Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus | Zendy

Jessica Marcandalli | Zendy; Brooke Fiala | Zendy; Sebastian Ols | Zendy; Michela Perotti | Zendy; Willem de van der Schueren | Zendy; Joost Snijder | Zendy; Edgar A. Hodge | Zendy; Mark A. Benhaim | Zendy; Rashmi Ravichandran | Zendy; Lauren Carter | Zendy; William Sheffler | Zendy; Livia Brunner | Zendy; Maria Lawrenz | Zendy; Patrice Dubois | Zendy; Antonio Lanzavecchia | Zendy; Federica Sallusto | Zendy; Kelly K. Lee | Zendy; David Veesler | Zendy; Colin Correnti | Zendy; Lance Stewart | Zendy; David Baker | Zendy; Karin Loré | Zendy; Laurent Perez | Zendy; Neil P. King | Zendy

Open Access

Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus

Author(s) -

Jessica Marcandalli,

Brooke Fiala,

Sebastian Ols,

Michela Perotti,

Willem de van der Schueren,

Joost Snijder,

Edgar A. Hodge,

Mark A. Benhaim,

Rashmi Ravichandran,

Lauren Carter,

William Sheffler,

Livia Brunner,

Maria Lawrenz,

Patrice Dubois,

Antonio Lanzavecchia,

Federica Sallusto,

Kelly K. Lee,

David Veesler,

Colin Correnti,

Lance Stewart,

David Baker,

Karin Loré,

Laurent Perez,

Neil P. King

Publication year - 2019

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2019.01.046

Subject(s) - immunogen , biology , neutralizing antibody , virology , glycoprotein , virus , antibody , nanoparticle , trimer , immunogenicity , nanotechnology , immunology , materials science , chemistry , microbiology and biotechnology , monoclonal antibody , dimer , organic chemistry

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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