A polyvalent DNA prime with matched polyvalent protein/GLA-SE boost regimen elicited the most robust and broad IgG and IgG3 V1V2 binding antibody and CD4+ T cell responses among 13 HIV vaccine trials

Developing an effective HIV vaccine is a momentous challenge. An exceptionally wide range of candidate HIV vaccines have been tested, yet many were poorly immunogenic, and of the select few that advanced into efficacy trials, only one demonstrated any efficacy. Here we report the results of the largest-scale cross-protocol immunogenicity comparison to date: 13 HIV vaccine trials (including 36 vaccine regimens) conducted across nine countries worldwide, strengthened by standardized trial designs, validated assays in centralized laboratories, and harmonized immunogenicity endpoints - providing an objective approach to identify the HIV vaccine candidate(s) with the best immunogenicity. A polyvalent DNA prime + protein boost regimen (HVTN 124) including Env immunogens of four subtypes, matched between prime and boost, achieved the best anti-V1V2 antibody responses by a large margin and also induced high CD4+ T-cell responses - two key immune responses implicated in HIV vaccine protection. Our results provide strong support to test this promising HIV vaccine design in more advanced phase clinical trials and will also guide the future design of additional HIV vaccines.<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT01799954..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT02109354..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT02404311..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT02207920..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT02296541..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT03284710..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT02915016..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT02997969..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT03122223..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT03409276..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT02968849..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT03060629..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT00223080..

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Publication Details

Journal
Emerging Microbes & Infections
Published
2025-04-07
DOI
https://doi.org/10.1080/22221751.2025.2485317
Citations
2
Primary Topic
HIV Research and Treatment
Type
article
Field-Weighted Citation Impact
2.07

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article

A polyvalent DNA prime with matched polyvalent protein/GLA-SE boost regimen elicited the most robust and broad IgG and IgG3 V1V2 binding antibody and CD4+ T cell responses among 13 HIV vaccine trials

Sheetal Sawant, Kelly E. Seaton, Nigel Garrett, Nicole Grunenberg et al.
2 citations
Emerging Microbes & Infections
HIV Research and Treatment
2.07
article

A polyvalent DNA prime with matched polyvalent protein/GLA-SE boost regimen elicited the most robust and broad IgG and IgG3 V1V2 binding antibody and CD4+ T cell responses among 13 HIV vaccine trials

Sheetal Sawant, Kelly E. Seaton, Nigel Garrett, Nicole Grunenberg, Mina C. Hosseinipour, Zoe Moodie, One Dintwe, Glenda Gray, Paul A. Goepfert, James G. Kublin, Georgia D. Tomaras, Sandhya Vasan, Linda‐Gail Bekker, Shuying Sue Li, Shiyu Chen, Stephen De Rosa, Julie A. Ake, Fatima Laher, Punnee Pitisuttithum, Lawrence Corey, Ian Frank, Jack Heptinstall, Shan Lu, Erica Andersen‐Nissen, Sorachai Nitayaphan, Kathryn Mngadi, M. Juliana McElrath, Peter B. Gilbert, Lindsay Nicole Carpp, Elena E. Giorgi, LaTonya D. Williams, Lindsey Robert Baden, Lu Zhang, Shuying Liu, Giuseppe Pantaleo, Supachai Rerks‐Ngarm, Mike Chirenje, Frank Tomaka, Michael C. Keefer
article en
2 citations

Abstract

Developing an effective HIV vaccine is a momentous challenge. An exceptionally wide range of candidate HIV vaccines have been tested, yet many were poorly immunogenic, and of the select few that advanced into efficacy trials, only one demonstrated any efficacy. Here we report the results of the largest-scale cross-protocol immunogenicity comparison to date: 13 HIV vaccine trials (including 36 vaccine regimens) conducted across nine countries worldwide, strengthened by standardized trial designs, validated assays in centralized laboratories, and harmonized immunogenicity endpoints - providing an objective approach to identify the HIV vaccine candidate(s) with the best immunogenicity. A polyvalent DNA prime + protein boost regimen (HVTN 124) including Env immunogens of four subtypes, matched between prime and boost, achieved the best anti-V1V2 antibody responses by a large margin and also induced high CD4+ T-cell responses - two key immune responses implicated in HIV vaccine protection. Our results provide strong support to test this promising HIV vaccine design in more advanced phase clinical trials and will also guide the future design of additional HIV vaccines.<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT01799954..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT02109354..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT02404311..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT02207920..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT02296541..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT03284710..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT02915016..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT02997969..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT03122223..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT03409276..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT02968849..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT03060629..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT00223080..

Emerging Microbes & InfectionsVol. 14(1)
South African Medical Research Council (ZA), University of North Carolina at Chapel Hill (US), Henry M. Jackson Foundation (US), Brigham and Women's Hospital (US), International Vaccine Institute (KR), Ministry of Public Health (TH), Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa (ZA), Johnson & Johnson (United States) (US), Desmond Tutu HIV Foundation (ZA), University of Zimbabwe (ZW), University of Cape Town (ZA), University of Massachusetts Chan Medical School (US), Duke University (US), University of the Witwatersrand (ZA), University of Washington (US), Mahidol University (TH), Centre for the AIDS Programme of Research in South Africa (ZA), University of Alabama at Birmingham (US), California University of Pennsylvania (US), Fred Hutch Cancer Center (US), Aurum Institute (ZA), Perinatal HIV Research Unit (ZA), Janssen (United States) (US), Royal Thai Army, University of Rochester (US), Walter Reed Army Institute of Research (US), University of KwaZulu-Natal (ZA), University of Lausanne (CH)
U.S. Department of Defense, U.S. Department of Health and Human Services, Bill and Melinda Gates Foundation, Emory University, South African Medical Research Council, National Institutes of Health, Centers for Disease Control and Prevention, U.S. Public Health Service, University of North Carolina at Chapel Hill, National Institute of Allergy and Infectious Diseases, Medical Research and Materiel Command
Good health and well-being
Openalex Percentile: Top 15%
HIV Research and Treatment
2.07
DOIOpen Access PDFOpenAlex
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