Flavivirus production in animal cell culture

Flavivirus production in animal cell culture


The genus Flavivirus encompasses multiple viruses, such as yellow fever virus, Zika virus, West Nile virus, Dengue virus, and many more. They are typically circulating between primates and mosquitoes in a sylvatic transmission cycle. Accidental transmission of the virus to a person can cause very serious diseases. If these viruses spread to highly populated regions, such viruses can emerge and local outbreaks can turn into serious human threats at global level.

The lack of therapies for disease treatment renders vaccination into the only preventive countermeasure. Current yellow fever vaccine manufacturing processes rely on chicken eggs, a slow and elaborate method which cannot be simply ramped up as vaccine demands promptly increase.

Aim of the project

We investigate cell culture-based production processes using bioreactors to overcome limitations of current egg-based manufacturing processes. We develop a next-generation virus production platform, ideally transferable to a wide range of different flaviviruses, i.e. by process intensification and control for operation of high-cell-density perfusion cultivations with optimal infection conditions.

Fig. 1 Flaviviruses propagate in different cell substrates. For virus production, it is therefore of great interest to intensify cell concentrations. This sample from a perfusion bioreactor shows sedimented EB66 cells representing 30% of the volume of the total cultivation broth.


Nikolay, A.; Léon, A.; Schwamborn, K.; Genzel, Y.; Reichl, U.: Process intensification of EB66 ® cell cultivations leads to high-yield yellow fever and Zika virus production. Applied Microbiology and Biotechnology 102 (20), pp. 8725 - 8737 (2018)
Gallo Ramirez, L. E.; Nikolay, A.; Genzel, Y.; Reichl, U.: Bioreactor concepts for cell culture-based viral vaccine production. Expert Review of Vaccines 14 (9), pp. 1181 - 1191 (2015)
Nikolay, A.; Scharfenberg, K.; Patel, P.; Niedrig, M.; Genzel, Y.; Reichl, U.: Towards yellow fever 17D virus production in Vero suspension cells. ESACT, Barcelona (2015)
Nikolay, A.; Casthilho, L. R.; Reichl, U.; Genzel, Y.: Propagation of Brazilian Zika virus strains in static and suspension cultures using Vero and BHK cells. Vaccine 36 (28), pp. 3140 - 3145 (2018)
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