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Mathematical model of adherent Vero cell growth and poliovirus production in animal component free medium

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Abstract

Sabin–IPV (or sIPV, inactivated polio vaccine based on attenuated Sabin strains) is anticipated to replace the oral polio vaccine for the endgame in polio eradication. Optimization of sIPV production will lead to a better economically feasible vaccine. To assist process optimization, we studied Sabin type 1 poliovirus (PV) infection kinetics on Vero cells in controlled bioreactor vessels. The aim of our study was to develop a descriptive mathematical model able to capture the dynamics of adherent Vero cell growth and PV infection kinetics in animal component free medium. The model predicts the cell density, metabolites profiles, and viral yields in time. We found that the multiplicity of infection (MOI) and the time of infection (TOI) within the investigated range did not affect maximal PV yields, but they did affect the process time. The latter may be reduced by selecting a low TOI and a high MOI. Additionally, we present a correlation between viral titers and D-antigen, a measure for immunogenicity, of Sabin type 1 PV. The developed model is adequate for further studies of the cell metabolism and infection kinetics and may be used to identify control strategies to increase viral productivity. Increased viral yields reduce costs of polio vaccines with large implications on public health.

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Acknowledgments

The authors would like to thank Bella Monica for assistance in performing bioreactor experiments, Dionne David for performing the virus analysis and Alex de Haan for amino acid analysis.

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Authors and Affiliations

  1. Institute for Translational Vaccinology, Process Development, PO BOX 450, 3720 AL, Bilthoven, The Netherlands

    Ramona V. Ursache, Yvonne E. Thomassen, Gerco van Eikenhorst & Wilfried A. M. Bakker

  2. Biotechnology Department, Delft University of Technology, Julianalaan 67, 2628 BC, Delft, The Netherlands

    Ramona V. Ursache & Peter J. T. Verheijen

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  1. Ramona V. Ursache
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  2. Yvonne E. Thomassen
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  3. Gerco van Eikenhorst
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  4. Peter J. T. Verheijen
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  5. Wilfried A. M. Bakker
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Correspondence to Yvonne E. Thomassen.

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Ursache, R.V., Thomassen, Y.E., van Eikenhorst, G. et al. Mathematical model of adherent Vero cell growth and poliovirus production in animal component free medium. Bioprocess Biosyst Eng 38, 543–555 (2015). https://doi.org/10.1007/s00449-014-1294-2

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  • DOI: https://doi.org/10.1007/s00449-014-1294-2

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