Mechanisms of fibronectin-binding protein A (FnBPA110-263) vaccine efficacy in Staphylococcus aureus sepsis versus skin infection

Clin Immunol. 2018 Sep:194:1-8. doi: 10.1016/j.clim.2018.05.007. Epub 2018 Jun 12.

Abstract

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.

Keywords: Fibronectin-binding protein A; Immune protection; Staphylococcus aureus; Th17; Vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / immunology*
  • Animals
  • B-Lymphocytes / immunology
  • Bacterial Vaccines / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / microbiology
  • Immunity, Cellular / immunology
  • Interferon-gamma / immunology
  • Interleukin-17 / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Nude
  • Mice, SCID
  • Sepsis / immunology*
  • Sepsis / microbiology
  • Staphylococcal Infections / immunology*
  • Staphylococcus aureus / immunology*
  • Th17 Cells / immunology
  • Th17 Cells / microbiology
  • Vaccination / methods

Substances

  • Adhesins, Bacterial
  • Bacterial Vaccines
  • Interleukin-17
  • fibronectin-binding proteins, bacterial
  • Interferon-gamma