Downstream Processing of Influenza Virus
Influenza with its high morbidity and high mortality of up to half a million people per year (WHO, 2003) still belongs to the most important respiratory infection diseases. However, the greatest risk bears the high zoonotic potential due to antigenic shift as the pandemic outbreak in 2009 had shown. Disease-control is usually focused on prophylactic vaccination with inactivated viral vaccines in combination with antiviral medications. While most influenza vaccines are still produced in eggs, limited scalability and potential allergic reaction related to egg proteins have induced a change in industrial-processes to cell culture-based production (e.g. with MDCK or Vero cells). These changes require new downstream processes.
The project goal is the development of a complete downstream process for influenza virus with special focus on the contaminant levels requested from the vaccine manufacturer. The so far established chromatographic methods are not capable to reduce the DNA contamination sufficiently so far receiving therefore special attention within the project. In that context a variety of (novel) resin types, salt types and chromatography modes are tested for optimal yields and purities.
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Kalbfuss, B., M. Wolff, R. Morenweiser and U. Reichl (2007). "Purification of cell culture-derived human influenza a virus by size-exclusion and anion-exchange chromatography." Biotechnology and Bioengineering 96(5): 932-944.
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