Critical to evaluating Chlamydia trachomatis
vaccine candidates is the availability of appropriate animal models. At a minimum, models must mimic the essential features of transmission and
disease progression that contribute to the severe outcomes associated with upper
genital tract infection. Existing models, whether mouse, pig or nonhuman primate, are based on the generally accepted premise that upper
genital tract infection, when it occurs, is an event subsequent to cervical
infection. However, what this simple paradigm overlooks are many features of reproductive biology that could influence both the initial distribution and subsequent spread of C. trachomatis within the female genital tract, as well as the immune responses made at these site(s) of
infection. A review of the literature strongly suggests that the menstrual cycle and coitusrelated phenomena are likely to have a profound effect on the course and outcome of female genital tract
infection with C. trachomatis. Although the new paradigm that emerges raises concerns about the adequacy of existing animal models, it also suggests ways to modify these models to better mimic the complexities of human
infection and therefore serve as appropriate models in which to test the safety and efficacy of
vaccine candidates against C. trachomatis
infection in women.