Exploring immunogenic CD8 + T-cell epitopes for peptide-based vaccine development against evolving SARS-CoV-2 variants: An immunoinformatics approach

The COVID-19 pandemic originated in Wuhan in 2019 due to a novel SARS-COV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) responsible for the massive number of deaths across the globe. So far, several vaccines have been developed using highly antigenic Spike protein and authorized for emergency use, reducing the severity of the infection. Nonetheless, the virus continues to evolve through multiple mutations, resulting in numerous variants with enhanced transmission that evade the vaccine-induced immune response. Given the persistently mutating nature of the SARS-COV-2 virus, peptide-based vaccines with highly conserved epitopes may offer lasting protection against evolving variants. This study presents an immunoinformatics-based identification of potentially immunogenic CD8 + T-cell epitopes (CTLs) of Spike (S), Membrane (M), Nucleocapsid (N) and Envelope (E) proteins of SARS-COV-2. By utilizing the immunoinformatic approach, 21 epitopes have successfully been evaluated, where 15, 3, 2, and 1 epitopes are respectively from Spike, Membrane, Envelope and Nucleocapsid proteins. Out of these, 20 are found to be identical with experimentally verified immunogenic epitopes, except for the novel NTQEVFAQV epitope from spike protein. These epitopes show a high degree of conservation in both former variants of concerns (VOCs), variants of interest (VOIs) and current variants under monitoring (VUMs), are non-toxic, non-homologous to humans and have a wide range of global population coverage. Furthermore, utilizing molecular docking analysis followed by molecular dynamics simulation, these epitopes have been verified as having stable interactions with their respective HLA molecules. The described framework and projected immunogenic epitopes could significantly impact the development of SARS-COV-2 vaccines based on peptides.