Efficient serum clearance of botulinum neurotoxin achieved using a pool of small antitoxin binding agents.

Infection and Immunity
Jorge SepulvedaCharles B Shoemaker

Abstract

Antitoxins for botulinum neurotoxins (BoNTs) and other toxins are needed that can be produced economically with improved safety and shelf-life properties compared to conventional therapeutics with large-animal antisera. Here we show that protection from BoNT lethality and rapid BoNT clearance through the liver can be elicited in mice by administration of a pool of epitope-tagged small protein binding agents together with a single anti-tag monoclonal antibody (MAb). The protein binding agents used in this study were single-chain Fv domains (scFvs) with high affinity for BoNT serotype A (BoNT/A). The addition of increasing numbers of differently tagged scFvs synergistically increased the level of protection against BoNT/A. It was not necessary that any of the BoNT/A binding agents possess toxin-neutralizing activity. Mice were protected from a dose equivalent to 1,000 to 10,000 50% lethal doses (LD(50)) of BoNT/A when given three or four different anti-BoNT scFvs, each fused to an E-tag peptide, and an anti-E-tag IgG1 MAb. Toxin protection was enhanced when an scFv contained two copies of the E tag. Pharmacokinetic studies demonstrated that BoNT/A was rapidly cleared from the sera of mice given a pool of anti-BoNT/A scFvs and an ...Continue Reading

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Citations

Mar 23, 2013·Toxicon : Official Journal of the International Society on Toxinology·Lance Simpson
Dec 30, 2015·Applied Microbiology and Biotechnology·Parvaneh SaffarianAbbas Ali Imani Fooladi
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Nov 10, 2013·The Journal of Biological Chemistry·David J VanceCharles B Shoemaker
Aug 21, 2021·ACS Medicinal Chemistry Letters·Lewis D TurnerKim D Janda

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