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 FnBPA _110-263 mediated protection in Staphylococcus aureus infection. This study revealed FnBPA _110-263 broadly protected mice from seven FnBPA isotypes strains in the sepsis model. FnBPA _110-263 immunized B-cell deficient mice were protected against lethal challenge, while T-cell deficient mice were not. Reconstituting mice with FnBPA _110-263 specific CD4+ T-cells conferred antigen specific protection. In vitro assays indicated that isolated FnBPA _110-263 specific splenocytes from immunized mice produced abundant IL-17A. IL-17A deficient mice were not protected from a lethal challenge by FnBPA _110-263 vaccination. Moreover, neutralizing IL-17A, but not IFN-γ,reverses FnBPA _110-263 -induced protective efficacy in sepsis and skin infection model. These findings suggest that IL-17A producing Th17 cells play an essential role in FnBPA _110-263 vaccine-mediated defense against S. aureus sepsis and skin infection in mice.
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