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

TitleA bispecific nanobody to provide full protection against lethal scorpion envenoming.
Publication TypeJournal Article
Year of Publication2010
AuthorsHmila, I., D. Saerens, R. Ben Abderrazek, C. Vincke, N. Abidi, Z. Benlasfar, J. Govaert, M. El Ayeb, B. Bouhaouala-Zahar, and S. Muyldermans
JournalFASEB J
Volume24
Issue9
Pagination3479-89
Date Published2010 Sep
ISSN1530-6860
KeywordsAnimals, Camels, Epitope Mapping, Immunoglobulin Fragments, Male, Mice, Scorpion Venoms
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.

DOI10.1096/fj.09-148213
Alternate JournalFASEB J.
PubMed ID20410443