Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus.
Animals
Antibodies, Neutralizing
/ immunology
Antibodies, Viral
/ immunology
Caveolin 1
Cell Line
HEK293 Cells
Humans
Mice
Mice, Inbred BALB C
Nanoparticles
/ therapeutic use
Primary Cell Culture
Respiratory Syncytial Viruses
/ immunology
Vaccination
/ methods
Vaccines
/ immunology
Viral Fusion Proteins
/ immunology
computational protein design
nanoparticles
neutralizing antibodies
respiratory syncytial virus
self-assembly
vaccines
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
07 03 2019
07 03 2019
Historique:
received:
31
08
2018
revised:
26
11
2018
accepted:
25
01
2019
entrez:
9
3
2019
pubmed:
9
3
2019
medline:
7
1
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30849373
pii: S0092-8674(19)30109-6
doi: 10.1016/j.cell.2019.01.046
pmc: PMC6424820
pii:
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
CAV1 protein, human
0
Caveolin 1
0
F protein, human respiratory syncytial virus
0
Vaccines
0
Viral Fusion Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1420-1431.e17Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM099989
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM120553
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008268
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
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