The HIV field is in a critical period to develop rapidly and evaluate immunogens that build upon findings from the RV144 regimen and to put forth rational new paradigms for protection. Over the past seven years, the HVTN Laboratory Program was a major leader and substantial contributor to understanding vaccine effects and immune correlates in the VaxGen, Step and RV144 efficacy trials. We raised the standards of immune monitoring in clinical trials, consistently providing high quality data in a GCLP setting using validated or standardized assays. When indicated, we rapidly shifted priorities, broadened collaborations and improved assays. Our Laboratory Center proposes to continue the performance of high quality, state-of-the-art laboratory research, which will accelerate the development of a safe and efficacious HIV vaccine. To accomplish this, we will execute protocol-related, validated endpoint laboratory assays and more comprehensive immunologic investigations to provide unambiguous measurements of vaccine immunogenicity (Aim 1). We will improve existing and adopt novel technologies that can enhance our knowledge of ways vaccines prime the immune system (Aim 2). In phase 2b-3 trials, we will determine vaccine efficacy and investigate potential immune correlates and mechanisms of protection through vaccination (Aim 3). We will optimize strategies to assess vaccine-induced mucosal defense against HIV-1 invasion (Aim 4). Combination strategies with vaccines to prevent HIV will be an important direction for the HVTN, and we will investigate how these may alter and improve immune responses (Aim 5). Finally, we will apply our expertise to fill gaps in development of vaccines for other major global health concerns (Aim 6). Headquartered at FHCRC, the Laboratory Center will integrate its activities seamlessly with the HVTN Leadership and Operations Center and the Statistical and Data Management Center, and cooperatively with the DAIDS Vaccine Clinical Branch. Our core laboratories will continue to be based at FHCRC and Duke University, and we will expand laboratory capacity in South Africa as needed to support efficacy studies.
A safe and effective HIV vaccine is needed to halt the HIV epidemic. We will conduct high quality laboratory studies in support of HVTN HIV vaccine trials that can inform the field about what a candidate HIV vaccine can and cannot do in the populations who would benefit most. Our efforts will provide a rich database that will help advance vaccine development for HIV and other globally important pathogens.
|Barouch, Dan H; Tomaka, Frank L; Wegmann, Frank et al. (2018) Evaluation of a mosaic HIV-1 vaccine in a multicentre, randomised, double-blind, placebo-controlled, phase 1/2a clinical trial (APPROACH) and in rhesus monkeys (NHP 13-19). Lancet 392:232-243|
|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|
|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|
|Lemos, Maria P; Taylor, Terrie E; McGoldrick, Suzanne M et al. (2018) Pathology-Based Research in Africa. Clin Lab Med 38:67-90|
|Williams, Wilton B; Han, Qifeng; Haynes, Barton F (2018) Cross-reactivity of HIV vaccine responses and the microbiome. Curr Opin HIV AIDS 13:9-14|
|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:|
|Wills, Saintedym; Hwang, Kwan-Ki; Liu, Pinghuang et al. (2018) HIV-1-Specific IgA Monoclonal Antibodies from an HIV-1 Vaccinee Mediate Galactosylceramide Blocking and Phagocytosis. 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|
|Fong, Youyi; Huang, Ying; Lemos, Maria P et al. (2018) Rank-based two-sample tests for paired data with missing values. Biostatistics 19:281-294|
|Eren, Kemal; Murrell, Ben (2018) RIFRAF: a frame-resolving consensus algorithm. Bioinformatics 34:3817-3824|
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