Abstract
Mechanisms of protective immunity to Staphylococcus aureus infection in humans remain elusive. While the importance of cellular immunity has been shown in mice, T cell responses in humans have not been characterised. Using a murine model of recurrent S. aureus peritonitis, we demonstrated that prior exposure to S. aureus enhanced IFNγ responses upon subsequent infection, while adoptive transfer of S. aureus antigen-specific Th1 cells was protective in naïve mice. Translating these findings, we found that S. aureus antigen-specific Th1 cells were also significantly expanded during human S. aureus bloodstream infection (BSI). These Th1 cells were CD45RO+, indicative of a memory phenotype. Thus, exposure to S. aureus induces memory Th1 cells in mice and humans, identifying Th1 cells as potential S. aureus vaccine targets. Consequently, we developed a model vaccine comprising staphylococcal clumping factor A, which we demonstrate to be an effective human T cell antigen, combined with the Th1-driving adjuvant CpG. This novel Th1-inducing vaccine conferred significant protection during S. aureus infection in mice. This study notably advances our understanding of S. aureus cellular immunity, and demonstrates for the first time that a correlate of S. aureus protective immunity identified in mice may be relevant in humans.
Original language | English |
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Article number | e1005226 |
Number of pages | 32 |
Journal | PLoS pathogens |
Volume | 11 |
Issue number | 11 |
DOIs | |
Publication status | Published - 5 Nov 2015 |
Keywords
- Adjuvants, Immunologic/pharmacology
- Adoptive Transfer
- Adult
- Aged
- Animals
- Antigens/immunology
- Female
- Humans
- Immunologic Memory
- Interleukin-17/metabolism
- Male
- Mice, Inbred C57BL
- Mice, Knockout
- Middle Aged
- Staphylococcal Infections/immunology
- Staphylococcal Skin Infections/immunology
- Staphylococcus aureus/immunology
- Th1 Cells/drug effects