Determination immunogenic property of truncated MrpH.FliC as a vaccine candidate against urinary tract infections caused by Proteus mirabilis

Microb Pathog. 2018 Jan:114:99-106. doi: 10.1016/j.micpath.2017.11.015. Epub 2017 Nov 11.

Abstract

Proteus mirabilis is common cause of urinary tract infections (UTIs) especially in complicated UTIs which are resistant to antibiotic therapy, Consequently, an ideal vaccine is inevitably required. The N-terminal domain of MrpH (Truncated form of MrpH) lies between the most critical antigens of P. mirabilis to consider as vaccine candidate. FliC of Salmonella typhimurium induces several pathways of immunity system, which leads to produce antibody and cytokines. In this study, adjuvant properties of FliC and efficacy of truncated MrpH as important antigen, in tMrpH.FliC were determined in in vitro and in vivo circumstances. Three proteins including: FliC, MrpH and tMrpH.FliC were injected to mice and subsequently sera and supernatant of cell culture were collected to evaluate different immune responses. According to our findings, tMrpH.FliC could stimulate both humoral and cellular immune responses, so that serum IgG, urine IgA, IL.4, IFN-γ and IL.17 were increased significantly in comparison to MrpH and FliC alone, this augmentation was considerable. Results showed significant decrease of bacterial load in all of the challenged groups compared to the control group, although this protective effect was the highest in mice vaccinated with tMrpH.FliC. Our results showed truncated MrpH, without an unwanted domain is an ideal vaccine target and FliC, as adjuvant, increases its immunogenic property. Thus, fusion protein tMrpH.FliC can be considered as promising vaccine against P. mirabilis.

Keywords: Adjuvant; FliC; MrpH; Proteus mirabilis; Urinary tract infections.

MeSH terms

  • Adhesins, Bacterial / genetics
  • Adhesins, Bacterial / immunology*
  • Adjuvants, Immunologic*
  • Animals
  • Antibodies, Bacterial / blood
  • Antibody Formation
  • Cloning, Molecular
  • Cytokines / metabolism
  • DNA, Bacterial
  • Female
  • Fimbriae Proteins / genetics
  • Fimbriae Proteins / immunology*
  • Flagellin / genetics
  • Flagellin / immunology*
  • Gene Fusion
  • Immunity, Cellular
  • Immunity, Humoral
  • Immunogenicity, Vaccine / immunology*
  • Immunoglobulin A / urine
  • Immunoglobulin G / blood
  • Interferon-gamma / metabolism
  • Interferon-gamma / urine
  • Interleukin-17 / metabolism
  • Interleukin-4 / metabolism
  • Kidney / immunology
  • Mice
  • Mice, Inbred BALB C
  • Molecular Docking Simulation
  • Protein Interaction Domains and Motifs
  • Proteus Infections / immunology*
  • Proteus Infections / microbiology
  • Proteus mirabilis / pathogenicity*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Salmonella typhimurium / metabolism
  • Urinary Bladder / immunology
  • Urinary Tract Infections / microbiology
  • Urinary Tract Infections / prevention & control*

Substances

  • Adhesins, Bacterial
  • Adjuvants, Immunologic
  • Antibodies, Bacterial
  • Cytokines
  • DNA, Bacterial
  • Immunoglobulin A
  • Immunoglobulin G
  • Interleukin-17
  • MrpH protein, Proteus mirabilis
  • Recombinant Proteins
  • Flagellin
  • Fimbriae Proteins
  • Interleukin-4
  • Interferon-gamma