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Vaccine. 2009 May 5;27(20):2712-22. doi: 10.1016/j.vaccine.2009.02.027. Epub 2009 Feb 20.

Infection dynamics and virus-induced apoptosis in cell culture-based influenza vaccine production-Flow cytometry and mathematical modeling.

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Max Planck Institute for Dynamics of Complex Technical Systems, Bioprocess Engineering, Sandtorstrasse 1, 39106 Magdeburg, Germany.


Cell culture-based influenza vaccine manufacturing is of growing importance. Depending on virus strains, differences in infection dynamics, virus-induced apoptosis, cell lysis and virus yields are observed. Comparatively little is known concerning details of virus-host cell interaction on a cellular level and virus spreading in a population of cells in bioreactors. In this study, the infection of MDCK cells with different influenza A virus strains in lab-scale microcarrier culture was investigated by flow cytometry. Together with the infection status of cells, virus-induced apoptosis was monitored. A mathematical model has been formulated to describe changes in the concentration of uninfected and infected adherent cells, dynamics of virus particle release (infectious virions, hemagglutinin content), and the time course of the percentage composition of the cell population.

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