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 Naicker, Vaneshree 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, 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 Naicker, Vaneshree 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
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.
Keywords: HIV-1 vaccine; HVTN 702; RV144; T-cell immunogenicity; T-cell polyfunctionality; binding antibodies; correlates of risk; intracellular cytokine staining; vaccine efficacy trial; vaccine-induced immune response.
© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Source: PubMed