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Open AccessArticle

Cell Density Effects in Different Cell Culture Media and Their Impact on the Propagation of Foot-And-Mouth Disease Virus

1
Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Südufer 10, 17493 Greifswald–Insel Riems, Germany
2
Merck KGaA, Merck Life Sciences, Upstream R&D, Frankfurter Straße 250, 64293 Darmstadt, Germany
*
Author to whom correspondence should be addressed.
Viruses 2019, 11(6), 511; https://doi.org/10.3390/v11060511
Received: 20 February 2019 / Revised: 16 May 2019 / Accepted: 4 June 2019 / Published: 4 June 2019
(This article belongs to the Section Animal Viruses)
Foot-and-mouth disease virus (FMDV) is endemic in many parts of the world. Vaccination is an important control measure, limits viral spread, and can help to eradicate the disease. However, vaccination programs are cost-intensive because of the short shelf life of vaccines and the need for frequent re-vaccination. Animal-component-free (ACF) or chemically defined media (CDM) at high cell densities are a promising approach for the production of inexpensive high-quality vaccines, but the occurrence of cell density effects has been reported for various virus-cell systems in vaccine production. For FMDV, the use of CDM or ACF media for vaccine production has not been studied and no information about cell density effects is available. This work describes the propagation of FMDV in ACF or in CDM. Cells were grown at increasing cell densities and either 100% media exchange or addition of 30% fresh media was performed before infection with FMDV. Increasing cell densities reduced the viral titer and increased yield variability in all media except BHK300G. This effect can be mitigated by performing a 100% media exchange before infection or when using the controlled environment of a bioreactor. The media composition and also a fragile relationship between virus and cell metabolism seem to be causal for that phenomenon. View Full-Text
Keywords: foot-and-mouth disease virus; cell density; animal-component-free media; chemically defined media; antifoam; suspension cells foot-and-mouth disease virus; cell density; animal-component-free media; chemically defined media; antifoam; suspension cells
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Dill, V.; Ehret, J.; Zimmer, A.; Beer, M.; Eschbaumer, M. Cell Density Effects in Different Cell Culture Media and Their Impact on the Propagation of Foot-And-Mouth Disease Virus. Viruses 2019, 11, 511.

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