生物学杂志

生物学杂志 ›› 2021, Vol. 38 ›› Issue (1): 106-.doi: 10.3969/j.issn.2095-1736.2021.01.106

• 技术方法 • 上一篇    下一篇

新型固定床生物反应器在细胞源猪伪狂犬病毒生产中的应用

  

  1. 1. 江南大学 粮食发酵工艺与技术国家工程实验室， 无锡 214122; 2. 江南大学 工业生物技术教育部重点实验室， 无锡 214122; 3. 江南大学 生物工程学院， 无锡 214122
  • 出版日期:2021-02-18 发布日期:2021-02-22
  • 通讯作者: 白仲虎，教授，研究方向为生物医药蛋白的高效表达及发酵过程，E-mail: baizhonghu@jiangnan.edu.cn
  • 作者简介:聂简琪，博士研究生，研究方向为疫苗工艺开发，E-mail: 903551042@qq.com
  • 基金资助:
    国家自然科学基金（No. 21878124，31570034）；111计划（No.111-2- 06）；泰山产业领军人才（No. tscy20160307）

The application of novel fixed-bed bioreactor in cell-based pseudorabies virus production#br#

  1. 1．National Engineering Laboratory of Cereal Fermentation Technology, Jiangnan University, Wuxi 214112, China；2. Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China；3. School of Biotechnology, Jiangnan University, Wuxi 214122, China
  • Online:2021-02-18 Published:2021-02-22

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摘要： 针对目前固定床生物反应器结构复杂、易产生泡沫等缺点，研发结构简单且可无泡通气的新型固定床生物反应器，并对该反应器的混合时间、kLa、细胞分布均匀性和细胞捕获能力进行测定。并进一步利用该反应器实施低密度接种Vero细胞进行细胞培养并扩增猪伪狂犬病毒。试验结果表明，该新型固定床反应器的混合时间、kLa与传统STR反应器相当，细胞捕获能力良好且细胞在反应器中分布均匀。采用低密度接种时Vero细胞可在该反应器中进行良好的生长，接毒5 d后累计收获的病毒总颗粒数达到10.37 log10 TCID50，相当于2.3×105剂量疫苗。该研究为细胞源疫苗的生产提供了新的反应器与技术。

关键词: 固定床生物反应器, Vero细胞, 猪伪狂犬病毒, 低密度接种, 疫苗

Abstract: To overcome the drawback of complex structure and foaming aeration of available fixed-bed bioreactor, a simple structure fixed-bed bioreactor with bubble free aeration was developed. The mixing time, kLa, cell distribution and cell capture ability of the reactor were tested. Then, the bioreactor was inoculated with Vero cells in low density to produce pseudorabies virus. The results showed that the mixing time and kLa of this bioreactor were comparable to that of STR. Also, the bioreactor showed good cell capture ability and homogeneous distribution. Vero cells grew well in this bioreactor with low cell inoculum density, and the cumulative virus particles on the 5th day post infection reached 10.37 log10 TCID50, corresponding to 2.3×105 doses of vaccine. This research could provide new bioreactor and technology for cell-based vaccine production.

Key words: fixed-bed bioreactor, Vero cells, pseudorabies virus, low cell inoculum density, vaccine

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