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.
【저자키워드】 SARS-CoV-2, vaccination, Peptide vaccines, Antimicrobial responses, T cell epitope, HLA-A, 【초록키워드】 COVID-19, coronavirus disease, pathology, Vaccine, Antiviral, SARS-CoV, feasibility, peptide, in silico, CD8, Epitopes, T cell, SARS-CoV-2 variants, mice, T cell responses, Research, Patient, PBMC, NL63, experiment, in vivo, homologous, epitope, T cell response, OC43, HKU1, COVID-19 patients, binding, immune protection, 229E, Coronavirus-2, Amino acid, Combination, Asian, acute respiratory syndrome, RdRp protein, transgenic mice, wild-type, cell line, Host, populations, Cell, prevalent, healthy donor, robust, predicted, indicated, addition, generate, nine, provided, facilitate, functional, were used, induce, the S protein, expressing, elicited, 【제목키워드】 CD8, Screening, T cell, response, transgenic mice,