Intranasal immunisation with recombinant Lactococcus lactis displaying either anchored or secreted forms of Proteus mirabilis MrpA fimbrial protein confers specific immune response and induces a significant reduction of kidney bacterial colonisation in mice

Microbes Infect. 2007 Jun;9(7):821-8. doi: 10.1016/j.micinf.2007.02.023. Epub 2007 Mar 12.

Abstract

Proteus mirabilis, a common cause of urinary tract infections in humans, can express different fimbriae. MR/P fimbriae may contribute to bacterial colonisation, and its structural protein MrpA represents a promising candidate antigen for mucosal vaccination. Commercial complex vaccines have limited, short-lived protection and are incapable of eliciting mucosal responses against putative antigens related to virulence. The development of mucosal live vaccines using food-grade lactic acid bacterium Lactococcus lactis as antigen vehicle is an attractive alternative and a safe vaccination strategy against P. mirabilis infection. Here, we report the construction of L. lactis strains modified to produce MrpA via two cellular locations, cell wall-anchored and secreted. Protection assays against P. mirabilis infection and evaluation of the immune response generated after immunisation were conducted in a mouse model. MrpA protein was efficiently expressed by L. lactis strain and caused a significant induction of specific serum IgG and IgA in the animals immunised with L. lactis pSEC:mrpA and L. lactis pCWA:mrpA respectively. A significant reduction of renal bacterial colonisation was observed in both groups of mice (P<0.05) after P. mirabilis challenge. This is the first example of a P. mirabilis fimbrial antigen expressed in a food-grade live strain with promising applications in vaccine design.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antibodies, Bacterial / blood
  • Antibodies, Bacterial / urine
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology*
  • Bacterial Vaccines / immunology*
  • Bacterial Vaccines / pharmacology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Immunization / methods
  • Interferon-gamma / analysis
  • Lactococcus lactis / genetics
  • Lactococcus lactis / immunology*
  • Mice
  • Proteus Infections / immunology*
  • Proteus Infections / microbiology
  • Proteus Infections / prevention & control
  • Proteus mirabilis / immunology*
  • Spleen / immunology
  • Spleen / microbiology
  • Statistics, Nonparametric
  • Urinary Tract Infections / immunology
  • Urinary Tract Infections / microbiology*
  • Urinary Tract Infections / prevention & control
  • Vaccines, Synthetic / immunology
  • Vaccines, Synthetic / pharmacology

Substances

  • Antibodies, Bacterial
  • Bacterial Proteins
  • Bacterial Vaccines
  • Vaccines, Synthetic
  • mrpA protein, Proteus mirabilis
  • Interferon-gamma