10779/rcsi.10768154.v1 Aisling F. Brown Aisling F. Brown Alison G. Murphy Alison G. Murphy Stephen J. Lalor Stephen J. Lalor John M. Leech John M. Leech Kate M. O'Keeffe Kate M. O'Keeffe Micheál Mac Aogáin Micheál Mac Aogáin Dara P. O'Halloran Dara P. O'Halloran Keenan A. Lacey Keenan A. Lacey Mehri Tavakol Mehri Tavakol Claire H. Hearnden Claire H. Hearnden Deirdre Fitzgerald-Hughes Deirdre Fitzgerald-Hughes Hilary Humphreys Hilary Humphreys Jérôme P. Fennell Jérôme P. Fennell Willem J. van Wamel Willem J. van Wamel Timothy J. Foster Timothy J. Foster Joan A. Geoghegan Joan A. Geoghegan Ed C. Lavelle Ed C. Lavelle Thomas R. Rogers Thomas R. Rogers Rachel M. McLoughlin Rachel M. McLoughlin Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection. Royal College of Surgeons in Ireland 2019 Adjuvants Immunologic Adoptive Transfer Adult Aged Animals Antigens Female Humans Immunologic Memory Interleukin-17 Male Mice Inbred C57BL Knockout Middle Aged Staphylococcal Infections Staphylococcal Skin Infections Staphylococcus aureus Th1 Cells Clinical Microbiology 2019-11-22 15:19:12 Journal contribution https://repository.rcsi.com/articles/journal_contribution/Memory_Th1_Cells_Are_Protective_in_Invasive_Staphylococcus_aureus_Infection_/10768154 <p>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.</p>