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
Year: 2025
Type: article
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.Trial registration: ClinicalTrials.gov identifier: NCT01799954..Trial registration: ClinicalTrials.gov identifier: NCT02109354..Trial registration: ClinicalTrials.gov identifier: NCT02404311..Trial registration: ClinicalTrials.gov identifier: NCT02207920..Trial registration: ClinicalTrials.gov identifier: NCT02296541..Trial registration: ClinicalTrials.gov identifier: NCT03284710..Trial registration: ClinicalTrials.gov identifier: NCT02915016..Trial registration: ClinicalTrials.gov identifier: NCT02997969..Trial registration: ClinicalTrials.gov identifier: NCT03122223..Trial registration: ClinicalTrials.gov identifier: NCT03409276..Trial registration: ClinicalTrials.gov identifier: NCT02968849..Trial registration: ClinicalTrials.gov identifier: NCT03060629..Trial registration: ClinicalTrials.gov identifier: NCT00223080..
Source: Emerging Microbes & Infections
Authors: Zoe Moodie, Shuying Sue Li, Elena E. Giorgi, LaTonya D. Williams, One Dintwe, Lindsay N. Carpp, Shiyu Chen, Kelly E. Seaton, Sheetal S. Sawant, Lu Zhang, Jack Heptinstall, Shuying Liu, Nicole Grunenberg, Frank Tomaka, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayaphan, Julie A. Ake, Sandhya Vasan, Giuseppe Pantaleo, Ian Frank, Lindsey R. Baden, Paul A. Goepfert, Michael Keefer, Mike Chirenje, Mina C. Hosseinipour, Kathryn Mngadi, Fatima Laher, Nigel Garrett, Linda-Gail Bekker, Stephen De Rosa, Erica Andersen-Nissen, James G. Kublin, Shan Lu, Peter B. Gilbert, Glenda E. Gray, Lawrence Corey, M. Juliana McElrath, Georgia D. Tomaras
Institutions: Fred Hutch Cancer Center, Duke University, Johnson & Johnson (United States), Janssen (United States), Ministry of Public Health, Mahidol University, Royal Thai Army, Walter Reed Army Institute of Research, Henry M. Jackson Foundation, Centre Hospitalier Universitaire Vaudois, University of Lausanne, University of Pennsylvania, Brigham and Women's Hospital, University of Alabama at Birmingham, University of Rochester, University of Zimbabwe, University of North Carolina at Chapel Hill, Aurum Institute, University of the Witwatersrand, Perinatal HIV Research Unit, Witshealth Consortium (Pty) Ltd. (South Africa), Desmond Tutu HIV Foundation, University of Cape Town, Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, University of Massachusetts Chan Medical School, University of Washington, South African Medical Research Council
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,643
Funders: 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
Awards: G1214792496, G1386795942, G1781567339, G4064436708, G7656363126, G819814859, G8580238280, HIV Vaccine Trials Network Laboratory Center, University of Pennsylvania HIV Clinical Trials Unit, HIV Vaccines Clinical Trials Network Leadership and Operations Center, Aurum Clinical Trials Unit, University of North Carolina Global HIV Prevention and Treatment Clinical Trials Unit
OpenAlex ID: W4409207648