Yu Yun-Zhou, Li Na, Zhu Heng-Qi, Wang Rui-Lin, Du Yun, Wang Shuang, Yu Wei-Yuan, Sun Zhi-Wei
Beijing Institute of Biotechnology, 20 Dong Dajie Street, Fengtai District, Beijing 100071, China.
Vaccine. 2009 May 11;27(21):2816-22. doi: 10.1016/j.vaccine.2009.02.091. Epub 2009 Mar 11.
Vaccination with recombinant His-tagged isoforms of the Clostridium botulinum Hc domain of neurotoxin serotype A (rAHc) have effectively protected against challenge with active botulinum neurotoxin serotype A. To establish a formulation suitable for human use, rAHc was expressed in Escherichia coli without a His-tag and purified by sequential chromatography on ion-exchange and hydrophobic-interaction resins. Purified rAHc was used to vaccinate mice and survival was evaluated following challenge with active toxin. rAHc-vaccinated mice were protected against an active toxin challenge in mouse models of disease and a dose-response relationship was observed between the dose of rAHc administered and protection. Vaccination with rAHc in the presence or absence of adjuvants was also tested following intramuscular or subcutaneous vaccination to determine the optimal route of vaccination in the context of active toxin challenge. The data presented in the report suggested that rAHc administered with or without adjuvants functioned effectively over time in protecting mice against challenge with neurotoxin suggesting that this form of rAHc may be developed into a human vaccine candidate designed for the prevention of botulism.
用重组的A型肉毒杆菌神经毒素Hc结构域His标签亚型（rAHc）进行疫苗接种，可有效抵御活性A型肉毒杆菌神经毒素的攻击。为了建立适合人类使用的制剂，rAHc在无His标签的大肠杆菌中表达，并通过离子交换和疏水相互作用树脂的顺序色谱法进行纯化。纯化后的rAHc用于给小鼠接种疫苗，并在活性毒素攻击后评估存活率。在疾病小鼠模型中，接种rAHc的小鼠受到活性毒素攻击时得到了保护，并且在所给予的rAHc剂量与保护效果之间观察到了剂量反应关系。还在肌肉注射或皮下接种后测试了在有无佐剂的情况下用rAHc进行疫苗接种，以确定在活性毒素攻击情况下的最佳接种途径。报告中呈现的数据表明，无论有无佐剂，随着时间的推移，给予rAHc都能有效地保护小鼠免受神经毒素攻击，这表明这种形式的rAHc可能会被开发成一种用于预防肉毒中毒的人类候选疫苗。
