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, Séverin Coléon, Sandra Zurawski, Nathalie Dereuddre‐Bosquet, Mariangela Cavarelli, Anne-Sophie Gallouët, Pauline Maisonnasse, Léa Dupaty, Craig Fenwick, Thibaut Naninck, Julien Lemaître, Mario Gomez-Pacheco, Nidhal Kahlaoui, Vanessa Contreras, Francis Relouzat, Raphaël Ho Tsong Fang, Zhiqing Wang, Jerome Ellis, Catherine Chapon, Mireille Centlivre, Aurélie Wiedemann, Christine Lacabaratz, Mathieu Surénaud, Inga Szurgot, Peter Liljeström, Delphine Planas, Timothée Bruel, Olivier Schwartz, Sylvie van der Werf, Giuseppe Pantaleo, Mélanie Prague, Rodolphe Thiébaut, Gérard Zurawski, Yves Lévy, Roger Le Grand
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.