Efficient and stable production of Modified Vaccinia Ankara virus in two-stage semi-continuous and in continuous stirred tank cultivation systems

PloS One
Felipe TapiaUdo Reichl

Abstract

One important aim in cell culture-based viral vaccine and vector production is the implementation of continuous processes. Such a development has the potential to reduce costs of vaccine manufacturing as volumetric productivity is increased and the manufacturing footprint is reduced. In this work, continuous production of Modified Vaccinia Ankara (MVA) virus was investigated. First, a semi-continuous two-stage cultivation system consisting of two shaker flasks in series was established as a small-scale approach. Cultures of the avian AGE1.CR.pIX cell line were expanded in the first shaker, and MVA virus was propagated and harvested in the second shaker over a period of 8-15 days. A total of nine small-scale cultivations were performed to investigate the impact of process parameters on virus yields. Harvest volumes of 0.7-1 L with maximum TCID50 titers of up to 1.0×109 virions/mL were obtained. Genetic analysis of control experiments using a recombinant MVA virus containing green-fluorescent-protein suggested that the virus was stable over at least 16 d of cultivation. In addition, a decrease or fluctuation of infectious units that may indicate an excessive accumulation of defective interfering particles was not observed. The pr...Continue Reading

References

Apr 1, 1990·Applied Microbiology and Biotechnology·F L van LierJ Tramper
Mar 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·B MossN Cooper
Mar 5, 1990·Biotechnology and Bioengineering·P J Westgate, A H Emery
Jan 18, 2011·Biologicals : Journal of the International Association of Biological Standardization·Ingo JordanVolker Sandig
Jun 13, 2012·Methods in Molecular Biology·Melanie KremerGerd Sutter
Nov 25, 2014·Journal of Pharmaceutical Sciences·Konstantin B Konstantinov, Charles L Cooney
Jan 30, 2015·The New England Journal of Medicine·Tommy RamplingAdrian V S Hill
May 28, 2015·Journal of Biotechnology·Jason WaltherKonstantin Konstantinov
Aug 14, 2015·Science Translational Medicine·Christopher A GreenAndrew J Pollard
Oct 16, 2015·Methods in Molecular Biology·Alejandro Marín-López, Javier Ortego
Oct 30, 2015·Expert Review of Vaccines·Sarah Sebastian, Sarah C Gilbert
Apr 20, 2016·JAMA : the Journal of the American Medical Association·Iain D MilliganMatthew D Snape
Mar 1, 2015·Journal of Pharmaceutical Sciences·Konstantin B Konstantinov, Charles L Cooney

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Methods Mentioned

BETA
fluorescence microscopy
PCR
electrophoreses

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