Seed Train Intensification and TFDF-Based Perfusion for MDCK Cell-Based Influenza A Virus Production

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Publié dans:Processes vol. 13, no. 5 (2025), p. 1286
Auteur principal: Zinnecker Tilia
Autres auteurs: Wicke Emelie, Reichl Udo, Göbel Sven, Genzel, Yvonne
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MDPI AG
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022 |a 2227-9717 
024 7 |a 10.3390/pr13051286  |2 doi 
035 |a 3212099440 
045 2 |b d20250101  |b d20251231 
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100 1 |a Zinnecker Tilia  |u Max Planck Institute for Dynamics of Complex Technical Systems, 39106 Magdeburg, Germany 
245 1 |a Seed Train Intensification and TFDF-Based Perfusion for MDCK Cell-Based Influenza A Virus Production 
260 |b MDPI AG  |c 2025 
513 |a Journal Article 
520 3 |a The production of influenza A virus (IAV) using Madin-Darby Canine Kidney (MDCK) cells is a key strategy for efficient influenza vaccine manufacturing. However, challenges remain in optimizing cell culture processes for higher yield and efficiency. This study aims to evaluate different process intensification strategies on two distinct clonal MDCK suspension cell lines (C59 and C113) for improved IAV production. A semi-perfusion strategy was used to push cells towards high cell density (HCD), achieving up to 17 × 106 C113 cells/mL and 42 × 106 C59 cells/mL, respectively. Next, a Tangential Flow Depth Filtration (TFDF)-based perfusion process with direct harvest during IAV production was established, resulting in high titers and a 10-fold higher space-time yield for C59 and a 4-fold improvement for C113 compared to batch operation. In addition, the suitability of N-1 perfusion was evaluated for batch and intensified fed-batch processes. Cells taken from the N-1 perfusion showed different cell-specific growth rates, but this had no effect on virus titers except for processes started from oxygen-deprived precultures. Finally, comparable virus titers were obtained when the production bioreactor was directly inoculated from an HCD cryovial. Taken together, seed train intensification and TFDF-based perfusion majorly reduced process times and improved IAV production. 
651 4 |a United States--US 
651 4 |a Germany 
653 |a Infections 
653 |a Perfusion 
653 |a Cell density 
653 |a Process intensification 
653 |a Vaccines 
653 |a Cell culture 
653 |a Cell lines 
653 |a Productivity 
653 |a Cryopreservation 
653 |a Influenza 
653 |a Batch culture 
653 |a Manufacturing 
653 |a Immunization 
653 |a Batch processing 
653 |a Influenza A 
653 |a Batch processes 
653 |a Process controls 
653 |a Bioreactors 
653 |a Viruses 
653 |a Pore size 
653 |a Enzymes 
700 1 |a Wicke Emelie  |u Max Planck Institute for Dynamics of Complex Technical Systems, 39106 Magdeburg, Germany 
700 1 |a Reichl Udo  |u Max Planck Institute for Dynamics of Complex Technical Systems, 39106 Magdeburg, Germany 
700 1 |a Göbel Sven  |u Max Planck Institute for Dynamics of Complex Technical Systems, 39106 Magdeburg, Germany 
700 1 |a Genzel, Yvonne  |u Max Planck Institute for Dynamics of Complex Technical Systems, 39106 Magdeburg, Germany 
773 0 |t Processes  |g vol. 13, no. 5 (2025), p. 1286 
786 0 |d ProQuest  |t Materials Science Database 
856 4 1 |3 Citation/Abstract  |u https://www.proquest.com/docview/3212099440/abstract/embedded/L8HZQI7Z43R0LA5T?source=fedsrch 
856 4 0 |3 Full Text + Graphics  |u https://www.proquest.com/docview/3212099440/fulltextwithgraphics/embedded/L8HZQI7Z43R0LA5T?source=fedsrch 
856 4 0 |3 Full Text - PDF  |u https://www.proquest.com/docview/3212099440/fulltextPDF/embedded/L8HZQI7Z43R0LA5T?source=fedsrch