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Biotechnol Prog. 2011 Jan-Feb;27(1):241-50. doi: 10.1002/btpr.539. Epub 2011 Jan 7.

High-density microcarrier cell cultures for influenza virus production.

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Max Planck Institute for Dynamics of Complex Technical Systems, Bioprocess Engineering, 39106 Magdeburg, Germany.


Influenza virus A/PR/8/34 virus propagation in adherent Madin-Darby canine kidney cells in high-density microcarrier cultures is described. To improve virus yields, perfusion and repeated fed-batch modes were applied using cell-specific feed rates. Cell densities up to 1.1 × 10(7) cells/mL were achieved. Cell-specific virus yields in high-density cultures were at similar levels compared with standard, low-density cultivations. In the average 2,400 and 3,300 virions per cell were obtained for two variants of the virus strain A/PR/8/34, PR8-National Institute for Biological Standards and Control (NIBSC) and PR8-Robert Koch Institute, respectively. Maximum virus titer (HA activity = 1,778 HAU/100 μL) for virus variant PR8-NIBSC was obtained for a cultivation infected before maximum cell concentration was reached.

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