Team Leader (DSP)

Prof. Dr. Michael Wolff
Prof. Dr. Michael Wolff
Phone: +49 391 67 546 76
Fax: +49 391 6110 588
Room: G25-114

Downstream Processing of Influenza Virus

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Downstream Processing of Influenza Virus

Motivation

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.

Aim of the project

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.

<b>Fig. 1</b> <i>Proposal for a complete downstream process for influenza virus (The green box indicate optional downstream units; the red box shows the concentration-limits for the vaccine and the contaminants)</i> Zoom Image
Fig. 1 Proposal for a complete downstream process for influenza virus (The green box indicate optional downstream units; the red box shows the concentration-limits for the vaccine and the contaminants) [less]

References

1.
Kalbfuss, B.; Genzel, Y.; Wolff, M. W.; Zimmermann, A.; Morenweiser, R.; Reichl, U.: Harvesting and concentration of human influenza A virus produced in serum-free mammalian cell culture for the production of vaccines. Biotechnology and Bioengineering 97 (1), pp. 73 - 85 (2007)
2.
Kalbfuss, B.; Wolff, M. W.; Morenweiser, R.; Reichl, U.: Purification of cell culture-derived human influenza A virus by size-exclusion and anion-exchange chromatography. Biotechnology and Bioengineering 96, pp. 932 - 944 (2007)
3.
Opitz, L.; Salaklang, J.; Büttner, H.; Reichl, U.; Wolff, M. W.: Lectin-affinity chromatography for downstream processing of MDCK cell culture derived human influenza A viruses. Vaccine 25 (5), pp. 939 - 947 (2007)
 
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