Multi-epitope vaccine construct against Staphylococcus aureus : insights from immunoinformatics and molecular dynamics simulations

The persistent challenge posed by multi-drug resistant Staphylococcus aureus infections worldwide necessitates new solutions. We describe the creation of a multi-epitope vaccine aimed at offering cross-strain immunity. Antigens α-haemolysin (Hla) and staphylococcal enterotoxin B (SEB) were chosen considering their high immunodominance and sequence conservation levels. B-cell and T-cell epitopes were combined into a multi-epitope vaccine with the proper adjuvant and linker sequences included to allow for maximum immunogenicity and structural stability. Physicochemical characterization demonstrated that the construct is non-allergenic, heat-stable, and immunogenic. Structural optimization and modelling were performed, with confirmation by Ramachandran plot analysis and ProSA z-score, which verified the correctness of the model. Molecular docking indicated robust and stable interactions between the vaccine and major immune receptors, such as TLR3, MHC class I, and MHC class II. In addition, 200 ns molecular dynamics simulations and binding free energy calculations indicated stability and longevity of these complexes. Codon optimization and in silico cloning indicated efficient expression in E. coli. Immune simulations also anticipated strong activation of humoral and cellular immune elements such as B-cells, cytotoxic T lymphocytes, and antigen-presenting cells, and rising Ig levels. The vaccine's ability to induce overall immune protection against S. aureus requires further experimental confirmation.