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

Zoe Moodie, One Dintwe, Sheetal Sawant, Doug Grove, Yunda Huang, Holly Janes, Jack Heptinstall, Faatima Laher Omar, Kristen Cohen, Stephen C. De Rosa, Lu Zhang, Nicole L. Yates, Marcella Sarzotti-Kelsoe, Kelly E. Seaton, Fatima Laher, Linda Gail Bekker, Mookho Malahleha, Craig Innes, Sheetal Kassim, Nivashnee NaickerVaneshree Govender, Modulakgotla Sebe, Nishanta Singh, Philip Kotze, Erica Lazarus, Maphoshane Nchabeleng, Amy M. Ward, William Brumskine, Thozama Dubula, April K. Randhawa, Nicole Grunenberg, John Hural, Jia Jin Kee, David Benkeser, Yutong Jin, Lindsay N. Carpp, Mary Allen, Patricia D'Souza, James Tartaglia, Carlos A. DiazGranados, Marguerite Koutsoukos, Peter B. Gilbert, James G. Kublin, Lawrence Corey, Erica Andersen-Nissen, Glenda E. Gray, Georgia D. Tomaras, M. Juliana McElrath

Research output: Contribution to journalArticlepeer-review

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; Pmag < .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.

Original languageEnglish
Pages (from-to)246-257
Number of pages12
JournalThe Journal of infectious diseases
Volume226
Issue number2
DOIs
Publication statusPublished - 24 Aug 2022

Keywords

  • binding antibodies
  • correlates of risk
  • HIV-1 vaccine
  • HVTN 702
  • intracellular cytokine staining
  • RV144
  • T-cell immunogenicity
  • T-cell polyfunctionality
  • vaccine efficacy trial
  • vaccine-induced immune response

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