Oral immunization of mice with lactic acid bacteria producing Helicobacter pylori urease B subunit partially protects against challenge with Helicobacter felis

J Infect Dis. 2005 Oct 15;192(8):1441-9. doi: 10.1086/444425. Epub 2005 Sep 13.

Abstract

Background: The development of an efficacious vaccine against infection with Helicobacter pylori, the causative agent of chronic gastritis, peptic ulcer disease, and gastric adenocarcinoma, remains a challenge. Since the use of mucosal adjuvants is limited in human application, we have evaluated the potential of recombinant Lactobacillus strains producing H. pylori urease B (UreB) subunit to deliver this antigen to the gastrointestinal tract.

Methods: Mice were injected orally 3 times with a triple dose of recombinant Lactobacillus plantarum NCIMB8826, the recombinant isogenic cell-wall mutant (alr(-) MD007 strain) expressing UreB, or a mixture of recombinant UreB and cholera toxin (rUreB/CT) as a control. Urease-specific seric immunoglobulin (Ig) G and IgA were measured by use of an enzyme-linked immunosorbent assay. After challenge with Helicobacter felis, stomach infection was examined by use of the rapid urease test and by polymerase chain reaction detection of Helicobacter genomic DNA.

Results: Intragastric immunization with both recombinant Lactobacillus strains and rUreB/CT elicited UreB-specific antibodies. After challenge, reduction of H. felis load in the stomachs of mice was observed only after immunization with the recombinant mutant strain MD007 or with rUreB/CT.

Conclusions: This is the first report of successful induction of partial protection against H. felis with a mucosal prime-boost regimen in which recombinant Lactobacillus strains were used as antigen-delivery vehicles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Administration, Oral
  • Animals
  • Antibody Formation
  • Bacterial Vaccines / administration & dosage*
  • Bacterial Vaccines / immunology
  • Disease Models, Animal
  • Helicobacter / isolation & purification
  • Helicobacter Infections / immunology
  • Helicobacter Infections / prevention & control*
  • Helicobacter pylori / enzymology*
  • Helicobacter pylori / genetics
  • Immunoglobulin A, Secretory / biosynthesis*
  • Immunoglobulin A, Secretory / blood
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / blood
  • Lactobacillus / genetics
  • Lactobacillus / immunology*
  • Mice
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / immunology
  • Urease / administration & dosage*
  • Urease / biosynthesis
  • Urease / genetics
  • Urease / immunology

Substances

  • Adjuvants, Immunologic
  • Bacterial Vaccines
  • Immunoglobulin A, Secretory
  • Immunoglobulin G
  • Recombinant Proteins
  • Urease