Targeting SARS-CoV-2 receptor-binding domain to cells expressing CD40 improves protection to infection in convalescent macaques.
Animals
Antigen-Presenting Cells
/ immunology
B-Lymphocytes
/ immunology
CD40 Antigens
/ immunology
COVID-19
/ prevention & control
COVID-19 Vaccines
/ immunology
Convalescence
Humans
Macaca
Mice
Mutation
Protein Domains
Reinfection
/ prevention & control
SARS-CoV-2
/ genetics
Spike Glycoprotein, Coronavirus
/ chemistry
T-Lymphocytes
/ immunology
Vaccination
Vaccines, Subunit
/ immunology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
01 09 2021
01 09 2021
Historique:
received:
18
02
2021
accepted:
21
07
2021
entrez:
2
9
2021
pubmed:
3
9
2021
medline:
14
9
2021
Statut:
epublish
Résumé
Achieving sufficient worldwide vaccination coverage against SARS-CoV-2 will require additional approaches to currently approved viral vector and mRNA vaccines. Subunit vaccines may have distinct advantages when immunizing vulnerable individuals, children and pregnant women. Here, we present a new generation of subunit vaccines targeting viral antigens to CD40-expressing antigen-presenting cells. We demonstrate that targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein to CD40 (αCD40.RBD) induces significant levels of specific T and B cells, with long-term memory phenotypes, in a humanized mouse model. Additionally, we demonstrate that a single dose of the αCD40.RBD vaccine, injected without adjuvant, is sufficient to boost a rapid increase in neutralizing antibodies in convalescent non-human primates (NHPs) exposed six months previously to SARS-CoV-2. Vaccine-elicited antibodies cross-neutralize different SARS-CoV-2 variants, including D614G, B1.1.7 and to a lesser extent B1.351. Such vaccination significantly improves protection against a new high-dose virulent challenge versus that in non-vaccinated convalescent animals.
Identifiants
pubmed: 34471122
doi: 10.1038/s41467-021-25382-0
pii: 10.1038/s41467-021-25382-0
pmc: PMC8410935
doi:
Substances chimiques
CD40 Antigens
0
COVID-19 Vaccines
0
Spike Glycoprotein, Coronavirus
0
Vaccines, Subunit
0
spike protein, SARS-CoV-2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5215Subventions
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-10-LABX-77
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-20-COV6-0004-01
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-11-INBS-0008
Organisme : Fondation pour la Recherche Médicale (Foundation for Medical Research in France)
ID : AM-CoV-Path
Informations de copyright
© 2021. The Author(s).
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