期刊
CELLULAR & MOLECULAR IMMUNOLOGY
卷 18, 期 12, 页码 2588-2608出版社
CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/s41423-021-00784-8
关键词
SARS-CoV-2; T cell epitope; HLA-A; Vaccination
类别
资金
- National Nature Science Foundation of China [82041006]
- COVID-19 Emergency Research Fund of Zhejiang University of China [2020XGZX021]
This study validated multiple T cell epitopes related to SARS-CoV-2 and developed vaccines that induce specific T cell responses. Utilizing different combination strategies and immunogens, the vaccines successfully elicited robust and specific CD8(+) T cell responses.
Since severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific T cells have been found to play essential roles in host immune protection and pathology in patients with coronavirus disease 2019 (COVID-19), this study focused on the functional validation of T cell epitopes and the development of vaccines that induce specific T cell responses. A total of 120 CD8(+) T cell epitopes from the E, M, N, S, and RdRp proteins were functionally validated. Among these, 110, 15, 6, 14, and 12 epitopes were highly homologous with SARS-CoV, OC43, NL63, HKU1, and 229E, respectively; in addition, four epitopes from the S protein displayed one amino acid that was distinct from the current SARS-CoV-2 variants. Then, 31 epitopes restricted by the HLA-A2 molecule were used to generate peptide cocktail vaccines in combination with Poly(I:C), R848 or poly (lactic-co-glycolic acid) nanoparticles, and these vaccines elicited robust and specific CD8(+) T cell responses in HLA-A2/DR1 transgenic mice as well as wild-type mice. In contrast to previous research, this study established a modified DC-peptide-PBL cell coculture system using healthy donor PBMCs to validate the in silico predicted epitopes, provided an epitope library restricted by nine of the most prevalent HLA-A allotypes covering broad Asian populations, and identified the HLA-A restrictions of these validated epitopes using competitive peptide binding experiments with HMy2.CIR cell lines expressing the indicated HLA-A allotype, which initially confirmed the in vivo feasibility of 9- or 10-mer peptide cocktail vaccines against SARS-CoV-2. These data will facilitate the design and development of vaccines that induce antiviral CD8(+) T cell responses in COVID-19 patients.
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