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Direct Probing of Germinal Center Responses Reveals Immunological Features and Bottlenecks for Neutralizing Antibody Responses to HIV Env Trimer.
Havenar-Daughton, Colin; Carnathan, Diane G; Torrents de la Peña, Alba; Pauthner, Matthias; Briney, Bryan; Reiss, Samantha M; Wood, Jennifer S; Kaushik, Kirti; van Gils, Marit J; Rosales, Sandy L; van der Woude, Patricia; Locci, Michela; Le, Khoa M; de Taeye, Steven W; Sok, Devin; Mohammed, Ata Ur Rasheed; Huang, Jessica; Gumber, Sanjeev; Garcia, AnaPatricia; Kasturi, Sudhir P; Pulendran, Bali; Moore, John P; Ahmed, Rafi; Seumois, Grégory; Burton, Dennis R; Sanders, Rogier W; Silvestri, Guido; Crotty, Shane.
Afiliação
  • Havenar-Daughton C; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla, CA 92037, USA.
  • Carnathan DG; Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla, CA 92037, USA; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA.
  • Torrents de la Peña A; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
  • Pauthner M; Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Briney B; Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Reiss SM; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla, CA 92037, USA.
  • Wood JS; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA.
  • Kaushik K; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla, CA 92037, USA.
  • van Gils MJ; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
  • Rosales SL; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
  • van der Woude P; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
  • Locci M; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla, CA 92037, USA.
  • Le KM; Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • de Taeye SW; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
  • Sok D; Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Mohammed AUR; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Huang J; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Gumber S; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA.
  • Garcia A; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA.
  • Kasturi SP; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Pulendran B; Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla, CA 92037, USA; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Moore JP; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10065, USA.
  • Ahmed R; Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla, CA 92037, USA; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Seumois G; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
  • Burton DR; Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Sanders RW; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10065, USA.
  • Silvestri G; Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla, CA 92037, USA; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Crotty S; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla, CA 92037, USA; Department of Medicine, Division of Infectious Diseases, University of California, San Diego, La Jol
Cell Rep ; 17(9): 2195-2209, 2016 11 22.
Article em En | MEDLINE | ID: mdl-27880897
ABSTRACT
Generating tier 2 HIV-neutralizing antibody (nAb) responses by immunization remains a challenging problem, and the immunological barriers to induction of such responses with Env immunogens remain unclear. Here, some rhesus monkeys developed autologous tier 2 nAbs upon HIV Env trimer immunization (SOSIP.v5.2) whereas others did not. This was not because HIV Env trimers were immunologically silent because all monkeys made similar ELISA-binding antibody responses; the key difference was nAb versus non-nAb responses. We explored the immunological barriers to HIV nAb responses by combining a suite of techniques, including longitudinal lymph node fine needle aspirates. Unexpectedly, nAb development best correlated with booster immunization GC B cell magnitude and Tfh characteristics of the Env-specific CD4 T cells. Notably, these factors distinguished between successful and unsuccessful antibody responses because GC B cell frequencies and stoichiometry to GC Tfh cells correlated with nAb development, but did not correlate with total Env Ab binding titers.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: HIV-1 / Centro Germinativo / Produtos do Gene env do Vírus da Imunodeficiência Humana / Multimerização Proteica / Anticorpos Neutralizantes / Formação de Anticorpos Limite: Animals Idioma: En Ano de publicação: 2016 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: HIV-1 / Centro Germinativo / Produtos do Gene env do Vírus da Imunodeficiência Humana / Multimerização Proteica / Anticorpos Neutralizantes / Formação de Anticorpos Limite: Animals Idioma: En Ano de publicação: 2016 Tipo de documento: Article