title: Production and characterization of protective human antibodies against Shiga toxin 1.
abstract: Hemolytic-uremic syndrome (HUS) is a serious complication which is predominantly associated in children with infection by Shiga toxin-producing Escherichia coli (STEC). By using HuMAb-Mouse (Medarex) animals, human monoclonal antibodies (Hu-MAbs) were developed against Shiga toxin 1 (Stx1) for passive immunotherapy of HUS. Ten stable hybridomas comprised of fully human heavy- and light-chain immunoglobulin elements and secreting Stx1-specific Hu-MAbs (seven immunoglobulin M(kappa)() [IgM(kappa)] elements [one specific for the A subunit and six specific for the B subunit] and three IgG1(kappa) elements specific for subunit B) were isolated. Two IgM(kappa) Hu-MAbs (2D9 and 15G9) and three IgG1(kappa) Hu-MAbs (5A4, 10F4, and 15G2), all specific for subunit B, demonstrated marked neutralization of Stx1 in vitro and significant prolongation of survival in a murine model of Stx1 toxicosis.
authors.affiliation: Division of Infectious Diseases, Tufts University School of Veterinary Medicine, North Grafton, Massachusetts, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Mukherjee
authors.forename: Kerry
authors.initials: K
authors.lastname: Chios
authors.forename: Dianne
authors.initials: D
authors.lastname: Fishwild
authors.forename: Deborah
authors.initials: D
authors.lastname: Hudson
authors.forename: Susan
authors.initials: S
authors.lastname: O'Donnell
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Rich
authors.forename: Arthur
authors.initials: A
authors.lastname: Donohue-Rolfe
authors.forename: Saul
authors.initials: S
authors.lastname: Tzipori
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000627:therapeutic use; D002648:Child; D004926:Escherichia coli / Q000276:immunology* / Q000472:pathogenicity; D005260:Female; D006367:HeLa Cells; D006463:Hemolytic-Uremic Syndrome / Q000209:etiology / Q000276:immunology / Q000628:therapy*; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000627:therapeutic use; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000627:therapeutic use; D066298:In Vitro Techniques; D051379:Mice; D009500:Neutralization Tests; D022622:Shiga Toxin 1 / Q000276:immunology* / Q000633:toxicity
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D022622:Shiga Toxin 1