Human Responses to Candidate Chlamydial Antigens

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Chlamydia trachomatis (CT) is a sexually transmitted bacteria. Each year it infects 100 million people. Most infections do not have any symptoms so infected people are left untreated. In women the consequences of CT are severe. Approximately, 1 in every 100 untreated CT infections results in infertility. CT infections in women can also result in ectopic pregnancy and chronic pelvic pain. Despite the great need, no chlamydial vaccine is currently available. The broader goal of this research program is to accelerate development of a novel vaccine that prevents CT-associated infertility and other disease. The goal of this research project is to better understand how our immune system responds to CT replication in the female genital tract (FGT). The FGT is a unique organ in our body. To effectively function, the FGT actively suppresses immune responses. The rationale of this research project is that control of CT replication requires effective immune cells, called T cells, both in the blood and in the female genital tract. Memory T cells can detect and induce rapid killing of CT-infected cells. Here, we will investigate CT replication and the host T cell response in two unique female cohorts. In the first cohort called TRAC, women at high risk of CT infection were followed for 12 months. The second cohort, TRAC2, will be established during this project and will similarly follow women with high risk of CT infection. Detailed clinical and behavioral data will be available from both cohorts enabling participants to be classified into several groups – CT-resistant, CT-susceptible, CT-infected but controlling infection, CT-infected with disseminated infection. Critically, immune cells from both blood and the FGT will be collected from our participants and available for analysis. To comprehensively examine the role of T cells both in the blood and FGT, in combatting CT infection we will pursue the following aims: Aim 1. Establish a comprehensive approach to identify chlamydial antigens that would be most likely to contribute to anti-chlamydial immunity. Here we will perform the first study to examine expression of CT proteins in a woman’s female genital tract. Strongly expressed CT proteins are excellent targets for vaccines. Aim 2. Characterize the protective memory T cell response to CT in the blood of women who exhibit resistance to CT reinfection. Here, we aim to identify the types and functions of T cells in the blood that provide resistance against CT. Aim 3. Compare and characterize infiltrating and resident T cells in the blood and FGT of women who limit infection to the endocervix with women who experience CT ascension. Here, we will directly examine the frequency and function of T cells in the FGT of women who whilst CT infected are able to limit bacterial replication, with women who fail to limit infection and are therefore at risk of CT-associated disease.