title: Oral immunization with recombinant Helicobacter pylori urease induces secretory IgA antibodies and protects mice from challenge with Helicobacter felis.
abstract: Helicobacter pylori, a gram-negative spiral bacterium, is the cause of chronic superficial (type B) gastritis and peptic ulcer disease. The urease enzyme of H. pylori was expressed as an inactive recombinant protein in Escherichia coli, purified as particulate structures of 550-600 kDa molecular mass with a diameter of approximately 12 nm. Given orally, 5 micrograms of urease with an appropriate mucosal adjuvant, such as the labile toxin of E. coli, protected 60%-100% of mice against challenge with virulent Helicobacter felis. Protection correlated with the level of secretory IgA antibodies against urease. Oral administration of antigen was as effective or better than intragastric administration. Parenteral injection of antigen or intragastric administration of high-dose antigen without adjuvant elicited serum IgG but no IgA antibodies and did not confer protection. Recombinant urease as an oral vaccine candidate deserves further investigation as an approach to the prevention of Helicobacter-induced chronic gastroduodenal diseases in humans.
authors.affiliation: OraVax, Inc., Cambridge, MA 02139, USA.
authors.forename: C K
authors.initials: CK
authors.lastname: Lee
authors.forename: R
authors.initials: R
authors.lastname: Weltzin
authors.forename: W D
authors.initials: WD
authors.lastname: Thomas
authors.forename: H
authors.initials: H
authors.lastname: Kleanthous
authors.forename: T H
authors.initials: TH
authors.lastname: Ermak
authors.forename: G
authors.initials: G
authors.lastname: Soman
authors.forename: J E
authors.initials: JE
authors.lastname: Hill
authors.forename: S K
authors.initials: SK
authors.lastname: Ackerman
authors.forename: T P
authors.initials: TP
authors.lastname: Monath
mesh_terms: D000276:Adjuvants, Immunologic; D000284:Administration, Oral; D000818:Animals; D000917:Antibody Formation; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers; D005243:Feces / Q000382:microbiology; D005753:Gastric Mucosa / Q000382:microbiology; D016998:Helicobacter / Q000302:isolation & purification; D016481:Helicobacter Infections / Q000276:immunology* / Q000517:prevention & control*; D016480:Helicobacter pylori / Q000201:enzymology / Q000276:immunology*; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis* / Q000097:blood; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping; D012463:Saliva / Q000276:immunology; D013270:Stomach / Q000382:microbiology; D014510:Urease / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D001428:Bacterial Vaccines; D017931:DNA Primers; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D014614:Vaccines, Synthetic; D014510:Urease