Chlamydia -Specific IgA Secretion in the Female Reproductive Tract Induced via Per-Oral Immunization Confers Protection against Primary Chlamydia Challenge

Abstract

Chlamydia trachomatis is an obligate intracellular pathogen that causes sexually transmitted disease. In women, chlamydial infections may cause pelvic inflammatory disease (PID), ectopic pregnancy, and infertility. The role of antibodies in protection against a primary Chlamydia infection is unclear and was a focus of this work. Using the C. muridarum mouse infection model, we show that intestinal mucosa is infected via intra-nasal (IN) or per-oral (PO) Chlamydia inoculation and unlike the female reproductive tract (FRT) mucosa, it halts systemic Chlamydia dissemination. Moreover, PO immunization or infection with Chlamydia confers protection against per-vaginal (PV) challenge, resulting in significantly decreased bacterial burden in the FRT, accelerated Chlamydia clearance, and reduced hydrosalpinx pathology. In contrast, sub-cutaneous (SC) immunization conferred no protection against the PV challenge. Both PO and SC immunizations induced Chlamydia-specific serum IgA. However, IgA was found only in the vaginal washes and fecal extracts of PO-immunized animals. Following a PV challenge, unimmunized control and SC-SC immunized animals developed Chlamydia-specific intestinal IgA, yet failed to develop IgA in the FRT indicating that IgA response in the FRT relies on the FRT to gastrointestinal tract (GIT) antigen transport. Vaginal secretions of PO-immunized animals neutralize Chlamydia in vivo, resulting in significantly lower Chlamydia burden in the FRT and Chlamydia transport to the GIT. We also show that infection of the GIT is not necessary for induction of protective immunity in the FRT, a finding that is important for the development of PO subunit vaccines to target Chlamydia and possibly other sexually transmitted pathogens.

Enhanced IgA coating of bacteria in women with Lactobacillus crispatus-dominated vaginal microbiota

“…Specific IgA against pathogens can be elicited in the female genital tract, for example, against virulence factors from G. vaginalis , a bacterium commonly present in women with diverse microbiota [ 29 – 31 ]. In a mouse model for Chlamydia , specific IgA is present which protects against Chlamydia infection [ 32 ]. In our study, we were not able to distinguish between polyreactive and specific immunoglobulins.…”

The Role of Mucoadhesion and Mucopenetration in the Immune Response Induced by Polymer-Based Mucosal Adjuvants

“…On the other hand, presented in the form of a spray for nasal administration, there are the influenza vaccines against type A and B viruses (FluMist ® Quadrivalent and Nasovac-S™) [ 23 , 24 ]. Mucosal vaccines induce diverse immune responses in strength, efficiency, and long-term protection [ 25 , 26 , 27 ]. Most of these formulations contain live attenuated or inactivated whole-cell organisms or viruses [ 28 , 29 ]; consequently, the limitations and challenges are many, especially those related to safety.…”