Human antibodies that specifically recognize the toxin Cn2 from Centruroides noxius scorpion venom

摘要

The present invention is directed to recombinant human antibodies specific for Cn2 toxin from C. noxius scorpion venom. The antibodies are able to recognize the toxin and preferably neutralize it as well as the whole venom of C. noxius scorpion. This invention is also directed to a human non-immune phage display library. One clone that specifically binds the Cn2 toxin was affinity matured by directed evolution. Three cycles of maturation were performed and several scFv clones were isolated which specifically recognize toxin Cn2 with increased Kd of 446 fold. All variants were monomeric and only variants 6009F, 6105F and 6103E showed to be capable of neutralizing toxin Cn2 and the whole venom. Variant 6009F recognizes a different epitope than that of BCF2, a murine monoclonal antibody raised against scorpion toxin Cn2 which is also capable of neutralizing both Cn2 toxin and the whole venom when tested in mice, as well as that of commercially available polyclonal antibody fragments antivenom from horse. The scFv 6009F is the first reported recombinant human antibody fragment capable of neutralizing a scorpion venom. These results pave the way for the generation of safer autologous recombinant neutralizing antivenom against scorpion stings. The antibodies of the present invention can be used as part of a composition to treat those in need of treatment including those already stung by one or more scorpions, particularly C. noxius scorpions.