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Infection and Immunity, October 2002, p. 5896-5899, Vol. 70, No. 10
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.10.5896-5899.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Production and Characterization of Protective Human Antibodies against Shiga Toxin 1

Division of Infectious Diseases, Tufts University School of Veterinary Medicine, North Grafton, Massachusetts,¹ Medarex, San Jose, California²

Received 9 April 2002/ Returned for modification 14 May 2002/ Accepted 24 June 2002

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() [IgM()] elements [one specific for the A subunit and six specific for the B subunit] and three IgG1() elements specific for subunit B) were isolated. Two IgM() Hu-MAbs (2D9 and 15G9) and three IgG1() 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.

Editor: J. D. Clements

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