTN is to develop a vaccine or monoclonal antibody combination that will, either alone or in combination, reduce HIV acquisition in adults and children by more than 60 percent.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project with Complex Structure Cooperative Agreement (UM1)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Renzullo, Philip O
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Fred Hutchinson Cancer Research Center
United States
Zip Code
Lennard, Katie; Dabee, Smritee; Barnabas, Shaun L et al. (2018) Microbial Composition Predicts Genital Tract Inflammation and Persistent Bacterial Vaginosis in South African Adolescent Females. Infect Immun 86:
Dietrich, Janan J; Lazarus, Erica; Andrasik, Michele et al. (2018) Mobile Phone Questionnaires for Sexual Risk Data Collection Among Young Women in Soweto, South Africa. AIDS Behav 22:2312-2321
Huang, Yunda; Karuna, Shelly; Carpp, Lindsay N et al. (2018) Modeling cumulative overall prevention efficacy for the VRC01 phase 2b efficacy trials. Hum Vaccin Immunother 14:2116-2127
Mngadi, Kathryn Therese; Maharaj, Bhavna; Duki, Yajna et al. (2018) Using Mobile Technology (pMOTAR) to Assess Reactogenicity: Protocol for a Pilot Randomized Controlled Trial. JMIR Res Protoc 7:e175
Bekker, Linda-Gail; Moodie, Zoe; Grunenberg, Nicole et al. (2018) Subtype C ALVAC-HIV and bivalent subtype C gp120/MF59 HIV-1 vaccine in low-risk, HIV-uninfected, South African adults: a phase 1/2 trial. Lancet HIV 5:e366-e378
de Montigny, Simon; Adamson, Blythe J S; Mâsse, Benoît R et al. (2018) Projected effectiveness and added value of HIV vaccination campaigns in South Africa: A modeling study. Sci Rep 8:6066
Auclair, Sarah; Liu, Fengliang; Niu, Qingli et al. (2018) Distinct susceptibility of HIV vaccine vector-induced CD4 T cells to HIV infection. PLoS Pathog 14:e1006888
Yates, Nicole L; deCamp, Allan C; Korber, Bette T et al. (2018) HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees. J Virol 92:
Fong, Youyi; Shen, Xiaoying; Ashley, Vicki C et al. (2018) Modification of the Association Between T-Cell Immune Responses and Human Immunodeficiency Virus Type 1 Infection Risk by Vaccine-Induced Antibody Responses in the HVTN 505 Trial. J Infect Dis 217:1280-1288
Thiam-Diouf, Arame; Metch, Barbara; Sharpe, Cameron et al. (2018) Substance use patterns of HVTN phase I clinical trial participants: Enrollment, risk reduction counseling and retention. Vaccine 36:1235-1242

Showing the most recent 10 out of 174 publications