Selection and characterization of a human monoclonal neutralizing antibody for Clostridium Botulinum neurotoxin serotype B.
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.
Zhou
Heyue
H
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.
Zhou
Bin
B
Pellett
Sabine
S
Johnson
Eric A
EA
Janda
Kim D
KD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D000992:Antitoxins / Q000737:chemistry; D001905:Botulinum Toxins / Q000737:chemistry*; D019274:Botulinum Toxins, Type A; D001906:Botulism / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003014:Clostridium botulinum / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D009500:Neutralization Tests; D019151:Peptide Library; D051381:Rats; D013116:Spinal Cord / Q000166:cytology
D000911:Antibodies, Monoclonal; D000992:Antitoxins; D019151:Peptide Library; C096323:rimabotulinumtoxinB; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A