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.

dx.doi.org/10.1371/journal.ppat.1005226, hdl.handle.net/1765/82304
PLoS Pathogens
Department of Medical Microbiology and Infectious Diseases

Brown, A.F, Murphy, A.G, Lalor, S.J, Leech, J.M, O’Keeffe, K.M, Mac Aogáin, M, … McLoughlin, R.M. (2015). Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection. PLoS Pathogens, 11(11). doi:10.1371/journal.ppat.1005226