IMMUNOLOGY OF HUMAN CHLAMYDIAL INFECTIONS

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Chlamydia trachomatis is an obligate intracellular bacterial pathogen that infects the ocular and genital tract mucosa, to cause a number of clinically distinct syndromes. Despite significant advances in our understanding of the biology and antigenic structure of chlamydiae, and the epidemiology and clinical spectrum of chlamydial disease, the magnitude of morbidity from human chlamydial infections remains an important public health concern. Control of chlamydial disease will likely depend on a multidisciplinary approach, including the development of immunoprophylactic or immunotherapeutic strategies. Reasonable progress has been made in understanding specific immune mechanisms that contribute to host immunity in experimental models of chlamydial infection. However, studies of human immunity have not been so successful. This is particularly evident in that studies to address the development and role of mucosal immune responses to chlamydial urogenital infections having not been forthcoming. Because chlamydiae infect, replicate and cause damage to the mucosal epithelium, studies are needed that examine the role of mucosal immune responses in immune protection. The overall goal of this project is to analyze the mucosal anti-chlamydial antibody response that develops following genital tract infection of women and men. That goal will be achieved through 3 specific aims. Initially the secretory and systemic anti-chlamydial antibody responses will be characterized and compared in men and women with-or without chlamydial genital tract infection. The subclass specificity of the anti-chlamydial antibody response will be determined and compared to the shedding of infectious organism (specific aim #1). The antigenic specificity of the serum and secretory antibody responses will be analyzed by immunoblotting and the antigenic specificity of the predominant immunoglobulin isotypes will be determined (specific aim #2). A functional role for secretory antibodies will be evaluated using an in vitro neutralization assay. Serum and secretory neutralizing antibody responses will be compared, and the immunoglobulin subclass of the neutralizing antibodies will be determined (specific aim #3). This project, which is inter-related with the Clinical Core Project (Core B), Project 1 (Hook), and Project 2 (Schwebke), will contribute useful information regarding immunity to chlamydial genital tract infection in women and men. Furthermore, results from these studies may provide insight into the design of an effective chlamydial vaccine.