面向口蹄疫O型疫苗分离纯化的高载量金属螯合层析介质的设计、制备与应用研究  

Design,Preparation and Application of High-Capacity Metal Chelated Chomatography Media for Purification of FMD(Type O)Vaccine

作　　者：高警威 黄永东[2,3] 赵岚 朱凯[2,3] 阳燕 王瑞 程妍[2,3] 孟宪泽 马光辉 王启宝[1] GAO Jingwei;HUANG Yongdong;ZHAO Lan;ZHU Kai;YANG Yan;WANG Rui;CHENG Yan;MENG Xianze;MA Guanghui;WANG Qibao(School of Chemical&Environmental Engineering,China University of Mining&Technology-Beijing,Beijing 100083,China;State Key Laboratory of Biochemical Engineering,Institute of Process Engineering,Chinese Academy of Sciences,Beijing 100190,China;Key Laboratory of Biopharmaceutical Preparation and Delivery,Chinese Academy of Sciences,Beijing 100190,China)

机构地区：[1]中国矿业大学(北京)化学与环境工程学院,北京100083 [2]中国科学院过程工程研究所生化工程国家重点实验室,北京100190 [3]生物药制备与递送重点实验室(中国科学院),北京100190

出　　处：《离子交换与吸附》2023年第6期477-488,共12页Ion Exchange and Adsorption

基　　金：国家重点研发计划资助项目(No.2021YFC2103403,No.2023YFC2812001,No.2023YFC2812002,No.2021YFC2103402);国家自然科学基金资助项目(No.22278411)。

摘　　要：口蹄疫(FMD)是一种危害极大的动物传染病,给畜牧业带来巨大损失,现阶段我国以免疫预防为主。口蹄疫O型亚单位疫苗安全性高、易于大规模表达和收获,高效分离纯化是其生产过程的关键步骤。以琼脂糖微球4FF为基质,分别经烯丙基缩水甘油醚(AGE)和环氧氯丙烷(ECH)活化,接枝葡聚糖后再偶联亚氨基二乙酸(IDA),最后螯合Ni2+。制备得到Ni-IDA-琼脂糖微球4FF介质,并与常规Ni-IDA-琼脂糖介质及市售大孔聚合物微球介质进行比较。结果表明,Ni-IDA-接枝型琼脂糖微球4FF介质的微观结构更适用于纯化口蹄疫O型疫苗,动态载量高于商品介质,纯度高达90%以上。介质的构效关系与调控机制研究为口蹄疫O型疫苗高效分离纯化提供新思路。Foot-and-mouth disease(FMD)is a very harmful animal infectious disease,which brings great losses to animal husbandry.At present,China focuses on immune prevention.Footand-mouth disease(Type O)subunit vaccine has high safety and easy large-scale expression and harvest,and efficient purification is a key step in its production process.Using agarose microsphere 4FF as the matrix,followed by being activated by allyl glycidyl ether(AGE)and epichlorohydrin(ECH),grafted with dextran and then coupled to iminodiacetic acid(IDA),and finally chelated with Ni2+.Ni-IDA-agarose 4FF media was prepared and compared with conventional Ni-IDA-agarose media and commercially available macroporous polymer microsphere media.The results show that the microstructure of Ni-IDA-grafted agarose 4FF is more suitable for purifying FMD(Type O)vaccine with both a higher dynamic capacity and a purity of more than 90%than commercial media.The study provides new ideas for the efficient purification of FMD(Type O)vaccine.

关 键 词：口蹄疫O型疫苗 金属螯合层析介质 高载量 分离纯化 接枝 

分 类 号：Q503[生物学—生物化学]