Designing a novel in-silico multi-epitope vaccine against penicillin-binding protein 2A in Staphylococcus aureus

Abstract

Research has shown the implication of Penicillin-Binding Protein 2A (PBP2A) as a critical factor in Methicillin-Resistant Staphylococcus aureus (MRSA) as it confers resistance to β‐lactam antibiotics on S. aureus, resulting in an increase in morbidity and mortality rate globally. The introduction of immuno-informatics methods has transformed vaccine development since antigen proteins can be used to elicit antibody responses as well as cell-mediated immunity.The present study aimed to design and propose a multi-epitope-based vaccine candidate against S. aureus by targeting PBP2A. Using an in-silico approach, 6 cytotoxic T-lymphocyte (CTL) epitopes, 3 helper T-lymphocyte (HTL) epitopes, and 8 B-cell epitopes were predicted from all target protein sequences.The multi-epitope vaccine construct was generated by mapping the entire shortlisted epitopes with appropriate adjuvant and linkers. The total amino acid residues are 350, with a molecular weight of 37,357.88 Da, while the Protrusion Index (PI) of the construct is 8.49. The docked complex of our vaccine (ligand) and TLR4 (receptor) predicted an excellent binding affinity between the two molecules with a plausible scoring function. The final multi-epitope vaccine candidate is considered potently antigenic, non-allergenic, and non-toxic. Antibodies that were generated against the designed vaccines showed higher levels of IgM, IgM + IgG, and IgG1 + IgG2 in secondary and tertiary immune responses. The multi-epitope vaccine construct was successfully cloned into the pET-28a (+) plasmid vector of Escherichia coli (strain-K12) for expression capacity. Our results demonstrate the potential of an in silico designed multi-epitope vaccine and suggest the need to further investigate efficacy in humans in vivo.