Immunology of Chlamydia infection: implications for a Chlamydia trachomatis vaccine

Sexually transmitted diseases caused by Chlamydia trachomatis are an important public-health concern worldwide. Infection causes pelvic inflammatory disease (PID), fallopian-tube scarring and sequelae that include infertility and ectopic pregnancy.Immunity to infection with Chlamydia spp. mainly involves CD4+ T helper 1 (TH1) effector cells, which secrete interferon-γ (IFN-γ), and B cells. IFN-γ mediates depletion of tryptophan, which is required for the growth of Chlamydia spp., whereas antibodies assist in the clearance of Chlamydia spp. on secondary infection.The upper compartment of the female genital tract strongly responds to infection with Chlamydia spp. Infected epithelial and immune cells in this compartment secrete pro-inflammatory cytokines, which trigger immune effector functions that clear infection but can damage tissue.The female genital mucosa contains inductive sites that are controlled by sex hormones. Infection with C. trachomatis further induces recruitment of lymphoid cells, which enlarge the inductive sites before the initiation of an immune response to C. trachomatis.Persistent forms of C. trachomatis that are generated in response to low concentrations of IFN-γ are metabolically active and seem to promote continuous secretion of pro-inflammatory cytokines, a condition that might contribute to tissue scarring.C. trachomatis antigens, together with an appropriate adjuvant, are crucial for the formulation of a protective vaccine against infection with C. trachomatis. Expression of the C. muridarum antigens major outer-membrane protein (MOMP) and outer-membrane protein 2 (OMP2) in Vibrio chlolerae ghosts constitutes a vaccine formulation that induces TH1-type immune responses and highly protects mice against infection with Chlamydia muridarum (which has most of the same genes as C. trachomatis).