title: Transcutaneous immunization with combined cholera toxin and CpG adjuvant protects against Chlamydia muridarum genital tract infection.
abstract: Chlamydia trachomatis is a pathogen of the genital tract and ocular epithelium. Infection is established by the binding of the metabolically inert elementary body (EB) to epithelial cells. These are taken up by endocytosis into a membrane-bound vesicle termed an inclusion. The inclusion avoids fusion with host lysosomes, and the EBs differentiate into the metabolically active reticulate body (RB), which replicates by binary fission within the protected environment of the inclusion. During the extracellular EB stage of the C. trachomatis life cycle, antibody present in genital tract or ocular secretions can inhibit infection both in vivo and in tissue culture. The RB, residing within the intracellular inclusion, is not accessible to antibody, and resolution of infection at this stage requires a cell-mediated immune response mediated by gamma interferon-secreting Th1 cells. Thus, an ideal vaccine to protect against C. trachomatis genital tract infection should induce both antibody (immunoglobulin A [IgA] and IgG) responses in mucosal secretions to prevent infection by chlamydial EB and a strong Th1 response to limit ascending infection to the uterus and fallopian tubes. In the present study we show that transcutaneous immunization with major outer membrane protein (MOMP) in combination with both cholera toxin and CpG oligodeoxynucleotides elicits MOMP-specific IgG and IgA in vaginal and uterine lavage fluid, MOMP-specific IgG in serum, and gamma interferon-secreting T cells in reproductive tract-draining caudal and lumbar lymph nodes. This immunization protocol resulted in enhanced clearance of C. muridarum (C. trachomatis, mouse pneumonitis strain) following intravaginal challenge of BALB/c mice.
authors.affiliation: Discipline of Immunology and Microbiology, School of Biomedical Science, The University of Newcastle and Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Berry
authors.forename: Danica K
authors.initials: DK
authors.lastname: Hickey
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Skelding
authors.forename: Shisan
authors.initials: S
authors.lastname: Bao
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Rendina
authors.forename: Philip M
authors.initials: PM
authors.lastname: Hansbro
authors.forename: Christine M
authors.initials: CM
authors.lastname: Gockel
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Beagley
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000279:Administration, Cutaneous; D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage*; D002690:Chlamydia Infections / Q000517:prevention & control*; D002692:Chlamydia trachomatis / Q000276:immunology*; D002772:Cholera Toxin / Q000008:administration & dosage*; D005260:Female; D005831:Genital Diseases, Female / Q000517:prevention & control*; D007114:Immunization; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007371:Interferon-gamma / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage*; D018272:Porins / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D014621:Vagina / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D001428:Bacterial Vaccines; C408982:CPG-oligonucleotide; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D018272:Porins; D012333:RNA, Messenger; C071677:omp1 protein, Chlamydia trachomatis; D007371:Interferon-gamma; D002772:Cholera Toxin