MARLIN, Romain; GODOT, Veronique; CARDINAUD, Sylvain; GALHAUT, Mathilde; COLEON, Severin; ZURAWSKI, Sandra; DEREUDDRE-BOSQUET, Nathalie; CAVARELLI, Mariangela; GALLOUET, Anne Sophie; MAISONNASSE, Pauline; DUPATY, Lea; FENWICK, Craig; NANINCK, Thibaut; LEMAITRE, Julien; GOMEZ-PACHECO, Mario; KAHLAOUI, Nidhal; CONTRERAS, Vanessa; RELOUZAT, Francis; FANG, Raphael Ho Tsong; WANG, Zhiqing; ELLIS, Jerome 3rd; CHAPON, Catherine; CENTLIVRE, Mireille; WIEDEMANN, Aurelie; LACABARATZ, Christine; SURENAUD, Mathieu; SZURGOT, Inga; LILJESTROM, Peter; PLANAS, Delphine; BRUEL, Timothee; SCHWARTZ, Olivier; VAN DER WERF, Sylvie; PANTALEO, Giuseppe; PRAGUE, Melanie; THIEBAUT, Rodolphe; ZURAWSKI, Gerard; LEVY, Yves; LE GRAND, Roger

doi:10.1038/s41467-021-25382-0

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Nature Communications. 2021-09-01, vol. 12, n° 1, p. 5215

Résumé en anglais

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 (alphaCD40.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 alphaCD40.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.< Réduire

URI

https://oskar-bordeaux.fr/handle/20.500.12278/182837

DOI

http://dx.doi.org/10.1038/s41467-021-25382-0

Project ANR

Initiative for the creation of a Vaccine Research Institute
Développement de vaccins anti-SARS-CoV-2
Infrastructure nationale pour la modélisation des maladies infectieuses humaines

Unités de recherche

Bordeaux Population Health Research Center (BPH) - UMR 1219

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

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