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Potent neutralization of botulinum neurotoxin by recombinant oligoclonal antibody.

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.

SUBMITTER: Nowakowski A 

PROVIDER: S-EPMC123259 | biostudies-literature | 2002 Aug

REPOSITORIES: biostudies-literature

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Potent neutralization of botulinum neurotoxin by recombinant oligoclonal antibody.

Nowakowski A A   Wang C C   Powers D B DB   Amersdorfer P P   Smith T J TJ   Montgomery V A VA   Sheridan R R   Blake R R   Smith L A LA   Marks J D JD  

Proceedings of the National Academy of Sciences of the United States of America 20020812 17

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 g  ...[more]

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