Xing Yingying, Liu Wei, Li Xiaokang, Guo Le, Lv Xiaobo, Xi Tao
Biotechnology Center, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
School of Laboratory Medicine, Ningxia Medical University, Yinchuan, China.
Biochem Biophys Res Commun. 2015 Jul 3;462(3):269-74. doi: 10.1016/j.bbrc.2015.04.130. Epub 2015 May 6.
Urease is considered as an excellent vaccine candidate antigen against Helicobacter pylori (H. pylori) infection. Our previous study reported a novel multi-epitope vaccine CTB-UE which was composed of the mucosal adjuvant cholera toxin B subunit (CTB) and five cell epitopes from urease subunits. Murine experiments indicated that it could induce cellular and humoral immune responses intensively and attenuate H. pylori infection effectively in mice model. However, the body expression and lack of suitable adjuvant of this epitope vaccine restricted its application. In this study, new recombinant Escherichia coli strains was established to increase the solubility by fusing thioredoxin (Trx) and the combination adjuvants which composed of the chitosan and CpG were adopted to enhance the immunogenicity of CTB-UE for oral immunization. The experimental results indicated that the levels of IgG2a, IgG1 and IgA in the serum and the levels of sIgA in stomach, intestine and feces were significantly higher in the vaccinated group compared with the model control group. Additionally, chitosan-CpG combination adjuvants changed the ratio of IgG2a/IgG1 and conferred Th1/Th17-mediated protective immune responses. These results demonstrate that the oral vaccine with chitosan-CpG as combination adjuvants may be a promising vaccine candidate against H. pylori infection.
脲酶被认为是一种针对幽门螺杆菌（H. pylori）感染的优秀疫苗候选抗原。我们之前的研究报道了一种新型多表位疫苗CTB-UE，它由黏膜佐剂霍乱毒素B亚基（CTB）和来自脲酶亚基的五个细胞表位组成。小鼠实验表明，它能在小鼠模型中强烈诱导细胞免疫和体液免疫反应，并有效减轻幽门螺杆菌感染。然而，这种表位疫苗在体内的表达以及缺乏合适的佐剂限制了其应用。在本研究中，通过融合硫氧还蛋白（Trx）建立了新的重组大肠杆菌菌株以提高溶解性，并采用由壳聚糖和CpG组成的联合佐剂来增强CTB-UE口服免疫的免疫原性。实验结果表明，与模型对照组相比，接种组血清中的IgG2a、IgG1和IgA水平以及胃、肠道和粪便中的分泌型IgA水平显著更高。此外，壳聚糖-CpG联合佐剂改变了IgG2a/IgG1的比例，并赋予Th1/Th17介导的保护性免疫反应。这些结果表明，以壳聚糖-CpG作为联合佐剂的口服疫苗可能是一种有前景的抗幽门螺杆菌感染疫苗候选物。
