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.
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.
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DOI：
10.1016/j.vaccine.2014.07.041
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发表时间：
2014-09
期刊：
影响因子：
5.5
通讯作者：
Xiaobo Lv;Jue Yang;Hui Song;Tong Li;Le Guo;Yingying Xing;Tao Xi
中科院分区：
文献类型：
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作者：
Xiaobo Lv;Jue Yang;Hui Song;Tong Li;Le Guo;Yingying Xing;Tao Xi
接种疫苗是预防传染病的有效方法，包括幽门螺杆菌引起的传染病。本研究利用霍乱毒素B亚单位和霍乱弧菌B、Th细胞表位的串联拷贝构建了一种新型多表位疫苗CTB-UE。幽门螺杆菌尿素酶A和B亚基。我们评价了多表位疫苗CTB-UE对H的治疗效果。幽门螺杆菌感染蒙古沙土鼠模型，并研究其免疫保护机制。试验结果表明，脲酶活性、H.与模型对照组相比，免疫组大鼠胃粘膜炎症反应明显减轻，胃粘膜炎性反应明显减轻，胃粘膜炎性反应明显减轻，血清IgG水平和脾淋巴细胞IFN-γ水平显著升高，血清IL-8和TNF-α水平显著降低，胃组织考克斯-2和NAP水平显著降低。结果表明CTB-UE对H.幽门感染免疫保护机制与microRNA-155介导的免疫应答密切相关，CTB-UE给药后microRNA-155的表达强烈上调。microRNA-155靶蛋白IFN-γRα、AID和PU.1的表达水平显著下调;这些结果表明CTB-UE通过上调microRNA-155以抑制IFN-γRα表达诱导偏向Th 1细胞的免疫应答，并通过上调microRNA-155以抑制PU.1和AID表达诱导针对B细胞的体液免疫应答。这些结果表明，CTB-UE多表位疫苗可能是一种有前途的治疗性疫苗。幽门螺杆菌感染，并且是用于人类的新的治疗工具。
Vaccination is an effective means of preventing infectious diseases, including those caused byHelicobacter 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 theH. pyloriurease A and B subunits. We evaluated the therapeutic efficacy of the multi-epitope vaccine CTB-UE againstH. pyloriinfection in a Mongolian gerbil model and studied its immuno-protective mechanisms. The experimental results indicated that urease activity,H. pyloricolonisation 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 onH. pyloriinfection. 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 againstH. pyloriinfection and is a new therapeutic tool for human use.