title: Therapeutic efficacy of the multi-epitope vaccine CTB-UE against Helicobacter pylori infection in a Mongolian gerbil model and its microRNA-155-associated immuno-protective mechanism.
abstract: Vaccination is an effective means of preventing infectious diseases, including those caused by Helicobacter pylori. In this study, we constructed a novel multi-epitope vaccine, CTB-UE, composed of the cholera toxin B subunit and tandem copies of the B and Th cell epitopes from the H. pylori urease A and B subunits. We evaluated the therapeutic efficacy of the multi-epitope vaccine CTB-UE against H. pylori infection in a Mongolian gerbil model and studied its immuno-protective mechanisms. The experimental results indicated that urease activity, H. pylori colonisation density, the levels of IL-8 and TNF-α in the serum, and the levels of COX-2 and NAP in gastric tissue were significantly lower and the IgG level in the serum and the IFN-γ level in spleen lymphocytes were significantly higher in the vaccinated group compared with the model control group; additionally, gastric mucosal inflammation was notably alleviated following vaccination. The results showed that CTB-UE had a good therapeutic effect on H. pylori infection. The immuno-protective mechanism was closely related to the immune response mediated by microRNA-155, the expression of which was strongly up-regulated after CTB-UE administration. The expression levels of the microRNA-155 target proteins IFN-γRα, AID, and PU.1 were significantly down-regulated; these results indicated that CTB-UE induced an immune response biased towards Th1 cells by up-regulating microRNA-155 to inhibit IFN-γRα expression and induced a humoral immune response towards B cells by up-regulating microRNA-155 to inhibit PU.1 and AID expression. These results demonstrate that the multi-epitope vaccine CTB-UE may be a promising therapeutic vaccine against H. pylori infection and is a new therapeutic tool for human use.
authors.affiliation: Biotechnology Center, School of Life Science and Technology, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China. Electronic address: lvxiaobo_007@163.com.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Lv
authors.affiliation: Biotechnology Center, School of Life Science and Technology, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China. Electronic address: yaodadewo@163.com.
authors.forename: Jue
authors.initials: J
authors.lastname: Yang
authors.affiliation: Biotechnology Center, School of Life Science and Technology, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China. Electronic address: songhui620@126.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Song
authors.affiliation: Biotechnology Center, School of Life Science and Technology, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China. Electronic address: litong198824@163.com.
authors.forename: Tong
authors.initials: T
authors.lastname: Li
authors.affiliation: School of Laboratory Medicine, Ningxia Medical University, Yinchuan 750004, China. Electronic address: GUOLETIAN1982@163.com.
authors.forename: Le
authors.initials: L
authors.lastname: Guo
authors.affiliation: Biotechnology Center, School of Life Science and Technology, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Xing
authors.affiliation: Biotechnology Center, School of Life Science and Technology, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China. Electronic address: xitao18@hotmail.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Xi
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines / Q000276:immunology*; D003564:Cytidine Deaminase / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000517:prevention & control*; D016480:Helicobacter pylori; D056724:Immunity, Humoral; D008297:Male; D035683:MicroRNAs / Q000276:immunology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D013270:Stomach / Q000201:enzymology / Q000382:microbiology; D018417:Th1 Cells / Q000276:immunology; D015534:Trans-Activators / Q000378:metabolism; D014510:Urease / Q000378:metabolism; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D003564:Cytidine Deaminase; D016207:Cytokines; D000939:Epitopes; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014510:Urease; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D000099232:Proto-Oncogene Protein Spi-1
keywords: Epitope vaccine; Helicobacter pylori; Infection; microRNA-155