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.

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.

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. Conclusions: 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.