Subunit protein CD40.SARS.CoV2 vaccine induces SARS-CoV-2-specific stem cell-like memory CD8⁺ T cells.

Authors

Laury Nguema, Florence Picard, Marwa El Hajj, Léa Dupaty, Craig Fenwick, Sylvain Cardinaud, Aurélie Wiedemann, Giuseppe Pantaleo, Sandra Zurawski, Mireille Centlivre, Gerard Zurawski, Yves Lévy, Véronique Godot

Published in

EBioMedicine. Volume 111. Pages 105479. Epub Dec 11, 2024.

Abstract

Ideally, vaccination should induce protective long-lived humoral and cellular immunity. Current licensed COVID-19 mRNA vaccines focused on the spike (S) region induce neutralizing antibodies that rapidly wane.
Herein, we show that a subunit vaccine (CD40.CoV2) targeting spike and nucleocapsid antigens to CD40-expressing cells elicits broad specific human (hu)Th1 CD4⁺ and CD8⁺ T cells in humanized mice.
CD40.CoV2 vaccination selectively enriched long-lived spike- and nucleocapsid-specific CD8⁺ progenitors with stem-cell-like memory (Tscm) properties, whereas mRNA BNT162b2 induced effector memory CD8⁺ T cells. CD8⁺ Tscm cells produced IFNγ and TNF upon antigenic restimulation and showed a high proliferation rate. We demonstrate that CD40 activation is specifically required for the generation of huCD8⁺ Tscm cells.
These results support the development of a CD40-vaccine platform capable of eliciting long-lasting T-cell immunity.
This work was supported by Inserm, Université Paris-Est Créteil, and the Investissements d'Avenir program, Vaccine Research Institute (VRI), managed by the ANR.

PMID:
39667270
Bibliographic data and abstract were imported from PubMed on 21 Aug 2026.

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