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
2014
Lv, Xiaobo | Yang, Jue | Song, Hui | Li, Tong | Le, Guo | Xing, Yingying | Xi, Tao
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.
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