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

• Published in: The Journal of infectious diseases 2024-09
• Main Authors: Li, Yanli, Warren, Joanna A, Poston, Taylor B, Clutton, Genevieve, Shaw, Fiona R, Conrad, Shayla Z, Xu, Yinyan, Zheng, Xiaojing, Yount, Kacy S, O'Connell, Catherine M, Wiesenfeld, Harold C, Darville, Toni, Goonetilleke, Nilu
• Format: Article
• Language: English
• ISSN: 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiae443

Chlamydia trachomatis (CT) is a globally prevalent sexually transmitted infection (STI) 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 (STCL). CT-specific T cells were characterized by IFN-γ ELISpot and flow cytometry. Ex vivo CT-specific T cells were rarely detected; however, following in vitro expanded CT-specific T cells were detected by IFN-γ ELISpot in 90% (27/30) of participants. Notably, over 50% of participants had T cell responses targeting chlamydial protease-like activity factor (CPAF). T cell epitopes were dispersed across the CPAF protein. Flow cytometry analysis of STCL found CT-specific cells, were mainly CD4+, produced IFN-γ and TNF-α and were sustained over 12 months. Ex vivo analysis suggested 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.