Large‐Scale Screening of CD4+ T‐Cell Epitopes From SARS‐CoV‐2 Proteins and the Universal Detection of SARS‐CoV‐2 Specific T Cells for Northeast Asian Population

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ABSTRACT The polymorphism of human leukocyte antigens in the Northeast Asian populations and the lack of broad‐spectrum T‐cell epitopes covering this cohort markedly limited the development of T cell‐directed vaccines against SARS‐CoV‐2 infection, and also hampered the universal detection of SARS‐CoV‐2 specific T cells. In this study, 93 CD4+ T‐cell epitopes restricted by 12 prevalent HLA‐DRB1 allotypes, which covering over 80% Chinese and Northeast Asian populations, were identified from the S, E, M, N and RdRp proteins of SARS‐CoV‐2 by in silico prediction, DC‐peptide‐PBL coculture experiment, and immunization in HLA‐A2/DR1 transgenic mice. Furthermore, by using validated 215 CD8+ T cell epitope peptides and 123 CD4+ T‐cell epitope peptides covering Northeast Asian cohort, the universal ELISpot detection systems of SARS‐CoV‐2 specific CD8+ T cells and CD4+ T cells were established, for the first time, and followed by the tests for 50 unexposed and 100 convalescent samples. The median of spot‐forming units for CD8+ T cells and CD4+ T cells were 68 and 15, respectively, in the unexposed donors, but were 137 and 52 in the convalescent donors 6 months after recovery while 128 and 47 in the convalescent donors 18 months after recovery. This work initially provided the broad‐spectrum CD4+ T‐cell epitope library of SARS‐CoV‐2 for the design of T cell‐directed vaccines and the universal T cell detection tool tailoring to Northeast Asian population, and confirmed the long‐term memory T cell immunity after SARS‐CoV‐2 infection.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.