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Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11346-50. Epub 2002 Aug 12.

Potent neutralization of botulinum neurotoxin by recombinant oligoclonal antibody.

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  • 1Department of Anesthesia and Pharmaceutical Chemistry, University of California, Room 3C-38, San Francisco General Hospital, 1001 Potrero Avenue, San Francisco, CA 94110, USA.

Abstract

The botulinum neurotoxins (BoNTs) cause the paralytic human disease botulism and are one of the highest-risk threat agents for bioterrorism. To generate a pharmaceutical to prevent or treat botulism, monoclonal antibodies (mAbs) were generated by phage display and evaluated for neutralization of BoNT serotype A (BoNT/A) in vivo. Although no single mAb significantly neutralized toxin, a combination of three mAbs (oligoclonal Ab) neutralized 450,000 50% lethal doses of BoNT/A, a potency 90 times greater than human hyperimmune globulin. The potency of oligoclonal Ab was primarily due to a large increase in functional Ab binding affinity. The results indicate that the potency of the polyclonal humoral immune response can be deconvoluted to a few mAbs binding nonoverlapping epitopes, providing a route to drugs for preventing and treating botulism and diseases caused by other pathogens and biologic threat agents.

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