The processes of influenza vaccine production are studied experimentally and theoretically. In industrial vaccine production processes mammalian host cells become infected by the seed virus. These cells produce infectious virions which infect further host cells. In order to monitor the progress of an infection and to correlate the infection status with other physiological parameters we investigate samples from bioreactors on a single-cell level with flow cytometry.

The gained quantitative data provides the basis for mathematical modeling. Mathematical models developed within this project deal with the interaction of cell and virus population in a bioreactor (Fig. 1). Used as a starting point is a reduced single cell model of influenza virus replication, which was derived by lumping together the linear sequences of infection steps in the detailed single cell model. Structure parameters are represented by the number of viral components in different cellular compartments (e.g., the number of virions on the surface of the cell, the number of viral messenger RNA in the cytoplasm and in the nucleus, the number of viral proteins in the cytoplasm). For the model formulation either population balances or kinetic Monte-Carlo approaches are considered.

Figure 1. Laser-scan microscope picture (LSM 510, Zeiss, 200x) of Madin-Darby canine kidney (MDCK) cells infected with equine influenza A virus, stained with Influenza A-specific FITC-conjugated monoclonal antibodies.

Figure 2. Flow cytomety FITC (green) fluorescence histograms (Epics XL, Beckman Coulter) of equine influenza MDCK cells stained with FITC-conjugated monoclonal antibodies against Influenza A virus.

Interconnections with other projects of Bioprocess Engineering

Hierarchical Structures

Influenza Virus Replication in MDCK Cells

Coupled Processes

Physiological Status of Mammalian Cells during Growth and Viral Infection

Interconnections with other research groups

Process Synthesis and Process Dynamics (Prof. Dr.-Ing. Achim Kienle)

back to overview on bioprocess engineering