Introduction of Two Prolines and Removal of the Polybasic Cleavage Site Lead to Higher Efficacy of a Recombinant Spike-Based SARS-CoV-2 Vaccine in the Mouse Model.
COVID-19
SARS-CoV-2
spike
vaccine
Journal
mBio
ISSN: 2150-7511
Titre abrégé: mBio
Pays: United States
ID NLM: 101519231
Informations de publication
Date de publication:
02 03 2021
02 03 2021
Historique:
entrez:
3
3
2021
pubmed:
4
3
2021
medline:
16
3
2021
Statut:
epublish
Résumé
The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as the prime target for vaccine development. The spike protein mediates both binding to host cells and membrane fusion and is also so far the only known viral target of neutralizing antibodies. Coronavirus spike proteins are large trimers that are relatively unstable, a feature that might be enhanced by the presence of a polybasic cleavage site in SARS-CoV-2 spike. Exchange of K986 and V987 for prolines has been shown to stabilize the trimers of SARS-CoV-1 and the Middle East respiratory syndrome coronavirus spike proteins. Here, we test multiple versions of a soluble spike protein for their immunogenicity and protective effect against SARS-CoV-2 challenge in a mouse model that transiently expresses human angiotensin-converting enzyme 2 via adenovirus transduction. Variants tested include spike proteins with a deleted polybasic cleavage site, proline mutations, or a combination thereof, besides the wild-type protein. While all versions of the protein were able to induce neutralizing antibodies, only the antigen with both a deleted cleavage site and the K986P and V987P (PP) mutations completely protected from challenge in this mouse model.
Identifiants
pubmed: 33653892
pii: mBio.02648-20
doi: 10.1128/mBio.02648-20
pmc: PMC8092267
pii:
doi:
Substances chimiques
COVID-19 Vaccines
0
Spike Glycoprotein, Coronavirus
0
Proline
9DLQ4CIU6V
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
Subventions
Organisme : NIAID NIH HHS
ID : R21 AI157606
Pays : United States
Organisme : NIAID NIH HHS
ID : 75N93019C00051
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201400008C
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
Copyright © 2021 Amanat et al.
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