title: Systemic immunization with conserved pilus-associated adhesins protects against mucosal infections.
abstract: Colonization and infection of the bladder mucosa by Escherichia coli, the major uropathogenic organism, is dependent on the expression of pilus organelles. Type 1 pili are expressed by the majority of E. coli strains derived from patients with cystitis and pyelonephritis. FimH is the adhesin protein located at the distal tip of the heteropolymeric type-1 pilus which mediates binding to bladder cells through mannose receptors. We have shown that humoral antibody raised against two forms of purified FimH adhesin inhibited 94% (49/52) of E. coli UTI clinical isolates from binding to bladder tissue in vitro. Animals immunized with FimH-containing vaccines by a systemic route reduced colonization of the bladder mucosa in vivo in a murine cystitis model by > 99%. IgG antibody to FimH was detected in urinary samples obtained from immunized, protected mice. Passive systemic administration of immune sera from FimH-inoculated mice to naive animals also resulted in reduced colonization of bladder mucosa by uropathogenic E. coli. These studies demonstrate that systemic immunization with an anti-bacterial vaccine targeting a highly conserved adhesin on uropathogenic E. coli can induce IgG-mediated protection at a mucosal surface and may be a means of preventing recurrent and acute infections of the urogenital tract mucosa.
authors.affiliation: Department of Mucosal Immunity and Vaccines, MedImmune, Inc., Gaithersburg, MD, USA.
authors.forename: S
authors.initials: S
authors.lastname: Palaszynski
authors.forename: J
authors.initials: J
authors.lastname: Pinkner
authors.forename: S
authors.initials: S
authors.lastname: Leath
authors.forename: P
authors.initials: P
authors.lastname: Barren
authors.forename: C G
authors.initials: CG
authors.lastname: Auguste
authors.forename: J
authors.initials: J
authors.lastname: Burlein
authors.forename: S
authors.initials: S
authors.lastname: Hultgren
authors.forename: S
authors.initials: S
authors.lastname: Langermann
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology*; D018830:Adhesins, Escherichia coli; D000818:Animals; D001422:Bacterial Adhesion / Q000187:drug effects; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D001426:Bacterial Proteins; D001428:Bacterial Vaccines / Q000276:immunology*; D002478:Cells, Cultured; D003556:Cystitis / Q000517:prevention & control; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000276:immunology*; D029968:Escherichia coli Proteins; D036781:Fimbriae Proteins; D006801:Humans; D007114:Immunization / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D001743:Urinary Bladder / Q000276:immunology / Q000382:microbiology; D014552:Urinary Tract Infections / Q000276:immunology / Q000517:prevention & control
chemical_list: D018829:Adhesins, Bacterial; D018830:Adhesins, Escherichia coli; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D029968:Escherichia coli Proteins; C489721:fimC protein, E coli; C058769:fimH protein, E coli; D036781:Fimbriae Proteins