NOVEL APPROACH TO CHLAMYDIA VACCINE DEVELOPMENT

DESCRIPTION (provided by applicant): Chlamydia trachomatis is the leading bacterial cause of sexually transmitted disease (STD) in the United States and continues to spread in the population as >50% of the infected individuals show no overt symptoms and fail to obtain treatment. These untreated chlamydial infections pose a particular health risk in women by leading to severe complications including pelvic inflammation, tubal infertility, and ectopic pregnancy. Although a high priority, it has proven difficult to design an effective vaccine for Chlamydia trachomatis. It has been shown that T cells are necessary for immune protection, but they may also contribute to inflammation associated with pathogenesis. Thus, it is of great importance to delineate the roles of immune T cells during infection. Although T cell clones specific for C. trachomatis have been reported, it has been difficult to obtain sufficient numbers of such homogeneous lines to analyze the repertoire of the T cell response to this pathogen. Thus, we have exploited T cell hybridoma technology in order to generate panels of cloned helper (CD4 +) and cytotoxic (CD8 +) T cells from mice that had been vaginally inoculated with viable Chlamydia trachomatis. The T cell hybridomas will provide us with a unique tool for use in identifying the antigens from C. trachomatis that are capable of eliciting a broadbased T cell response in mice. In addition, through a new collaboration with clinical investigators at Wilford Hall Medical Center, Lackland Air Force Base, it will be possible to assess whether T cells from humans infected with Chlamydia respond to the same antigens that were identified in mice. These aims represent the first time that T cell hybridomas have been used to assess the activation of T cells in response to an infection with viable Chlamydia and should provide important insights into novel approaches for enhancing immunity to C. trachomatis and to other intracellular pathogens.