Antigen-specific CD8 T cell response following genital chlamydial challenge is a predictive biomarker of vaccine efficacy in protection against reproductive tract pathology

Abstract TNF-α producing antigen (Ag)-specific CD8 T cells induce upper genital tract (UGT) pathology following primary C. muridarum infection; therefore, we hypothesized that a vaccine regimen must subvert Ag-specific CD8 T cell response following immunization, and/or challenge to attenuate Chlamydia-induced UGT pathology. We evaluated three immunization regimens: live-chlamydial elementary body intranasal (EB-i.n.), live-EB i.m. (EB-i. m.), and irrelevant antigen bovine serum albumin i.n. (BSA-i.n.) that induced near-total (90%), partial (50%), and no (0% ) protection, respectively against oviduct pathology following i.vag. C. muridarum challenge in C57BL6/J animals. Live-EB-specific IFN-γ, TNF-α, and IL-17 response from purified splenic CD8 T cells was evaluated on days 7, 14, and 21 after immunization. There was no detectable reduction of Ag-specific CD8 T cell response following immunization with protective vaccine regimens. We evaluated splenic live-EB-specific CD8 T cell responses on days 3, 6, 9, and 12 following i.vag. chlamydial challenge. All groups of challenged animals displayed comparable induction of Ag-specific CD8 T cell cytokine responses on day 6 after challenge. As early as day 9 after challenge, Ag-specific IFN-γ and TNF-α production from CD8 T cells was significantly reduced in EB-i.n.-, compared to the EB-i.m.- or BSA-i.n.-immunized animals. On day 12, both EB-i.n.- and EB-i.m.-immunized animals displayed minimal Ag-specific TNF-α production, compared to enhanced TNF-α production from CD8 T cells in BSA-i.n. immunized animals. These results suggest that TNF-α producing CD8 T cell response could serve as a predictive biomarker of anti-chlamydia vaccine efficacy against reproductive pathology.