Per oral inoculation with live or killed Chlamydia muridarum induces protection against per-vaginal C. muridarum challenge

Abstract

In addition to infecting the female reproductive tract (FRT), Chlamydia spp. infect the gastro-intestinal (GI) tract of animals and humans. In the GI tract Chlamydia spp. persists without causing pathology, is more resistant to azithromycin treatment, and can be a reservoir for reinfection of the FRT. To date no effective vaccines have been licensed for use in humans. We have found that sIgA responses in the FRT mirror the responses in the GI tract following feeding with a high dose soluble Ova, leading us to hypothesize that immunity in the FRT may be induced via per-oral (PO) antigen administration. To test this hypothesis, 6 week-old C57BL/6 mice were PO or sub-cutaneously (SC) primed with live or killed C. muridarum, then 28 days later SC boosted with killed C. muridarum. At day 42 mice were per vaginally challenged with 2×105 IFUs of C. muridarum and six weeks following challenge mice were euthanized for determination of hydrosalpinx severity and C. muridarum tissue loads. 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. Neither form of immunization affected C. muridarum titers in the GI tract, in spite of relatively high Chlamydia-specific sIgA titers. Further analysis revealed that intestinal sIgA are almost exclusively specific for a single antigen (HSP60, a cytoplasmic antigen), while serum antibodies recognize multiple antigens. Our results indicate that while mucosal priming is essential for induction of protective immunity in the FRT, colonization of the GI tract by live Chlamydia is not necessary for mucosal priming.