Analysis of the HIV Vaccine Trials Network 702 Phase 2b–3 HIV-1 Vaccine Trial in South Africa Assessing RV144 Antibody and T-Cell Correlates of HIV-1 Acquisition Risk. (27th June 2022)

• Record Type: Journal Article
• Authors: Moodie, Zoe; Dintwe, One; Sawant, Sheetal; Grove, Doug; Huang, Yunda; Janes, Holly; Heptinstall, Jack; Omar, Faatima Laher; Cohen, Kristen; De Rosa, Stephen C; Zhang, Lu; Yates, Nicole L; Sarzotti-Kelsoe, Marcella; Seaton, Kelly E; Laher, Fatima; Bekker, Linda Gail; Malahleha, Mookho; Innes, Craig; Kassim, Sheetal; Naicker, Nivashnee; Govender, Vaneshree; Sebe, Modulakgotla; Singh, Nishanta; Kotze, Philip; Lazarus, Erica; Nchabeleng, Maphoshane; Ward, Amy M; Brumskine, William; Dubula, Thozama; Randhawa, April K; Grunenberg, Nicole; Hural, John; Kee, Jia Jin; Benkeser, David; Jin, Yutong; Carpp, Lindsay N; Allen, Mary; D'Souza, Patricia; Tartaglia, James; DiazGranados, Carlos A; Koutsoukos, Marguerite; Gilbert, Peter B; Kublin, James G; Corey, Lawrence; Andersen-Nissen, Erica; Gray, Glenda E; Tomaras, Georgia D; McElrath, M Juliana;
• Is Part Of: Journal of infectious diseases. Volume 226:Number 2(2022)
• Page Start: 246
• Page End: 257
• Publication Date: 2022-06-27
• Subjects: HIV-1 vaccine -- HVTN 702 -- RV144 -- vaccine efficacy trial -- T-cell immunogenicity -- T-cell polyfunctionality -- binding antibodies -- correlates of risk -- intracellular cytokine staining -- vaccine-induced immune response; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiac260
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: Background: The ALVAC/gp120 + MF59 vaccines in the HIV Vaccine Trials Network (HVTN) 702 efficacy trial did not prevent human immunodeficiency virus-1 (HIV-1) acquisition. Vaccine-matched immunological endpoints that were correlates of HIV-1 acquisition risk in RV144 were measured in HVTN 702 and evaluated as correlates of HIV-1 acquisition. Methods: Among 1893 HVTN 702 female vaccinees, 60 HIV-1–seropositive cases and 60 matched seronegative noncases were sampled. HIV-specific CD4 + T-cell and binding antibody responses were measured 2 weeks after fourth and fifth immunizations. Cox proportional hazards models assessed prespecified responses as predictors of HIV-1 acquisition. Results: The HVTN 702 Env-specific CD4 + T-cell response rate was significantly higher than in RV144 (63% vs 40%, P = .03) with significantly lower IgG binding antibody response rate and magnitude to 1086.C V1V2 (67% vs 100%, P < .001; P mag < .001). Although no significant univariate associations were observed between any T-cell or binding antibody response and HIV-1 acquisition, significant interactions were observed (multiplicity-adjusted P ≤ .03). Among vaccinees with high IgG A244 V1V2 binding antibody responses, vaccine-matched CD4 + T-cell endpoints associated with decreased HIV-1 acquisition (estimated hazard ratios = 0.40–0.49 per 1-SD increase in CD4 + T-cell endpoint). Conclusions: HVTN 702 and RV144 had distinct immunogenicity profiles. However, both identified significant correlations (univariate or interaction) for IgG V1V2 and polyfunctional CD4 + T cells with HIV-1 acquisition. Clinical Trials Registration . NCT02968849. Abstract : The immunogenicity profile of HVTN 702 differed from that of RV144. Both identified significant correlations (univariate or interaction) for IgG to V1V2 and polyfunctional CD4 + T cells with HIV-1 acquisition.