Protective effects of immunization with a novel 4 recombinant pore-forming toxoid combination vaccine in a rabbit model of systemic methicillin-resistant Staphylococcus aureus infection.

PURPOSE: Staphylococcus aureus is a Gram-positive bacterium that most frequently acquires antibiotic resistance. As an opportunistic pathogen, it can cause conditions such as bacteremia, sepsis, and myocarditis. Due to the social need for a vaccine against methicillin-resistant Staphylococcus aureus (MRSA), many research groups have been designing and studying vaccines for decades. In this study, we developed a multivalent vaccine and evaluated its efficacy by applying a novel adjuvant, β-glucan.

MATERIALS AND

METHODS

A vaccine composed of four pore-forming toxins from S. aureus was administered to rabbits 3 times, after which they were challenged with S. aureus USA 300 LAC strain. We measured changes in the rabbits' body weight to monitor systemic adverse reactions and analyzed the total immunoglobulin G antibody titer against the four antigens using enzyme-linked immunosorbent assay. For each rabbit, the number of abscesses and colony-forming units (CFU) in the kidneys were measured.

RESULTS

In all vaccinated groups, strong antibody responses against the four antigens were observed. After challenging with MRSA, the vaccinated groups showed less weight change compared to the non-vaccinated groups (average 5.7% versus 13.5%). Additionally, the number of renal abscesses was significantly lower in the vaccinated groups, with three individuals in group 1 (four antigens adjuvanted with β-glucan_PK1) showing no abscess formation. The number of bacteria identified in the kidneys was also statistically significantly lower in the vaccinated group compared to the non-vaccinated group.

CONCLUSION

We demonstrated that the four toxoid antigens we selected can protect against S. aureus infection in a rabbit model and that β-glucan could be used as an immune enhancer. Overall, our study shows that new antigen combinations can induce protective immunity in animal models and that a toxin-based vaccine can help control bacterial colonization.