Abstract
Development of a strategy to combat Staphylococcus aureus is a high priority for the World Health Organization. B cell and helper T lymphocyte (HTL) epitopes of leukotoxin ED (LukED) were predicted using computational tools. The predicted epitopes were screened for conservancy, allergenicity, toxicity, autoreactivity, and population coverage. The immunogenic regions of LukED were linked together and to Human β-defensin 3 (hBD3) as adjuvant with appropriate linkers. The predicted 3D structure of the vaccine validated by molecular dynamics (MD) simulations. Subsequently, the 3D structure was docked with the Toll-like receptor (TLR)1/2 to evaluate the binding capacity of the adjuvant. Finally, MD simulation was employed to characterizing the conformational dynamics and stability of this interaction. The predicted epitopes were found to be non-toxic and non-allergenic, with no homology to the human proteome. The vaccine demonstrated a population coverage of 65.15% globally. It was composed of the immunogenic regions of LukED. Molecular docking and MD simulation indicated a stable interaction between hBD3 in the vaccine and TLR1/2 during the simulation period. We have designed vaccine against S. aureus LukED that targets epitope-rich regions, which helps maintain a native-like conformation. This work lays the groundwork for further experimental studies to evaluate the vaccine's neutralizing effects.