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

Abstract

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.

Identification and assessment of TCR-T cells targeting an epitope conserved in SARS-CoV-2 variants for the treatment of COVID-19

“…SARS-CoV-2 specific T cells targeting a highly conserved epitope derived from the RdRp protein (RdRp 829-838, LPYPDPSRIL) were identified from several healthy donors in our previous study, and this epitope was predicted to be HLA-B*51:01 restricted by NetMHCpan4.1 [17] , [20] . CD8 + 4-1BB + T cells were sorted from one pre-pandemic healthy donor for expansion followed by activity verification.…”

“…Pre-existing T cells targeting a highly conserved epitope from RdRp protein have been identified in previous study [17] . The epitope-specific T cells were then sorted and expanded as follows.…”

“…ELISPOT assay was performed as described previously [17] . Briefly, Primary antibody was coated on 96-well PVDF plates (Millipore, MSIPS4510) overnight at 4 °C.…”

Role of Peptides in Diagnostics

“…Results obtained by using these methods suggested that generation of effective adaptive immunity against SARS-CoV-2 requires the participation of both CD4+ and CD8+ T cells. This finding is very important for the preparation of a functional vaccine, as it is clear that it is necessary to incorporate both HLA-I-restricted and HLA-II-restricted epitopes in peptide-based vaccines to obtain optimal vaccination [53].…”

Predicted CTL responses from pressured epitopes in SARS-CoV-2 correlate with COVID-19 severity

“…Among the variants of SARS-CoV-2, the Delta variant (B.1.617.2) has dominated over other variants during the intense COVID-19 wave in India in April-May 2021, due to its higher transmissibility and partial evasion of the host immune responses 15 . Previous studies have suggested the possibility of T cell immune escape in SARS-CoV-2 variants 16,17,19 as well as isolates of the Wuhan strain 18 either restricted to certain HLA alleles 16,17,19 or covering larger populations 18,20 . On the contrary, mutations arising in the emerging variants have been reported to facilitate escape, mainly from the neutralizing antibody response rather than the T cell responses which are relatively more conserved across variants 21,22 .…”