title: In silico and in vivo studies of truncated forms of flagellin (FliC) of enteroaggregative Escherichia coli fused to FimH from uropathogenic Escherichia coli as a vaccine candidate against urinary tract infections.
abstract: The new generation of vaccines against infectious diseases is based on recombinant fusion proteins. Flagellin (FliC) of enteroaggregative Escherichia coli (EAEC) could be considered as a potent adjuvant in designing new vaccines. However, because of its large size, incorporation of this protein with a vaccine antigen might negatively influence recognition of the vaccine epitopes by the immune system. Designing the truncated forms of FliC, capable of inducing innate immune response, enhances the immune responses to the target antigen. We have previously shown that two truncated forms of FliC are able to induce Interleukine-8 production in HT-29 epithelial cell line. In this study we designed recombinant vaccine against urinary tract infections (UTIs) using truncated forms of FliC and type 1 fimbrial FimH adhesin from uropathogenic Escherichia coli (UPEC) and studied their in silico interactions with Toll-like receptor 5 (TLR-5) via docking protocols. The best fusion protein was subjected to cloning and expression. The ability of the recombinant vaccine and the truncated forms in inducing immune responses was investigated. Our results showed that truncated forms are capable of inducing Th1 (forms A and B) and Th2 (form A) responses and fusion vaccine induced strong cellular and humoral immune responses.
authors: Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran.
authors: Nastaran Sadat
authors: NS
authors: Savar
authors: Department of Pharmaceutical Biotechnology, and Bioinformatics Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences and Health Services, Isfahan, Iran.
authors: Ali
authors: A
authors: Jahanian-Najafabadi
authors: Department of Virology, Pasteur Institute of Iran, Tehran, Iran.
authors: Mehdi
authors: M
authors: Mahdavi
authors: National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran.
authors: Mohammad Ali
authors: MA
authors: Shokrgozar
authors: Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran.
authors: Anis
authors: A
authors: Jafari
authors: Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran. Electronic address: saeidbouzari@yahoo.com.
authors: Saeid
authors: S
authors: Bouzari
mesh_terms: D018830:Adhesins, Escherichia coli / Q000276:immunology / Q000378:metabolism; D000818:Animals; D004926:Escherichia coli / Q000145:classification / Q000235:genetics* / Q000276:immunology; D029968:Escherichia coli Proteins / Q000276:immunology / Q000378:metabolism*; D022361:Escherichia coli Vaccines / Q000235:genetics / Q000276:immunology*; D036781:Fimbriae Proteins / Q000276:immunology / Q000378:metabolism; D005408:Flagellin; D019073:HT29 Cells; D006801:Humans; D056724:Immunity, Humoral; D007113:Immunity, Innate; D051379:Mice; D008807:Mice, Inbred BALB C; D062105:Molecular Docking Simulation; D051198:Toll-Like Receptor 5 / Q000378:metabolism*; D014552:Urinary Tract Infections / Q000276:immunology* / Q000517:prevention & control; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
chemical_list: D018830:Adhesins, Escherichia coli; D029968:Escherichia coli Proteins; D022361:Escherichia coli Vaccines; C516095:FliC protein, E coli; D051198:Toll-Like Receptor 5; D014614:Vaccines, Synthetic; C058769:fimH protein, E coli; D005408:Flagellin; D036781:Fimbriae Proteins
keywords: FimH; FliC; Fusion vaccine; In silico study; Truncated forms