A comprehensive proteomic screening technology was previously used to characterize T cell responses to Chlamydia trachomatis infection. In this study, we demonstrated that T cells specific for protein antigens identified through this comprehensive technology home to the site of infection after mucosal challenge with C. trachomatis. In addition, T cell responses to these proteins were elicited in multiple genetic backgrounds. Two protein antigens, CT823 and CT144, were evaluated as vaccine candidates. When administered with AbISCO-100 adjuvant, these antigens stimulated potent CD8(+) T cell responses, polyfunctional T(H)1-polarized CD4(+) T cell responses, and high titer protein-specific T(H)1-skewed antibody responses. Vaccination with either antigen with AbISCO-100 provided long-lived protection against intravaginal challenge with C. trachomatis. Adoptive transfer of immune T cells also conferred protection in the challenge model whereas passive transfer of immune serum did not, indicating the critical role for T cell responses in control of this infection. The ability of these antigens to induce potent immune responses and provide long-lived protection in response to challenge provides a basis for the rational design of a C. trachomatis subunit vaccine.

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