Downstream processing of cell culture-derived virus particles

Abstract

Manufacturing of cell culture-derived virus particles for vaccination and gene therapy is a rapidly growing field in the biopharmaceutical industry. The process involves a number of complex tasks and unit operations ranging from selection of host cells and virus strains for the cultivation in bioreactors to the purification and formulation of the final product. For the majority of cell culture-derived products, efforts focused on maximization of bioreactor yields, whereas design and optimization of downstream processes were often neglected. Owing to this biased focus, downstream procedures today often constitute a bottleneck in various manufacturing processes and account for the majority of the overall production costs. For efficient production methods, particularly in sight of constantly increasing economic pressure within human healthcare systems, highly productive downstream schemes have to be developed. Here, we discuss unit operations and downstream trains to purify virus particles for use as vaccines and vectors for gene therapy.

A Genotype of Modified Vaccinia Ankara (MVA) that Facilitates Replication in Suspension Cultures in Chemically Defined Medium

“…If only culture supernatant, and not a complete lysate, needs to be purified, such levels should be obtained more easily. Because downstream processing contributes significantly to the costs of injectable vaccines [43] a strain with simplified purification requirements may help to reduce economic pressures on MVA-based vaccines.…”

Optimization and miniaturization of aqueous two phase systems for the purification of recombinant human immunodeficiency virus-like particles from a CHO cell supernatant

“…However, there are still barriers to achieving high recovery efficiencies and maintaining the product quality after the downstream processing. The separation techniques currently used for purification of VLPs take advantage of the relatively large size of the particles and are based on gradient ultracentrifugation, ultrafiltration, precipitation or size exclusion chromatography (SEC) [4]. However, all these methods share general drawbacks and are in general labor-intensive, timeconsuming and not easily amenable to scaling-up [5].…”

High-Purity Preparation of HSV-2 Vaccine Candidate ACAM529 Is Immunogenic and Efficacious In Vivo

“…As reviewed by Wolf et al [37], cell culture-derived virus particles are of increasing importance medicinally. A variety of downstream processing methods for generation of cell culture derived virus particles have been described (reviewed by [37]).…”