Elicitation of potent neutralizing antibody responses by designed protein nanoparticle vaccines for SARS-CoV-2
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2020-11-25
Date Acceptance
2020-10-26
Citation
Cell, 2020, 183 (5), pp.1367-1382.e17
ISSN
0092-8674
Publisher
Elsevier
Start Page
1367
End Page
1382.e17
Journal / Book Title
Cell
Volume
183
Issue
5
Copyright Statement
© 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/33160446
PII: S0092-8674(20)31450-1
Subjects
RBD
SARS-CoV-2
computational protein design
nanoparticle
protein
vaccine
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2020-10-31