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Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus.
Marcandalli, Jessica; Fiala, Brooke; Ols, Sebastian; Perotti, Michela; de van der Schueren, Willem; Snijder, Joost; Hodge, Edgar; Benhaim, Mark; Ravichandran, Rashmi; Carter, Lauren; Sheffler, Will; Brunner, Livia; Lawrenz, Maria; Dubois, Patrice; Lanzavecchia, Antonio; Sallusto, Federica; Lee, Kelly K; Veesler, David; Correnti, Colin E; Stewart, Lance J; Baker, David; Loré, Karin; Perez, Laurent; King, Neil P.
Afiliação
  • Marcandalli J; Università della Svizzera italiana, Faculty of Biomedical Sciences, Institute for Research in Biomedicine, Bellinzona, Switzerland.
  • Fiala B; Department of Biochemistry, University of Washington, Seattle, WA, USA; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Ols S; Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Perotti M; Università della Svizzera italiana, Faculty of Biomedical Sciences, Institute for Research in Biomedicine, Bellinzona, Switzerland; Institute of Microbiology, ETH Zürich, Switzerland.
  • de van der Schueren W; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Snijder J; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Hodge E; Department of Medicinal Chemistry, University of Washington, Seattle, WA, USA.
  • Benhaim M; Department of Medicinal Chemistry, University of Washington, Seattle, WA, USA.
  • Ravichandran R; Department of Biochemistry, University of Washington, Seattle, WA, USA; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Carter L; Department of Biochemistry, University of Washington, Seattle, WA, USA; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Sheffler W; Department of Biochemistry, University of Washington, Seattle, WA, USA; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Brunner L; Vaccine Formulation Laboratory, University of Lausanne, Epalinges, Switzerland.
  • Lawrenz M; Vaccine Formulation Institute, Godalming, UK.
  • Dubois P; Vaccine Formulation Institute, Godalming, UK.
  • Lanzavecchia A; Università della Svizzera italiana, Faculty of Biomedical Sciences, Institute for Research in Biomedicine, Bellinzona, Switzerland.
  • Sallusto F; Università della Svizzera italiana, Faculty of Biomedical Sciences, Institute for Research in Biomedicine, Bellinzona, Switzerland; Institute of Microbiology, ETH Zürich, Switzerland.
  • Lee KK; Department of Medicinal Chemistry, University of Washington, Seattle, WA, USA; Biological Physics Structure and Design Program, University of Washington, Seattle, WA, USA.
  • Veesler D; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Correnti CE; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Stewart LJ; Department of Biochemistry, University of Washington, Seattle, WA, USA; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Baker D; Department of Biochemistry, University of Washington, Seattle, WA, USA; Institute for Protein Design, University of Washington, Seattle, WA, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA.
  • Loré K; Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Perez L; Università della Svizzera italiana, Faculty of Biomedical Sciences, Institute for Research in Biomedicine, Bellinzona, Switzerland; European Virus Bioinformatics Center, Jena, Germany. Electronic address: laurent.perez@irb.usi.ch.
  • King NP; Department of Biochemistry, University of Washington, Seattle, WA, USA; Institute for Protein Design, University of Washington, Seattle, WA, USA. Electronic address: neilking@uw.edu.
Cell ; 176(6): 1420-1431.e17, 2019 03 07.
Article em En | MEDLINE | ID: mdl-30849373
ABSTRACT
Respiratory syncytial virus (RSV) is a worldwide public health concern for which no vaccine is available. Elucidation of the prefusion structure of the RSV F glycoprotein and its identification as the main target of neutralizing antibodies have provided new opportunities for development of an effective vaccine. Here, we describe the structure-based design of a self-assembling protein nanoparticle presenting a prefusion-stabilized variant of the F glycoprotein trimer (DS-Cav1) in a repetitive array on the nanoparticle exterior. The two-component nature of the nanoparticle scaffold enabled the production of highly ordered, monodisperse immunogens that display DS-Cav1 at controllable density. In mice and nonhuman primates, the full-valency nanoparticle immunogen displaying 20 DS-Cav1 trimers induced neutralizing antibody responses ∼10-fold higher than trimeric DS-Cav1. These results motivate continued development of this promising nanoparticle RSV vaccine candidate and establish computationally designed two-component nanoparticles as a robust and customizable platform for structure-based vaccine design.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Vírus Sinciciais Respiratórios / Vacinação / Anticorpos Neutralizantes Idioma: En Ano de publicação: 2019 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Vírus Sinciciais Respiratórios / Vacinação / Anticorpos Neutralizantes Idioma: En Ano de publicação: 2019 Tipo de documento: Article