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中国生物工程杂志

China Biotechnology
China Biotechnology  2021, Vol. 41 Issue (11): 74-81    DOI: 10.13523/j.cb.2106011
    
Research Progress of Human Diploid Cells for Vaccine Production
XIAO Yun-xi1,ZHANG Jun-he1,2,3,**(),YANG Wen-wen2,3,CHENG Hong-wei1
1 Institutes of Health Central Plains, Xinxiang Medical University, Xinxiang 453003, China
2 Department of Biochemistry and Molecular Biology, Xinxiang Medical University, Xinxiang 453003, China
3 Henan International Joint Laboratory of Recombinant Pharmaceutical Protein Expression System, Xinxiang Medical University, Xinxiang 453003, China
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Abstract  

Human diploid cells (HDCs) have attracted much attention as an important culture cell matrix for vaccine preparation. Since human diploid cells are the same as the human genome without exogenous factor, susceptible to a variety of viruses, and without potential tumorigenicity, and the preparation of human diploid cell vaccine (HDCV) has good immunogenicity and safety, they are suitable for industrial production of vaccine. Currently, the inactivated, attenuated or subunit vaccines used in the population all rely on primary cells, continuous cells and human diploid cells, of which WI-38, MRC-5, 2BS and KMB-17 cell lines are the main human diploid cells used in vaccine preparation. However, human diploid cells are limited cells, and there are some defects in cell sources and culture techniques, which further affect their application. In this paper, the research progress of human diploid cells used in vaccine production and vaccine preparation technology were reviewed, and the existing problems and improvement strategies were analyzed.



Key wordsHuman diploid cells      Vaccine      Cell line      Vaccine preparation technology     
Received: 08 June 2021      Published: 01 December 2021
ZTFLH:  Q819  
Corresponding Authors: Jun-he ZHANG     E-mail: zjh@xxmu.edu.cn
Cite this article:

XIAO Yun-xi,ZHANG Jun-he,YANG Wen-wen,CHENG Hong-wei. Research Progress of Human Diploid Cells for Vaccine Production. China Biotechnology, 2021, 41(11): 74-81.

URL:

https://manu60.magtech.com.cn/biotech/10.13523/j.cb.2106011     OR     https://manu60.magtech.com.cn/biotech/Y2021/V41/I11/74

细胞 首次发现来源 研发应用
WI-38 1961年人胚胎肺组织 狂犬病毒、脊髓灰质炎病毒、甲型肝炎病毒、麻疹病毒等
MRC-5 1966年人胚胎肺组织 狂犬病毒、风疹病毒、麻疹病毒等
2BS 1973年人胚胎肺组织 甲型肝炎疫苗、脊髓灰质炎疫苗、EV71病毒疫苗、腮腺炎病毒、流感病毒等
KMB-17 1981年人胚胎肺组织 甲型肝炎病毒、脊髓灰质炎病毒、登革热病毒等
Walvax-2 2015年人胚胎肺组织 甲型肝炎病毒、狂犬病毒、水痘病毒等
Table 1 Application of main human diploid cells in vaccine development
细胞途径 细胞途径的调整策略 对病毒生长特性的影响
脂质代谢 脂肪酸和磷脂的生物合成增加
脂质生物合成酶的表达或活性增加
脂质生物合成相关转录因子的募集
减少脂质氧化
脂质摄取机制的上调
脂质补充剂提高了逆转录病毒和慢病毒载体的产量
脂质补充增加了逆转录病毒和慢病毒载体的稳定性
脂质的补充可使HIV-VLP的产量提高2.4倍
在非肝细胞中表达脂质代谢基因以全面重建HCV生命周期
蛋白质加工和翻译后修饰
细胞周期和凋亡的调控 改变宿主蛋白质合成机制
宿主糖基化机制的调节和糖基转移酶的差异激活
控制细胞周期检查点以提高病毒复制效率
对抗促凋亡机制,增强抗凋亡防御,或编码抗凋亡基因同源基因
过表达囊泡运输蛋白munc18b可使慢病毒载体滴度增加2倍
糖基化模式的工程使逆转录病毒载体的稳定性提高了3.5倍
化学阻断介导的细胞周期同步化结合温度变化使腺病毒载体的产量增加了7.3倍
下调促凋亡的细胞内天然防御系统使流感病毒产量增加9倍,慢病毒和腺病毒载体增加5~10倍,辛德比斯病毒增加100倍
Table 2 Effects of different cellular pathways changes in cellular genetic engineering on virus growth characteristics
病毒 优点 缺点
痘病毒 批准的兽用疫苗MVA载体临床安全,可插入大的基因序列,有多个稳定的毒株可获得 已接种天花疫苗可能有预存免疫问题;可能需要多次免疫,增加复杂性和成本
腺病毒
腺相关病毒
已有口服腺病毒疫苗,很强的免疫应答,许多毒株可以获得
在眼部疾病治疗中,作为小基因片段的载体具有非常明显的效果;在小基因片段试验中安全性高
对某种毒株存在的免疫可能需要排除,人类腺病毒株在动物体内发现有致癌性
安全性存在质疑;插入的基因片段大小有限
假病毒 病毒粒子或DNA复制子高表达,因为RNA粒子可以激活树突状细胞(DC),没有基因整合的担忧 基因的容量适中
疱疹病毒 对包括DC在内的多种细胞有趋化性 亲神经性可能导致安全问题,可能存在预存免疫
麻疹病毒 可能通过黏膜免疫;RNA病毒,无基因整合的担忧 可能存在预存免疫
水疱性口炎病毒 对包括DC在内的多种细胞有趋化性 亲神经性可能导致安全问题
Table 3 Advantages and disadvantages of viral vectors in vaccine development
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