Development of a Novel Pan-Species Multi-Epitope Vaccine (PS-MEV) Targeting Nine Staphylococcus Species to Combat...

The increasing prevalence of antibiotic-resistant Staphylococcus species, including methicillin-resistant strains, calls for innovative approaches like a pan-species multi-epitope vaccine (PS-MEV). In this study, Sortase A (SrtA) was selected as the target protein due to its conserved role in Staphylococcus pathogenesis, and the MEV was designed to target nine Staphylococcus species. After stringent filtration of epitopes to ensure antigenicity, non-toxicity, and non-allergenicity, structural models of the MEV construct were generated using I-TASSER, AlphaFold, and RoseTTAFold. Docking analyses confirmed strong binding interactions between the MEV and TLR-3, with the AlphaFold model exhibiting the lowest binding energy of - 1284.1 kcal/mol and a center energy of - 1066.5 kcal/mol. The I-TASSER and RoseTTAFold models showed slightly higher binding energies, with lowest binding energies of - 938.5 kcal/mol and - 950.9 kcal/mol, respectively, and center energies of - 842.2 kcal/mol and - 825.4 kcal/mol. These values demonstrate consistent receptor binding across the models. Molecular dynamics (MD) simulations confirmed the stability of the interactions with the immune receptor, and immune simulations showed notable cytokine peaks, memory cell production, and a sustained T-cell response, indicating the potential for long-lasting immunity. Physicochemical profiling indicated that the vaccine construct is stable, moderately thermostable, and hydrophilic, which can enhance bioavailability and immunogenic effectiveness. This pan-species MEV presents a promising avenue in Staphylococcus vaccine development, with implications for broader applications in combating antibiotic-resistant pathogens.