The guinea pig as a model for genital chlamydial pathogenesis and vaccine development

Genital Chlamydia trachomatis infections in humans can lead to severe tubal damage such as pelvic inflammatory disorder and infertility, if left untreated. Taking into consideration of the complications associated with C. trachomatis infection in women, it appears guinea pig model may more closely resemble human disease. We have established the Guinea Pig model with C. caviae and C. trachomatis D genital infections in our laboratory, where we have characterized the primary infection in the genital tract of Guinea Pigs. In this study, we evaluated host immune responses following genital guinea pig inclusion conjunctivitis (GPIC) agent (Chlamydia caviae) infection in intranasally C. caviae vaccinated guinea pigs. C. caviae -vaccinated guinea pigs resolved the genital tract infection as early as day 3 with reduced pathology, whereas mock-vaccinated animals shed C. caviae up to day 18 post-challenge with a greater degree of upper genital pathology at 80 days post-challenge. C. caviae -vaccinated animals displayed elevated levels of antigen specific IgG, IgG1 and IgG2 responses, able to neutralize GPIC in vitro. Using a guinea pig specific transcriptome RT-PCR array, we observed co-regulation of innate, Th2-humoral, and Th1-cellular/inflammatory immune genes following infection. The expression of these Th-1 and Th-2 associated genes was found to be higher in EB-vaccinated, compared to mock-vaccinated, animals at day 3 post challenge and correlated with early clearance of bacterial shedding. These findings were validated using single target qRT-PCRs, and provide evidence for guinea pig specific B and T cell related genes being activated at local sites of infection. This report adds to previous findings on the usefulness of this animal model to study chlamydial pathogenesis and test putative vaccine candidates against genital infection.