Chlamydia trachomatis is the leading cause worldwide of sexually transmitted disease and the most prevalent ocular pathogen. In addition to being the major cause of non-gonococcal urethritis and pelvic inflammatory disease, chlamydia are also the leading cause of preventable infectious blindness (trachoma) and are also associated with arthritis in a significant number of patients with Reiter's syndrome/Reactive arthritis. The public health costs of chlamydial infections and their sequelae are enormous. Identification of a protective anti-chlamydial vaccine would have important public health significance. We propose studies in a BALB/c ocular infection model induced by a human chlamydial biovar to further characterize the demonstrated long-lasting protective immunity against ocular infection induced by oral or systemic immunization with a monoclonal anti-idiotypic antibody (mAb2). The mAb2 is a functional and molecular mimic of the genus-specific chlamydial glycolipid exo-antigen, GLXA. We hypothesize that the basis for anti-id induced protection is that detrimental Th1- driven responses are shifted to Th2-mediated protection and that the targeted specificity for GLXA rather than for surface proteins such as MOMP accounts for the protective responses. Since the anti-id is an immunogenic protein, it induces more effective immune responses than would be induced by the glycolipid GLXA Ag itself. Studies will be performed to test this hypothesis using primarily the mouse ocular model as a mucosal infection paradigm; immunization with the mAb, vaccine candidate will be used to (1) characterize the relative role of T and B cells in protective responses, (2) distinguish between requirements for mucosal versus systemic immunization with encapsulated vaccine, (3) determine requirements for maximal protection including adjuvants or additional chlamydial antigens in a cocktail vaccine, and (4) test for anti-id- induced protection in other chlamydial infection models including C. trachomatis and C. psittaci genital infection and arthritides. Humoral responses in sera and secretions and cytokine responses will be used to define the Th1 and Th2 components of protective immunity; immunohistochemistry, in situ hybridization, RT-PCR methods and functional assays will be used in normal and immunodeficient mice to distinguish local and systemic immune responses which correlated with reduced microbiologic and clinical disease. These studies will potentially reveal strategies to assess protection against chlamydial disease induced by other vaccine candidates.
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