Date of Award
Master of Science
Molecular Biology Microbiology and Biochemistry
Chlamydia spp. is the most commonly reported sexually transmitted bacterial pathogen in the developed and developing world. Chlamydia spp. infect the epithelial cells (ECs) of the respiratory, reproductive, and gastrointestinal (GI) tracts. Following female reproductive tract (FRT) infections, C. trachomatis can ascend to, and infect the uterus and ovaries, causing pathologies such as tissue scarring, pelvic inflammatory disease (PID), ectopic pregnancy, salpingitis, and infertility. In contrast, infection of the GI tract of animals and humans by Chlamydia spp. is a long lasting, persistent infection that does not induce significant pathology. Unlike FRT infections, GI tract infections with Chlamydia are more resistant to antimicrobial therapy such as Azithromycin treatment. In addition, Chlamydia in the GI tract can be a reservoir for re-infecting the FRT. Although sexually-transmitted infections present major health challenge worldwide, there is a paucity of vaccines that target such pathogens. With specific regard to Chlamydia, no vaccine has been licensed for use in humans thus far. In order to elicit immune responses at mucosal surfaces such as that of the FRT, mucosal immunization is necessary. However, the FRT is a poor site of induction of immunity. Based on our previous observations that immune responses in the FRT were elicited following per-oral (PO) immunization, we hypothesized that protective immunity in the FRT could be elicited through in the GI tract following mucosal (PO) immunization, and that PO immunization could provide protection against genital Chlamydia challenge. To test this hypothesis, 6 to 8 week-old female C57BL/6 mice were PO or sub-cutaneously (SC) primed with either live or killed C. muridarum EBs, then at day 28 SC boosted with killed PBS or killed C. muridarum. At day 42 post-priming mice were per-vaginally (PV) challenged with 2x〖10〗^5IFUs of C. muridarum, and 6 weeks following the PV challenge FRT tissues were excised, C. muridarum tissue loads were determined, and upper FRT pathology was scored. We found that PO inoculation with live or killed C. muridarum followed by SC boosting significantly reduced hydrosalpinx pathology and C. muridarum titers in ovaries, uterus and vaginal swabs compared to unimmunized controls and to mice primed and boosted SC with killed EBs (SC(K)-SC(K)). Neither form of immunization affected C. muridarum titers in GI tract, although mucosally immunized animals developed relatively high Chlamydia-specific sIgA titers prior to PV challenge. Our results indicate that mucosal priming is essential for induction of protective immunity in the FRT, and that oral immunization is an effective approach for vaccination against mucosal pathogens like Chlamydia.
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