Immunogenicity and protective efficacy on non-adjuvanted CD40-targeting SARS-CoV-2 vaccines in non-human primates.

Authors

Romain Marlin, Mireille Centlivre, Laetitia Bossevot, Anne-Sophie Gallouët, Marie Alexandre, Delphine Planas, Mariangela Cavarelli, Isabelle Staropoli, Wesley Gros, Mathieu Surenaud, Craig Fenwick, Sylvain Cardinaud, Mathilde Galhaut, Sandra Zurawski, Victor Magneron, Loïc Pintore, Cécile Hérate, Marie-Anne Rameix Welti, Paul Mazet, Vanessa Contreras, Francis Relouzat, Nathalie Dereuddre-Bosquet, Giuseppe Pantaleo, Rodolphe Thiébaut, Mélanie Prague, Olivier Schwartz, Gerard Zurawski, Véronique Godot, Roger Le Grand, Yves Lévy

Published in

EBioMedicine. Volume 129. Pages 106361. Epub Jul 01, 2026.

Abstract

The emergence of antigenically distinct SARS-CoV-2 variants increases the risk of immune escape and requires continually updated vaccines. In addition, short-lived specific immunity is a limitation faced by current COVID-19 mRNA vaccines against Sarbecoviruses. This underscores the need for new vaccine approaches providing lasting immunity against SARS-CoV-2.
Here, we demonstrate the capacity of two non-adjuvanted subunit vaccines to induce long-lasting and protective immunity against SARS-CoV-2 variants in macaques. We designed antibody-mediated vaccines (AMV) leveraging an anti-CD40 monoclonal antibody to enhance immune responses by targeting selected antigens to antigen-presenting cells through the CD40 receptor. The CD40.RBDv vaccine targets sequences from the original Wuhan RBD and a mutated RBD, while CD40.Pan.CoV incorporates a conserved nucleocapsid sequence and a mutated RBD region.
We show that both adjuvant-free vaccines induce robust and durable systemic and mucosal anti-RBD antibody responses that neutralise multiple SARS-CoV-2 variants in naive and SARS-CoV-2 convalescent animals, including recent variants such as XFG. In convalescents, mathematical modelling predicted persistence of vaccine-induced antibody for decades. Additionally, the vaccines boost immune responses in mRNA-vaccinated animals, demonstrating the efficiency of CD40-based vaccines as boosters. Both vaccines protect animals against B.1.617.2 Delta and BA.1 Omicron challenges. Viral control correlates with vaccine-induced systemic and mucosal antibody levels and T-cell responses.
These findings support the ability of AMV targeting CD40 to induce strong, long-lasting responses against adapted antigens and broad protection against evolving SARS-CoV-2 variants without requiring adjuvant. These two vaccine candidates are currently under clinical testing.
The Investissements d'Avenir program (ANR-10-LABX-77-01 and ANR-11-INBS-0008), the PSPC COVID-19 - Project EVIDENCE.

PMID:
42385611
Bibliographic data and abstract were imported from PubMed on 15 Sep 2026.

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