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The Amm VIII protein was previously isolated from the venom of the scorpion Androctonus mauretanicus mauretanicus. Despite 87% identity with AaH II, the most toxic alpha-type scorpion toxin, Amm VIII is not toxic to mice. However, antisera against Amm VIII protect mice from AaH II lethal action. Here, we report that the Amm VIII protein elicits antibodies that only recognize discontinuous-type epitopes since we could not observe any antibody binding to overlapping 12-mer peptides covering the whole Amm VIII sequence. By using a new bioinformatic tool, 24 peptides mimicking discontinuous regions of Amm VIII were designed in silico, then prepared by Spot synthesis. Seven of these discontinuous-continuous peptides were recognized by anti-Amm VIII antibodies. Analysis of the 3D location of the segments that compose the antigenically reactive discontinuous-continuous peptides, allowed us to group those antigenic segments into three regions of Amm VIII, putatively corresponding to discontinuous antigenic regions of alpha-type scorpion toxins. Anti-Amm VIII antibodies were also found to cross-react towards several of the discontinuous-continuous peptides designed from the AaH II structure, pointing to a possible involvement of the corresponding discontinuous epitopes in the capacity displayed by anti-Amm VIII antibodies to neutralize AaH II. Altogether, our results show that it is possible to design antibody-reactive peptides from discontinuous parts of scorpion toxins. The position of the reactive segments in the structural context of scorpion toxins highlights the antigenic properties of the Amm VIII anatoxin and concurs to explain the capacity of anti-Amm VIII antibodies to neutralize the potent AaH II toxin.

Serum therapy remains the only specific treatment against envenoming, but anti-venoms are still prepared by fragmentation of polyclonal antibodies isolated from hyper-immunized horse serum. Most of these anti-venoms are considered to be efficient, but their production is tedious, and their use may be associated with adverse effects. Recombinant antibodies and smaller functional units are now emerging as credible alternatives and constitute a source of still unexploited biomolecules capable of neutralizing venoms. This review will be a walk through the technologies that have recently been applied leading to novel antibody formats with better properties in terms of homogeneity, specific activity and possible safety.