Design of a Conserved LukS-PV-Based Multi-Epitope Vaccine Candidate Against PVL-Positive Staphylococcus aureus: An Immunoinformatics Approach for MRSA and MSSA Coverage
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Abstract
Background: Staphylococcus aureus is a versatile Gram-positive pathogen responsible for a wide range of infections, from mild skin diseases to life-threatening conditions such as pneumonia, sepsis, and endocarditis. Panton–Valentine leukocidin (PVL), particularly its LukS-PV component, is a key virulence factor contributing to immune evasion and tissue damage. As PVL genes occur in both methicillin-sensitive and methicillin-resistant S. aureus (MSSA and MRSA), LukS-PV represents a conserved vaccine target. Objective: This study aimed to design a conserved LukS-PV-based multi-epitope vaccine candidate against PVL-positive S. aureus using an immunoinformatics approach. Methods: T-cell and B-cell epitopes from LukS-PV were identified and screened based on antigenicity, conservancy, allergenicity, toxicity, and physicochemical properties. Selected epitopes were evaluated for MHC binding affinity and population coverage. A multi-epitope construct was designed using linkers and an adjuvant, followed by structural modeling, molecular docking with TLR2, molecular dynamics simulation, immune simulation, and in silico cloning. Results: The core epitope ITYGRNMDV showed 100% conservancy, while FEITYGRNMDVTHAT showed 95.83% conservancy and strong MHC-II binding with 73.44% population coverage. The vaccine construct demonstrated an antigenicity score of 1.0244 and good solubility. Docking with TLR2 revealed stable binding, supported by molecular dynamics simulation. Immune simulation indicated potential activation of both humoral and cellular responses, and in silico cloning suggested feasible expression in E. coli. Conclusion: The designed vaccine construct shows strong in silico potential against PVL-positive S. aureus. However, experimental validation is required to confirm immunogenicity, safety, and efficacy.
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