Identification of potent nanobodies to neutralize the most poisonous polypeptide from scorpion venom

• DOI: 10.1042/bj20090697
• Publication Date: 2009-09-07T14:34:32Z
• Authors: Rahma Ben Abderrazek; Issam Hmila; Cécile Vincke; Zakaria Benlasfar; Mireille Pellis; Hafedh Dabbek; Dirk Saerens; Mohamed El Ayeb; Serge Muyldermans; Balkiss Bouhaoual...
• Keywords: MESH: Neurotoxicity Syndromes; MESH: Epitopes; Camelus; MESH: Sequence Homology, Amino Acid; [SDV]Life Sciences [q-bio]; Molecular Sequence Data; Neurotoxins; MESH: Sequence Alignment; Scorpion Venoms; MESH: Amino Acid Sequence; Antibodies; Scorpions; Epitopes; Mice; 03 medical and health sciences; dromedary; MESH: Scorpion Venoms; Antibody Specificity; recombinant antibody; Animals; MESH: Animals; Amino Acid Sequence; MESH: Antibody Specificity; MESH: Mice; single-domain antibody; MESH: Neurotoxins; 0303 health sciences; MESH: Molecular Sequence Data; Sequence Homology, Amino Acid; MESH: Peptides; MESH: Antibodies; MESH: Camels; MESH: Scorpions; MESH: Antibody Formation; Scorpion toxin; 3. Good health; Antibody Formation; Female; Neurotoxicity Syndromes; Peptides; anti-venom; MESH: Female; Sequence Alignment

Scorpion venom, containing highly toxic, small polypeptides that diffuse rapidly within the patient, causes serious medical problems. Nanobodies, single-domain antigen-binding fragments derived from dromedary heavy-chain antibodies, have a size that closely matches that of scorpion toxins. Therefore these nanobodies might be developed into potent immunotherapeutics to treat scorpion envenoming. Multiple nanobodies of sub-nanomolar affinity to AahII, the most toxic polypeptide within the Androctonus australis hector venom, were isolated from a dromedary immunized with AahII. These nanobodies neutralize the lethal effect of AahII to various extents without clear correlation with the kinetic rate constants kon or koff, or the equilibrium dissociation constant, KD. One particular nanobody, referred to as NbAahII10, which targets a unique epitope on AahII, neutralizes 7 LD50 of this toxin in mice, corresponding to a neutralizing capacity of approx. 37000 LD50 of AahII/mg of nanobody. Such high neutralizing potency has never been reached before by any other monoclonal antibody fragment.