Enhancing enterovirus A71 vaccine production yield by microcarrier profusion bioreactor culture

Chia Chyi Liu, Suh Chin Wu, Shang Rung Wu, Hsiao Yu Lin, Meng Shin Guo, Alan Yung-Chih Hu, Yen Hung Chow, Jen Ron Chiang, Dar Bin Shieh, Pele Chong

研究成果: Article同行評審

12 引文 斯高帕斯(Scopus)


Hand, foot and mouth diseases (HFMD) are mainly caused by Enterovirus A71 (EV-A71) infections. Clinical trials in Asia conducted with formalin-inactivated EV-A71 vaccine candidates produced from serum-free Vero cell culture using either roller bottle or cell factory technology, are found to be safe and highly efficacious. To increase vaccine yields and reduce the production costs, the bioprocess improvement for EV-A71 vaccine manufacturing is currently being investigated. The parameters that could affect and enhance the production yields of EV-A71 virus growth in the microcarrier bioreactor were investigated. The medium replacement culture strategy included a multi-harvested semi-batch process and perfusion technology and was found to increase the production yields more than 7–14 folds. Based on the western blot and cryo-EM analyses of the EV-A71 virus particles produced from either the multi-harvested semi-batch (MHSBC) or perfusion cultures were found to be similar to those virus particles obtained from the single batch culture. Mouse immunogenicity studies indicate that the EV-A71 vaccine candidates produced from the perfusion culture have similar potency to those obtained from single batch bioprocess. The physical structures of the EV-A71 particles revealed by the cryo-EM analysis were found to be spherical capsid particles. These results provide feasible technical bioprocesses for increasing virus yields and the scale up of EV-A71 vaccine manufacturing using the bioreactor cell culture methods.

頁(從 - 到)3134-3139
出版狀態Published - 2018 5月 24

All Science Journal Classification (ASJC) codes

  • 分子醫學
  • 一般免疫學和微生物學
  • 一般獸醫學
  • 公共衛生、環境和職業健康
  • 傳染性疾病


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