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. 2024 Oct 25;14(1):25413.
doi: 10.1038/s41598-024-75658-w.

In-silico evaluation of the T-cell based immune response against SARS-CoV-2 omicron variants

Shivangi Sharma  1 , Diya Roy  1 , Sarah Cherian  2
Affiliations

In-silico evaluation of the T-cell based immune response against SARS-CoV-2 omicron variants

Shivangi Sharma et al. Sci Rep. .

Abstract

During of COVID-19 pandemic, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has continuously evolved, resulting in the emergence of several new variants of concerns (VOCs) with numerous mutations. These VOCs dominate in various regions due to increased transmissibility and antibody evasion, potentially reducing vaccine effectiveness. Nonetheless, it remains uncertain whether the recent SARS-CoV-2 VOCs have the ability to circumvent the T cell immunity elicited by either COVID-19 vaccination or natural infection. To address this, we conducted in-silico analysis to examine the impact of VOC-specific mutations at the epitope level and T cell cross-reactivity with the ancestral SARS-CoV-2. According to the in-silico investigation, T cell responses triggered by immunization or prior infections still recognize the variants in spite of mutations. These variants are expected to either maintain their dominant epitope HLA patterns or bind with new HLAs, unlike the epitopes of the ancestral strain. Our findings indicate that a significant proportion of immuno-dominant CD8 + and CD4 + epitopes are conserved across all the variants, implying that existing vaccines might maintain efficacy against new variations. However, further in-vitro and in-vivo studies are needed to validate the in-silico results and fully elucidate immune sensitivities to VOCs.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Analysis of spike specific SARS-CoV2 T cell epitopes. Number of spike specific SARS-CoV2 T cell epitopes with and without mutations present in the seven variants. (a) CD8 + T cell epitopes (b) CD4 + T cell epitopes.
Fig. 2
Fig. 2
Investigation of mutated dominant epitopes and associated variants of concern (VOCs). CD8+ (a) and (b) CD4 + T cell epitopes with variant specific mutations in the spike protein from omicron VoCs are shown. The figure illustrates how these mutations affect the dominant CD8 + and CD4 + T cell epitopes, with connecting lines representing mutations that occurred between variants. Distinct colors are used to highlight the immunodominant epitopes that have undergone mutations among all the variants. The alluvial plots were generated by using RAWGraphs.
Fig. 3
Fig. 3
The HLA-I and II allele restriction patterns of mutated CD8 (a) and CD4 (b) epitopes from the spike protein of all VOCs were investigated. To evaluate the EL rank scores, CD8 and CD4 epitopes of SARS-CoV-2, along with their corresponding mutated epitopes from different variants, were analyzed using NetMHCIPan 4.1 EL and NetMHCIIpan v.4.0. A total of 27 HLA Class-I and 25 HLA Class-II alleles (as part of the reference set) were taken into account, and a binding threshold of 2% and 5% was applied to select binders. In the analysis, the epitopes on the left side represent the mutated epitopes. The mutated epitopes that bind to the HLA alleles are shown in light blue squares and non-binders are left blank. Furthermore, the mutated epitopes found in the studied variants are denoted in black color.
Fig. 3
Fig. 3
The HLA-I and II allele restriction patterns of mutated CD8 (a) and CD4 (b) epitopes from the spike protein of all VOCs were investigated. To evaluate the EL rank scores, CD8 and CD4 epitopes of SARS-CoV-2, along with their corresponding mutated epitopes from different variants, were analyzed using NetMHCIPan 4.1 EL and NetMHCIIpan v.4.0. A total of 27 HLA Class-I and 25 HLA Class-II alleles (as part of the reference set) were taken into account, and a binding threshold of 2% and 5% was applied to select binders. In the analysis, the epitopes on the left side represent the mutated epitopes. The mutated epitopes that bind to the HLA alleles are shown in light blue squares and non-binders are left blank. Furthermore, the mutated epitopes found in the studied variants are denoted in black color.
Fig. 4
Fig. 4
RMSD plot of dominant epitope, YGFQPTNGV (a), and mutant epitope, YSFRPTYGV (b) with the MHC-I allele, HLA-A*02:01 (PDB id: 4U6Y).
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