Q1 · CROSS-FIELD
ArticleOA
Author: Gallouët, Anne-Sophie ; Godot, Veronique ; Kahlaoui, Nidhal ; Grand, Roger Le ; Pantaleo, Giuseppe ; Lemaitre, Julien ; Naninck, Thibaut ; Schwartz, Olivier ; Thiébaut, Rodolphe ; Wiedemann, Aurelie ; Galhaut, Mathilde ; Zurawski, Gerard ; Centlivre, Mireille ; Szurgot, Inga ; Dupaty, Léa ; Marlin, Romain ; Contreras, Vanessa ; Gomez-Pacheco, Mario ; Wang, Zhiqing ; Werf, Sylvie van der ; Lévy, Yves ; Zurawski, Sandra ; Coleon, Severin ; Surenaud, Mathieu ; Cavarelli, Mariangela ; Ellis, Jerome ; Cardinaud, Sylvain ; Relouzat, Francis ; Prague, Mélanie ; Fenwick, Craig ; Bruel, Timothée ; Planas, Delphine ; Chapon, Catherine ; Liljeström, Peter ; Lacabaratz, Christine ; Maisonnasse, Pauline ; Dereuddre-Bosquet, Nathalie ; Fang, Raphaël Ho Tsong
AbstractAchieving 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.
