Production and characterization of protective human antibodies against Shiga toxin 1

Infect Immun. 2002 Oct;70(10):5896-9. doi: 10.1128/iai.70.10.5896-5899.2002.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Bacterial / biosynthesis*
  • Antibodies, Bacterial / therapeutic use
  • Antibodies, Monoclonal / biosynthesis
  • Antibodies, Monoclonal / therapeutic use
  • Child
  • Escherichia coli / immunology*
  • Escherichia coli / pathogenicity
  • Female
  • HeLa Cells
  • Hemolytic-Uremic Syndrome / etiology
  • Hemolytic-Uremic Syndrome / immunology
  • Hemolytic-Uremic Syndrome / therapy*
  • Humans
  • Hybridomas / immunology
  • Immunization, Passive
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / therapeutic use
  • Immunoglobulin M / biosynthesis
  • Immunoglobulin M / therapeutic use
  • In Vitro Techniques
  • Mice
  • Neutralization Tests
  • Shiga Toxin 1 / immunology*
  • Shiga Toxin 1 / toxicity

Substances

  • Antibodies, Bacterial
  • Antibodies, Monoclonal
  • Immunoglobulin G
  • Immunoglobulin M
  • Shiga Toxin 1