Use of 3M-052-AF with Alum adjuvant in HIV trimer vaccine induces human autologous neutralizing antibodies

Author:

Hahn William O.12ORCID,Parks K. Rachael1ORCID,Shen Mingchao1ORCID,Ozorowski Gabriel3ORCID,Janes Holly1ORCID,Ballweber-Fleming Lamar1ORCID,Woodward Davis Amanda S.1ORCID,Duplessis Chris4ORCID,Tomai Mark5ORCID,Dey Antu K.6ORCID,Sagawa Zachary K.7ORCID,De Rosa Stephen C.18ORCID,Seese Aaron1ORCID,Kallur Siddaramaiah Latha1ORCID,Stamatatos Leonidas1ORCID,Lee Wen-Hsin3ORCID,Sewall Leigh M.3ORCID,Karlinsey Dalton3ORCID,Turner Hannah L.3ORCID,Rubin Vanessa1ORCID,Furth Sarah1ORCID,MacPhee Kellie1ORCID,Duff Michael1ORCID,Corey Lawrence18ORCID,Keefer Michael C.9ORCID,Edupuganti Srilatha10ORCID,Frank Ian11ORCID,Maenza Janine12ORCID,Baden Lindsey R.12ORCID,Hyrien Ollivier1ORCID,Sanders Rogier W.13ORCID,Moore John P.14ORCID,Ward Andrew B.3ORCID,Tomaras Georgia D.15ORCID,Montefiori David C.16ORCID,Rouphael Nadine17ORCID,McElrath M. Juliana12ORCID

Affiliation:

1. Fred Hutchinson Cancer Center 1 Vaccine and Infectious Disease Division, , Seattle, WA, USA

2. University of Washington 11 Department of Medicine, , Seattle, WA, USA

3. The Scripps Research Institute 2 Department of Integrative Structural and Computational Biology, , La Jolla, CA, USA

4. National Institute of Allergy and Infectious Diseases 3 Division of AIDS, , Bethesda, MD, USA

5. 3M Healthcare 4 , St. Paul, MD, USA

6. International AIDS Vaccine Initiative 5 , New York, NY, USA

7. Access to Advanced Health Institute 6 , Seattle, WA, USA

8. University of Washington 7 Department of Laboratory Medicine and Pathology, , Seattle, WA, USA

9. University of Rochester 8 Department of Medicine, , Rochester, NY, USA

10. Emory University School of Medicine 9 Division of Infectious Diseases, Department of Medicine, , Atlanta, GA, USA

11. School of Medicine, University of Pennsylvania 10 , Philadelphia, PA, USA

12. Brigham and Women’s Hospital 12 , Boston, MA, USA

13. Academic Medical Center, University of Amsterdam 13 Department of Medical Microbiology, , Amsterdam, Netherlands

14. Weill Medical College of Cornell University 14 Department of Microbiology and Immunology, , New York, NY, USA

15. Duke University School of Medicine 15 Center for Human Systems Immunology and Departments of Surgery and Integrative Immunobiology, , Durham, NC, USA

16. Duke University 16 Department of Surgery, , Durham, NC, USA

17. Hope Clinic, Emory University 17 , Atlanta, GA, USA

Abstract

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.

Funder

National Institute of Allergy and Infectious Disease

Gates Foundation

Publisher

Rockefeller University Press

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