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

被引:0
|
作者
Silva, Cristina A. T. [1 ,2 ]
Kamen, Amine A. [2 ]
Henry, Olivier [1 ]
机构
[1] Polytech Montreal, Dept Chem Engn, Montreal, PQ H3T 1J4, Canada
[2] McGill Univ, Dept Bioengn, Montreal, PQ, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
fed-batch; HEK293; cells; high cell density; process intensification; suspension cells; viral vector; SERUM-FREE PRODUCTION; PERFUSION; RECOMBINANT; VACCINE; IMMUNOGENICITY; BIOREACTOR; EFFICACY; INSIGHTS; SAFETY;
D O I
10.1002/btpr.3506
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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 x 106 cells/mL, respectively resulting in 3.9 and 5.0-fold increase in total yield (YT) 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 x 1010 TCID50/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.
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页数:9
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