Development a scalable production process for truncated human papillomavirus type-6 L1 protein using WAVE Bioreactor and hollow fiber membrane

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• 作者：Bo Sun ; Dandan Zhao ; Xizhen Zhang ; Tiejun Gu…
• 关键词：Human papillomavirus type ; 6 ; Sf9 cells ; Virus ; like particle ; Hollow fiber membrane ; Bioreactor
• 刊名：Applied Microbiology and Biotechnology
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：100
• 期：3
• 页码：1231-1240
• 全文大小：782 KB
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• 作者单位：Bo Sun (1)
  Dandan Zhao (1)
  Xizhen Zhang (1)
  Tiejun Gu (1)
  XiangHui Yu (1)
  Shiyang Sun (1)
  Xinghong Zhao (1)
  Liu Wei (3)
  Dawei Liu (2)
  Hui Yan (2)
  Xiangyu Meng (1)
  Wei Kong (1)
  Fei Xu (1)
  Ping Yang (2)
  Chunlai Jiang (1)
  
  1. Nation Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun, 130012, China
  3. Jilin Medical University, Jilin City, Jilin Province, 132013, China
  2. BCHT Biotechnology Company, Changchun, 130012, China
  
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Chemistry
  Biotechnology
  Microbiology
  Microbial Genetics and Genomics
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0614

文摘

Here, we describe a process for expression, purification, and characterization of truncated human papillomavirus type-6 (HPV-6) L1 virus-like particles (VLPs). The scalable cultivation process in a WAVE Bioreactor at the 10-L scale was optimized to express HPV-6 L1 VLPs using the baculovirus insect expression system. A hollow fiber membrane system was used for the integrated operation, including concentration, diafiltration, extraction, and clarification. The HPV-6 L1 protein was further purified by anion-exchange chromatography and hydrophobic chromatography. The HPV-6 L1 protein could self-assemble into VLPs with a diameter of approximately 50–60 nm after removal of the reductant dithiothreitol (DTT). The final purified HPV-6 L1 VLPs product was characterized to estimate yield and purity, and exceeds the requirements for pharmaceutical-grade VLP vaccine. Immunization of mice demonstrated that the vaccine could elicit high titer neutralizing antibodies in vivo. This study confirms the feasibility of producing pharmaceutical-grade HPV type-6 L1 VLPs on an industrial scale for clinical trials.