Screening HLA-A-restricted T cell epitopes of SARS-CoV-2 and the induction of CD8+ T cell responses in HLA-A transgenic mice.

Abstract

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.

• Authors: Xiaoxiao Jin, Yan Ding, Shihui Sun, Xinyi Wang, Zining Zhou, Xiaotao Liu, Miaomiao Li, Xian Chen, Anran Shen, Yandan Wu, Bicheng Liu, Jianqiong Zhang, Jian Li, Yi Yang, Haibo Qiu, Chuanlai Shen, Yuxian He, Guangyu Zhao
• Journal: Cellular & molecular immunology (Cell Mol Immunol) Vol. 18 Issue 12 Pg. 2588-2608 (12 2021) ISSN: 2042-0226 [Electronic] China
• PMID: 34728796 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• COVID-19 Vaccines
• Epitopes, T-Lymphocyte
• HLA-A2 Antigen
• Peptide Library

Topics

• Animals
• CD8-Positive T-Lymphocytes (immunology)
• COVID-19 Vaccines (immunology)
• Cell Line
• Drug Evaluation, Preclinical
• Epitopes, T-Lymphocyte (immunology)
• Female
• HLA-A2 Antigen (immunology)
• Humans
• Immunogenicity, Vaccine
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Peptide Library
• SARS-CoV-2 (immunology)
• Vaccine Development