title: Single chain variable fragment antibodies against Shiga toxins isolated from a human antibody phage display library.
abstract: Shiga toxins (Stxs) are involved in the pathogenesis of hemolytic-uremic syndrome and other severe systemic complications following enterohemorrhagic Escherichia coli infection in humans. Passive immunotherapies using monoclonal antibodies have been shown to be effective for neutralizing the toxic effects of Stxs. However, animal-derived monoclonal antibodies are sometimes immunogenic and their production is both laborious and expensive. We here report the isolation of single-chain variable fragment antibodies against Stxs by screening a phage display library constructed from a naïve human repertoire. An antibody among the selected clones designated B22 bound to the binding subunits of both Stx-1 and Stx-2, and strongly neutralized the cytotoxicity of Stx-1. This is the first example of a monovalent antibody showing Stx-neutralizing activity. The B22 antibody is also completely naturally occurring in human, which reduces the possibility of adverse immunological effects, and can be easily produced using bacterial protein synthesis systems.
authors.affiliation: Department of Microbiology, School of Medicine Fujita Health University, Toyoake, Aichi 470-1192, Japan.
authors.forename: Paola
authors.initials: P
authors.lastname: Neri
authors.forename: Naoko
authors.initials: N
authors.lastname: Shigemori
authors.forename: Susumu
authors.initials: S
authors.lastname: Hamada-Tsutsumi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tsukamoto
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Arimitsu
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Shimizu
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Akahori
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kurosawa
authors.forename: Takao
authors.initials: T
authors.lastname: Tsuji
mesh_terms: D000907:Antibodies, Bacterial / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D019151:Peptide Library; D011485:Protein Binding; D022603:Shiga Toxins / Q000276:immunology* / Q000378:metabolism; D057127:Single-Chain Antibodies / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D019151:Peptide Library; D022603:Shiga Toxins; D057127:Single-Chain Antibodies