Mechanisms of fibronectin-binding protein A (FnBPA 110-263 ) vaccine efficacy in Staphylococcus aureus sepsis versus skin infection.

Increasing rates of life-threatening infections and decreasing susceptibility to antibiotics urge an effective vaccine targeting Staphylococcus aureus. Here we investigate the role of cellular immunity in FnBPA110–263 mediated protection in Staphylococcus aureus infection. This study revealed FnBPA110–263 broadly protected mice from seven FnBPA isotypes strains in the sepsis model. FnBPA110–263 immunized B-cell deficient mice were protected against lethal challenge, while T-cell deficient mice were not. Reconstituting mice with FnBPA110–263 specific CD4+ T-cells conferred antigen specific protection. In vitro assays indicated that isolated FnBPA110–263 specific splenocytes from immunized mice produced abundant IL-17A. IL-17A deficient mice were not protected from a lethal challenge by FnBPA110–263 vaccination. Moreover, neutralizing IL-17A, but not IFN-γ,reverses FnBPA110–263-induced protective efficacy in sepsis and skin infection model. These findings suggest that IL-17A producing Th17 cells play an essential role in FnBPA110–263 vaccine-mediated defense against S. aureus sepsis and skin infection in mice.