Investigation of cell culture conditions for optimal foot-and-mouth disease virus production

BMC Biotechnol. 2019 Jun 7;19(1):33. doi: 10.1186/s12896-019-0527-5.

Abstract

Background: Foot-and-mouth disease is a highly contagious and economically devastating disease with endemic occurrence in many parts of the world. Vaccination is the method of choice to eradicate the disease and to limit the viral spread. The vaccine production process is based on mammalian cell culture, in which the viral yield varies in dependence of the composition of the culture media. For foot-and-mouth disease virus (FMDV), very little is known about the culture media components that are necessary to grow the virus to high titers in cell culture.

Results: This study examined the influence of increasing concentrations of glucose, glutamine, ammonium chloride and different cell densities on the yield of FMDV. While an excess of glucose or glutamine does not affect the viral yield, increasing cell density reduces the viral titer by a log10 step at a cell density of 3 × 106 cells/mL. This can be mitigated by performing a 100% media exchange before infection of the cells.

Conclusions: The reasons for the diminished viral growth, if no complete media exchange has been performed prior to infection, remain unclear and further studies are necessary to investigate the causes more deeply. For now, the results argue for a vaccine production process with 100% media exchange to reliably obtain high viral titers.

Keywords: Animal-component free; Cell density; Foot-and-mouth disease virus; Glucose; Glutamine; Suspension cells; Vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ammonium Compounds / pharmacology
  • Animals
  • Cell Count
  • Cell Culture Techniques / methods*
  • Cell Survival / drug effects
  • Cell Survival / immunology
  • Cricetinae
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / virology
  • Foot-and-Mouth Disease / immunology
  • Foot-and-Mouth Disease / prevention & control*
  • Foot-and-Mouth Disease / virology
  • Foot-and-Mouth Disease Virus / immunology*
  • Foot-and-Mouth Disease Virus / metabolism
  • Foot-and-Mouth Disease Virus / physiology
  • Glucose / pharmacology
  • Glutamine / pharmacology
  • Vaccination / methods
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / immunology*
  • Viral Vaccines / metabolism
  • Virus Replication / drug effects
  • Virus Replication / immunology*

Substances

  • Ammonium Compounds
  • Viral Vaccines
  • Glutamine
  • Glucose