Expression of Helicobacter pylori urease subunit B gene in Lactococcus lactis MG1363 and its use as a vaccine delivery system against H. pylori infection in mice

Vaccine. 2001 Jul 16;19(28-29):3927-35. doi: 10.1016/s0264-410x(01)00119-0.

Abstract

The use of Lactococcus lactis as an antigen delivery vehicle for mucosal immunisation has been proposed. To determine whether L. lactis could effectively deliver Helicobacter pylori antigens to the immune system, a recombinant L. lactis expressing H. pylori urease subunit B (UreB) was constructed. Constitutive expression of UreB by a pTREX1 vector resulted in the intracellular accumulation of UreB to approximately 6.25% of soluble cellular protein. Five different oral regimens were used to vaccinate C57BL/6 mice and the immune response measured. One regimen, which consisted of four weekly doses of 10(10) bacteria, followed after an interval of approximately 4 weeks by three successive daily doses, was able to elicit a systemic antibody response to UreB in the mice, although subsequently, a similar regimen produced a significant antibody response in only one out of six mice. The other three regimes, in which mice were vaccinated with two or three sets of three consecutive daily doses of recombinant bacteria over 30 days, failed to elicit significant anti-UreB serum antibody responses. In three regimens, the immunised mice were then challenged by H. pylori strain SS1 and no protective effect was observed. These findings suggest that any adjuvant effects of L. lactis are unlikely to be sufficient to produce an effective immune response and to protect against H. pylori challenge, when used to deliver a weak immunogen, such as UreB.

MeSH terms

  • Animals
  • Antibodies, Bacterial / biosynthesis
  • Antigens, Bacterial / administration & dosage
  • Bacterial Vaccines / administration & dosage*
  • Base Sequence
  • Cloning, Molecular
  • Female
  • Gene Expression
  • Genes, Bacterial*
  • Genetic Vectors
  • Helicobacter Infections / immunology*
  • Helicobacter Infections / prevention & control*
  • Helicobacter pylori / enzymology*
  • Helicobacter pylori / genetics*
  • Helicobacter pylori / immunology
  • Immunity, Mucosal
  • Immunoglobulin G / biosynthesis
  • Lactococcus lactis / genetics*
  • Lactococcus lactis / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Plasmids / genetics
  • Protein Subunits
  • Urease / chemistry
  • Urease / genetics*
  • Urease / immunology
  • Vaccination

Substances

  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Vaccines
  • Immunoglobulin G
  • Protein Subunits
  • Urease