Pseudo-affinity capture of cell culture derived influenza virus particles by sulphated cellulose membranes : an economic tool for vaccine production

Influenza is a contagious respiratory illness that can cause mild to severe symptoms and can lead to death. Control of annual spreading of influenza has centered on prophylactic vaccinations in combination with antiviral medications. Currently, efforts are undertaken to switch from conventional vaccine production processes using embryonated hen’s eggs, to continuous cell line cultures. Therefore, new downstream processing strategies have to be developed. 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