Chlamydia trachomatis induces low-frequency, sustained CD4 T cell responses in most women, predominantly targeting chlamydial protease-like activity factor, CPAF

Chlamydia trachomatis (CT) is a globally prevalent sexually transmitted infection that can result in pelvic inflammatory disease, ectopic pregnancy, and infertility in women. Currently, there is no prophylactic vaccine. This study examined T-cell immunity in a cohort of women recently infected with CT. Participants were screened against peptides spanning 33 of 894 possible CT proteins, either ex vivo or using short-term cell lines. CT-specific T cells were characterized by interferon (IFN) γ enzyme-linked immunospot (ELISPOT) assay and flow cytometry. Ex vivo CT-specific T cells were rarely detected; however, in vitro expanded CT-specific T cells were detected by IFN-γ ELISPOT in 90% (27 of 30) of participants. Notably, >50% of participants had T-cell responses targeting chlamydial proteaselike activity factor (CPAF). T-cell epitopes were dispersed across the CPAF protein. Flow cytometric analysis of short-term cell lines found that CT-specific cells, mainly CD4, produced IFN-γ and tumor necrosis factor (TNF) α and were sustained over 12 months. Ex vivo analysis suggested that CT-specific T cells mostly exhibited a central memory phenotype. Our results indicate that CT infection elicits low-frequency, persistent CD4 T-cell responses in most women and that the secreted protein, CPAF, is an immunoprevalent CT antigen. Altogether, these data support development and testing of CT vaccines that enhance CD4 T cells against CPAF.