Intranasal immunization with fusion protein MrpH·FimH and MPL adjuvant confers protection against urinary tract infections caused by uropathogenic Escherichia coli and Proteus mirabilis

Mol Immunol. 2015 Apr;64(2):285-94. doi: 10.1016/j.molimm.2014.12.008. Epub 2015 Jan 4.

Abstract

Urinary tract infections (UTIs) caused by Uropathogenic Escherichia coli (UPEC) and Proteus mirabilis are among the most common infections in the world. Currently there are no vaccines available to confer protection against UTI in humans. In this study, the immune responses and protection of FimH of UPEC with MrpH antigen of P. mirabilis in different vaccine formulations with and without MPL adjuvant were assessed. Mice intranasally immunized with the novel fusion protein MrpH·FimH induced a significant increase in IgG and IgA in serum, nasal wash, vaginal wash, and urine samples. Mice immunized with fusion MrpH·FimH also showed a significant boost in cellular immunity. Addition of MPL as the adjuvant enhanced FimH and MrpH specific humoral and cellular responses in both systemic and mucosal samples. Vaccination with MrpH·FimH alone or in combination with MPL showed the highest efficiency in clearing bladder and kidney infections in mice challenged with UPEC and P. mirabilis. These findings may indicate that the protection observed correlates with the systemic, mucosal and cellular immune responses induced by vaccination with these preparations. Our data suggest MrpH·FimH fusion protein with or without MPL as adjuvant could be potential vaccine candidates for elimination of UPEC and P. mirabilis. These data altogether are promising and these formulations are good candidates for elimination of UPEC and P. mirabilis.

Keywords: FimH; MPL; MrpH; Proteus mirabilis; UPEC; UTI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / administration & dosage
  • Adhesins, Bacterial / genetics
  • Adhesins, Bacterial / immunology*
  • Adhesins, Escherichia coli / administration & dosage
  • Adhesins, Escherichia coli / genetics
  • Adhesins, Escherichia coli / immunology*
  • Adjuvants, Immunologic / administration & dosage
  • Administration, Intranasal
  • Animals
  • Antibodies, Bacterial / biosynthesis*
  • Antibodies, Bacterial / blood
  • Female
  • Fimbriae Proteins / administration & dosage
  • Fimbriae Proteins / genetics
  • Fimbriae Proteins / immunology*
  • Gene Expression
  • Humans
  • Immunity, Humoral / drug effects
  • Immunity, Mucosal / drug effects
  • Immunization
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / blood
  • Mice
  • Mice, Inbred BALB C
  • Proteus mirabilis / immunology*
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Urinary Tract Infections / immunology
  • Urinary Tract Infections / microbiology
  • Urinary Tract Infections / prevention & control*
  • Uropathogenic Escherichia coli / immunology*

Substances

  • Adhesins, Bacterial
  • Adhesins, Escherichia coli
  • Adjuvants, Immunologic
  • Antibodies, Bacterial
  • Immunoglobulin G
  • MrpH protein, Proteus mirabilis
  • Recombinant Fusion Proteins
  • fimH protein, E coli
  • Fimbriae Proteins