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A Four-Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotypes C and D

Authors
  • garcia-rodriguez, consuelo
  • yan, shude
  • geren, isin n.
  • knopp, kristeene a.
  • dong, jianbo
  • sun, zhengda
  • lou, jianlong
  • conrad, fraser
  • wen, wei-hua
  • farr-jones, shauna
  • smith, theresa j.
  • brown, jennifer l.
  • skerry, janet c.
  • smith, leonard a.
  • marks, james d.
Publication Date
Sep 10, 2021
Identifiers
DOI: 10.3390/toxins13090641
OAI: oai:mdpi.com:/2072-6651/13/9/641/
Source
MDPI
Keywords
Language
English
License
Green
External links

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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