Immunoinformatics prediction of overlapping CD8+ T-cell, IFN-γ and IL-4 inducer CD4+ T-cell and linear B-cell epitopes based vaccines against COVID-19 (SARS-CoV-2)

Abstract

At the beginning of the year 2020, the world was struck with a global pandemic virus referred to as SARS-CoV-2 (COVID-19) which has left hundreds of thousands of people dead. To control this virus, vaccine design becomes imperative. In this study, potential epitopes-based vaccine candidates were explored. Six hundred (600) genomes of SARS-CoV-2 were retrieved from the viPR database to generate CD8⁺ T-cell, CD4+ T-cell and linear B-cell epitopes which were screened for antigenicity, immunogenicity and non-allergenicity. The results of this study provide 19 promising candidate CD8⁺ T-cell epitopes that strongly overlap with 8 promising B-cells epitopes. Another 19 CD4⁺ T-cell epitopes were also identified that can induce IFN-γ and IL-4 cytokines. The most conserved MHC-I and MHC-II for both CD8⁺ and CD4⁺ T-cell epitopes are HLA-A*02:06 and HLA-DRB1*01:01 respectively. These epitopes also bound to Toll-like receptor 3 (TLR3). The population coverage of the conserved Major Histocompatibility Complex Human Leukocyte Antigen (HLA) for both CD8⁺ T-cell and CD4⁺ T-cell ranged from 65.6% to 100%. The detailed analysis of the potential epitope-based vaccine and their mapping to the complete COVID-19 genome reveals that they are predominantly found in the location of the surface (S) and membrane (M) glycoproteins suggesting the potential involvement of these structural proteins in the immunogenic response and antigenicity of the virus. Since the majority of the potential epitopes are located on M protein, the design of multi-epitope vaccine with the structural protein is highly promising though the whole M protein could also serve as a viable epitope for the development of an attenuated vaccine. Our findings provide a baseline for the experimental design of a suitable vaccine against SARS-CoV-2.

Keywords: Immune-response; Immunoinformatics; Multi-epitope; SARS-CoV-2; Vaccine.

Fig. 1

Population coverage rate of overlapping CD8⁺ T cell epitopes and CD4⁺ T cell epitopes in SARS-CoV-19.

Fig. 2

The whole genome sequence (GenBank number MN908947.2) of COVID-19 built using Snapgene showing the position of the promising CD4⁺ T-cell epitopes and B-cell epitopes. The CD4⁺ T-cell epitopes were named from E1-CD4 to E19-CD4 representing alphabetically the epitopes as found in Table 2, the B-cell epitopes number E1-Bcell to E8-Bcell represented as found in Table 3.

Fig. 3

The feature of the (a) binding interaction of the most promising CD8⁺ T-cell epitope RNRFLYIIK with HLA-A*02:06 and (b) the residue interaction showing the binding site residues that are contributing to the binding interactions. The residues of the receptor that are involved in hydrogen bonding are labeled in green while those involved in hydrophobic interaction are represented with red semicircle. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 4

The feature of the (a) binding interaction of the most promising CD4⁺ T-cell epitope IGYYRRATRRIRGGD with HLA-DRB1*01:0 and (b) the residue interaction showing the binding site residues that are contributing to the binding interactions. The residues of the receptor that are involve in hydrogen bonding are labeled in green while those involved in hydrophobic interaction are represented with red semicircle. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 5

The interaction of the whole M−protein and selected epitopes part (M−sel in orange and its position on the whole M−protein (green) colour in grey). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)