High titer MVA and influenza A virus production using a hybrid fed-batch/perfusion strategy with an ATF system

Applied Microbiology and Biotechnology
Daniel Vázquez-RamírezUdo Reichl

Abstract

A cultivation strategy to increase the productivity of Modified Vaccinia Ankara (MVA) virus in high-cell density processes is presented. Based on an approach developed in shake flask cultures, this strategy was established in benchtop bioreactors, comprising the growth of suspension AGE1.CR.pIX cells to high cell densities in a chemically defined medium before infection with the MVA-CR19 virus strain. First, a perfusion regime was established to optimize the cell growth phase. Second, a fed-batch regime was chosen for the initial infection phase to facilitate virus uptake and cell-to-cell spreading. Afterwards, a switch to perfusion enabled the continuous supply of nutrients for the late stages of virus propagation. With maximum infectious titers of 1.0 × 1010 IU/mL, this hybrid fed-batch/perfusion strategy increased product titers by almost one order of magnitude compared to conventional batch cultivations. Finally, this strategy was also applied to the production of influenza A/PR/8/34 (H1N1) virus considered for manufacturing of inactivated vaccines. Using the same culture system, a total number of 3.8 × 1010 virions/mL was achieved. Overall, comparable or even higher cell-specific virus yields and volumetric productivities ...Continue Reading

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Feb 13, 2018·Vaccine·Daniel Vázquez-RamírezUdo Reichl

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Citations

Nov 28, 2019·Expert Opinion on Biological Therapy·Mafalda G MoleirinhoCristina Peixoto
Apr 16, 2020·Applied Microbiology and Biotechnology·Gwendal GränicherUdo Reichl
Jul 28, 2020·Frontiers in Bioengineering and Biotechnology·Juliana CoronelUdo Reichl
Jan 31, 2021·Applied Microbiology and Biotechnology·Yixiao WuWen-Song Tan
Jul 3, 2021·Vaccines·Anna OffersgaardJudith Margarete Gottwein

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