title: Evaluation of the effect of MPL and delivery route on immunogenicity and protectivity of different formulations of FimH and MrpH from uropathogenic Escherichia coli and Proteus mirabilis in a UTI mouse model.
abstract: Urinary tract infections (UTIs) caused by Escherichia coli and Proteus mirabilis are an important cause of morbidity and with the high rate of relapse and spread of multi-drug resistant pathogens, pose a significant public health challenge worldwide. Lack of an efficacious commercial vaccine targeting both uropathogens makes development of a combined vaccine highly desirable. In this study the immunogenicity and protective efficacy of different formulations of FimH of UPEC, MrpH of P. mirabilis and their fusion protein (MrpH.FimH) subcutaneously administered with and without Monophosphoryl lipid A (MPL) adjuvant were evaluated. Our data showed that the subcutaneously administered proteins induced both serum and mucosal IgG, which MPL significantly improved developing a mixed Th1 and Th2 immune response. However, the preparations induced a higher systemic and mucosal IgG and IL-2 levels by this route compared to the intranasal. Immunization of mice with MrpH.FimH fusion with MPL or a mixture of FimH, MrpH and MPL conferred the highest protection of the bladder and kidneys when challenged with UPEC and P. mirabilis in a UTI mouse model. Therefore considering these results MrpH.FimH fusion with MPL administered subcutaneously or intranasally could be a promising vaccine candidate for elimination of UTIs caused by UPEC and P. mirabilis.
authors.affiliation: Department of Molecular Biology, Pasteur Institute of Iran, Pasteur Ave., Tehran 13164, Iran.
authors.forename: Mehri
authors.initials: M
authors.lastname: Habibi
authors.affiliation: Department of Molecular Biology, Pasteur Institute of Iran, Pasteur Ave., Tehran 13164, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Asadi Karam
authors.affiliation: Department of Molecular Biology, Pasteur Institute of Iran, Pasteur Ave., Tehran 13164, Iran. Electronic address: saeidbouzari@yahoo.com.
authors.forename: Saeid
authors.initials: S
authors.lastname: Bouzari
mesh_terms: D018829:Adhesins, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D018830:Adhesins, Escherichia coli / Q000008:administration & dosage / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D036781:Fimbriae Proteins / Q000008:administration & dosage / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000096:biosynthesis; D007668:Kidney / Q000276:immunology; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D011513:Proteus mirabilis / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D001743:Urinary Bladder / Q000276:immunology; D014552:Urinary Tract Infections / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D056689:Uropathogenic Escherichia coli / Q000276:immunology*
chemical_list: D018829:Adhesins, Bacterial; D018830:Adhesins, Escherichia coli; D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D007376:Interleukin-2; D008050:Lipid A; C119575:MrpH protein, Proteus mirabilis; C058769:fimH protein, E coli; D036781:Fimbriae Proteins; C048436:monophosphoryl lipid A
keywords: FimH; MPL; MrpH; Proteus mirabilis; UPEC; Urinary tract infection