Abstract
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.
Highlights
Foot-and-mouth disease (FMD), caused by an aphthovirus of the family Picornaviridae (FMD virus, Foot-and-mouth disease virus (FMDV)), remains a threat to industrial and developing countries alike for diverse reasons
Cells were grown at increasing cell densities and either 100% media exchange or addition of 30% fresh media was performed before infection with FMDV
Up to 1.7% of antifoam in the cell culture media had no significant impact on the viral yield, even though a decreasing trend was evident above a concentration of 0.3%
Summary
Foot-and-mouth disease (FMD), caused by an aphthovirus of the family Picornaviridae (FMD virus, FMDV), remains a threat to industrial and developing countries alike for diverse reasons. East still suffer from its endemic occurrence [3]. In these countries, FMD threatens the livelihood of farmers, independent of farm size due to losses in milk and meat production as well as the death of young animals [4]. Vaccination campaigns, supported by the Food and Agriculture Organization of the United Nations (FAO) and the World Organisation for Animal Health (OIE), are an important tool to eradicate FMD in endemic areas. Suitable vaccines prevent clinical disease and reduce viral spread [5]. Such programs can become quite cost-intensive, especially due to the short shelf life of the vaccine and the necessity to re-vaccinate every four to twelve months [5]. FMD vaccines are traditionally produced in Viruses 2019, 11, 511; doi:10.3390/v11060511 www.mdpi.com/journal/viruses
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