Reverse vaccinology as a platform for antigen discovery: towards the development of an effective staphylococcal vaccine

BACKGROUND: Gram-positive cocci, particularly Staphylococcus aureus and Staphylococcus epidermidis , are common components of the human microbiota but can act as opportunistic pathogens, causing a wide range of infections. The increasing prevalence of antimicrobial resistance has highlighted the urgent need for alternative preventive strategies, including effective preventive vaccines. However, despite extensive research, no approved vaccines against these pathogens are currently available. OBJECTIVE: To evaluate the role of reverse vaccinology in identifying potential vaccine antigens for the prevention of infections caused by S. aureus and S. epidermidis . METHODS: This review examines current antigen discovery approaches based on whole-genome sequencing, comparative genomics, and reverse vaccinology. Relevant literature on antigen discovery, genetic diversity, and vaccine candidate identification was examined, with a focus on conserved and infection-specific targets. RESULTS: Genomic approaches enable the identification of novel antigenic targets and provide insights into pathogen diversity and virulence mechanisms. Reverse vaccinology has facilitated the identification of conserved surface proteins and virulence- associated factors as promising targets for vaccine development. However, most vaccine candidates remain at the preclinical stage and their protective efficacy as well as immunogenicity of vaccine targets require further validation. CONCLUSION: Reverse vaccinology represents a promising platform for accelerating antigen discovery and improving vaccine design against staphylococcal infections. Integration of genomic, proteomic, and immunological data, combined with rigorous experimental and clinical validation, is essential to overcome current challenges and advance the development of effective vaccines.