Abderrazek Rahma Ben, Hmila Issam, Vincke Cécile, Benlasfar Zakaria, Pellis Mireille, Dabbek Hafedh, Saerens Dirk, El Ayeb Mohamed, Muyldermans Serge, Bouhaouala-Zahar Balkiss
Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, 13 Place Pasteur, BP-74, 1002 Tunis, Tunisia.
Biochem J. 2009 Nov 11;424(2):263-72. doi: 10.1042/BJ20090697.
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.
蝎毒含有剧毒的小多肽，可在患者体内迅速扩散，会引发严重的医学问题。纳米抗体是源自单峰驼重链抗体的单域抗原结合片段，其大小与蝎毒素的大小非常匹配。因此，这些纳米抗体可能会被开发成有效的免疫疗法来治疗蝎蜇伤。从用澳大利亚杀人蝎毒液中毒性最强的多肽AahII免疫的单峰驼中分离出了多个对AahII具有亚纳摩尔亲和力的纳米抗体。这些纳米抗体在不同程度上中和了AahII的致死作用，与动力学速率常数kon或koff以及平衡解离常数KD没有明显关联。一种名为NbAahII10的特殊纳米抗体靶向AahII上的一个独特表位，可在小鼠体内中和7个半数致死量的这种毒素，相当于约37000个AahII半数致死量/毫克纳米抗体的中和能力。此前任何其他单克隆抗体片段都从未达到过如此高的中和效力。
