Investigation of novel putative immunogenic targets against Staphylococcus aureus using a reverse vaccinology strategy.

ABSTRACT

BACKGROUND: The emergence of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) strains is a significant public health concern. Considering the high morbidity and mortality of invasive S. aureus infections and multi-drug resistant strains, there is an urgent need for non-antibiotic immune-based approaches to cure these infections. Despite all efforts, vaccine candidates targeting S. aureus failed in human clinical trials, and no approved vaccine is available against this pathogen. Therefore, this study aimed to introduce suitable candidates for immunization against S. aureus using a comprehensive reverse vaccinology approach. METHODS: In this study, we retrieved putative immunogenic targets from three different levels (literature review, automated reverse vaccinology, and manual reverse vaccinology) and evaluated them using several immunoinformatics analyses including antigenicity, allergenicity, PSI-BLAST to human proteome, physiochemical properties, B-cell, and T-cell epitopes. In the next step, the quartile method scoring was used to the shortlisted proteins. Finally, the molecular docking and immune simulation of immunogenic targets were performed. RESULTS: This study presents 12 vaccine candidates, including three enzymatic proteins (WP_000222271.1, WP_001170274, and WP_000827736.1), three cell wall-associated proteins (WP_001125631.1, WP_000731642, and WP_000751265.1), two hemolysins (WP_000594517.1, and WP_000916697.1), one secretion involved protein (WP_000725226.1), one heme­iron binding protein (WP_001041573.1), one superantigen like protein (WP_000668994.1) and one hypothetical proteins (WP_000737711.1). CONCLUSION: Through quartile scoring method, immune simulation and molecular docking, four promising targets including lytic transglycosylase IsaA, HlgA, secretory antigen precursor SsaA, and heme uptake protein IsdB were selected as the shortlisted proteins. It seems that a polarized immunization (Th1/Th17) response is needed for protection against this bacterium. An optimized formulation based on these putative immunogenic proteins and a wisely adjuvant selection may drive the immune system toward a full protection.