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.
(2019) Cell, volume 176, issue 6, pp. 1420 - 1431
(Article)
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
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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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Keywords: computational protein design, nanoparticles, neutralizing antibodies, respiratory syncytial virus, self-assembly, vaccines, General Biochemistry,Genetics and Molecular Biology
ISSN: 0092-8674
Publisher: Cell Press
(Peer reviewed)
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