Potent neutralization of botulinum neurotoxin by recombinant oligoclonal antibody
2002; National Academy of Sciences; Volume: 99; Issue: 17 Linguagem: Inglês
10.1073/pnas.172229899
ISSN1091-6490
AutoresA Nowakowski, C. Wang, David B. Powers, Peter Amersdorfer, Theresa J. Smith, Vicki A. Montgomery, Robert E. Sheridan, Robert C. Blake, Lewis J. Smith, James D. Marks,
Tópico(s)Streptococcal Infections and Treatments
ResumoThe 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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