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

Autor:	Hahn WO; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Department of Medicine, University of Washington, Seattle, WA, USA., Parks KR; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Shen M; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Ozorowski G; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA., Janes H; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Ballweber-Fleming L; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Woodward Davis AS; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Duplessis C; Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Tomai M; 3M Healthcare , St. Paul, MD, USA., Dey AK; International AIDS Vaccine Initiative , New York, NY, USA., Sagawa ZK; Access to Advanced Health Institute , Seattle, WA, USA., De Rosa SC; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Seese A; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Kallur Siddaramaiah L; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Stamatatos L; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Lee WH; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA., Sewall LM; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA., Karlinsey D; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA., Turner HL; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA., Rubin V; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Furth S; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., MacPhee K; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Duff M; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Corey L; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Keefer MC; Department of Medicine, University of Rochester, Rochester, NY, USA., Edupuganti S; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA., Frank I; School of Medicine, University of Pennsylvania , Philadelphia, PA, USA., Maenza J; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Department of Medicine, University of Washington, Seattle, WA, USA., Baden LR; Brigham and Women's Hospital , Boston, MA, USA., Hyrien O; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Sanders RW; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands., Moore JP; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY, USA., Ward AB; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA., Tomaras GD; Center for Human Systems Immunology and Departments of Surgery and Integrative Immunobiology, Duke University School of Medicine, Durham, NC, USA., Montefiori DC; Department of Surgery, Duke University, Durham, NC, USA., Rouphael N; Hope Clinic, Emory University , Atlanta, GA, USA., McElrath MJ; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Department of Medicine, University of Washington, Seattle, WA, USA.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2024 Oct 07; Vol. 221 (10). Date of Electronic Publication: 2024 Sep 05.
DOI:	10.1084/jem.20240604
Abstrakt:	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. (© 2024 Hahn et al.)
Databáze:	MEDLINE
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