In vaccine enterprises there are two goals that must be achieved to be successful. Priority is usually given to the vaccine components, which antigen(s) and adjuvants. However an equally important goal is to understand the parameters of protective immunity, or the immunologic goal of vaccination. Chlamydia trachomatis infections pose a unique challenge for host immunity. In the majority of infected individuals the invading bacteria replicate only in the epithelial monolayer lining the reproductive tract. The business end (mechanism) of an effective vaccine is likely to be T cells functioning at the epithelial interface. During natural infections individuals’ immune responses range from asymptomatic clearance, to asymptomatic infertility, to hospitalisation for PID. Early Chlamydia vaccine attempts were associated with enhanced immunopathology. It is possible that Chlamydiavaccine candidates will cause enhanced immunopathology, with or without enhanced protection from bacterial replication in the reproductive tract. Evaluation of Chlamydia vaccines will need to include their ability to limit bacterial replication and immunopathology. There are some after-the-fact correlates for bad outcomes in women infected with C. trachomatis including circulating peripheral mononuclear cells that make too little IFN-γ, too much IL-10 or TNFα when activated by C. trachomatisantigens. The Chlamydia muridarum mouse model provides an opportunity to define the parameters of protective immunity in the genital tract, and then evaluate/validate them in humans. The mouse model has shown the CD4 T cells are critical to protection and CD8 T cells likely responsible for immunopathology. More recently it was demonstrated that there are redundant mechanisms for clearing C. muridarumfrom the genital tract. This presentation will cover the newest mouse model data, correlating it with what is known in humans. The practicable human correlates of protective immunity and immunopathology are likely to be novel CD4 and CD8 T cell subsets, with antibody possibly falling into disfavour.
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