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Potent neutralization of botulinum neurotoxin by recombinant oligoclonal antibody
Open accessAbstract
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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Cited by
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Harmsen, M. M., & De Haard, H. J. (2007) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-007-1142-2 · Cited by 809
“The use of mixtures of a limited number of monoclonal antibodies (oligoclonal antibodies) is advantageous over single monoclonal antibodies for particular applications, such as toxin neutralization (Nowakowski et al. 2002).”
BackgroundAlternative molecular formats and therapeutic applications for bispecific antibodies
Spiess, C., Zhai, Q., & Carter, P. J. (2015) · Molecular Immunology · doi:10.1016/j.molimm.2015.01.003 · Cited by 607
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Arnon, S. S., Schechter, R., Maslanka, S. E., Jewell, N. P., & Hatheway, C. L. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa051926 · Cited by 498
Hudson, P. J., & Souriau, C. (2003) · Nature Medicine · doi:10.1038/nm0103-129 · Cited by 398
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Oostindie, S. C., Lazar, G. A., Schuurman, J., & Parren, P. W. H. I. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00501-8 · Cited by 298
Metadata
- Authors
- Nowakowski, A., Wang, C., Powers, D. B., Amersdorfer, P., Smith, T. J., Montgomery, V. A., Sheridan, R., Blake, R., Smith, L. A., & Marks, J. D.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2002-08-12
- Volume
- 99
- Issue
- 17
- Pages
- 11346-11350
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2013757167
- Cited by
- 331
- References
- 0
- FWCI
- 9.84
- Type
- journal article
- Language
- en
- Open access
- green
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- Nowakowski, A., Wang, C., Powers, D. B., Amersdorfer, P., Smith, T. J., Montgomery, V. A., Sheridan, R., Blake, R., Smith, L. A., & Marks, J. D. (2002). Potent neutralization of botulinum neurotoxin by recombinant oligoclonal antibody. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.172229899
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