Efficient Serum Clearance of Botulinum Neurotoxin Achieved Using a Pool of Small Antitoxin Binding Agents

摘要: Antitoxins for botulinum neurotoxins (BoNTs) and other toxins are needed that can be produced economically with improved safety shelf-life properties compared to conventional therapeutics large-animal antisera. Here we show protection from BoNT lethality rapid clearance through the liver elicited in mice by administration of a pool epitope-tagged small protein binding agents together single anti-tag monoclonal antibody (MAb). The used this study were single-chain Fv domains (scFvs) high affinity serotype A (BoNT/A). addition increasing numbers differently tagged scFvs synergistically increased level against BoNT/A. It was not necessary any BoNT/A possess toxin-neutralizing activity. Mice protected dose equivalent 1,000 10,000 50% lethal doses (LD50) when given three or four different anti-BoNT scFvs, each fused an E-tag peptide, anti-E-tag IgG1 MAb. Toxin enhanced scFv contained two copies E tag. Pharmacokinetic studies demonstrated rapidly cleared sera anti-BoNT/A MAb but alone alone. administered up 2 h following exposure 10 LD50 These results suggest it will possible develop produce therapeutic antitoxins consisting pools single, stockpiled