title: Evaluation of recombinant forms of the shiga toxin variant Stx2eB subunit and non-toxic mutant Stx2e as vaccine candidates against porcine edema disease.
abstract: Porcine edema disease (ED) is a communicable disease of shoats caused by infection with Shiga toxin (Stx)-producing Escherichia coli. Stx2e is classified as a 1A5B-type toxin and is a decisive virulence determinant of ED. The single A subunit of Stx2e possesses enzymatic activity and is accompanied by a pentamer of B subunits, which binds to the host receptor and delivers the A subunit into the cell. In the present study, we used a mouse model to evaluate the immunogenicity of 3 ED vaccine candidates: a non-toxic mutant holotoxin mStx2e and 2 Stx2eB-based fusion proteins, Stx2eA2B-His and Stx2eB-His. Systemic inoculation of mice with mStx2e- and the Stx2eB-derived antigens induced anti-Stx2e IgG responses that were fully and partially capable of neutralizing Stx2e cellular cytotoxicity, respectively. Intranasal immunization with mStx2e protected the mice from subsequent intraperitoneal challenge with a lethal dose of Stx2e, whereas immunization with Stx2eA2B-His and Stx2eB-His afforded partial protection. Analysis of serum cytokines revealed that mStx2e, but not the Stx2eB-based antigens, was capable of inducing a Th2-type immune response. These results suggest that although the Stx2eB-based antigens elicited an immune response to Stx2e, they did so through a different mechanism to the Th2-type response induced by mStx2e.
authors.affiliation: Advanced Technology Research Laboratories, Idemitsu Kosan Co. Ltd., 1280 Kamiizumi, Sodegaura, Chiba 299-0293, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Sato
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsui
authors.forename: Eiji
authors.initials: E
authors.lastname: Takita
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kadoyama
authors.forename: Sou-Ichi
authors.initials: S
authors.lastname: Makino
authors.forename: Ko
authors.initials: K
authors.lastname: Kato
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Sawada
authors.forename: Takashi
authors.initials: T
authors.lastname: Hamabata
mesh_terms: D000281:Administration, Intranasal / Q000662:veterinary; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines / Q000235:genetics / Q000276:immunology; D004487:Edema / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control / Q000662:veterinary*; D004927:Escherichia coli Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control / Q000662:veterinary*; D005260:Female; D007114:Immunization / Q000379:methods / Q000662:veterinary; D007274:Injections, Intraperitoneal / Q000662:veterinary; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology*; D022641:Shiga Toxin 2 / Q000235:genetics / Q000276:immunology*; D054323:Shiga-Toxigenic Escherichia coli / Q000235:genetics / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D013552:Swine; D013553:Swine Diseases / Q000276:immunology / Q000382:microbiology* / Q000517:prevention & control
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D011994:Recombinant Proteins; D022641:Shiga Toxin 2; C450841:shiga toxin 2 B subunit