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Publication . Article . 2021

Targeting SARS-CoV-2 receptor-binding domain to cells expressing CD40 improves protection to infection in convalescent macaques

Romain Marlin; Véronique Godot; Sylvain Cardinaud; Mathilde Galhaut; Severin Coleon; Sandra Zurawski; Nathalie Dereuddre-Bosquet; +31 Authors
Open Access
English
Published: 01 Dec 2021 Journal: Nature Communications, volume 12 (eissn: 2041-1723, Copyright policy )
Publisher: Nature Publishing Group UK
Country: France
Abstract
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.
In this study, Marlin et al. provide insights into the potential use of subunit vaccines that induce a high level of protection against SARS-CoV-2 in animal models.
Subjects by Vocabulary

Microsoft Academic Graph classification: Vaccination Viral vector Protein domain Adjuvant medicine.medical_treatment medicine Antibody biology.protein biology Virology Virulence CD40 Humanized mouse

Medical Subject Headings: skin and connective tissue diseases fungi body regions

Subjects

Article, Viral infection, Protein vaccines, SARS-CoV-2, Preclinical research, [SDV]Life Sciences [q-bio], General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Science, Q

Funded by
EC| EVAg
Project
EVAg
European Virus Archive goes global
  • Funder: European Commission (EC)
  • Project Code: 653316
  • Funding stream: H2020 | RIA
,
ANR| IDMIT
Project
IDMIT
Infrastructure nationale pour la modélisation des maladies infectieuses humaines
  • Funder: French National Research Agency (ANR) (ANR)
  • Project Code: ANR-11-INBS-0008
,
EC| TRANSVAC2
Project
TRANSVAC2
European Vaccine Research and Development Infrastructure
  • Funder: European Commission (EC)
  • Project Code: 730964
  • Funding stream: H2020 | RIA
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