Fed-batch strategies for intensified rVSV vector production in high cell density cultures of suspension HEK293 cells.

Publication date: Sep 17, 2024

Vesicular stomatitis virus (VSV) has been increasingly demonstrated as a promising viral vector platform. As the interest over this modality for vaccine and gene therapy applications increases, the need for intensified processes to produce these vectors emerge. In this study, we develop fed-batch-based operations to intensify the production of a recombinant VSV-based vaccine candidate (rVSV-SARS-CoV-2) in suspension cultures of HEK293 cells. A feeding strategy, in which a commercial concentrated medium was added to cultures based on cell growth through a fixed cell specific feeding rate (CSFR), was applied for the development of two different processes using Ambr250 modular bioreactors. Cultures operated in hybrid fed-batch/perfusion (FB/P) or fed-batch (FB) were able to sustain infections performed at 8. 0 cD7 10 cells/mL, respectively resulting in 3. 9 and 5. 0-fold increase in total yield (Y) and 1. 7 and 5. 6-fold increase in volumetric productivity (VP) when compared with a batch reference. A maximum viral titer of 4. 5 cD7 10 TCID/mL was reached, which is comparable or higher than other processes for VSV production in different cell lines. Overall, our study reports efficient fed-batch options to intensify the production of a rVSV-based vaccine candidate in suspension HEK293 cells.

Concepts Keywords
510tcid fed‐batch
Biotechnol HEK293 cells
Efficient high cell density
Therapy process intensification
Vaccines suspension cells
viral vector

Semantics

Type Source Name
disease IDO production
disease IDO cell
disease MESH infections
disease IDO process

Original Article

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