Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2.
Adolescent
Adult
Aged
Animals
Antibodies, Neutralizing
/ immunology
Antibodies, Viral
/ immunology
COVID-19
/ prevention & control
COVID-19 Vaccines
/ immunology
Chlorocebus aethiops
Cohort Studies
Epitopes
/ immunology
Female
HEK293 Cells
Humans
Macaca nemestrina
Male
Mice, Inbred BALB C
Middle Aged
Nanoparticles
/ chemistry
Protein Domains
/ immunology
SARS-CoV-2
/ genetics
Spike Glycoprotein, Coronavirus
/ chemistry
Vaccination
Vero Cells
Young Adult
RBD
SARS-CoV-2
computational protein design
nanoparticle
protein
vaccine
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
25 11 2020
25 11 2020
Historique:
received:
11
08
2020
revised:
10
10
2020
accepted:
26
10
2020
pubmed:
9
11
2020
medline:
15
12
2020
entrez:
8
11
2020
Statut:
ppublish
Résumé
A safe, effective, and scalable vaccine is needed to halt the ongoing SARS-CoV-2 pandemic. We describe the structure-based design of self-assembling protein nanoparticle immunogens that elicit potent and protective antibody responses against SARS-CoV-2 in mice. The nanoparticle vaccines display 60 SARS-CoV-2 spike receptor-binding domains (RBDs) in a highly immunogenic array and induce neutralizing antibody titers 10-fold higher than the prefusion-stabilized spike despite a 5-fold lower dose. Antibodies elicited by the RBD nanoparticles target multiple distinct epitopes, suggesting they may not be easily susceptible to escape mutations, and exhibit a lower binding:neutralizing ratio than convalescent human sera, which may minimize the risk of vaccine-associated enhanced respiratory disease. The high yield and stability of the assembled nanoparticles suggest that manufacture of the nanoparticle vaccines will be highly scalable. These results highlight the utility of robust antigen display platforms and have launched cGMP manufacturing efforts to advance the SARS-CoV-2-RBD nanoparticle vaccine into the clinic.
Identifiants
pubmed: 33160446
pii: S0092-8674(20)31450-1
doi: 10.1016/j.cell.2020.10.043
pmc: PMC7604136
pii:
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
COVID-19 Vaccines
0
Epitopes
0
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1367-1382.e17Subventions
Organisme : NIAID NIH HHS
ID : R01 AI118803
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI106677
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007750
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI142001
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests A.C.W, D.V., and N.P.K. are named as inventors on patent applications filed by the University of Washington based on the studies presented in this paper. N.P.K. is a co-founder, shareholder, paid consultant, and chair of the scientific advisory board of Icosavax, Inc. and has received an unrelated sponsored research agreement from Pfizer. D.V. is a consultant for and has received an unrelated sponsored research agreement from Vir Biotechnology Inc. H.Y.C. is a consultant for Merck and Pfizer and has received research funding from Sanofi-Pasteur, Roche-Genentech, Cepheid, and Ellume outside of the submitted work. P.K., A.P., and S.C. are employees and shareholders of Kymab Ltd. The other authors declare no competing interests.
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