Identification of CPAF as the immunoprevalent antigen of Chlamydia trachomatis

Abstract

Abstract Chlamydia trachomatis (CT) is a common sexually transmitted bacterial infection, that in women can cause pelvic inflammatory disease and infertility. No preventative vaccine has been developed against CT. Immunity to CT is primarily mediated by Th1 CD4+ T cells. We are defining immunoprevalent CT proteins in a well-defined cohort of CT seropositive women with the goal of defining novel vaccine immunogens. We screened 30 women one month after a CT-positive test by cultured IFN-γ ELISpot. Ten-day short-term cell lines (STCL) were generated against overlapping peptides spanning 21 CT antigens. The threshold for a positive CT-specific T cell response (≥ 300 spot-forming cells, SFU, per 106 cells) was defined following a screening of 12 CT seronegative donors. CT− specific T cell responses were detected in 27/30 CT-seropositive women. On average, women harbored T cell responses to two CT proteins (range 0–6). Strikingly, CT858 (CPAF) elicited a T cell response in 16/30 women with an average of 966 IFN-g SFU/106 cells (range 300–3,633 SFU/106 cells). Data to date suggest CPAF-specific T cell responses are predominantly CD4-restricted. In preliminary studies, we have also detected CT-specific T cell responses in men with documented CT infection, including a T cell response to CPAF. We are currently mapping CPAF T cell epitopes and expanding our screen to other CT secreted proteins. In summary, CT858 (CPAF) is an immunoprevalent antigen in women and a promising vaccine immunogen. Supported by UNC Chlamydia Vaccine Initiative (U19AI144181)