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

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

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、k L a、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、k L a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 log 10 TCID 50,相当于2.3×10^5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。

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,k L a,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 k L a 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 log 10 TCID 50,corresponding to 2.3×10^5 doses of vaccine.This research could provide new bioreactor and technology for cell-based vaccine production.