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A diabody cocktail providing full protection against (...)

J Biol Chem. 2012 Feb ; [Epub ahead of print]
A diabody cocktail providing full protection against experimental scorpion envenoming with crude Androctonus australis venom.
Di Tommaso A, Juste MO, Martin-Eauclaire MF, Dimier-Poisson I, Billiald P, Aubrey N.

Androctonus australis is primarily involved in envenomations in North Africa, notably in Tunisia and Algeria, and constitutes a significant public health problem in this region. The toxicity of the venom is mainly due to various neurotoxins that belong to two distinct structural and immunological groups : group I (the AahI and AahIII toxins) and group II (AahII). Here we report the use of a diabody cocktail in which the molar ratio matches the characteristics of toxins and polymorphism of the venom. The cocktail consists of the Db9C2 diabody (anti-group I) and the Db4C1op diabody (anti-AahII), the latter being modified to facilitate in vitro production and purification. The effectiveness of the antivenom was tested in vivo under conditions simulating scorpion envenomation. The i.p. injection of 30 μg of the diabody cocktail protected almost all the mice exposed to 3 LD50 s.c. of venom. We also show that the presence of both diabodies is necessary for the animals to survive. Our results are the first demonstration of the strong protective power of small quantities of antivenom used in the context of severe envenomation with crude venom.


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