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Infection and Immunity, June 2003, p. 3125-3130, Vol. 71, No. 6
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.6.3125-3130.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Stx2-Specific Human Monoclonal Antibodies Protect Mice against Lethal Infection with Escherichia coli Expressing Stx2 Variants

Abhineet S. Sheoran,1 Susan Chapman,1 Pradeep Singh,2 Arthur Donohue-Rolfe,1 and Saul Tzipori1*

Division of Infectious Diseases, Tufts University School of Veterinary Medicine, North Grafton, Massachusetts 01536,1 Department of Mathematics, Southeast Missouri State University, Cape Girardeau, Missouri 637012

Received 11 December 2002/ Returned for modification 14 February 2003/ Accepted 28 February 2003

Shiga toxin-producing Escherichia coli (STEC) strains are responsible for causing hemolytic-uremic syndrome (HUS), and systemic administration of Shiga toxin (Stx)-specific human monoclonal antibodies (HuMAbs) is considered a promising approach for prevention or treatment of the disease in children. The goal of the present study was to investigate the ability of Stx2-specific HuMAbs to protect against infections with STEC strains that produce Stx2 variants. Dose-response studies on five HuMAbs, using the mouse toxicity model, revealed that only the three directed against the A subunit were protective against Stx2 variants, and 5C12 was the most effective among the three tested. Two HuMAbs directed against the B subunit, while highly effective against Stx2, were ineffective against Stx2 variants. In a streptomycin-treated mouse model, parenteral administration of 5C12 significantly protected mice up to 48 h after oral bacterial challenge. We conclude that 5C12, reactive against the Stx2 A subunit, is an excellent candidate for immunotherapy against HUS and that antibodies directed against the A subunit of Stx2 have broad-spectrum activity that includes Stx2 variants, compared with those directed against the B subunit.

* Corresponding author. Mailing address: Tufts University School of Veterinary Medicine, Division of Infectious Diseases, 200 Westboro Rd., Building 20, North Grafton, MA 01536. Phone: (508) 839-7955. Fax: (508) 839-7911. E-mail: Saul.tzipori{at}tufts.edu.

Editor: J. D. Clements

Infection and Immunity, June 2003, p. 3125-3130, Vol. 71, No. 6
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.6.3125-3130.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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