|Title||A bispecific nanobody to provide full protection against lethal scorpion envenoming.|
|Publication Type||Journal Article|
|Year of Publication||2010|
|Authors||Hmila, I., D. Saerens, R. Ben Abderrazek, C. Vincke, N. Abidi, Z. Benlasfar, J. Govaert, M. El Ayeb, B. Bouhaouala-Zahar, and S. Muyldermans|
|Date Published||2010 Sep|
|Keywords||Animals, Camels, Epitope Mapping, Immunoglobulin Fragments, Male, Mice, Scorpion Venoms|
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.
|Alternate Journal||FASEB J.|