Membrane chromatography is consistently used for the purification of viral particles such as adenoviruses or influenza viruses. Chromatographic membranes exhibit high mass transfer rates for large biological particles, e.g. viruses in a pre-packed, disposable format, making them a viable alternative to the commonly used resin-based column chromatography. The recent COVID crisis has undermined the need for robust and scalable purification processes of virus-based therapeutics. In this work, we present the application of convective chromatography membranes for the purification of adenovirus. Adenoviruses are a gene delivery vehicle for recombinant viruses, especially recently developed and manufactured vector vaccines against the SARS-COV-19. The results document that the quality of an adenovirus-based product is achieved with a two-step process using Q and STIC ion exchangers. Further, economic advantages by using membrane chromatography are presented. Secondly, an optimized cellulose-based chromatographic membrane is presented with optimized pore size, specific surface area, and ligand accessibility designed to capture large target molecules. This membrane utilizes highly selective pseudo-affinity ligands for influenza viruses, resulting in a significantly higher binding capacity without compromising on selectivity and product recovery. The performance of the sulfated cellulose membrane adsorber is evaluated in comparison with commercially available sulfated carbohydrate resins, with three different influenza virus strains produced in a cell culture. The unique capabilities of this membrane-based separation media not only contribute to the cost reduction associated with the capture-step in purification trains of virus particles, but - due to its ease-of-use and single-(batch-)use character – also constitute one step forward in the development of an optimized and efficient platform process for the viral-vaccine industry.

Improved matrix design and interaction principles for membrane chromatography of virus based therapeutics

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.