Mechanisms of fibronectin-binding protein A (FnBPA) 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 FnBPA mediated protection in Staphylococcus aureus infection. This study revealed FnBPA broadly protected mice from seven FnBPA isotypes strains in the sepsis model. FnBPA immunized B-cell deficient mice were protected against lethal challenge, while T-cell deficient mice were not. Reconstituting mice with FnBPA specific CD4+ T-cells conferred antigen specific protection. In vitro assays indicated that isolated FnBPA specific splenocytes from immunized mice produced abundant IL-17A. IL-17A deficient mice were not protected from a lethal challenge by FnBPA vaccination. Moreover, neutralizing IL-17A, but not IFN-γ,reverses FnBPA-induced protective efficacy in sepsis and skin infection model. These findings suggest that IL-17A producing Th17 cells play an essential role in FnBPA vaccine-mediated defense against S. aureus sepsis and skin infection in mice.