Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines.
COVID-19
SARS-CoV-2
mosaic nanoparticle
receptor-binding domain
sarbecovirus
self-assembling nanoparticle
spike glycoprotein
vaccine design
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
14 10 2021
14 10 2021
Historique:
received:
05
04
2021
revised:
18
06
2021
accepted:
09
09
2021
pubmed:
8
10
2021
medline:
8
10
2021
entrez:
7
10
2021
Statut:
ppublish
Résumé
Understanding vaccine-elicited protection against SARS-CoV-2 variants and other sarbecoviruses is key for guiding public health policies. We show that a clinical stage multivalent SARS-CoV-2 spike receptor-binding domain nanoparticle (RBD-NP) vaccine protects mice from SARS-CoV-2 challenge after a single immunization, indicating a potential dose-sparing strategy. We benchmarked serum neutralizing activity elicited by RBD-NPs in non-human primates against a lead prefusion-stabilized SARS-CoV-2 spike (HexaPro) using a panel of circulating mutants. Polyclonal antibodies elicited by both vaccines are similarly resilient to many RBD residue substitutions tested, although mutations at and surrounding position 484 have negative consequences for neutralization. Mosaic and cocktail nanoparticle immunogens displaying multiple sarbecovirus RBDs elicit broad neutralizing activity in mice and protect mice against SARS-CoV challenge even in the absence of SARS-CoV RBD in the vaccine. This study provides proof of principle that multivalent sarbecovirus RBD-NPs induce heterotypic protection and motivates advancing such broadly protective sarbecovirus vaccines to the clinic.
Identifiants
pubmed: 34619077
pii: S0092-8674(21)01062-X
doi: 10.1016/j.cell.2021.09.015
pmc: PMC8440233
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5432-5447.e16Subventions
Organisme : NIAID NIH HHS
ID : F32 AI152296
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM120553
Pays : United States
Organisme : NIAID NIH HHS
ID : DP1 AI158186
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007151
Pays : United States
Organisme : NIH HHS
ID : P51 OD010425
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI149644
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201700059C
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI127521
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI151698
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008268
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests A.C.W., N.P.K., and D.V. 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.C. is an employee of Vir Biotechnology and may hold shares in Vir Biotechnology. D.V. is a consultant for and has received an unrelated sponsored research agreement from Vir Biotechnology, Inc. R.R., D.T.O., and R.V.D.M. are employees of GlaxoSmithKline. C.-L.H. and J.S.M. are inventors on US patent application no. 63/032,502, “Engineered Coronavirus Spike (S) Protein and Methods of Use Thereof”. R.S.B. has collaborative research agreements with Takeda, Pfizer, Eli Lily, Gilead, Ridgeback Biosciences, and VaxArt, unrelated to the current research. The other authors declare no competing interests.
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