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- Title
Targeting SARS-CoV-2 receptor-binding domain to cells expressing CD40 improves protection to infection in convalescent macaques.
- Authors
Marlin, Romain; Godot, Veronique; Cardinaud, Sylvain; Galhaut, Mathilde; Coleon, Severin; Zurawski, Sandra; Dereuddre-Bosquet, Nathalie; Cavarelli, Mariangela; Gallouët, Anne-Sophie; Maisonnasse, Pauline; Dupaty, Léa; Fenwick, Craig; Naninck, Thibaut; Lemaitre, Julien; Gomez-Pacheco, Mario; Kahlaoui, Nidhal; Contreras, Vanessa; Relouzat, Francis; Fang, Raphaël Ho Tsong; Wang, Zhiqing
- 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
SARS-CoV-2; VIRAL antigens; GENETIC vectors; LABORATORY mice; MACAQUES; T cells; B cells
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-25382-0