A bispecific nanobody to provide full protection against lethal scorpion envenoming.

Abstract : 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.
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Submitted on : Thursday, July 28, 2011 - 11:45:13 AM
Last modification on : Tuesday, August 20, 2019 - 6:14:02 PM

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Issam Hmila, Dirk Saerens, Rahma Ben Abderrazek, Cécile Vincke, Naima Abidi, et al.. A bispecific nanobody to provide full protection against lethal scorpion envenoming.. FASEB Journal, Federation of American Society of Experimental Biology, 2010, 24 (9), pp.3479-89. ⟨10.1096/fj.09-148213⟩. ⟨pasteur-00612182⟩

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