title: Novel fusion protein protects against adherence and toxicity of enterohemorrhagic Escherichia coli O157:H7 in mice.
abstract: Infection with Escherichia coli (E. coli) O157:H7 may develop into bloody diarrhea, or hemorrhagic uremic syndrome (HUS), which usually causes kidney failure or even death. Considered as the pathogenesis mechanism of E. coli O157:H7 infection, attachment or adhesion that is directly mediated by intimin is the first step of E. coli O157:H7 interaction with its host, and all these serious sequelae are mainly due to Shiga toxins (Stxs) released by E. coli O157:H7. In this study, a novel SSI fusion protein that contains the critical toxin-antigens Stx2B and Stx1B, and the critical adhesion-antigen fragment Int281 was constructed. The protein induced complete immune protection, with both anti-toxin and anti-adhesion effects. The dominant increase in IgG1 and the high level of Th2-typical cytokine (IL-4 and IL-10) expression showed that SSI significantly induced Th2-mediated humoral immune response. In the mouse model, the SSI fusion protein not only elicited neutralizing antibodies against both Stx1 and Stx2 toxins, but also induced a high level of anti-adhesion antibodies. The SSI-immunized mice did not show any pathologic changes. SSI provides evident protection with two-time immunization against a highly lethal dose of E. coli O157:H7.
authors: State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, No. 20 Dongdajie, Fengtai District, Beijing 100071, PR China.
authors: Xiang
authors: X
authors: Gao
authors: Kun
authors: K
authors: Cai
authors: Tao
authors: T
authors: Li
authors: Qin
authors: Q
authors: Wang
authors: Xiaojun
authors: X
authors: Hou
authors: Renmao
authors: R
authors: Tian
authors: Hao
authors: H
authors: Liu
authors: Wei
authors: W
authors: Tu
authors: Le
authors: L
authors: Xiao
authors: Lihua
authors: L
authors: Fang
authors: Sen
authors: S
authors: Luo
authors: Yuenan
authors: Y
authors: Liu
authors: Hui
authors: H
authors: Wang
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D057134:Antibodies, Neutralizing / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D054324:Enterohemorrhagic Escherichia coli / Q000235:genetics / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology / Q000517:prevention & control*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000276:immunology*; D022361:Escherichia coli Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D012376:Rodent Diseases / Q000276:immunology / Q000517:prevention & control; D022603:Shiga Toxins / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D016207:Cytokines; D029968:Escherichia coli Proteins; D022361:Escherichia coli Vaccines; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D022603:Shiga Toxins; D014614:Vaccines, Synthetic; C073819:eaeA protein, E coli