Novel fusion antigen displayed-bacterial ghosts vaccine candidate against infection of Escherichia coli O157:H7.

Novel fusion antigen displayed-bacterial ghosts vaccine candidate against infection of Escherichia coli O157:H7.
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新型融合抗原展示-抗大肠杆菌 O157:H7 感染的菌影候选疫苗。

DOI:
10.1038/srep17479
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发表时间:
2015-12-02
期刊:
影响因子:
4.6
通讯作者:
Wang H
Wang H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cai K;Tu W;Liu Y;Li T;Wang H

文献摘要

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感染大肠杆菌 O157:H7 可能发展为出血性结肠炎或溶血性尿毒症综合征 (HUS),通常会导致肾衰竭甚至死亡。粘附和毒素是重要的毒力因素。在这项研究中,基于细菌幽灵(BG)构建了一种新型候选疫苗rSOBG。 rSOBGs保持了细胞形态的完整性,并在外膜表面展示线性Stx2Am-Stx1B抗原。在本研究中,rSOBG 在血清中有效诱导 Stxs 特异性 IgA/IgG 抗体和更强的 intimin 特异性 IgA/IgG 抗体。在体内,当用高剂量 (500 LD50) 活大肠杆菌 O157:H7 进行胃内攻击时,rSOBG 提供比天然细菌幽灵 OBG (12%) 更高的保护率 (52%)。同时,当用 2 LD50 甚至 5 LD50 裂解的大肠杆菌 O157:H7 进行攻击时,rSOBG 提供了比 OBG 更高的保护率 (73.33%)。在体外,rSOBGs 免疫血清对裂解的病原菌具有中和活性。此外,组织病理学结果还表明,给予rSOBGs具有减轻或抑制器官​​粘连病变和毒素损伤的能力。新型候选疫苗 rSOBG 能够诱导抗毒素和抗粘附免疫保护,这表明有可能预防由大肠杆菌 O157:H7 引起的传染病。
Infection with Escherichia coli O157:H7 may develop into hemorrhagic colitis, or hemolytic uremic syndrome (HUS), which usually causes kidney failure or even death. The adhesion and toxins are the important virulent factors. In this study, a novel vaccine candidate rSOBGs was constructed based on the bacterial ghost (BG). rSOBGs maintained the integrity of cellular morphology and displayed the linear Stx2Am-Stx1B antigen on the surface of outer membrane. rSOBGs induced Stxs-specific IgA/IgG antibodies and stronger intimin-specific IgA/IgG antibodies effectively in sera in this study. In vivo, the rSOBGs provided the higher protection rate (52%) than native bacterial ghost-OBGs (12%) when challenged intragastricly with high dose (500 LD50) viable E. coli O157:H7. Meanwhile, the rSOBGs provided higher protection rate (73.33%) than OBGs when challenged with 2 LD50 even to 5 LD50 lysed E. coli O157:H7. In vitro, the rSOBGs-immunized sera possessed neutralizing activity to lysed pathogenic bacteria. Furthermore, the results of histopathology also displayed that the administration of rSOBGs have the ability to reduce or inhibit the adhesion lesions and toxins damages of organs. The novel vaccine candidate rSOBGs induced both anti-toxin and anti-adhesion immune protection, suggesting the possibility to prevent the infectious diseases caused by Escherichia coli O157:H7.