title: Production of influenza H1N1 vaccine from MDCK cells using a novel disposable packed-bed bioreactor.
abstract: 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 O(2) (DO), agitation, and temperature. During 6 days of culture, the total cell number increased from 2.0 × 10(9) to 3.2 × 10(10) cells. The maximum virus titers of 768 hemagglutinin units/100 μL and 7.8 × 10(7) 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.
authors.affiliation: Nation Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun, 130012, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.forename: Xianghui
authors.initials: X
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
authors.forename: Shiyang
authors.initials: S
authors.lastname: Sun
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Changlin
authors.initials: C
authors.lastname: Zhu
authors.forename: Haihong
authors.initials: H
authors.lastname: Zhang
authors.forename: Yongge
authors.initials: Y
authors.lastname: Wu
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Shi
authors.forename: Xizhen
authors.initials: X
authors.lastname: Zhang
authors.forename: Chunlai
authors.initials: C
authors.lastname: Jiang
mesh_terms: D019149:Bioreactors; D001709:Biotechnology / Q000379:methods*; D003470:Culture Media / Q000737:chemistry; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053118:Influenza A Virus, H1N1 Subtype / Q000254:growth & development / Q000302:isolation & purification*; D007252:Influenza Vaccines / Q000302:isolation & purification*; D061985:Madin Darby Canine Kidney Cells; D010100:Oxygen / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature; D019562:Viral Load; D014776:Virus Cultivation / Q000379:methods
chemical_list: D003470:Culture Media; D007252:Influenza Vaccines; D005947:Glucose; D010100:Oxygen