Chlamydial vaccine design is focused on eradicating infection. However, infection-associated infertility is the direct consequence of the same pro-inflammatory immune response required to eliminate the infection, which complicates vaccine design. Using the mouse model of Chlamydia pathogenesis, we immunized animals with the chlamydial Major Outer Membrane Protein (MOMP), via various routes of administration, with a number of adjuvant combinations (CTA1-DD, CT and CpG). This approach identified two contrasting vaccine candidates. One vaccine (sublingual delivered MOMP/CTA1-DD) induced a 70% reduction in infertility, without altering the course of infection. Another vaccine (intranasal delivered MOMP/CT/CpG) eradicated the infection in the upper reproductive tract, yet lacked any beneficial influence on incidence of infertility. This presented a unique opportunity to study how immunity against pathology can develop independently from immunity against infection. Comparing the gene expression in disease susceptible oviduct tissues, between infertility- and infection-protected vaccinated animals, identified a major difference in IL-17 signaling. While both vaccines expressed high levels of IL-17 cytokines, the infertility-protected group displayed reduced expression of corresponding IL-17 receptors. Therefore, the inhibition of IL-17 signaling in infertility-protected mice suggests a role for IL-17 not only in the resolution of infection, but also the development of infertility.
- Copyright © 2013 by The American Association of Immunologists, Inc.