An Engineered Receptor-Binding Domain Improves the Immunogenicity of Multivalent SARS-CoV-2 Vaccines.
Angiotensin-Converting Enzyme 2
/ genetics
Animals
Binding Sites
COVID-19 Vaccines
/ chemistry
Female
Genetic Engineering
Glycosylation
HEK293 Cells
Humans
Immunogenicity, Vaccine
Mice
Mice, Inbred BALB C
Models, Molecular
Protein Domains
Rats
Rats, Sprague-Dawley
Receptors, Coronavirus
/ genetics
Spike Glycoprotein, Coronavirus
/ genetics
Vaccines, Conjugate
/ genetics
Vaccines, Synthetic
/ chemistry
ACE2
COVID-19
RBD
SARS-CoV-2
ferritin
receptor-binding domain
vaccine
Journal
mBio
ISSN: 2150-7511
Titre abrégé: mBio
Pays: United States
ID NLM: 101519231
Informations de publication
Date de publication:
11 05 2021
11 05 2021
Historique:
entrez:
12
5
2021
pubmed:
13
5
2021
medline:
25
5
2021
Statut:
epublish
Résumé
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein mediates viral entry into cells expressing angiotensin-converting enzyme 2 (ACE2). The S protein engages ACE2 through its receptor-binding domain (RBD), an independently folded 197-amino-acid fragment of the 1,273-amino-acid S-protein protomer. The RBD is the primary SARS-CoV-2 neutralizing epitope and a critical target of any SARS-CoV-2 vaccine. Here, we show that this RBD conjugated to each of two carrier proteins elicited more potent neutralizing responses in immunized rodents than did a similarly conjugated proline-stabilized S-protein ectodomain. Nonetheless, the native RBD is expressed inefficiently, limiting its usefulness as a vaccine antigen. However, we show that an RBD engineered with four novel glycosylation sites (gRBD) is expressed markedly more efficiently and generates a more potent neutralizing responses as a DNA vaccine antigen than the wild-type RBD or the full-length S protein, especially when fused to multivalent carriers, such as a
Identifiants
pubmed: 33975938
pii: mBio.00930-21
doi: 10.1128/mBio.00930-21
pmc: PMC8262850
pii:
doi:
Substances chimiques
COVID-19 Vaccines
0
Receptors, Coronavirus
0
Spike Glycoprotein, Coronavirus
0
Vaccines, Conjugate
0
Vaccines, Synthetic
0
spike protein, SARS-CoV-2
0
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R01 AI129868
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
Copyright © 2021 Guo et al.
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