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

Romain Marlin, Veronique Godot, Sylvain Cardinaud, Mathilde Galhaut, Severin Coleon, Sandra Zurawski, Nathalie Dereuddre-Bosquet, Mariangela Cavarelli, Anne-Sophie Gallouët, Pauline Maisonnasse, Léa Dupaty, Craig Fenwick, Thibaut Naninck, Julien Lemaitre, Mario Gomez-Pacheco, Nidhal Kahlaoui, Vanessa Contreras, Francis Relouzat, Raphaël Ho Tsong Fang, Zhiqing Wang, Jerome Ellis, Catherine Chapon, Mireille Centlivre, Aurelie Wiedemann, Christine Lacabaratz, Mathieu Surenaud, Inga Szurgot, Peter Liljeström, Delphine Planas, Timothée Bruel, Olivier Schwartz, Sylvie van der Werf, Giuseppe Pantaleo, Mélanie Prague, Rodolphe Thiébaut, Gerard Zurawski, Yves Lévy () and Roger Le Grand ()
Additional contact information
Romain Marlin: Université Paris-Saclay, Inserm, CEA
Veronique Godot: Vaccine Research Institute
Sylvain Cardinaud: Vaccine Research Institute
Mathilde Galhaut: Université Paris-Saclay, Inserm, CEA
Severin Coleon: Vaccine Research Institute
Sandra Zurawski: Vaccine Research Institute
Nathalie Dereuddre-Bosquet: Université Paris-Saclay, Inserm, CEA
Mariangela Cavarelli: Université Paris-Saclay, Inserm, CEA
Anne-Sophie Gallouët: Université Paris-Saclay, Inserm, CEA
Pauline Maisonnasse: Université Paris-Saclay, Inserm, CEA
Léa Dupaty: Vaccine Research Institute
Craig Fenwick: Service of Immunology and Allergy Lausanne University Hospital
Thibaut Naninck: Université Paris-Saclay, Inserm, CEA
Julien Lemaitre: Université Paris-Saclay, Inserm, CEA
Mario Gomez-Pacheco: Université Paris-Saclay, Inserm, CEA
Nidhal Kahlaoui: Université Paris-Saclay, Inserm, CEA
Vanessa Contreras: Université Paris-Saclay, Inserm, CEA
Francis Relouzat: Université Paris-Saclay, Inserm, CEA
Raphaël Ho Tsong Fang: Université Paris-Saclay, Inserm, CEA
Zhiqing Wang: Vaccine Research Institute
Jerome Ellis: Vaccine Research Institute
Catherine Chapon: Université Paris-Saclay, Inserm, CEA
Mireille Centlivre: Vaccine Research Institute
Aurelie Wiedemann: Vaccine Research Institute
Christine Lacabaratz: Vaccine Research Institute
Mathieu Surenaud: Vaccine Research Institute
Inga Szurgot: Karolinska Institutet
Peter Liljeström: Karolinska Institutet
Delphine Planas: Vaccine Research Institute
Timothée Bruel: Vaccine Research Institute
Olivier Schwartz: Vaccine Research Institute
Sylvie van der Werf: Université de Paris
Giuseppe Pantaleo: Vaccine Research Institute
Mélanie Prague: Vaccine Research Institute
Rodolphe Thiébaut: Vaccine Research Institute
Gerard Zurawski: Vaccine Research Institute
Yves Lévy: Vaccine Research Institute
Roger Le Grand: Université Paris-Saclay, Inserm, CEA

Nature Communications, 2021, vol. 12, issue 1, 1-9

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-25382-0

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