A bispecific nanobody to provide full protection against lethal scorpion envenoming

Issam Hmila, Dirk Saerens, Rahma Ben Abderrazek, Cécile Vincke, Naima Abidi, Zakaria Benlasfar, Jochen Govaert, Mohamed El Ayeb, Balkiss Bouhaouala-Zahar, Serge Muyldermans

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75 Citations (Scopus)

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 LD50 of AahI′ administered intracerebroventricularly. Moreover, where PAS failed completely to neutralize 2 LD50 of crude venom injected subcutaneously, the designed bispecific NbF12-10 against AahI′/AahII toxins succeeded in neutralizing 5 LD50. Finally, in a challenge assay in which mice were subcutaneously injected with a lethal dose of scorpion venom, the subsequent intravenous injection of 85 μg 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.

Original languageEnglish
Pages (from-to)3479-3489
Number of pages11
JournalFASEB Journal
Volume24
Issue number9
DOIs
Publication statusPublished - 1 Sep 2010
Externally publishedYes

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ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Hmila, I., Saerens, D., Abderrazek, R. B., Vincke, C., Abidi, N., Benlasfar, Z., Govaert, J., El Ayeb, M., Bouhaouala-Zahar, B., & Muyldermans, S. (2010). A bispecific nanobody to provide full protection against lethal scorpion envenoming. FASEB Journal, 24(9), 3479-3489. https://doi.org/10.1096/fj.09-148213