Immune correlates of the Thai RV144 HIV vaccine regimen in South Africa
Open Access
- 18 September 2019
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Translational Medicine
- Vol. 11 (510)
- https://doi.org/10.1126/scitranslmed.aax1880
Abstract
One of the most successful HIV vaccines to date, the RV144 vaccine tested in Thailand, demonstrated correlates of protection including cross-clade V1V2 immunoglobulin G (IgG) breadth, Env-specific CD4+ T cell polyfunctionality, and antibody-dependent cellular cytotoxicity (ADCC) in vaccinees with low IgA binding. The HIV Vaccine Trials Network (HVTN) 097 trial evaluated this vaccine regimen in South Africa, where clade C HIV-1 predominates. We compared cellular and humoral responses at peak and durability immunogenicity time points in HVTN 097 and RV144 vaccinee samples, and evaluated vaccine-matched and cross-clade immune responses. At peak immunogenicity, HVTN 097 vaccinees exhibited significantly higher cellular and humoral immune responses than RV144 vaccinees. CD4+ T cell responses were more frequent in HVTN 097 irrespective of age and sex, and CD4+ T cell Env-specific functionality scores were higher in HVTN 097. Env-specific CD40L+ CD4+ T cells were more common in HVTN 097, with individuals having this pattern of expression demonstrating higher median antibody responses to HIV-1 Env. IgG and IgG3 binding antibody rates and response magnitude to gp120 vaccine– and V1V2 vaccine–matched antigens were higher or comparable in HVTN 097 than in RV144 ADCC, and ADCP functional antibody responses were elicited in HVTN 097. Env-specific IgG and CD4+ Env responses declined significantly over time in both trials. Overall, cross-clade immune responses associated with protection were better than expected in South Africa, suggesting wider applicability of this regimen.Keywords
Funding Information
- National Institute of Allergy and Infectious Diseases (UM1 AI068614)
- National Institute of Allergy and Infectious Diseases (UM1 AI068618)
- National Institute of Allergy and Infectious Diseases (UM1 AI068635)
- National Institute of Allergy and Infectious Diseases (UM1 AI069519)
- National Institute of Allergy and Infectious Diseases (UM1 AI069453)
- National Institute of Allergy and Infectious Diseases (UM1 AI069469)
- Bill and Melinda Gates Foundation
- James B. Pendleton Charitable Trust
- South African Medical Research Council
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