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Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-neutralizing Epitopes.
de Taeye, Steven W; Ozorowski, Gabriel; Torrents de la Peña, Alba; Guttman, Miklos; Julien, Jean-Philippe; van den Kerkhof, Tom L G M; Burger, Judith A; Pritchard, Laura K; Pugach, Pavel; Yasmeen, Anila; Crampton, Jordan; Hu, Joyce; Bontjer, Ilja; Torres, Jonathan L; Arendt, Heather; DeStefano, Joanne; Koff, Wayne C; Schuitemaker, Hanneke; Eggink, Dirk; Berkhout, Ben; Dean, Hansi; LaBranche, Celia; Crotty, Shane; Crispin, Max; Montefiori, David C; Klasse, P J; Lee, Kelly K; Moore, John P; Wilson, Ian A; Ward, Andrew B; Sanders, Rogier W.
Afiliação
  • de Taeye SW; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands.
  • Ozorowski G; Department of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Torrents de la Peña A; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands.
  • Guttman M; Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
  • Julien JP; Department of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
  • van den Kerkhof TL; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands; Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands.
  • Burger JA; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands.
  • Pritchard LK; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
  • Pugach P; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA.
  • Yasmeen A; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA.
  • Crampton J; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, Center for HIV-1/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), La Jolla, CA 92037, USA.
  • Hu J; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, Center for HIV-1/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), La Jolla, CA 92037, USA.
  • Bontjer I; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands.
  • Torres JL; Department of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Arendt H; International AIDS Vaccine Initiative, New York, NY 10004, USA.
  • DeStefano J; International AIDS Vaccine Initiative, New York, NY 10004, USA.
  • Koff WC; International AIDS Vaccine Initiative, New York, NY 10004, USA.
  • Schuitemaker H; Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands.
  • Eggink D; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands.
  • Berkhout B; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands.
  • Dean H; International AIDS Vaccine Initiative, New York, NY 10004, USA.
  • LaBranche C; Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
  • Crotty S; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, Center for HIV-1/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), La Jolla, CA 92037, USA.
  • Crispin M; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
  • Montefiori DC; Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
  • Klasse PJ; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA.
  • Lee KK; Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
  • Moore JP; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA.
  • Wilson IA; Department of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute,
  • Ward AB; Department of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Sanders RW; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA. Electronic address: r.w.sanders@amc.uva.nl.
Cell ; 163(7): 1702-15, 2015 Dec 17.
Article em En | MEDLINE | ID: mdl-26687358
The envelope glycoprotein trimer mediates HIV-1 entry into cells. The trimer is flexible, fluctuating between closed and more open conformations and sometimes sampling the fully open, CD4-bound form. We hypothesized that conformational flexibility and transient exposure of non-neutralizing, immunodominant epitopes could hinder the induction of broadly neutralizing antibodies (bNAbs). We therefore modified soluble Env trimers to stabilize their closed, ground states. The trimer variants were indeed stabilized in the closed conformation, with a reduced ability to undergo receptor-induced conformational changes and a decreased exposure of non-neutralizing V3-directed antibody epitopes. In rabbits, the stabilized trimers induced similar autologous Tier-1B or Tier-2 NAb titers to those elicited by the corresponding wild-type trimers but lower levels of V3-directed Tier-1A NAbs. Stabilized, closed trimers might therefore be useful components of vaccines aimed at inducing bNAbs.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Vacinas contra a AIDS Limite: Animals Idioma: En Ano de publicação: 2015 Tipo de documento: Article
Texto completo
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PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Vacinas contra a AIDS Limite: Animals Idioma: En Ano de publicação: 2015 Tipo de documento: Article