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Sulphated Cellulose Membranes – An Economic Virus Capturing Method for Influenza Virus Purification

Lars Opitz, Nadine Solf, Udo Reichl, and Michael W. Wolff. Bioprocess Engineering, Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstrasse 1, Magdeburg, 39106, Germany

Influenza is one of the most worldwide spread diseases. Besides antiviral medical treatments, prophylactic vaccinations are crucial to control seasonal influenza epidemics. Hence, every year large amounts of vaccine doses have to be produced. Conventionally, embryonated chicken eggs are used for human influenza vaccine production. This production process has only a limited scalability. In addition, these vaccines contain egg derived proteins which may cause allergic reactions. Hence, cell culture based vaccine production processes have been developed, which require an adapted downstream processing strategy. One unit operation, which is often used in influenza virus purification, is column chromatography based on cellufine® sulphate. The main disadvantage of this method for this application is the limited flow rate due to the high back pressure, leading to a suboptimal productivity rate of the process.

The present study describes a capturing method for cell culture derived influenza viruses based on sulphated reinforced cellulose membranes. Purification studies have been done using different MDCK cell derived influenza virus strains: A/Wisconsin/67/2005 (H3N2), A/Puerto Rico/8/34 (H1N1) and B/Malaysia/2506/2004. Purification efficiency concerning viral yield as well as total protein and host cell dsDNA reduction using sulphated membranes was directly compared to commercially available cation exchange adsorbers and to column based cellufine® sulphate resin. The modified membranes achieved high product recoveries and contaminant reduction. Due to a fast binding kinetic and a low back pressure, membrane adsorbers enable to operate the capturing process at an increased flow rate. Hence, the productivity can be significantly enhanced making them to a valuable choice for industrial influenza vaccine production processes.