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

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_9448E40DDE5A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus.
Journal
Cell
Author(s)
Marcandalli J., Fiala B., Ols S., Perotti M., de van der Schueren W., Snijder J., Hodge E., Benhaim M., Ravichandran R., Carter L., Sheffler W., Brunner L., Lawrenz M., Dubois P., Lanzavecchia A., Sallusto F., Lee K.K., Veesler D., Correnti C.E., Stewart L.J., Baker D., Loré K., Perez L., King N.P.
ISSN
1097-4172 (Electronic)
ISSN-L
0092-8674
Publication state
Published
Issued date
07/03/2019
Peer-reviewed
Oui
Volume
176
Number
6
Pages
1420-1431.e17
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
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.
Keywords
computational protein design, nanoparticles, neutralizing antibodies, respiratory syncytial virus, self-assembly, vaccines
Pubmed
Web of science
Open Access
Yes
Create date
08/04/2019 16:52
Last modification date
30/04/2021 6:12
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