Antibody Production and Th1-biased Response Induced by an Epitope Vaccine Composed of Cholera Toxin B Unit and Helicobacter pylori Lpp20 Epitopes

Antibody Production and Th1-biased Response Induced by an Epitope Vaccine Composed of Cholera Toxin B Unit and Helicobacter pylori Lpp20 Epitopes
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由霍乱毒素 B 单元和幽门螺杆菌 Lpp20 表位组成的表位疫苗诱导的抗体产生和 Th1 偏向反应

DOI:
10.1111/hel.12268
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发表时间:
2016-06-01
期刊:
影响因子:
4.4
通讯作者:
Ning, Yunshan
Ning, Yunshan
中科院分区:
医学2区
文献类型:
--
作者:
Li, Yan;Chen, Zhongbiao;Ning, Yunshan

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背景:表位疫苗在预防和治疗幽门螺杆菌感染方面具有很大的潜力。Lpp20是幽门螺杆菌入侵宿主后触发免疫应答的主要保护性抗原之一,被认为是控制幽门螺杆菌感染的优良候选疫苗。在我们之前的研究中,我们鉴定了Lpp20的一个b细胞表位和两个CD4(+) t细胞表位。目的:构建由黏膜佐剂霍乱毒素B亚基(CTB)和这3个已鉴定的Lpp20表位组成的表位疫苗,研究该表位疫苗对小鼠的免疫效果。方法:构建包含CTB、1个b细胞和2个CD4+ t细胞表位的Lpp20表位疫苗,命名为CTB-Lpp20,在大肠杆菌中表达,用于BALB/c小鼠腹腔免疫。免疫原性、特异性和诱导抗Lpp20抗体和细胞因子分泌的能力进行了评估。然后对CTB-Lpp20进行灌胃免疫,观察其对感染小鼠的预防和治疗效果。结果:CTB-Lpp20表位疫苗具有良好的免疫原性和免疫反应性,可诱导特异性高水平的抗Lpp20和细胞因子ifn - γ、IL-17的抗体。此外,CTB-Lpp20显著降低幽门螺杆菌侵袭小鼠的幽门螺杆菌定植,其保护作用与IgG、IgA、sIgA抗体和th1型细胞因子相关。结论:本研究将更好地了解表位疫苗的保护性免疫,CTB-Lpp20可能是对抗幽门螺杆菌侵袭的一种替代策略。
Background : The epitope vaccine is an attractive potential for prophylactic and therapeutic vaccination against Helicobacter pylori (H. pylori) infection. Lpp20 is one of major protective antigens which trigger immune response after H. pylori invades host and has been considered as an excellent vaccine candidate for the control of H. pylori infection. In our previous study, one B-cell epitope and two CD4(+) T-cell epitopes of Lpp20 were identified.Objective: In this study, an epitope vaccine composed of mucosal adjuvant cholera toxin B subunit (CTB) and these three identified Lpp20 epitopes were constructed to investigate the efficacy of this epitope vaccine in mice.Methods: The epitope vaccine including CTB, one B-cell, and two CD4+ T-cell epitopes of Lpp20 was constructed and named CTB-Lpp20, which was then expressed in Escherichia coli and used for intraperitoneal immunization in BALB/c mice. The immunogenicity, specificity, and ability to induce antibodies against Lpp20 and cytokine secretion were evaluated. After that, CTB-Lpp20 was intragastrically immunized to investigate the prophylactic and therapeutic efficacy in infected mice.Results: The results indicated that the epitope vaccine CTB-Lpp20 possessed good immunogenicity and immunoreactivity and could elicit specific high level of antibodies against Lpp20 and the cytokine of IFN-gamma and IL-17. Additionally, CTB-Lpp20 significantly decreased H. pylori colonization in H. pylori challenging mice, and the protection was correlated with IgG, IgA, and sIgA antibody and Th1-type cytokines.Conclusion: This study will be better for understanding the protective immunity of epitope vaccine, and CTB-Lpp20 may be an alternative strategy for combating H. pylori invasion.