Cai Kun, Tu Wei, Liu Yuenan, Li Tao, Wang Hui
State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, No. 20 Dongdajie, Fengtai District, Beijing 100071, PR China.
Department of Microbiology, Anhui Medical University, Hefei, 230032, PR China.
Sci Rep. 2015 Dec 2;5:17479. doi: 10.1038/srep17479.
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.
感染大肠杆菌O157:H7可能会发展为出血性结肠炎或溶血性尿毒综合征（HUS），后者通常会导致肾衰竭甚至死亡。黏附素和毒素是重要的致病因素。在本研究中，基于细菌幽灵（BG）构建了一种新型候选疫苗rSOBGs。rSOBGs保持了细胞形态的完整性，并在外膜表面展示了线性Stx2Am-Stx1B抗原。在本研究中，rSOBGs能有效诱导血清中针对志贺毒素的特异性IgA/IgG抗体以及更强的针对紧密黏附素的特异性IgA/IgG抗体。在体内，当用高剂量（500 LD50）的活大肠杆菌O157:H7进行胃内攻击时，rSOBGs提供的保护率（52%）高于天然细菌幽灵-OBGs（12%）。同时，当用2 LD50甚至5 LD50的裂解大肠杆菌O157:H7进行攻击时，rSOBGs提供的保护率（73.33%）高于OBGs。在体外，经rSOBGs免疫的血清对裂解的病原菌具有中和活性。此外，组织病理学结果还显示，给予rSOBGs有能力减少或抑制器官的黏附损伤和毒素损害。新型候选疫苗rSOBGs诱导了抗毒素和抗黏附的免疫保护，提示其具有预防由大肠杆菌O157:H7引起的传染病的可能性。
