Development of Membrane Adsorbers for Virus Purification Processes

Development of Membrane Adsorbers for Virus Purification Processes


Viruses are large bioparticles, which vary in surface structure, size, shape, and composition. For manufacturing of vaccines produced in cell culture or eggs, inhomogeneous mixtures of whole virus particles have to be separated from a complex blend of process- and product-related impurities. Obviously, this task can only be achieved by a combination of different unit operations in downstream processing, whereby chromatographic techniques represent commonly an integral part. Solid phases used for these applications include porous particles, membrane adsorbers and monoliths. The main advantage of the latter two is not only the predominant convective mass transport of the sample but also a comparatively high binding capacity for macromolecules. In particular, the convective mass transport eliminates or reduces diffusion limitations of the solutes allowing high flow rates, which has a positive impact on process productivity.

Aim of the project

Porous beads with pseudo-affinity ligands are commonly used in virus purification processes. However, pseudo-affinity membranes and monolithic materials relying primarily on convective mass transport provide options to design more efficient processes with significant improvements in productivity. In order to take advantage of this technology we are developing and optimizing membrane adsorbers as a platform technology to purify or deplete a variety of viruses, e.g. influenza virus, vaccinia virus, and baculovirus. 

Fig. 1. Binding capacities of cell culture derived influenza virus A (H1N1) on optimized sulfated cellulose membrane adsorbers compared to the bead based resins CellufineTM sulfate and CaptoTM DeVirs.


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)
Carvalho, S. B.; Fortuna, A. R.; Wolff, M. W.; Peixoto, C.; Alves, P. M.; Reichl, U.; Carrondo, M. J. T.: Purification of influenza virus-like particles using sulfated cellulose membrane adsorbers. Journal of Chemical Technology and Biotechnology 93 (7), pp. 1988 - 1996 (2018)
Wolff, M.; Siewert, C.; Lehmann, S.; Hansen, S.P.; Djurup, R.; Faber, R.; Reichl, U.: Capturing of Cell Culture-Derived Modified Vaccinia Ankara Virus by Ion Exchange and Pseudo-Affinity Membrane Adsorbers. Biotechnology and Bioengineering 105 (4), pp. 761 - 769 (2010)
Wolff, M.; Siewert, C.; Hansen, S. P.; Faber, R.; Reichl, U.: Purification of cell culture-derived modified Vaccinia Ankara virus by pseudo-affinity membrane adsorbers and hydrophobic interaction chromatography. Biotechnology and Bioengineering 107 (2), pp. 312 - 320 (2010)
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)


Post Hansen, S.; Faber, R.; Reichl, U.; Wolff, M.W.:
Purification Of Vaccinia Viruses Using Hydrophobic Interaction Chromatography.
Patent US 8470578 B2 (2013)
Wolff, M.W.; Reichl, U.; Opitz, L.:
Method for the preparation of sulfated cellulose membranes and sulfated cellulose membranes.
Patent EP 2144937 B1 (2012)
Patent US 8,173,021 B2 (2012)
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