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

Autor: Silva CAT; Department of Chemical Engineering, Polytechnique Montréal, Montreal, Quebec, Canada.; Department of Bioengineering, McGill University, Montreal, Quebec, Canada., Kamen AA; Department of Bioengineering, McGill University, Montreal, Quebec, Canada., Henry O; Department of Chemical Engineering, Polytechnique Montréal, Montreal, Quebec, Canada.
Jazyk: angličtina
Zdroj: Biotechnology progress [Biotechnol Prog] 2024 Sep 17, pp. e3506. Date of Electronic Publication: 2024 Sep 17.
DOI: 10.1002/btpr.3506
Abstrakt: 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 × 10 6  cells/mL, respectively resulting in 3.9 and 5.0-fold increase in total yield (Y T ) 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 × 10 10  TCID 50 /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.
(© 2024 The Author(s). Biotechnology Progress published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)
Databáze: MEDLINE
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