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Selection and characterization of a human monoclonal neutralizing antibody for Clostridium Botulinum neurotoxin serotype B
Authors:Heyue Zhou  Bin Zhou  Sabine Pellett  Eric A Johnson  Kim D Janda
Institution:1. Department of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA;2. Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA;3. Food Research Institute, Department of Bacteriology, University of Wisconsin, Madison, WI 53706, USA
Abstract:Botulinum neurotoxins (BoNTs) are causative agents for botulism and are identified as a category A bioterror agents by the Centers for Disease Control and Prevention (CDC). Current antitoxins against BoNTs intoxication have some limitations including side effects or limited supply. As an alternative, neutralizing monoclonal antibodies will play an increasing role as BoNTs therapeutics. To date, no human anti-BoNT/B neutralizing monoclonal antibodies have yet to be reported. Herein, we describe an improved selection approach and characterization of a human monoclonal antibody, F2, which is capable of binding BoNT/B with high specificity and displays neutralizing activity in an in vitro cell-based assay. Through surface plasmon resonance studies, we have determined its association and dissociation rate constants. In sum, our data demonstrate that monoclonal antibody F2 is a promising BoNT/B therapeutic lead for further development.
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