Infection with Chlamydia trachomatis is responsible for significant morbidity and healthcare costs throughout the world. Work from our lab has demonstrated that T cells are a key mediator of immune protection against C. trachomatis. Our long-term goal has been to gain an understanding of how CD8+ T cells are stimulated in response to C. trachomatis infection. The reagents we developed in the previous funding period have allowed us to use contemporary approaches in cellular immunology to define how Chlamydia- specific T cells respond to infection. We have shown that transfer of cultured Chlamydia-specific CD8+ T cells into mice can protect against infection, yet surprisingly, a protective CD8+ T cell memory response is not stimulated following natural infection of mice or people. The apparent failure of the adaptive immune system to effectively clear the organism and/or prevent repeat infection is a hallmark of human infection with C. trachomatis, resulting in sequelae of infection such as permanent reproductive tract damage. Consistent with the findings in humans, we have observed that CD8+ T cells respond extremely well to primary infection, yet the memory cells that result from initial infection are impaired in their capacity to robustly respond to subsequent encounters with the organism. Here, our goal is to 1) understand the mechanism by which CD8+ T memory is inhibited during infection and develop methods to overcome it, and 2) identify vaccine formulations that stimulate protective CD8+ T cells and test their capacity to enhance vaccine-mediated CD4+ T cellimmunity. The vaccine strategies we will use build on a successful experimental approach using nanoparticles encapsulating an adjuvant and bound to whole inactivated organisms. Ultimately we anticipate this work will drive selection of appropriate strategies for vaccine development that provide robust protection against C. trachomatis.
After an initial infection with most pathogens, the immune system provides protection against re-infection with the same pathogen. However, infection of the human female reproductive tract with Chlamydia trachomatis provides limited protection against reinfection, and reoccurring infections can cause permanent damage and infertility. The goal of this proposal is to 1) determine why the cells of the immune system fail to provide protection against C. trachomatis, and 2) reprogram these faulty cells using new vaccine approaches to provide protection.
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