Downstream Processing of Influenza Virus

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.

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.

Fig. 1. Proposal for a complete downstream process for influenza virus including two membrane based chromatographic purification steps: Sulfated cellulose membrane adsorbers (SCMA) and Sartobind STIC®PA [1].


Weigel, T.; Solomaier, T.; Wehmeyer, S.; Peuker, A.; Wolff, M. W.; Reichl, U.: A membrane-based purification process for cell culture-derived influenza A virus. Journal of Biotechnology 220, pp. 12 - 20 (2016)
Fortuna, A. R.; Taft, F.; Villain, L.; Wolff, M. W.; Reichl, U.: Optimization of cell culture-derived influenza A virus particles purification using sulfated cellulose membrane adsorbers. Engineering in Life Sciences 18 (1), pp. 29 - 39 (2018)
Weigel, T.; Solomaier, T.; Peuker, A.; Pathapati, T.; Wolff, M. W.; Reichl, U.: A flow-through chromatography process for influenza A and B virus purification. Journal of Virological Methods 207, pp. 45 - 53 (2014)
Opitz, L.; Lehmann, S.; Reichl, U.; Wolff, M. W.: Sulfated membrane adsorbers for economic pseudo-affinity capture of influenza virus particles. Biotechnology and Bioengineering 103 (6), pp. 1144 - 1154 (2009)
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