Mechanisms of fibronectin-binding protein A (FnBPA110-263) 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.