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Abstract

Viral vaccines play an important role in the prevention, control and eradication of infectious diseases. Due to their enormous economical importance and difficulties in controlling existing or up-coming risks, development of vaccines is still in the focus of todays research. When changing from vaccine production in chicken eggs to animal cell culture based bioprocesses in roller bottles or microcarrier systems, many aspects of upstream as well as downstream processing have to be evaluated. Our main goal is to develop integrated concepts to optimize such processes. As an example we investigate equine influenza replication (equine influenza Newmarket 1/93 H3N8) in MDCK cells in roller bottles and largescale microcarrier systems. Based on extensive experimental data from different process levels and a thorough analysis of theoretical aspects by mathematical modeling, yield and reproducibility of vaccine production processes as well as efficacy, purity and safety of the vaccine can be improved considerably. At present, we focus on optimization of cell growth and virus titers in large-scale cultures, scale-up, high cell density cultivations and characterization of virus particles. Therefore, we analyze standard on-line data together with off-line data such as the concentration of glucose, lactate, ammonia, glutamine, glutamate, LDH, cell infection and virus titers. Additionally, the amino acid composition is measured. These profiles during cell growth and virus production will be compared with other on- & off-line data, to evaluate the importance of some amino acids during different phases of cell metabolism. Results from roller bottle experiments and five liter microcarrier cultivation will de discussed.