Production of influenza H1N1 vaccine from MDCK cells using a novel disposable packed-bed bioreactor

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• 作者：Bo Sun (1)
  XiangHui Yu (1)
  Wei Kong (1)
  Shiyang Sun (1)
  Ping Yang (2)
  Changlin Zhu (2)
  Haihong Zhang (1)
  Yongge Wu (1)
  Yan Chen (1)
  Yuhua Shi (1)
  Xizhen Zhang (1)
  Chunlai Jiang (1)
  
• 关键词：Influenza virus ; MDCK cells ; Vaccine production ; Bioreactor
• 刊名：Applied Microbiology and Biotechnology
• 出版年：2013
• 出版时间：February 2013
• 年：2013
• 卷：97
• 期：3
• 页码：1063-1070
• 全文大小：392KB
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• 作者单位：Bo Sun (1)
  XiangHui Yu (1)
  Wei Kong (1)
  Shiyang Sun (1)
  Ping Yang (2)
  Changlin Zhu (2)
  Haihong Zhang (1)
  Yongge Wu (1)
  Yan Chen (1)
  Yuhua Shi (1)
  Xizhen Zhang (1)
  Chunlai Jiang (1)
  
  1. Nation Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun, 130012, China
  2. BCHT Biotechnology Company, Changchun, 130012, China
  
• ISSN：1432-0614

文摘

A process for human influenza H1N1 virus vaccine production from Madin–Darby canine kidney (MDCK) cells using a novel packed-bed bioreactor is described in this report. The mini-bioreactor was used to study the relationship between cell density and glucose consumption rate and to optimize the infection parameters of the influenza H1N1 virus (A/New Caledonia/20/99). The MDCK cell culture and virus infection were then monitored in a disposable perfusion bioreactor (AmProtein Current Perfusion Bioreactor) with proportional–integral–derivative control of pH, dissolved O2 (DO), agitation, and temperature. During 6?days of culture, the total cell number increased from 2.0?×-09 to 3.2?×-010 cells. The maximum virus titers of 768 hemagglutinin units/100?μL and 7.8?×-07 50?% tissue culture infectious doses/mL were obtained 3?days after infection. These results demonstrate that using a disposable perfusion bioreactor for large-scale cultivation of MDCK cells, which allows for the control of DO, pH, and other conditions, is a convenient and stable platform for industrial-scale production of influenza vaccines.