Enhanced immunogenicity of Staphylococcus aureus IsdE vaccine with SeNPs and BCG adjuvants in mice

Staphylococcus aureus is a major cause of nosocomial infections and antimicrobial resistance, emphasizing the urgent need for an effective vaccine. The IsdE protein, a heme-iron transporter, has been identified as a promising antigen target. In this study, we evaluated the immunogenicity and protective efficacy of recombinant IsdE (r-IsdE) formulated with the MF59 adjuvant and co-adjuvanted with Bacillus Calmette–Guérin (BCG) and synthetic SeNPs (SeNPs) in BALB/c mice. Mice were immunized three times at two-week intervals, and immune responses were analyzed through cytokine assays, antibody isotyping, opsonophagocytic activity, bacterial load measurement, and survival following methicillin-resistant S. aureus (MRSA) challenge. The formulation containing r-IsdE + MF59 + BCG + SeNPs induced the highest levels of TNF-α, IFN-γ, IL-12, and IL-4, along with elevated total IgG, IgG1, and IgG2a responses. This group also demonstrated enhanced opsonophagocytic activity, markedly reduced bacterial loads in internal organs, and an 85% survival rate after infection, significantly higher than other experimental groups. These findings demonstrate that the combination of MF59, BCG, and SeNPs as adjuvants markedly enhances the immunogenicity and protective efficacy of the r-IsdE vaccine candidate, suggesting its potential as a promising strategy against S. aureus infections.