title: Protection of mice against enterotoxigenic E. coli by immunization with a polyvalent enterotoxin comprising a combination of LTB, STa, and STb.
abstract: Currently available enterotoxigenic Escherichia coli (ETEC) vaccines are based on colonization factors and/or the heat-labile enterotoxin B subunit (LTB). However, the induction of antitoxic responses against heat-stable enterotoxin a (STa) and b (STb) has merit as these two poorly immunogenic toxins are frequently associated with ETEC strains. In this study, we genetically constructed a trivalent enterotoxin fusion protein (STa-LTB-STb, abbreviated to SLS) in an effort to develop a single toxoid containing these three enterotoxins for vaccination against ETEC. Mutagenesis at one disulfide-bridge-forming cysteine in STa led to a dramatic reduction in the STa toxicity of SLS; however, the fusion peptide retained the STb-associated toxicity. Immunization of mice with SLS protein elicited significant antibody responses to LTB, STa, and STb. Significantly, the mice antisera were able to neutralize the biological activity of both STa and STb. In the experiment to assess the protective effect of SLS immunization, the mortality of mice receiving SLS was significantly lower than their control cohorts (P < 0.01) after intraperitoneal challenge with ETEC. These results show that the trivalent fusion enterotoxin SLS has the potential to serve as a useful toxin-based vaccine against ETEC-induced diarrheal disease via a single immunogen.
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian, Liaoning, China.
authors.forename: Jiansong
authors.initials: J
authors.lastname: You
authors.forename: Yongping
authors.initials: Y
authors.lastname: Xu
authors.forename: Maolong
authors.initials: M
authors.lastname: He
authors.forename: Tim A
authors.initials: TA
authors.lastname: McAllister
authors.forename: Philip A
authors.initials: PA
authors.lastname: Thacker
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Li
authors.forename: Tingting
authors.initials: T
authors.lastname: Wang
authors.forename: Liji
authors.initials: L
authors.lastname: Jin
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000992:Antitoxins / Q000097:blood; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D054307:Enterotoxigenic Escherichia coli / Q000276:immunology* / Q000472:pathogenicity; D004768:Enterotoxins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D029968:Escherichia coli Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D022361:Escherichia coli Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D007114:Immunization / Q000379:methods*; D051379:Mice; D009500:Neutralization Tests; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D016019:Survival Analysis; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000992:Antitoxins; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D022361:Escherichia coli Vaccines; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; C034151:heat stable toxin (E coli); C027538:heat-labile enterotoxin, E coli