title: Protection against Shiga toxin-producing Escherichia coli infection by transcutaneous immunization with Shiga toxin subunit B.
abstract: Enterohemorrhagic Escherichia coli (EHEC) strains are important human food-borne pathogens. EHEC strains elaborate potent Shiga toxins (Stx1, and/or Stx2) implicated in the development of hemorrhagic colitis (HC) or hemolytic-uremic syndrome (HUS). In this report, we evaluated the immunogenicity and protective efficacy of Stx1 subunit B (StxB1) administered by transcutaneous immunization (TCI). Three groups of Dutch Belted rabbits received patches containing StxB1, StxB1 in combination with Escherichia coli heat-labile enterotoxin (LT), or LT alone. An additional group of naïve rabbits served as controls. The protective efficacy following TCI with StxB1 was assessed by challenging rabbits with a virulent Stx1-producing strain, RDEC-H19A, capable of inducing HC and HUS in rabbits. Antibodies specific to StxB1 from serum and bile samples were determined by enzyme-linked immunosorbent assay and toxin neutralization test. Rabbits immunized with StxB1 demonstrated improved weight gain and reduced Stx-induced histopathology. Rabbits receiving StxB or StxB1/LT showed a significant increase in serum immunoglobulin G titers specific to StxB1 as well as toxin neutralization titers. These data demonstrated that the StxB delivered by TCI could induce significant systemic immune responses. Thus, Stx subunit B vaccine delivered by a patch for a high-risk population may be a practical approach to prevent (and/or reduce) Stx-induced pathology.
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: C
authors.initials: C
authors.lastname: Zhu
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.forename: Z
authors.initials: Z
authors.lastname: Yang
authors.forename: K
authors.initials: K
authors.lastname: Davis
authors.forename: H
authors.initials: H
authors.lastname: Rios
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.forename: G
authors.initials: G
authors.lastname: Glenn
authors.forename: E C
authors.initials: EC
authors.lastname: Boedeker
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000279:Administration, Cutaneous; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis / Q000097:blood; D000992:Antitoxins / Q000032:analysis / Q000097:blood; D001427:Bacterial Toxins / Q000008:administration & dosage; D001646:Bile / Q000276:immunology; D001835:Body Weight / Q000276:immunology; D002432:Cecum / Q000473:pathology; D003092:Colitis / Q000517:prevention & control; D004768:Enterotoxins / Q000008:administration & dosage; D004927:Escherichia coli Infections / Q000276:immunology / Q000517:prevention & control*; D029968:Escherichia coli Proteins / Q000008:administration & dosage; D005243:Feces / Q000382:microbiology; D006463:Hemolytic-Uremic Syndrome / Q000517:prevention & control; D007413:Intestinal Mucosa / Q000473:pathology; D007668:Kidney / Q000473:pathology; D021122:Protein Subunits / Q000008:administration & dosage / Q000276:immunology; D011817:Rabbits; D044967:Serum / Q000276:immunology; D022621:Shiga Toxin / Q000008:administration & dosage / Q000276:immunology*; D054323:Shiga-Toxigenic Escherichia coli / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000992:Antitoxins; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D021122:Protein Subunits; D022223:Vaccines, Subunit; D022621:Shiga Toxin; C027538:heat-labile enterotoxin, E coli