title: Transcutaneous immunization with a novel lipid-based adjuvant protects against Chlamydia genital and respiratory infections.
abstract: Mucosal adjuvants are important to overcome the state of immune tolerance normally associated with mucosal delivery and to enhance adaptive immunity to often-weakly immunogenic subunit vaccine antigens. Unfortunately, adverse side effects of many experimental adjuvants limit the number of adjuvants approved for vaccination. Lipid C is a novel, non-toxic, lipid oral vaccine-delivery formulation, developed originally for oral delivery of the live Mycobacterium bovis Bacille Calmette-Guerin (BCG) vaccine. In the present study, murine models of chlamydial respiratory and genital tract infections were used to determine whether transcutaneous immunization (TCI) with Lipid C-incorporated protein antigens could elicit protective immunity at the genital and respiratory mucosae. BALB/c mice were immunized transcutaneously with Lipid C containing the chlamydial major outer membrane protein (MOMP), with and without addition of cholera toxin and CpG-ODN 1826 (CT/CpG). Both vaccine combinations induced mixed cell-mediated and mucosal antibody immune responses. Immunization with Lipid C-incorporated MOMP (Lipid C/MOMP), either alone or with CT/CpG resulted in partial protection following live challenge with Chlamydia muridarum as evidenced by a significant reduction in recoverable Chlamydia from both the genital secretions and lung tissue. Protection induced by immunization with Lipid C/MOMP alone was not further enhanced by the addition of CT/CpG. These results highlight the potential of Lipid C as a novel mucosal adjuvant capable of targeting multiple mucosal surfaces following TCI. Protection at both the respiratory and genital mucosae was achieved without the requirement for potentially toxic adjuvants, suggesting that Lipid C may provide a safe effective mucosal adjuvant for human vaccination.
authors.affiliation: School of Biomedical Sciences, The University of Newcastle, Newcastle, Australia and Hunter Medical Research Institute, Newcastle, Australia.
authors.forename: Danica K
authors.initials: DK
authors.lastname: Hickey
authors.forename: Frank E
authors.initials: FE
authors.lastname: Aldwell
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Beagley
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000279:Administration, Cutaneous; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000276:immunology; D002690:Chlamydia Infections / Q000276:immunology / Q000517:prevention & control*; D023502:Chlamydia muridarum / Q000276:immunology*; D005260:Female; D005831:Genital Diseases, Female / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D018272:Porins / Q000276:immunology; D012141:Respiratory Tract Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D013601:T-Lymphocytes / Q000276:immunology; D014280:Triglycerides / Q000008:administration & dosage / Q000276:immunology*; D014621:Vagina / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D018272:Porins; D014280:Triglycerides; C071677:omp1 protein, Chlamydia trachomatis