Neutralizing Dromedary-Derived Nanobodies Against BotI-Like Toxin From the Most Hazardous Scorpion Venom in the Middle East and North Africa Region

• DOI: 10.3389/fimmu.2022.863012
• Publication Date: 2022-04-19T13:00:20Z
• Authors: Rahma Ben Abderrazek; Ayoub Ksouri; Faten Idoudi; Sayda Dhaouadi; Emna Hamdi; Cécile Vincke; Azer Farah; Zakaria Benlasfar; Hafedh Majdoub; Mohamed El Ayeb; Serge Muyldermans; Balkiss Bouhaoual...
• Keywords: Scorpion Venoms; Buthidae; Lethal dose; Median lethal dose; Scorpion toxin

Scorpion envenoming is a severe health problem in many regions causing significant clinical toxic effects and fatalities. In the Middle East/North Africa (MENA) region, Buthidae scorpion stings are responsible for devastating outcomes human. The only available specific immunotherapeutic treatment based on IgG fragments of animal origin. To overcome limitations classical immunotherapy, we have demonstrated vivo efficacy NbF12-10 bispecific nanobody at preclinical level. Nanobodies were developed against BotI analogues belonging to distinct structural antigenic group toxins, occurring MENA region. From Buthus occitanus tunetanus venom, BotI-like toxin was purified. 41 N-terminal amino acid residues sequenced, LD50 estimated 40 ng/mouse. used dromedary immunization. An immune VHH library constructed, after screening, two nanobodies selected with nanomolar sub-nanomolar affinity recognizing an overlapping epitope. NbBotI-01 able neutralize 50% lethal effect 13 toxins mice when injected by i.c.v route, whereas NbBotI-17 neutralized 7 LD50. Interestingly, completely reduced 2 BotG50 1:4 molar ratio excess. More interestingly, equimolar mixture 5 or AahG50, 1:2 ratio, respectively. Hence, display synergic effects, leading novel therapeutic candidate treating