BoNT/A intoxication is prevented by administering a single anti-BoNT/A VHH heterodimer in a clinically-relevant post-intoxication mouse model.

<p>A 10 LD₅₀ dose of toxin was administered by intraperitoneal injection either 1.5 or 3 hours prior to intravenous administration of antitoxin agents as indicated. Symptoms of BoNT/A intoxication and lethality were monitored following post-intoxication administration of double-tagged heterodimers of neutralizing or non-neutralizing anti-BoNT/A VHHs+/−clearing Ab. The time to death is plotted as % survival as a function of time following administration of toxin. Time to death for mice given no agents or the positive control sheep antitoxin are also shown. (<b>A</b>) The double-tagged heterodimer consisted of two non-neutralizing VHHs, ciA-F12 and ciA-D12 (F12/D12(2E)) and was administered with or without anti-E-tag clearing mAb (αE) as indicated. (<b>B</b>) The double-tagged heterodimer consisted of two BoNT/A neutralizing VHHs, ciA-H7 and ciA-B5 (H7/B5(2E)) and was administered with or without anti-E-tag clearing mAb (αE) as indicated.