title: Chlamydia trachomatis major outer membrane protein epitopes expressed as fusions with LamB in an attenuated aro A strain of Salmonella typhimurium; their application as potential immunogens.
abstract: The major outer-membrane protein (MOMP) of Chlamydia trachomatis is the focus of attention for chlamydial vaccine design, particularly those serovar- and subspecies-specific epitopes which provoke neutralizing immune responses. Selected surface-exposed B-cell epitopes of MOMP, incorporating B-subspecies specificities, were expressed as fusions with LamB, an inducible outer-membrane transport protein of Escherichia coli. These recombinant chlamydial-LamB proteins were correctly transported to the outer membrane of both E. coli and an aro A mutant of Salmonella typhimurium. The immunogenicity of the constructs was investigated in a mouse model of chlamydial salpingitis. After oral immunization, recombinant S. typhimurium were recovered from the livers of mice for up to two weeks, and a serum IgG response was induced both to the Salmonella and to the inserted chlamydial epitopes. By contrast, intravenous inoculation was ineffective. Although these LamB fusions proved only weakly immunogenic, this approach should be useful for investigating the ability of attenuated S. typhimurium vaccines incorporating chlamydial epitopes to stimulate protective mucosal immunity in the mouse model of chlamydial salpingitis.
authors.affiliation: Department of Microbiology, University of Southampton Medical School, Southampton General Hospital.
authors.forename: L J
authors.initials: LJ
authors.lastname: Hayes
authors.forename: J W
authors.initials: JW
authors.lastname: Conlan
authors.forename: J S
authors.initials: JS
authors.lastname: Everson
authors.forename: M E
authors.initials: ME
authors.lastname: Ward
authors.forename: I N
authors.initials: IN
authors.lastname: Clarke
mesh_terms: D000284:Administration, Oral; D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D001483:Base Sequence; D002690:Chlamydia Infections / Q000276:immunology*; D002692:Chlamydia trachomatis / Q000235:genetics / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D018272:Porins; D011991:Receptors, Virus / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000276:immunology; D012486:Salmonella typhimurium / Q000276:immunology / Q000378:metabolism; D012488:Salpingitis / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D000939:Epitopes; D018272:Porins; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; C016532:maltoporins; C071677:omp1 protein, Chlamydia trachomatis