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A bispecific nanobody to provide full protection against lethal scorpion envenoming
Author(s) -
Hmila Issam,
Saerens Dirk,
Abderrazek Rahma Ben,
Vincke Cécile,
Abidi Naima,
Benlasfar Zakaria,
Govaert Jochen,
Ayeb Mohamed El,
BouhaoualaZahar Balkiss,
Muyldermans Serge
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-148213
Subject(s) - venom , antivenom , scorpion , scorpion venoms , lethal dose , neutralization , toxin , pharmacology , median lethal dose , medicine , sting , antibody , biology , immunology , toxicology , toxicity , microbiology and biotechnology , biochemistry , engineering , aerospace engineering
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 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.—Hmila, I., Saerens, D., Ben Abderrazek, R., Vincke, C., Abidi, N., Benlasfar, Z., Govaert, J., El Ayeb, M., Bouhaouala‐Zahar, B., Muyldermans, S. A bispecific nanobody to provide full protection against lethal scorpion envenoming. FASEB J . 24, 3479–3489 (2010). www.fasebj.org