Oral Immunization with a Multivalent Epitope-Based Vaccine, Based on NAP, Urease, HSP60, and HpaA, Provides Therapeutic Effect on H. pylori Infection in Mongolian gerbils.
Oral Immunization with a Multivalent Epitope-Based Vaccine, Based on NAP, Urease, HSP60, and HpaA, Provides Therapeutic Effect on H. pylori Infection in Mongolian gerbils.
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DOI：
10.3389/fcimb.2017.00349
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发表时间：
2017
影响因子：
5.7
通讯作者：
Liu K
中科院分区：
文献类型：
--
作者：
Guo L;Yang H;Tang F;Yin R;Liu H;Gong X;Wei J;Zhang Y;Xu G;Liu K
基于表位的疫苗是一种很有前景的幽门螺杆菌治疗性疫苗接种策略。含有多种幽门螺杆菌抗原的多价亚单位疫苗优于单价亚单位疫苗。然而，在幽门螺杆菌的治疗性疫苗接种中，基于多价表位的疫苗是否优于基于单价表位的疫苗仍不清楚。本研究基于粘膜佐剂霍乱毒素B亚单位(CTB)、Th1型佐剂NAP、选定的B和Th细胞表位的多拷贝(UreA27-53、UreA183-203、HpaA132-141和HSP60189-203)，以及通过生物信息学预测的UreB158-251和UreB321-385，构建了一种针对Hp尿素酶、中性粒细胞激活蛋白(NAP)、热休克蛋白60(HSP60)和幽门螺杆菌粘附素A(HpaA)的多价表位疫苗。用BALB/c小鼠模型对CWAE疫苗的免疫学特性进行了研究。在幽门螺杆菌感染的蒙古沙土鼠模型中，通过与我们先前构建的幽门螺杆菌尿素酶单价表位疫苗CTB-UE的比较，评价其治疗效果。CWAE和CTB-UE均能诱导出相似水平的抗幽门螺杆菌尿素酶抗体，并具有相似的抑制幽门螺杆菌尿素酶活性的作用。然而，只有CWAE能诱导高水平的针对NAP、HSP60、HpaA以及合成肽表位(UreB158-172、UreB181-195、UreB211-225、UreB349-363、HpaA132-141和HSP60189-203)的抗体。此外，与CTB-UE或Hp尿素酶口服免疫相比，CWAE口服治疗性免疫显著减少了沙土鼠胃中幽门螺杆菌的菌落数量。CWAE的保护作用与较高水平的混合CD4+T细胞(Th细胞)反应、免疫球蛋白G和分泌性免疫球蛋白A(SIgA)抗幽门螺杆菌有关。这些结果表明，基于多价表位的疫苗可能是一种很有前途的疫苗，该疫苗包括不同Hp抗原的Th和B细胞表位。
Epitope-based vaccine is a promising strategy for therapeutic vaccination against Helicobacter pylori (H. pylori) infection. A multivalent subunit vaccine containing various antigens from H. pylori is superior to a univalent subunit vaccine. However, whether a multivalent epitope-based vaccine is superior to a univalent epitope-based vaccine in therapeutic vaccination against H. pylori, remains unclear. In this study, a multivalent epitope-based vaccine named CWAE against H. pylori urease, neutrophil-activating protein (NAP), heat shock protein 60 (HSP60) and H. pylori adhesin A (HpaA) was constructed based on mucosal adjuvant cholera toxin B subunit (CTB), Th1-type adjuvant NAP, multiple copies of selected B and Th cell epitopes (UreA27–53, UreA183–203, HpaA132–141, and HSP60189–203), and also the epitope-rich regions of urease B subunit (UreB158–251 and UreB321–385) predicted by bioinformatics. Immunological properties of CWAE vaccine were characterized in BALB/c mice model. Its therapeutic effect was evaluated in H. pylori-infected Mongolian gerbil model by comparing with a univalent epitope-based vaccine CTB-UE against H. pylori urease that was constructed in our previous studies. Both CWAE and CTB-UE could induce similar levels of specific antibodies against H. pylori urease, and had similar inhibition effect of H. pylori urease activity. However, only CWAE could induce high levels of specific antibodies to NAP, HSP60, HpaA, and also the synthetic peptides epitopes (UreB158–172, UreB181–195, UreB211–225, UreB349–363, HpaA132–141, and HSP60189–203). In addition, oral therapeutic immunization with CWAE significantly reduced the number of H. pylori colonies in the stomach of Mongolian gerbils, compared with oral immunization using CTB-UE or H. pylori urease. The protection of CWAE was associated with higher levels of mixed CD4+ T cell (Th cell) response, IgG, and secretory IgA (sIgA) antibodies to H. pylori. These results indic ate that a multivalent epitope-based vaccine including Th and B cell epitopes from various H. pylori antigens could be a promising candidate against H. pylori infection.