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

Appl Microbiol Biotechnol. 2013 Feb;97(3):1063-70. doi: 10.1007/s00253-012-4375-7. Epub 2012 Sep 4.

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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bioreactors*
  • Biotechnology / methods*
  • Culture Media / chemistry
  • Glucose / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Influenza A Virus, H1N1 Subtype / growth & development
  • Influenza A Virus, H1N1 Subtype / isolation & purification*
  • Influenza Vaccines / isolation & purification*
  • Madin Darby Canine Kidney Cells
  • Oxygen / metabolism
  • Technology, Pharmaceutical / methods*
  • Temperature
  • Viral Load
  • Virus Cultivation / methods

Substances

  • Culture Media
  • Influenza Vaccines
  • Glucose
  • Oxygen