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Use of 3M-052-AF with Alum adjuvant in HIV trimer vaccine induces human autologous neutralizing antibodies.
Hahn, William O; Parks, K Rachael; Shen, Mingchao; Ozorowski, Gabriel; Janes, Holly; Ballweber-Fleming, Lamar; Woodward Davis, Amanda S; Duplessis, Chris; Tomai, Mark; Dey, Antu K; Sagawa, Zachary K; De Rosa, Stephen C; Seese, Aaron; Kallur Siddaramaiah, Latha; Stamatatos, Leonidas; Lee, Wen-Hsin; Sewall, Leigh M; Karlinsey, Dalton; Turner, Hannah L; Rubin, Vanessa; Furth, Sarah; MacPhee, Kellie; Duff, Michael; Corey, Lawrence; Keefer, Michael C; Edupuganti, Srilatha; Frank, Ian; Maenza, Janine; Baden, Lindsey R; Hyrien, Ollivier; Sanders, Rogier W; Moore, John P; Ward, Andrew B; Tomaras, Georgia D; Montefiori, David C; Rouphael, Nadine; McElrath, M Juliana.
Afiliación
  • Hahn WO; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Parks KR; Department of Medicine, University of Washington, Seattle, WA, USA.
  • Shen M; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Ozorowski G; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Janes H; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 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; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Tomai M; Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.
  • Dey AK; 3M Healthcare , St. Paul, MD, USA.
  • Sagawa ZK; International AIDS Vaccine Initiative , New York, NY, USA.
  • De Rosa SC; Access to Advanced Health Institute , Seattle, WA, USA.
  • Seese A; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Kallur Siddaramaiah L; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
  • Stamatatos L; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Lee WH; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Sewall LM; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 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; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
  • Furth S; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 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.
  • Keefer MC; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Edupuganti S; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Frank I; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
  • Maenza J; Department of Medicine, University of Rochester, Rochester, NY, USA.
  • Baden LR; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
  • Hyrien O; School of Medicine, University of Pennsylvania , Philadelphia, PA, USA.
  • Sanders RW; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Moore JP; Department of Medicine, University of Washington, Seattle, WA, USA.
  • Ward AB; Brigham and Women's Hospital , Boston, MA, USA.
  • Tomaras GD; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Montefiori DC; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
  • Rouphael N; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY, USA.
  • McElrath MJ; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
J Exp Med ; 221(10)2024 Oct 07.
Article en En | MEDLINE | ID: mdl-39235529
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, 128-18647) 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adyuvantes Inmunológicos / Vacunas contra el SIDA / Productos del Gen env del Virus de la Inmunodeficiencia Humana / Compuestos de Alumbre / Anticuerpos Neutralizantes Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: J Exp Med Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adyuvantes Inmunológicos / Vacunas contra el SIDA / Productos del Gen env del Virus de la Inmunodeficiencia Humana / Compuestos de Alumbre / Anticuerpos Neutralizantes Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: J Exp Med Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos