Selection and characterization of a human monoclonal neutralizing antibody for Clostridium Botulinum neurotoxin serotype B

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:19

Article

Zhou, Heyue¹  Zhou, Bin¹  Pellett, Sabine³  Johnson, Eric A.³  Janda, Kim D.^1,2 

[1] Scripps Res Inst, Skaggs Inst Chem Biol, Dept Chem & Immunol, La Jolla, CA 92037 USA

[2] Scripps Res Inst, WIRM, La Jolla, CA 92037 USA

[3] Univ Wisconsin, Dept Bacteriol, Food Res Inst, Madison, WI 53706 USA

关键词: Phage display;    Botulinum neurotoxin;    Monoclonal antibody;    Neutralizing antibody;   

DOI  :  10.1016/j.bmcl.2008.12.055

来源: Elsevier

【 摘 要 】

Botulinum neurotoxins (BoNTs) are causative agents for botulism and are identified as a category A bio-terror 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. (c) 2008 Elsevier Ltd. All rights reserved.

【 授权许可】

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