Large-Scale Identification of T-Cell Epitopes Derived From Severe Acute Respiratory Syndrome Coronavirus 2 for the Development of Peptide Vaccines Against Coronavirus Disease 2019

background: Coronavirus disease-19 (COVID-19) continues to be a major public health challenge globally. The identification of SARS-CoV-2-derived T cell epitopes is of critical importance for peptide vaccines or diagnostic tools of COVID-19. methods: In this study, a number of SARS-CoV-2-derived HLA-I binding peptides were predicted by NetMHCpan-4.1 and selected by Popcover to achieve pancoverage of the Chinese population. The top 5 ranked peptides derived from each protein of SARS-CoV-2 were then evaluated using PBMCs from unexposed individuals (negative for SARS-CoV-2 IgG). results: Seven epitopes derived from 4 SARS-CoV-2 proteins were identified. Interestingly, most (5 out of 7) of the SARS-CoV-2-derived peptides with predicted affinities for HLA-I molecules were identified as HLA-II-restricted epitopes and induced CD4+ T cell-dependent responses. These results complete missing pieces of pre-existing SARS-CoV-2-specific T cells and suggest that pre-existing T cells targeting all SARS-CoV-2-encoded proteins can be discovered in unexposed populations. conclusions: In summary, in the current study, we present an alternative and effective strategy for the identification of T cell epitopes of SARS-CoV-2 in healthy subjects, which may indicate an important role in the development of peptide vaccines for COVID-19.