Institute of Materia Medica, School of Pharmacy, North Sichuan Medical College, Nanchong, China.
Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing, China.
Arch Toxicol. 2024 Dec;98(12):4187-4195. doi: 10.1007/s00204-024-03869-1. Epub 2024 Sep 23.
Botulinum toxin (BoNT) from Clostridium botulinum is the most toxic biotoxin known and is also an important bioterrorism agent. After poisoning, the only effective treatment is injection of antitoxin. However, neutralizing nanoantibodies are safer and more effective, representing a promising therapeutic approach. Therefore, it is important to obtain effective neutralizing nanoantibodies. Hence, the present study aimed to construct a phage antibody library by immunizing a camel and screening specific clones that bind to the L-HN domain of BoNT/F and constructing chimeric heavy-chain antibodies by fusing them with a human Fc fragment. The antibodies' affinity and in vivo neutralizing activities were evaluated. The results showed that 2 µg of F20 antibody could completely neutralize 20 × the median lethal dose (LD) of BoNT/F in vitro. Injection of 5 mg/kg F20 at 1 h, 2 h, 3 h, and 4 h into mice after BoNT/F challenge resulted in complete survival in vivo. Overall, the antibody might be a candidate for the development of new drugs to treat botulism.
肉毒杆菌毒素（BoNT）来自肉毒梭菌，是已知毒性最强的生物毒素，也是一种重要的生物恐怖剂。中毒后，唯一有效的治疗方法是注射抗毒素。然而，中和纳米抗体更安全、更有效，代表了一种有前途的治疗方法。因此，获得有效的中和纳米抗体非常重要。因此，本研究旨在通过免疫骆驼构建噬菌体抗体文库，并筛选与 BoNT/F 的 L-HN 结构域结合的特异性克隆，然后通过与人 Fc 片段融合来构建嵌合重链抗体。评估了抗体的亲和力和体内中和活性。结果表明，2μg 的 F20 抗体在体外可完全中和 BoNT/F 的 20 倍中位数致死剂量（LD）。在 BoNT/F 攻击后 1 h、2 h、3 h 和 4 h 给小鼠注射 5 mg/kg 的 F20，体内完全存活。总的来说，该抗体可能是开发治疗肉毒中毒新药的候选药物。
