Characterization of a vaccine against Chlamydia trachomatis

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DESCRIPTION (provided by applicant): Together with our collaborators at GlaxoSmithKline Biologicals, we have identified several new Chlamydia vaccine candidate antigens based on human humoral and T cell responses followed by animal protection studies. Priority has been given to those antigens that both elicit a T helper type1 (Th1) response from PBMC from healthy donors that are seropositive for Chlamydia and protect in rodent models of genital chlamydial infection. Based on our preliminary data, it appears that immunity to Chlamydia infection may be mediated primarily by a T helper type 1 immune response, requiring the induction and recruitment of specific T cells. We propose to examine in further detail the immunological factors that are involved in protective immunity to Chlamydia. Both serum- and splenocyte - based assays will be utilized to determine the level of antibody- and T-cell specific reactivity against the proteins comprising the candidate vaccine. This project will define the relevant effectors mediating immunity, including long-term memory, the antigens responsible for inducing these effectors, and will evaluate methods of vaccine delivery in a mouse model of genital chlamydial infection which we have developed. The work outlined in this proposal builds on our previous studies and expertise in antigen characterization, adjuvants/ formulations and vaccine delivery for infectious diseases. We hypothesize that the candidate chlamydial antigens, when properly presented to the immune system, may focus the immune response, provide long-term protection against Chlamydia and prevent disease. These priority recombinant antigens formulated with adjuvants and delivery systems acceptable for human use will be evaluated in mouse models of Chlamydia infection and disease. Chlamydia trachomatis bacteria cause much misery around the globe. The World Health Organization estimates that 2.8 million Americans are infected with the sexually transmitted form of the disease each year, while the ocular form causes 6 million cases of blindness and 11 million cases of trichiasis annually in Africa and Asia. Unfortunately, after decades of research, a vaccine has not been available perhaps due to the biological complexity of Chlamydia, the existence of multiple serovars, and the capacity to induce both protective and pathological immune responses.