大肠杆菌表达系统在基因工程疫苗研发中的应用与策略优化  

Escherichia coli expression system applied in the development of recombinant human vaccines and its potential improvement

作　　者：刘丽琴 陈婷婷 李少伟[1,2] 夏宁邵[1,2] LIU Li-qin;CHEN Ting-ting;LI Shao-wei;XIA Ning-shao(Xiamen University 1 National Institute of Diagnostics and Vaccine Development in Infectious Diseases,School of Life Sciences,2 State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics,School of Public Health,Xiamen 361102,China)

机构地区：[1]厦门大学生命科学学院,国家传染病诊断试剂与疫苗工程技术研究中心 [2]厦门大学公共卫生学院,分子疫苗学与分子诊断学国家重点实验室,厦门361102

出　　处：《中国新药杂志》2020年第21期2434-2442,共9页Chinese Journal of New Drugs

基　　金：国家高技术研究发展计划(863计划)(2014AA021302)。

摘　　要：大肠杆菌具有生长快速、培养成本低、遗传背景清楚等特点,已被广泛地应用于重组蛋白类药物的表达和生产。近年来,几种基于大肠杆菌表达的基因工程疫苗已投入市场(戊型肝炎疫苗、人乳头瘤病毒疫苗、脑膜炎球菌疫苗等)或进入临床研究(流感A型疫苗、疟疾疫苗、炭疽疫苗等),显示了大肠杆菌表达系统在疫苗研发中良好的应用前景。本文综述了大肠杆菌原核表达系统在基因工程疫苗研究中的应用与策略优化,包括已上市或进入临床疫苗的概述、大肠杆菌表达系统用于疫苗生产的可优化策略(二硫键形成、糖基化以及内毒素去除等),为大肠杆菌重组表达策略改进和基因工程疫苗的研发提供参考。Escherichia coli( E. coli) expression system has been widely used in the manufacture of numerous recombinant protein drugs in light of its excellent characteristics including rapid growth,lower culture cost and welldefined genetic profile. In recent years,several E. coli-derived genetically engineered vaccines have been approved( such as hepatitis E vaccine,human papillomavirus vaccine,meningococcal vaccine,etc.) or entered clinical trials( influenza A,malaria,anthrax vaccine,etc.),manifesting a bright blueprint for E. coli expression system utilized in vaccine development. Here,we review the application of E. coli expression system in genetic engineering vaccine development and suggest some strategies for the utilization improvement,including an synopsis of human vaccines that have been approved or entered clinical trials,and the optimization strategies for protein expression( disulfide bond formation,glycosylation and endotoxin removal,etc.),which shed light on the application and improvement of the expression system focusing on the development of recombinant human vaccines.

关 键 词：大肠杆菌 基因工程疫苗 重组蛋白 戊型肝炎疫苗 人乳头瘤病毒疫苗 脑膜炎球菌疫苗 

分 类 号：R979.5[医药卫生—药品]