Identification of potential vaccine targets for elicitation of host immune cells against SARS-CoV-2 by reverse vaccinology approach

The COVID-19 pandemic has emerged as a critical global health crisis, demanding urgent and effective strategies for containment. While some knowledge exists about epitope sequences recognized by human immune cells and their activation of CD8+ T cells within the HLA context, comprehensive information remains limited. This study employs reverse vaccinology to explore antigenic HLA-restricted T-cell epitopes capable of eliciting durable immunity. Screening reveals 187 consensus epitopes, with 23 offering broad population coverage worldwide, spanning over 5000 HLA alleles. Sequence alignment analysis highlights the genetic distinctiveness of these peptides from Homo sapiens and their intermediate to high TAP binding efficiency. Notably, these epitopes share 100 % sequence identity across strains from nine countries, indicating potential for a uniform protective immune response among diverse ethnic populations. Docking simulations further confirm their binding capacity with the HLA allele, validating them as promising targets for SARS-CoV-2 immune recognition. The anticipated epitopes are connected with suitable linkers and adjuvant, and then assessed for its translational efficacy within a bacterial expression vector through computational cloning. Through docking, it is observed that the chimeric vaccine construct forms lasting hydrogen bonds with Toll-like receptor (TLR4), while immune simulation illustrates an increased cytotoxic response aimed at CD8+ T cells. This comprehensive computational analysis suggests the chimeric vaccine construct's potential to provoke a robust immune response against SARS-CoV-2. By delineating these antigenic fragments, our study offers valuable insights into effective vaccine and immunotherapy development against COVID-19, contributing significantly to global efforts in combating this infectious threat.