Targeting SARS-CoV-2 receptor-binding domain to cells expressing CD40 improves protection to infection in convalescent macaques
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Romain Marlin
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Sylvain Cardinaud
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Mathilde Galhaut
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Severin Coleon
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Sandra Zurawski
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Nathalie Dereuddre-Bosquet
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Mariangela Cavarelli
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Pauline Maisonnasse
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Thibaut Naninck
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Nidhal Kahlaoui
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Jerome Ellis
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Mireille Centlivre
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Aurelie Wiedemann
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Christine Lacabaratz
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Mathieu Surenaud
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Delphine Planas
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Timothée Bruel
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Olivier Schwartz
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Sylvie van Der Werf
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Giuseppe Pantaleo
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Mélanie Prague
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Rodolphe Thiébaut
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Gerard Zurawski
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- ORCID : 0000-0002-0168-3523
Roger Le Grand
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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.
Domains
Life Sciences [q-bio]
Origin : Publication funded by an institution