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Mathematical Model of Influenza A Virus Production in Large-Scale Microcarrier Culture

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http://pubman.mpdl.mpg.de/cone/persons/resource/persons86410

Möhler,  L.
Bioprocess Engineering, Max Planck Institute for Dynamics of Complex Technical Systems, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons86167

Flockerzi,  D.
Systems and Control Theory, Max Planck Institute for Dynamics of Complex Technical Systems, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons86461

Sann,  H.
Bioprocess Engineering, Max Planck Institute for Dynamics of Complex Technical Systems, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons86448

Reichl,  U.
Otto-von-Guericke-Universität Magdeburg;
Bioprocess Engineering, Max Planck Institute for Dynamics of Complex Technical Systems, Max Planck Society;

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Citation

Möhler, L., Flockerzi, D., Sann, H., & Reichl, U. (2005). Mathematical Model of Influenza A Virus Production in Large-Scale Microcarrier Culture. Biotechnology and Bioengineering, 90(1), 46-58. doi:10.1002/bit.20363.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0013-9CEF-1
Abstract
A mathematical model that describes the replication of influenza A virus in animal cells in large-scale microcarrier culture is presented. The virus is produced in a two-step process, which begins with the growth of adherent Madin-Darby canine kidney (MDCK) cells. After several washing steps serum-free virus maintenance medium is added, and the cells are infected with equine influenza virus (A/Equi 2 (H3N8), Newmarket 1/93). A time-delayed model is considered that has three state variables: the number of uninfected cells, infected cells, and free virus particles. It is assumed that uninfected cells adsorb the virus culture.at the time of infection. The infection rate is proportional to the number of uninfected cells and free virions.Depending on multiplicity of infection (MOI), not necessarily all cells are infected by this first step leading to the production of free virions. Newly produced viruses can infect the remaining uninfected cells in a chain reaction. To follow the time course of virus replication, infected cells were stained with fluorescent antibodies. Quantitation of influenza viruses by a hemagglutination assay (HA) enabled the estimation of the total number of new virions produced, which is relevant for the production of inactivated influenza vaccines.