Passive immunization through polyclonal antibodies against IsdE showed protective activity in an experimental S.aureus challenge model.

Staphylococcus aureus, particularly methicillin-resistant strains (MRSA), continues to pose a major therapeutic challenge and highlights the need for alternative or supportive treatment strategies. In this study, the recombinant iron-regulated surface determinant E (IsdE) protein was expressed, purified, and used to generate rabbit polyclonal IgG antibodies.Antibody specificity was confirmed by ELISA and Western blotting, and functional activity was assessed using an opsonophagocytic assay.To evaluate in vivo efficacy, BALB/c mice were challenged with a 5 × 10⁸ CFU dose of MRSA and treated with anti-IsdE IgG. Bacterial burden in internal organs was measured; histopathological changes and survival rates were recorded.To investigate the regulation of inflammatory responses by the immune system, levels of inflammatory cytokines (IL-6 and TNF-α) were measured in the serum of the studied mice.Treatment with anti-IsdE IgG was associated with reduced bacterial burden in target organs, decreased levels of inflammatory cytokines (IL-6 and TNF-α), improved histopathological findings, and increased survival compared with the control groups. However, vancomycin treatment produced the highest overall protection.These findings suggest that antibodies directed against IsdE may contribute to immune-mediated protection under experimental conditions and could be considered as a potential adjunctive strategy alongside antibiotic therapy, pending further validation.Further investigations are required to clarify antigen-specific mechanisms and to assess the translational potential of this approach.