Use of 3M-052-AF with Alum adjuvant in HIV trimer vaccine induces human autologous neutralizing antibodies
Stabilized trimers preserving the native-like HIV envelope structure may be key components of a preventive HIV vaccine regimen to induce broadly neutralizing antibodies (bnAbs). We evaluated trimeric BG505 SOSIP.664 gp140 formulated with a novel TLR7/8 signaling adjuvant, 3M-052-AF/Alum, for safety, adjuvant dose-finding, and immunogenicity in a first-in-healthy adult (n = 17), randomized, and placebo-controlled trial (HVTN 137A). The vaccine regimen appeared safe. Robust, trimer-specific antibody, and B cell and CD4+ T cell responses emerged after vaccination. Five vaccinees developed serum autologous tier 2 nAbs (ID50 titer, 1:28-1:8647) after two to three doses targeting C3/V5 and/or V1/V2/V3 Env regions by electron microscopy and mutated pseudovirus-based neutralization analyses. Trimer-specific, B cell-derived monoclonal antibody activities confirmed these results and showed weak heterologous neutralization in the strongest responder. Our findings demonstrate the clinical utility of the 3M-052-AF/Alum adjuvant and support further improvements of trimer-based Env immunogens to focus responses on multiple broad nAb epitopes.
Authors
- Zachary K. Sagawa
- Lamar Ballweber-Fleming (ORCID: https://orcid.org/0000-0002-6180-5545)
- Leonidas Stamatatos (ORCID: https://orcid.org/0000-0002-1106-7097)
- Kellie J. MacPhee (ORCID: https://orcid.org/0009-0008-0993-4009)
- David C. Montefiori (ORCID: https://orcid.org/0000-0003-0856-6319)
- Vanessa Rubin (ORCID: https://orcid.org/0000-0003-2134-0576)
- Amanda S. Woodward Davis (ORCID: https://orcid.org/0000-0002-6901-8271)
- Mingchao Shen (ORCID: https://orcid.org/0000-0001-9714-8076)
- Srilatha Edupuganti (ORCID: https://orcid.org/0000-0001-6566-9969)
- Latha Kallur Siddaramaiah
- John P. Moore (ORCID: https://orcid.org/0000-0002-9902-6096)
- K. Rachael Parks (ORCID: https://orcid.org/0000-0002-5307-4455)
- Janine Maenza (ORCID: https://orcid.org/0000-0002-3992-4193)
- Georgia D. Tomaras (ORCID: https://orcid.org/0000-0001-8076-1931)
- Nadine Rouphael (ORCID: https://orcid.org/0000-0002-2512-7919)
- Michael C. Keefer (ORCID: https://orcid.org/0000-0001-9048-3621)
- William O. Hahn (ORCID: https://orcid.org/0000-0003-3181-2231)
- Gabriel Ozorowski (ORCID: https://orcid.org/0000-0002-9695-8138)
- Holly Janes (ORCID: https://orcid.org/0000-0002-3237-984X)
- Hannah L. Turner (ORCID: https://orcid.org/0000-0002-4745-8057)
- Antu Dey (ORCID: https://orcid.org/0000-0001-7438-9379)
- Mark A. Tomai (ORCID: https://orcid.org/0000-0002-6362-9151)
- Michael Duff
- Lawrence Corey (ORCID: https://orcid.org/0000-0002-2179-2436)
- Dalton C. Karlinsey (ORCID: https://orcid.org/0009-0004-1786-905X)
- Ian Frank (ORCID: https://orcid.org/0000-0002-7824-0106)
- Andrew B. Ward (ORCID: https://orcid.org/0000-0001-7153-3769)
- Wen-Hsin Lee (ORCID: https://orcid.org/0000-0001-9445-6671)
- Sarah Furth (ORCID: https://orcid.org/0000-0001-5181-4651)
- M. Juliana McElrath (ORCID: https://orcid.org/0000-0003-2276-7117)
- Rogier W. Sanders (ORCID: https://orcid.org/0000-0002-2324-8573)
- Ollivier Hyrien (ORCID: https://orcid.org/0000-0003-1909-2542)
- Aaron Seese (ORCID: https://orcid.org/0000-0002-5877-6229)
- Lindsey Robert Baden (ORCID: https://orcid.org/0009-0004-1752-1926)
- Leigh M. Sewall (ORCID: https://orcid.org/0000-0002-2020-2991)
- Stephen C. De Rosa (ORCID: https://orcid.org/0000-0003-3871-4618)
- Chris Duplessis
Institutions
- Scripps Research Institute (US)
- Brigham and Women's Hospital (US)
- International AIDS Vaccine Initiative (US)
- Emory University (US)
- Duke University (US)
- University of Washington (US)
- Cornell University (US)
- Amsterdam UMC Location University of Amsterdam (NL)
- Fred Hutch Cancer Center (US)
- HOPE Clinic (US)
- National Institute of Allergy and Infectious Diseases (US)
- Access to Wholistic and Productive Living Institute (US)
- Access to Advanced Health Institute
- University of Rochester (US)
- University of Pennsylvania (US)
- University of Amsterdam (NL)
Publication Details
- Journal
- The Journal of Experimental Medicine
- Published
- 2024-09-05
- DOI
- https://doi.org/10.1084/jem.20240604
- Citations
- 22
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 6.46
Funders
- Bill and Melinda Gates Foundation
- International AIDS Vaccine Initiative
- Fred Hutchinson Cancer Research Center
- Moderna
- National Institutes of Health
- Weill Cornell Medical College
- National Institute of Allergy and Infectious Diseases