AI Article Synopsis
- Human botulism is caused by different serotypes of botulinum neurotoxin (BoNT) and this study focused on developing an antitoxin using four human monoclonal antibodies (mAbs) targeting BoNT/C, BoNT/D, and their mosaic toxins.
- The mAbs were created from human immune libraries and showed strong binding to multiple serotypes, with three undergoing evolution to enhance their affinity.
- A combination of these mAbs demonstrated effective neutralization and has potential for therapeutic and diagnostic applications, with one derivative (NTM-1634) showing safety in a Phase 1 clinical trial.
Article Abstract
Human botulism can be caused by botulinum neurotoxin (BoNT) serotypes A to G. Here, we present an antibody-based antitoxin composed of four human monoclonal antibodies (mAbs) against BoNT/C, BoNT/D, and their mosaic toxins. This work built on our success in generating protective mAbs to BoNT /A, B and E serotypes. We generated mAbs from human immune single-chain Fv (scFv) yeast-display libraries and isolated scFvs with high affinity for BoNT/C, BoNT/CD, BoNT/DC and BoNT/D serotypes. We identified four mAbs that bound non-overlapping epitopes on multiple serotypes and mosaic BoNTs. Three of the mAbs underwent molecular evolution to increase affinity. A four-mAb combination provided high-affinity binding and BoNT neutralization of both serotypes and their mosaic toxins. The mAbs have potential utility as therapeutics and as diagnostics capable of recognizing and neutralizing BoNT/C and BoNT/D serotypes and their mosaic toxins. A derivative of the four-antibody combination (NTM-1634) completed a Phase 1 clinical trial (Snow et al., Antimicrobial Agents and Chemotherapy, 2019) with no drug-related serious adverse events.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472335 | PMC |
| http://dx.doi.org/10.3390/toxins13090641 | DOI Listing |
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