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Vaccination induces HIV broadly neutralizing antibody precursors in humans.
Leggat, David J; Cohen, Kristen W; Willis, Jordan R; Fulp, William J; deCamp, Allan C; Kalyuzhniy, Oleksandr; Cottrell, Christopher A; Menis, Sergey; Finak, Greg; Ballweber-Fleming, Lamar; Srikanth, Abhinaya; Plyler, Jason R; Schiffner, Torben; Liguori, Alessia; Rahaman, Farhad; Lombardo, Angela; Philiponis, Vincent; Whaley, Rachael E; Seese, Aaron; Brand, Joshua; Ruppel, Alexis M; Hoyland, Wesley; Yates, Nicole L; Williams, LaTonya D; Greene, Kelli; Gao, Hongmei; Mahoney, Celia R; Corcoran, Martin M; Cagigi, Alberto; Taylor, Alison; Brown, David M; Ambrozak, David R; Sincomb, Troy; Hu, Xiaozhen; Tingle, Ryan; Georgeson, Erik; Eskandarzadeh, Saman; Alavi, Nushin; Lu, Danny; Mullen, Tina-Marie; Kubitz, Michael; Groschel, Bettina; Maenza, Janine; Kolokythas, Orpheus; Khati, Nadia; Bethony, Jeffrey; Crotty, Shane; Roederer, Mario; Karlsson Hedestam, Gunilla B; Tomaras, Georgia D.
Afiliación
  • Leggat DJ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Cohen KW; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
  • Willis JR; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Fulp WJ; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • deCamp AC; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Kalyuzhniy O; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
  • Cottrell CA; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
  • Menis S; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Finak G; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Ballweber-Fleming L; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Srikanth A; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Plyler JR; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Schiffner T; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Liguori A; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Rahaman F; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Lombardo A; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Philiponis V; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
  • Whaley RE; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
  • Seese A; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Brand J; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Ruppel AM; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Hoyland W; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Yates NL; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Williams LD; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Greene K; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Gao H; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Mahoney CR; IAVI, New York, NY 10004, USA.
  • Corcoran MM; IAVI, New York, NY 10004, USA.
  • Cagigi A; IAVI, New York, NY 10004, USA.
  • Taylor A; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
  • Brown DM; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
  • Ambrozak DR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Sincomb T; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Hu X; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Tingle R; Center for Human Systems Immunology, Departments of Surgery, Immunology, Molecular Genetics and Microbiology, Duke University, Durham, NC 27701, USA.
  • Georgeson E; Center for Human Systems Immunology, Departments of Surgery, Immunology, Molecular Genetics and Microbiology, Duke University, Durham, NC 27701, USA.
  • Eskandarzadeh S; Duke University Medical Center, Durham, NC 27701, USA.
  • Alavi N; Duke University Medical Center, Durham, NC 27701, USA.
  • Lu D; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
  • Mullen TM; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
  • Kubitz M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Groschel B; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Maenza J; The Foundation for the National Institutes of Health, North Bethesda, MD 20852, USA.
  • Kolokythas O; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Khati N; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Bethony J; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Crotty S; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Roederer M; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Karlsson Hedestam GB; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Tomaras GD; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Science ; 378(6623): eadd6502, 2022 12 02.
Article en En | MEDLINE | ID: mdl-36454825
ABSTRACT
Broadly neutralizing antibodies (bnAbs) can protect against HIV infection but have not been induced by human vaccination. A key barrier to bnAb induction is vaccine priming of rare bnAb-precursor B cells. In a randomized, double-blind, placebo-controlled phase 1 clinical trial, the HIV vaccine-priming candidate eOD-GT8 60mer adjuvanted with AS01B had a favorable safety profile and induced VRC01-class bnAb precursors in 97% of vaccine recipients with median frequencies reaching 0.1% among immunoglobulin G B cells in blood. bnAb precursors shared properties with bnAbs and gained somatic hypermutation and affinity with the boost. The results establish clinical proof of concept for germline-targeting vaccine priming, support development of boosting regimens to induce bnAbs, and encourage application of the germline-targeting strategy to other targets in HIV and other pathogens.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Anticuerpos Anti-VIH / Infecciones por VIH / Vacunas contra el SIDA / Cadenas Pesadas de Inmunoglobulina / Cadenas Ligeras de Inmunoglobulina / Anticuerpos ampliamente neutralizantes / Células Germinativas Tipo de estudio: Clinical_trials Límite: Adult / Female / Humans / Male Idioma: En Revista: Science Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Anticuerpos Anti-VIH / Infecciones por VIH / Vacunas contra el SIDA / Cadenas Pesadas de Inmunoglobulina / Cadenas Ligeras de Inmunoglobulina / Anticuerpos ampliamente neutralizantes / Células Germinativas Tipo de estudio: Clinical_trials Límite: Adult / Female / Humans / Male Idioma: En Revista: Science Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos