Immunization with PLGA-encapsulated recombinant staphylococcal enterotoxin C confers protection against intramammary Staphylococcus aureus challenge in a murine mastitis model.

Mastitis caused by Staphylococcus aureus remains a significant challenge to control due to increasing antimicrobial resistance and the limited efficacy of existing vaccines. Staphylococcal enterotoxin C (SEC) is a critical virulence factor and a highly immunogenic determinant in S. aureus strains frequently isolated from bovine mastitis cases. In this study, we evaluated the immunogenicity and protective efficacy of recombinant SEC (rSEC) encapsulated within poly(lactide-co-glycolide) microparticles (PLGA-rSEC) using a murine mastitis model. Immunization with PLGA-rSEC induced significantly higher serum IgG responses (OD492) compared with bacterin, non-encapsulated rSEC and control groups (p < 0.05). Following intramammary challenge with S. aureus, mice immunized with PLGA-rSEC showed a marked reduction in mammary gland bacterial load, resulting in a 3.15 log10 CFU/gland reduction. This protective efficacy was significantly superior to that of the traditional bacterin group (2.23 log10 CFU/gland; p < 0.05). Furthermore, PLGA-rSEC-immunized mice exhibited attenuated inflammatory responses, characterized by lower serum C-reactive protein (CRP) levels and a rapid reduction in serum IL-10 concentrations post-challenge. Histopathological analysis confirmed the preservation of mammary gland architecture with minimal inflammatory cell infiltration in the PLGA-rSEC group, contrasting with the severe necrosis and abscess formation observed in control groups. Overall, PLGA-encapsulated rSEC elicited a robust humoral immune response and conferred significant protection against intramammary S. aureus challenge. These findings suggest that PLGA-rSEC is a promising subunit vaccine candidate for the prevention of S. aureus-associated bovine mastitis, offering improved protective efficacy compared with conventional vaccine formulations.