A majority of the Chlamydia trachomatis infections in women are symptomatic and thus, the only practical approach to prevent these disease is vaccinating the population at risk. In this proposal the investigators want to test the hypothesis that a vaccine consisting of the C. trachomatis major outer membrane protein (MOMP) will be able to induce protein in mice against a genital challenge with the C. trachomatis mouse pneumonitis (MoPn) biovar. To achieve this goal they want to utilize a MOMP preparation extracted from the native organisms that following purification has been "folded". They will first test this vaccine candidate in BALB/c mice and subsequently will optimize the vaccine protocol in this strain of mice for the dose, route, and adjuvant formulation. The optimized vaccine preparation will then be tested for its ability to protect C3H and C57BL/6 mice and for inducing long term protection in BALB/c mice. In the immunized animals they will be assessing the parameters that are critical for protection using different approaches. They will first compare the immune responses in protected and control groups of mice, and will attempt to identify epitopes of the MOMP recognized by the B and T-cells. Another group of immunocompetent animals will be first immunized and will subsequently be treated with monoclonal antibodies to block CD4 and CD8 cells before they are challenged. In addition, knockout mice for the MHC class I (52m-/-) and MHC class II (B2m-/-) genes, and B (JHD), and T and B (rag-2), cell deficient animals will be immunized, challenged and mater to assess protection. Finally, they will use Stat4 and Stat6-deficient mice to characterize the role of Th1 and Th2 cells in protection. In conclusion, their goal is to establish an immunization protocol utilizing a purified and folded MOMP preparation that protects against a genital challenge, and to characterize the immune parameters that are critical for protection.