Therapeutic Protection Against H. pylori Infection in Mongolian Gerbils by Oral Immunization With a Tetravalent Epitope-Based Vaccine With Polysaccharide Adjuvant
Therapeutic Protection Against H. pylori Infection in Mongolian Gerbils by Oral Immunization With a Tetravalent Epitope-Based Vaccine With Polysaccharide Adjuvant
复制标题
通过口服免疫多糖佐剂四价表位疫苗对蒙古沙鼠幽门螺杆菌感染的治疗性保护
DOI：
10.3389/fimmu.2019.01185
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发表时间：
2019-05-28
影响因子：
7.3
通讯作者：
Liu, Kunmei
中科院分区：
文献类型：
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作者：
Guo, Le;Hong, Dantong;Liu, Kunmei
尿素酶是设计幽门螺杆菌治疗性表位疫苗的有效靶点。pylori）。本课题组在前期研究中，成功构建了含有H. pylori尿素酶的构建，CTB-UE疫苗对H.小鼠幽门螺杆菌感染。然而，结合了参与H.幽门螺杆菌定植和发病机制，可能更有效的治疗疫苗比单价疫苗靶向尿素酶。因此，本研究构建了含有Th 1型免疫佐剂NAP、CagA和VacA功能片段以及CTB-UE中的尿素酶多表位肽（UE）的多价表位疫苗FVpE，以期获得比单价表位疫苗CTB-UE更好的杀菌免疫效果。以H.幽门螺杆菌感染蒙古沙鼠模型。结果表明，FvpE和CTB-UE疫苗均能诱导产生相似水平的特异性抗体。pylori尿素酶活性，对H. pylori尿素酶活性然而，只有FVpE可以诱导高水平的CagA，VacA和NAP的特异性抗体。此外，口服治疗性免疫与FVpE加PA显着减少H。与CTB-UE + PA或FVpE口服免疫相比，FVpE疫苗对蒙古沙土鼠胃内pylori菌落的抑制作用更强，而含PA的FVpE疫苗甚至表现出杀菌免疫。FVpE的保护作用与混合的CD 4 + T细胞反应和抗各种H. pylori抗原。这些结果表明，多价表位疫苗靶向各种H。pylori抗原可能是抗H.幽门感染
Urease is an effective target for design of a therapeutic epitope vaccine against Helicobacter pylori (H. pylori). In our previous studies, an epitope vaccine CTB-UE containing Th and B epitopes from H. pylori urease was constructed, and the CTB-UE vaccine could provide therapeutic effect on H. pylori infection in mice. However, a multivalent vaccine, combining different antigens participating in different aspects of H. pylori colonization and pathogenesis, may be more effective as a therapeutic vaccine than a univalent vaccine targetting urease. Therefore, a multivalent epitope vaccine FVpE, containing Th1-type immune adjuvant NAP, three selected functional fragments from CagA and VacA, and an urease multi-epitope peptide (UE) from CTB-UE, was constructed in this study and expected to obtain better sterilizing immunity than the univalent epitope vaccine CTB-UE. The therapeutic effect of multivalent epitope vaccine FVpE with polysaccharide adjuvant (PA) was evaluated in H. pylori-infected Mongolian gerbil model. The results showed that both FvpE and CTB-UE vaccine could induce similar levels of specific antibodies against H. pylori urease, and had similar inhibition effect on H. pylori urease activity. However, only FVpE could induce high levels of specific antibodies to CagA, VacA, and NAP. In addition, oral therapeutic immunization with FVpE plus PA significantly reduced the number of H. pylori colonies in the stomach of Mongolian gerbils compared with oral immunization with CTB-UE plus PA, or FVpE only, and the FVpE vaccine with PA even exhibited sterilizing immunity. The protection of FVpE was related to the mixed CD4+ T cell responses and epitope-specific antibodies against various H. pylori antigens. These results indicate that a multivalent epitope vaccine targetting various H. pylori antigens could be a promising candidate against H. pylori infection.