Nguema Laury, Picard Florence, El Hajj Marwa, Dupaty Léa, Fenwick Craig, Cardinaud Sylvain, Wiedemann Aurélie, Pantaleo Giuseppe, Zurawski Sandra, Centlivre Mireille, Zurawski Gerard, Lévy Yves, Godot Véronique
Vaccine Research Institute, Université Paris-Est Créteil, Faculté de Médecine, INSERM U955, Team 16, Créteil, France.
Service of Immunology and Allergy Lausanne University Hospital, Swiss Vaccine Research Institute, University Hospital, University of Lausanne, Lausanne, Switzerland.
EBioMedicine. 2025 Jan;111:105479. doi: 10.1016/j.ebiom.2024.105479. Epub 2024 Dec 11.
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.
理想情况下，疫苗接种应诱导产生具有保护性的长效体液免疫和细胞免疫。目前已获许可的新冠病毒mRNA疫苗聚焦于刺突（S）区域，可诱导产生的中和抗体迅速减少。
在此，我们表明，一种将刺突和核衣壳抗原靶向表达CD40的细胞的亚单位疫苗（CD40.CoV2），可在人源化小鼠中引发广泛特异性的人（hu）Th1 CD4和CD8 T细胞。
接种CD40.CoV2疫苗选择性地富集了具有干细胞样记忆（Tscm）特性的长效刺突特异性和核衣壳特异性CD8祖细胞，而mRNA疫苗BNT162b2诱导产生效应记忆CD8 T细胞。CD8 Tscm细胞在抗原再刺激时产生IFNγ和TNF，并表现出高增殖率。我们证明，huCD8 Tscm细胞的产生特别需要CD40激活。
这些结果支持开发一种能够引发持久T细胞免疫的CD40疫苗平台。
本研究得到了法国国家健康与医学研究院（Inserm）、巴黎东部克雷泰伊大学（Université Paris-Est Créteil）以及由法国国家研究机构（ANR）管理的未来投资计划疫苗研究所（VRI）的支持。
