TY - JOUR
T1 - 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
AU - Moodie, Zoe
AU - Dintwe, One
AU - Sawant, Sheetal
AU - Grove, Doug
AU - Huang, Yunda
AU - Janes, Holly
AU - Heptinstall, Jack
AU - Omar, Faatima Laher
AU - Cohen, Kristen
AU - De Rosa, Stephen C.
AU - Zhang, Lu
AU - Yates, Nicole L.
AU - Sarzotti-Kelsoe, Marcella
AU - Seaton, Kelly E.
AU - Laher, Fatima
AU - Bekker, Linda Gail
AU - Malahleha, Mookho
AU - Innes, Craig
AU - Kassim, Sheetal
AU - Naicker, Nivashnee
AU - Govender, Vaneshree
AU - Sebe, Modulakgotla
AU - Singh, Nishanta
AU - Kotze, Philip
AU - Lazarus, Erica
AU - Nchabeleng, Maphoshane
AU - Ward, Amy M.
AU - Brumskine, William
AU - Dubula, Thozama
AU - Randhawa, April K.
AU - Grunenberg, Nicole
AU - Hural, John
AU - Kee, Jia Jin
AU - Benkeser, David
AU - Jin, Yutong
AU - Carpp, Lindsay N.
AU - Allen, Mary
AU - D’Souza, Patricia
AU - Tartaglia, James
AU - DiazGranados, Carlos A.
AU - Koutsoukos, Marguerite
AU - Gilbert, Peter B.
AU - Kublin, James G.
AU - Corey, Lawrence
AU - Andersen-Nissen, Erica
AU - Gray, Glenda E.
AU - Tomaras, Georgia D.
AU - Juliana McElrath, M.
N1 - Funding Information:
This work was supported by the NIH, National Institute of Allergy and Infectious Diseases (NIAID) (grant numbers UM1 AI068614 to the HIV Vaccine Trials Network [HVTN], UM1 AI068635 to the HVTN Statistical Data and Management Center, Fred Hutchinson Cancer Research Center [FHCRC], and UM1 AI068618 to HVTN Laboratory Center, FHCRC); with additional support by the Center for AIDS Research, Duke University (NIH grant number AI P30 AI064518) and the Bill and Melinda Gates Foundation (grant number OPP1146996). Support was provided to Novartis Vaccines and Diagnostics (now part of the GlaxoSmithKline Biologicals SA) by NIAID (grant numbers HHSN272201300033C/HHSN272201600012C) for the selection and process development of the 2 gp120 envelope proteins TV1.C and 1086.C; and by the Bill and Melinda Gates Foundation Global Health (grant number OPP1017604) and NIAID for the manufacture and release of the gp120 clinical-grade material.
Publisher Copyright:
© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved.
PY - 2022/7/15
Y1 - 2022/7/15
N2 - 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.
AB - 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.
KW - HIV-1 vaccine
KW - HVTN 702
KW - RV144
KW - T-cell immunogenicity
KW - T-cell polyfunctionality
KW - binding antibodies
KW - correlates of risk
KW - intracellular cytokine staining
KW - vaccine efficacy trial
KW - vaccine-induced immune response
UR - http://www.scopus.com/inward/record.url?scp=85137125345&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiac260
DO - 10.1093/infdis/jiac260
M3 - Article
C2 - 35758878
AN - SCOPUS:85137125345
SN - 0022-1899
VL - 226
SP - 246
EP - 257
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 2
ER -