Designing of cytotoxic and helper T cell epitope map provides insights into the highly contagious nature of the pandemic novel coronavirus SARS-CoV-2

Abstract

Novel coronavirus, SARS-CoV-2, has emerged as one of the deadliest pathogens of this century, creating an unprecedented pandemic. Belonging to the betacoronavirus family, it primarily spreads through human contact via symptomatic and asymptomatic transmission. Despite several attempts since it emerged, there is no known treatment in the form of drugs or vaccines. Hence, work on developing a potential multi-subunit vaccine is the need of the hour. In this study, attempts have been made to find globally conserved epitopes from the entire set of SARS-CoV-2 proteins as there is as yet, no clear information on the immunogenicity of these proteins. Using diverse computational tools, a ranked list of probable immunogenic, promiscuous epitopes generated through all the three main stages of antigen processing and presentation pathways has been prioritized. Moreover, several useful insights were gleaned during these analyses. One of the most important insights is that all of the proteins in this pathogen present unique epitopes, so that the targeting of a few specific viral proteins is not likely to result in an effective immune response in humans. Due to the presence of these unique epitopes in all of the SARS-CoV-2 proteins, stronger immune responses generated by T cell hyperactivation may lead to cytokine storm and immunopathology and consequently, remote chances of human survival. These epitopes, after due validation in vitro, may thus need to be presented to the human body in that form of multi-subunit epitope-based vaccine that avoids such immunopathologies.

Keywords: SARS-CoV-2; SARS-CoV-2 proteome; T cell epitopes; cytokine storm; immunoinformatics; immunopathology.

Figure 1.

Depiction of the location of proteins in the SARS-CoV-2 proteome. Picture taken from NCBI Datasets (https://www.ncbi.nlm.nih.gov/datasets/). ORF7b was identified later in a paper [7].

Figure 2.

Bar diagram for CTL and HTL immunogenic epitope distribution across proteins. HTL(CD4epi) depicts immunogenic epitopes from CD4episcore tool. HTL(Combined) depicts epitopes common to CD4episcore and ITcell tools. First panel: all ORF1ab proteins.

Figure 3.

Multiple Peptide Match of 719 predicted SARS-CoV-2 coronaviral epitopes against Homo sapiens proteome from UniProt.