Publication date: Dec 11, 2024
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, UniversitcE9 Paris-Est CrcE9teil, and the Investissements d’Avenir program, Vaccine Research Institute (VRI), managed by the ANR.
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| Concepts | Keywords |
|---|---|
| Bnt162b2 | COVID-19 |
| Cd4 | Long-lasting T-cell immunity |
| Mice | Pre-clinical models |
| Paris | SARS-CoV-2 |
| Vaccine | Vaccine |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | IDO | protein |
| disease | IDO | cell |
| disease | MESH | COVID-19 |