Abstract

The current coronavirus disease 2019 (COVID-19) vaccines are used to prevent viral infection by inducing neutralizing antibody in the body, but according to the existing experience of severe acute respiratory syndrome coronavirus (SARS) infection, T-cell immunity could provide a longer durable protection period than antibody. The research on SARS-CoV-2-specific T-cell epitope can provide target antigen for the development and evaluation of COVID-19 vaccines, which is conducive to obtain COVID-19 vaccine that can provide long-term protection. For screening specific T-cell epitopes, a SARS-CoV-2 S protein peptide library with a peptide length of 15 amino acids was synthesized. Through flow cytometry to detect percentage of IFN-γ+ T cells after mixed COVID-19 convalescent patients’ peripheral blood mononuclear cell with peptide library, seven peptides (P77, P14, P24, P38, P48, P74, and P84) that can be recognized by the T cells of COVID-19 convalescent patients were found. After excluding the nonspecific cross-reactions with unexposed population, three SARS-CoV-2-specific T-cell potential epitopes (P38, P48, and P84) were finally screened with the positive reaction rates between 15.4% and 48.0% in COVID-19 convalescent patients. This study also provided the HLA allele information of peptide-positive-response COVID-19 convalescent patients, thus predicting the population coverage of these three potential epitopes. Some HLA alleles showed higher frequency of occurrence in COVID-19 patients than in total Chinese population but no HLA alleles related to the T-cell peptide response and the severity of COVID-19. This research provides three potential T-cell epitopes that are helpful for the design and efficacy evaluation of COVID-19 vaccines. The HLA information provided by this research supplies reference significance for subsequent research such as finding the relation of HLA genotype with disease susceptibility.

Highlights

  • Coronavirus disease 2019 (COVID-19) that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to just under 5.4 million deaths and over 278 million cases globally, as of December 26, 2021

  • We found that some HLA alleles showed higher frequency of occurrence in COVID-19 patients than in Chinese population, but no HLA alleles was related to T-cell response to peptide and the severity of COVID19

  • The results showed that P14 induced CD4+ IFN-g+ T-cell and CD8+ IFN-g+ T-cell-positive response in one peripheral blood mononuclear cell (PBMC) sample, and P74 induced positive CD8+ IFN-g+ T-cell response in another sample (Supplementary Figure S1), suggesting P14 and P74 had cross-reaction with T cells of unexposed people

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Summary

Introduction

Coronavirus disease 2019 (COVID-19) that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to just under 5.4 million deaths and over 278 million cases globally, as of December 26, 2021 (https://www.who.int/). SARSCoV-2 is the seventh identified coronavirus that could cause human disease till and it belongs to the same genus of bcoronavirus as severe acute respiratory syndrome coronavirus (SARS-CoV) [1]. Both SARS-CoV and SARS-CoV-2 cause similar clinical symptoms and disease outcome and possess similar transmission pattern. The memory B-cell response could not be detected after 6 years [4], but specific T-cell response remained detectable even after 17 years in some individuals [5] These results indicated that compared with antibody, memory T-cell immunity is more durable and plays a more long-term role in immune clearance of coronavirus infection. Monitoring the intensity and duration of specific Tcell response induced by vaccine is vital for comprehensively evaluating the protective efficacy of COVID-19 vaccine

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