Abstract

While individuals infected with coronavirus disease 2019 (COVID-19) manifested a broad range in susceptibility and severity to the disease, the pre-existing immune memory to related pathogens cross-reactive against SARS-CoV-2 can influence the disease outcome in COVID-19. Here, we investigated the potential extent of T cell cross-reactivity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be conferred by other coronaviruses and influenza virus, and generated an in silico map of public and private CD8+ T cell epitopes between coronaviruses. We observed 794 predicted SARS-CoV-2 epitopes of which 52% were private and 48% were public. Ninety-nine percent of the public epitopes were shared with SARS-CoV and 5.4% were shared with either one of four common coronaviruses, 229E, HKU1, NL63, and OC43. Moreover, to assess the potential risk of self-reactivity and/or diminished T cell response for peptides identical or highly similar to the host, we identified predicted epitopes with high sequence similarity with human proteome. Lastly, we compared predicted epitopes from coronaviruses with epitopes from influenza virus deposited in IEDB, and found only a small number of peptides with limited potential for cross-reactivity between the two virus families. We believe our comprehensive in silico profile of private and public epitopes across coronaviruses would facilitate design of vaccines, and provide insights into the presence of pre-existing coronavirus-specific memory CD8+ T cells that may influence immune responses against SARS-CoV-2.

Highlights

  • Faced by unprecedent health and economic crisis from the coronavirus disease 2019 (COVID-19), the scientific community is pushing forward with efforts to develop vaccines and treatments to mitigate its impact

  • In evaluating the accuracy of predicted epitopes with epitopes deposited in Immune Epitope Database and Analysis Resource (IEDB), the epitopes with matching sequence of predicted epitopes were retrieved

  • To analyze the extent of cross-reactive responses that can be conferred by common coronaviruses, we investigated the number of unique SARS-CoV-2 predicted epitopes shared with either one of the four coronaviruses, namely 229E, HKU1, NL63, and OC43

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Summary

Introduction

Faced by unprecedent health and economic crisis from the coronavirus disease 2019 (COVID-19), the scientific community is pushing forward with efforts to develop vaccines and treatments to mitigate its impact. As immune memory by related pathogens has shown to help reduce severity and spread of the diseases [5,6,7], pre-existing immunity through cross-reactivity to familial coronavirus strains may provide individuals with protection or enhanced susceptibility against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) without prior exposure [8,9,10]. The alphacoronavirus contains human coronavirus 229E (HCoV-229E) and HCoV-NL63, while the betacoronavirus contains HCoV-OC43, and HCoV-HKU1, Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV, and SARS-CoV-2 [11]. It is known that NL63, 229E, OC43, and HKU1 usually cause only mild to moderate symptoms such as cough, runny nose, fever, and sore throat like the common cold [12], whereas MERS-CoV and SARS-CoV cause more severe symptoms including respiratory tract disease

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