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A novel pentamer versus pentamer approach to generating neutralizers of verotoxin 1.

Authors
Type
Published Article
Journal
Molecular Immunology
0161-5890
Publisher
Elsevier
Publication Date
Volume
44
Issue
9
Pages
2487–2491
Identifiers
PMID: 17134756
Source
Medline
License
Unknown

Abstract

Verotoxins (VTs), or shiga-like toxins, are produced by enterohemorrhagic Escherichia coli (EHEC), which cause hemorrhagic colitis and hemolytic uremic syndrome. VTs are the major virulence factors in EHEC infection due to their cytotoxicity to various types of cells. Here, we present a novel type of VT neutralizer based on pentavalent single-domain antibodies, or pentabodies. Two single-domain antibodies (sdAbs) specific for the receptor binding sites of the B subunit of VT1 (VT1B) were isolated from a naïve llama phage display library. These two sdAbs were pentamerized to generate pentameric VT neutralizers, VTI-1 and VTI-3. Both VT neutralizers bound wild type VT1B specifically with superior functional affinity. In vitro neutralization assays showed that VTI-1 and VTI-3 were able to neutralize 90% and 40%, respectively, of the cytotoxicity caused by VT1. This effort provides the basis of a novel type of VT neutralizer that can potentially be produced at a relatively low cost.

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