A bispecific nanobody to provide full protection against lethal scorpion envenoming

FASEB J. 2010 Sep;24(9):3479-89. doi: 10.1096/fj.09-148213. Epub 2010 Apr 21.


Envenoming following scorpion sting is a common emergency in many parts of the world. Our aim was to ameliorate the current 100-kDa horse plasma antivenom serum (PAS)-derived Fab'(2) to more quickly reach the highly diffusible scorpion toxins (7 kDa). We immunized dromedaries with toxins from Androctonus australis hector (Aah) scorpions and cloned the single-domain antibody fragments or nanobodies (15 kDa) from their B cells. Nanobodies against AahI' toxin (with AahII the most toxic compound of the venom) were retrieved from the libraries, and their AahI'-toxin neutralization was monitored in mice. Remarkably, the NbAahI'F12 fully protected mice against 100 LD(50) of AahI' administered intracerebroventricularly. Moreover, where PAS failed completely to neutralize 2 LD(50) of crude venom injected subcutaneously, the designed bispecific NbF12-10 against AahI'/AahII toxins succeeded in neutralizing 5 LD(50). Finally, in a challenge assay in which mice were subcutaneously injected with a lethal dose of scorpion venom, the subsequent intravenous injection of 85 microg of NbF12-10 protected all mice, even if the whole procedure was repeated 3 times. Furthermore, the NbF12-10 remained fully protective when mice with severe signs of envenoming were treated a few minutes before the untreated mice died.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Camelus
  • Epitope Mapping
  • Immunoglobulin Fragments / immunology*
  • Immunoglobulin Fragments / isolation & purification
  • Male
  • Mice
  • Scorpion Venoms / immunology*


  • Immunoglobulin Fragments
  • Scorpion Venoms
  • scorpion toxin I, Androctonus
  • scorpion toxin II, Androctonus