Journal article

Induction of potent neutralizing antibody responses by a designed protein nanoparticle accine for respiratory syncytial virus

  • Marcandalli, Jessica Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland -
  • Fiala, Brooke Department of Biochemistry, University of Washington, Seattle, USA - Institute for Protein Design, University of Washington, Seattle, USA
  • Ols, Sebastian Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet, Stockholm, Sweden - Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
  • Perotti, Michela Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Institute of Microbiology, ETH Zürich, Switzerland
  • de van der Schueren, Willem Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, USA - Bluebird Bio, Seattle, USA
  • Snijder, Joost Department of Biochemistry, University of Washington, Seattle, USA
  • Hodge, Edgar Department of Medicinal Chemistry, University of Washington, Seattle, USA
  • Benhaim, Mark Department of Medicinal Chemistry, University of Washington, Seattle, USA
  • Ravichandran, Rashmi Department of Biochemistry, University of Washington, Seattle, USA - Institute for Protein Design, University of Washington, Seattle, USA
  • Carter, Lauren Department of Biochemistry, University of Washington, Seattle, USA - Institute for Protein Design, University of Washington, Seattle, USA
  • Sheffler, Will Department of Biochemistry, University of Washington, Seattle, USA - Institute for Protein Design, University of Washington, Seattle, USA
  • Brunner, Livia Vaccine Formulation Laboratory, University of Lausanne, Switzerland
  • Lawrenz, Maria Vaccine Formulation Institute, Godalming, UK
  • Dubois, Patrice Vaccine Formulation Institute, Godalming, UK
  • Lanzavecchia, Antonio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Sallusto, Federica Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Institute of Microbiology, ETH Zürich, Switzerland
  • Lee, Kelly K. Department of Medicinal Chemistry, University of Washington, Seattle, USA - Biological Physics Structure and Design Program, University of Washington, Seattle, USA
  • Veesler, David Department of Biochemistry, University of Washington, Seattle, USA
  • Correnti, Colin E. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, USA
  • Stewart, Lance J. Department of Biochemistry, University of Washington, Seattle, USA - Institute for Protein Design, University of Washington, Seattle, USA
  • Baker, David Department of Biochemistry, University of Washington, Seattle, USA - Institute for Protein Design, University of Washington, Seattle, USA - Howard Hughes Medical Institute, University of Washington, Seattle, USA
  • Loré, Karin Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet, Stockholm, Sweden - Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
  • Perez, Laurent Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - European Virus Bioinformatics Center, Jena, Germany
  • King, Neil P. Department of Biochemistry, University of Washington, Seattle, USA - Institute for Protein Design, University of Washington, Seattle, USA
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    07.03.2019
Published in:
  • Cell. - 2019, vol. 177, no. 6, p. 1420-1431.e17
English 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.
Language
  • English
Classification
Clinical medicine
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Persistent URL
https://susi.usi.ch/usi/documents/318938
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