Immunological features and efficacy of a multi-epitope vaccine CTB-UE against H. pylori in BALB/c mice model
Immunological features and efficacy of a multi-epitope vaccine CTB-UE against H. pylori in BALB/c mice model
复制标题
DOI：
10.1007/s00253-013-5408-6
复制
发表时间：
2014-04-01
影响因子：
5
通讯作者：
Xing, Yingying
中科院分区：
文献类型：
--
作者：
Guo, Le;Yin, Runting;Xing, Yingying
表位疫苗是预防和治疗幽门螺杆菌感染的一种很有前途的选择。脲酶是幽门螺杆菌必不可少的毒力因子和定殖因子。在这项研究中，我们构建了一种名为CTB- ue的多表位疫苗，该疫苗含有粘膜佐剂霍乱毒素B亚基（CTB）和幽门螺杆菌脲酶a和B亚基Th和B细胞表位的串联拷贝。在纯化后的BALB/c小鼠模型上评价CTB-UE疫苗的免疫原性、特异性、诱导幽门螺杆菌脲酶中和抗体的能力以及预防和治疗效果。实验结果表明，CTB-UE可诱导较高水平的特异性抗体，针对天然幽门螺杆菌脲酶、尿素、UreB或选定的与脲酶活性位点相关的B细胞表位尿素（183-203）和UreB(327-334)，对脲酶活性有有效抑制作用。此外，与口服rUreB或PBS免疫相比，口服CTB-UE预防或治疗性免疫可显著降低幽门螺杆菌定植，其保护作用与抗原特异性CD4(+) T细胞和IgG、IgA和粘膜sIgA抗体应答相关。该CTB-UE疫苗可能是控制幽门螺杆菌感染的一种有前景的候选疫苗。
Epitope vaccine is a promising option for prophylactic and therapeutic vaccination against Helicobacter pylori infection. Urease is an essential virulence factor and colonization factor for H. pylori. In this study, we constructed a multi-epitope vaccine named CTB-UE with mucosal adjuvant cholera toxin B subunit (CTB) and tandem copies of Th and B cell epitopes from H. pylori urease A and B subunits. The immunogenicity, specificity, ability to induce neutralizing antibodies against H. pylori urease, and prophylactic and therapeutic efficacy of the CTB-UE vaccine were evaluated in BALB/c mice model after purification. The experimental results indicated that CTB-UE could induce comparatively high levels of specific antibodies against native H. pylori urease, UreA, UreB, or the selected B cell epitopes UreA(183-203) and UreB(327-334) involved with the active site of urease and showed an effectively inhibitory effect on the enzymatic activity of urease. Besides, oral prophylactic or therapeutic immunization with CTB-UE significantly decreased H. pylori colonization compared with oral immunization with rUreB or PBS, and the protection was correlated with antigen-specific CD4(+) T cells and IgG, IgA, and mucosal sIgA antibody responses. This CTB-UE vaccine may be a promising vaccine candidate for the control of H. pylori infection.