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Functional convergence of a germline-encoded neutralizing antibody response in rhesus macaques immunized with HCV envelope glycoproteins.
Chen, Fang; Tzarum, Netanel; Lin, Xiaohe; Giang, Erick; Velázquez-Moctezuma, Rodrigo; Augestad, Elias H; Nagy, Kenna; He, Linling; Hernandez, Mayda; Fouch, Mallorie E; Grinyó, Ariadna; Chavez, Deborah; Doranz, Benjamin J; Prentoe, Jannick; Stanfield, Robyn L; Lanford, Robert; Bukh, Jens; Wilson, Ian A; Zhu, Jiang; Law, Mansun.
  • Chen F; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Tzarum N; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Lin X; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Giang E; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Velázquez-Moctezuma R; Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Hvidovre Hospital, and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
  • Augestad EH; Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Hvidovre Hospital, and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
  • Nagy K; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • He L; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Hernandez M; Integral Molecular, Inc., Philadelphia, PA 19104, USA.
  • Fouch ME; Integral Molecular, Inc., Philadelphia, PA 19104, USA.
  • Grinyó A; Integral Molecular, Inc., Philadelphia, PA 19104, USA.
  • Chavez D; Southwest National Primate Research Center at Texas Biomedical Research Institute, San Antonio, TX 788227, USA.
  • Doranz BJ; Integral Molecular, Inc., Philadelphia, PA 19104, USA.
  • Prentoe J; Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Hvidovre Hospital, and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
  • Stanfield RL; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Lanford R; Southwest National Primate Research Center at Texas Biomedical Research Institute, San Antonio, TX 788227, USA.
  • Bukh J; Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Hvidovre Hospital, and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
  • Wilson IA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: wilson@scripps.edu.
  • Zhu J; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: jiang@scripps.edu.
  • Law M; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: mlaw@scripps.edu.
Immunity ; 54(4): 781-796.e4, 2021 04 13.
Article en En | MEDLINE | ID: mdl-33675683
Human IGHV1-69-encoded broadly neutralizing antibodies (bnAbs) that target the hepatitis C virus (HCV) envelope glycoprotein (Env) E2 are important for protection against HCV infection. An IGHV1-69 ortholog gene, VH1.36, is preferentially used for bnAbs isolated from HCV Env-immunized rhesus macaques (RMs). Here, we studied the genetic, structural, and functional properties of VH1.36-encoded bnAbs generated by vaccination, in comparison to IGHV1-69-encoded bnAbs from HCV patients. Global B cell repertoire analysis confirmed the expansion of VH1.36-derived B cells in immunized animals. Most E2-specific, VH1.36-encoded antibodies cross-neutralized HCV. Crystal structures of two RM bnAbs with E2 revealed that the RM bnAbs engaged conserved E2 epitopes using similar molecular features as human bnAbs but with a different binding mode. Longitudinal analyses of the RM antibody repertoire responses during immunization indicated rapid lineage development of VH1.36-encoded bnAbs with limited somatic hypermutation. Our findings suggest functional convergence of a germline-encoded bnAb response to HCV Env with implications for vaccination in humans.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Glicoproteínas / Proteínas del Envoltorio Viral / Hepatitis C / Hepacivirus / Anticuerpos Neutralizantes / Células Germinativas / Macaca mulatta Tipo de estudio: Observational_studies Límite: Animals / Humans Idioma: En Año: 2021 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Glicoproteínas / Proteínas del Envoltorio Viral / Hepatitis C / Hepacivirus / Anticuerpos Neutralizantes / Células Germinativas / Macaca mulatta Tipo de estudio: Observational_studies Límite: Animals / Humans Idioma: En Año: 2021 Tipo del documento: Article