Most
vaccines developed against Chlamydia using animal models provide partial protection against a
genital tract infection. However, protection against the oviduct pathology associated with
infertility is highly variable and often has no defining immunological correlate. When comparing two adjuvants (CTA1-DD and a combination of
Cholera toxin plus CpG-
oligodeoxynucleotide-CT/CpG) combined with the chlamydial major outer
membrane protein (MOMP)
antigen and delivered via the intranasal (IN), sublingual (SL) or transcutaneous (TC) routes, we identified two
vaccine groups with contrasting outcomes following
infection. SL immunization with MOMP/CTA1-DD induced a 70% reduction in the incidence of oviduct pathology, without significantly altering the course of
infection. Conversely, IN immunization with
MOMP/CT/CpG prevented an ascending
infection, but not the oviduct pathology. This anomaly presented a unique opportunity to study the mechanisms by which
vaccines can prevent oviduct pathology, other than by controlling the
infection. The
IL-17 signaling in the oviducts was found to associate with both the enhancement of immunity to
infection and the development of oviduct pathology. This conflicting role of
IL-17 may provide some explanation for the discordance in protection between
infection and disease and suggests that controlling immunopathology, as opposed to the rapid eradication of the
infection, may be essential for an effective human chlamydial
vaccine that prevents
infertility.