title: Comparison of intranasal and transcutaneous immunization for induction of protective immunity against Chlamydia muridarum respiratory tract infection.
abstract: Chlamydia pneumoniae causes a range of respiratory infections including bronchitis, pharyngitis and pneumonia. Infection has also been implicated in exacerbation/initiation of asthma and chronic obstructive pulmonary disease (COPD) and may play a role in atherosclerosis and Alzheimer's disease. We have used a mouse model of Chlamydia respiratory infection to determine the effectiveness of intranasal (IN) and transcutaneous immunization (TCI) to prevent Chlamydia lung infection. Female BALB/c mice were immunized with chlamydial major outer membrane protein (MOMP) mixed with cholera toxin and CpG oligodeoxynucleotide adjuvants by either the IN or TCI routes. Serum and bronchoalveolar lavage (BAL) were collected for antibody analysis. Mononuclear cells from lung-draining lymph nodes were stimulated in vitro with MOMP and cytokine mRNA production determined by real time PCR. Animals were challenged with live Chlamydia and weighed daily following challenge. At day 10 (the peak of infection) animals were sacrificed and the numbers of recoverable Chlamydia in lungs determined by real time PCR. MOMP-specific antibody-secreting cells in lung tissues were also determined at day 10 post-infection. Both IN and TCI protected animals against weight loss compared to non-immunized controls with both immunized groups gaining weight by day 10-post challenge while controls had lost 6% of body weight. Both immunization protocols induced MOMP-specific IgG in serum and BAL while only IN immunization induced MOMP-specific IgA in BAL. Both immunization routes resulted in high numbers of MOMP-specific antibody-secreting cells in lung tissues (IN>TCI). Following in vitro re-stimulation of lung-draining lymph node cells with MOMP; IFNgamma mRNA increased 20-fold in cells from IN immunized animals (compared to non-immunized controls) while IFNgamma levels increased 6- to 7-fold in TCI animals. Ten days post challenge non-immunized animals had >7,000 IFU in their lungs, IN immunized animals <50 IFU and TCI immunized animals <1,500 IFU. Thus, both intranasal and transcutaneous immunization protected mice against respiratory challenge with Chlamydia. The best protection was obtained following IN immunization and correlated with IFNgamma production by mononuclear cells in lung-draining LN and MOMP-specific IgA in BAL.
authors.affiliation: Discipline of Immunology and Microbiology, School of Biomedical Sciences, Faculty of Health, The University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Skelding
authors.forename: Danica K
authors.initials: DK
authors.lastname: Hickey
authors.forename: Jay C
authors.initials: JC
authors.lastname: Horvat
authors.forename: Shisan
authors.initials: S
authors.lastname: Bao
authors.forename: Kathryn G
authors.initials: KG
authors.lastname: Roberts
authors.forename: Jane M
authors.initials: JM
authors.lastname: Finnie
authors.forename: Philip M
authors.initials: PM
authors.lastname: Hansbro
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Beagley
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid; D002690:Chlamydia Infections / Q000276:immunology* / Q000517:prevention & control*; D023502:Chlamydia muridarum / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004269:DNA, Bacterial / Q000302:isolation & purification; D005260:Female; D007115:Immunization Schedule; D007070:Immunoglobulin A / Q000032:analysis / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis; D007279:Injections, Subcutaneous; D008168:Lung / Q000737:chemistry; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000517:prevention & control*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D001428:Bacterial Vaccines; D016207:Cytokines; D004269:DNA, Bacterial; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D014614:Vaccines, Synthetic