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Vaccine Production

State of the Art and Future Needs in Upstream Processing

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Part of the book series: Methods in Biotechnology ((MIBT,volume 24))

Abstract

The production of viral vaccines in animal cell culture can be accomplished with primary, diploid, or continuous (transformed) cell lines. Each cell line, each virus type, and each vaccine definition requires a specific production and purification process. Media have to be selected as well as the production vessel, production conditions, and type of process. Here, we describe different issues that have to be considered during virus-production processes by discussing the influenza virus production in a microcarrier system in detail as an example. The use of serum-containing as well as serum-free media, but also the use of stirred tank bioreactors or wave bioreactors, is considered.

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References

  1. Kaufmann, S. H. E. (ed.) (2004) Novel Vaccination Strategies. Wiley-VCH, Weinheim.

    Google Scholar 

  2. Huang, D. B., Wu, J. J., and Tyring, S. K. (2004) A review of licensed viral vaccines, some of their safety concerns, and the advances in the development of investigational viral vaccines. J. Infect. 49, 179–209.

    Article  PubMed  Google Scholar 

  3. Aunins, J. G. (2000) Viral vaccine production in cell culture, in Encyclopedia of Cell Technology (Stier, R. E., ed.), Wiley & Sons, New York, pp. 1182–1217.

    Google Scholar 

  4. Reichl, U. (2000) ISCOM vaccines—antigen production and downstream processing, in Proc. 4th Int. Congress on Biochemical Engineering, Fraunhofer IRB Verlag, Stuttgart, pp. 314–318.

    Google Scholar 

  5. Genzel, Y., Voges, L., and Reichl, U. (2001) Development of bioprocess concepts on vaccine production: influenza virus as an example, in Animal Cell Technology: From Target to Market (Lindner-Olsson, Chatzissavidou, N., and Lüllau, E., eds.), Kluwer Academic Publishers, Dordrecht, The Netherlands, pp. 344–346.

    Google Scholar 

  6. Tree, J. A., Richardson, C., Fooks, A. R., Clegg, J. C., and Looby, D. (2001) Comparison of large-scale mammalian cell culture systems with egg culture for the production of influenza virus A vaccine strains. Vaccine 19, 3444–3450.

    Article  PubMed  CAS  Google Scholar 

  7. Robertson, J. S., Cook, P., Attwell, A.-M., and Williams, S. P. (1995) Replicative advantage in tissue culture of egg-adapted influenza virus over tissue culture derived virus: implications for vaccine manufacture. Vaccine 13(16), 1583–1588.

    Article  PubMed  CAS  Google Scholar 

  8. Govorkova, E. A., Kodihalli, S., Alymova, I. V., Fanget, B., and Webster, R. G. (1999) Growth and immunogenicity of influenza viruses cultivated in Vero or MDCK cells and in embryonated chicken eggs. Dev. Biol. Stand. 98, 39–51.

    PubMed  CAS  Google Scholar 

  9. Genzel, Y., Behrendt, I., König, S., Sann, H., and Reichl, U. (2004) Metabolism of MDCK Cells during cell growth and influenza virus production in large-scale microcarrier culture. Vaccine 22(17–18), 2202–2208.

    Article  PubMed  CAS  Google Scholar 

  10. Genzel, Y., Ritter, J. B., König, S., Alt, R., and Reichl, U. (2005) Substitution of glutamine by pyruvate to reduce ammonia formation and growth inhibition of mammalian cells. Biotechnol. Progr. 21(1), 58–69.

    Article  CAS  Google Scholar 

  11. Genzel, Y., Olmer, R. M., Schafer, B., and Reichl, U. (2006) Wave microcarriers cultivation of MDCK cells for influenza virus production in serum-containing and serum-free media. Vaccine 24(35–36), 6074–6087.

    Article  PubMed  CAS  Google Scholar 

  12. Kistner, O., Barrett, P. N., Mundt, W., Reiter, M., Schober-Bendixen, S., and Dorner, F. (1998) Development of a mammalian cell (Vero) derived candidate influenza virus vaccine. Vaccine 16(9/10), 960–968.

    Article  PubMed  CAS  Google Scholar 

  13. Pau, M. G., Ophorst, C., Koldijk, M. H., Schouten, G., Mehtali, M., and Uytdehaag, F. (2001) The human cell line PER.C6 provides a new manufacturing system for the production of influenza vaccines. Vaccine 19, 2716–2721.

    Article  PubMed  CAS  Google Scholar 

  14. Bahnemann, H. G. (1990) Inactivation of viral antigens for vaccine preparation with particular reference to the application of binary ethylenimine. Vaccine 8(4), 299–303.

    Article  PubMed  CAS  Google Scholar 

  15. Budowsky, E. I. and Zalesskaya, M. A. (1991) Principles of selective inactivation of viral genome. V. Rational selection of conditions for inactivation of the viral suspension infectivity to a given extent by the action of beta-propiolactone. Vaccine 9(5), 319–325.

    Article  PubMed  CAS  Google Scholar 

  16. Budowsky, E. I., Friedman, E. A., Zheleznova, N. V., and Noskov, F. S. (1991) Principles of selective inactivation of viral genome. VI. Inactivation of the infectivity of the influenza virus by the action of beta-propiolactone. Vaccine 9(6), 398–402.

    Article  PubMed  CAS  Google Scholar 

  17. Mahy, B. W. J. and Kangro, H. O. (eds.) (1996) Virology Methods Manual. Academic Press, London, pp. 41–43.

    Google Scholar 

  18. “The Orange Guide”: Rules and Guidance for Pharmaceutical Manufactures and Distributors (2002), Medicines Control Agency, 6th ed. London, United Kingdom, ISBN 0113225598.

    Google Scholar 

  19. European Pharmacopoeia (EP), Maisonneuve S. A. France, continuously updated.

    Google Scholar 

  20. United States Pharmacopoeia (USP), US Pharmacopeial Convention, Rockville, MD, continuously updated.

    Google Scholar 

  21. Points to consider in the characterization of cell lines used to produce biologicals. (1993) Department of Health and Human Services, Food and Drug Administration, Docket No. 84N-0154.

    Google Scholar 

  22. Guidance on viral safety evaluation of biotechnology products derived from cell lines of human and animal origin. (1998) Department of Health and Human Services, Food and Drug Administration (FDA), Docket No. 96D-0058.

    Google Scholar 

  23. Gregersen, J.-P. (1994) Research and Development of Vaccines and Pharmaceuticals from Biotechnology. VCH, Weinheim, Germany.

    Book  Google Scholar 

  24. Möhler, L., Flockerzi, D., Sann, H., and Reichl, U. (2005) Mathematical model of influenza A virus production in large-scale microcarrier culture. Biotechnol. Bioeng. 90(1), 46–58.

    Article  PubMed  Google Scholar 

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© 2007 Humana Press Inc., Totowa, NJ

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Genzel, Y., Reichl, U. (2007). Vaccine Production. In: Pörtner, R. (eds) Animal Cell Biotechnology. Methods in Biotechnology, vol 24. Humana Press. https://doi.org/10.1007/978-1-59745-399-8_21

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  • DOI: https://doi.org/10.1007/978-1-59745-399-8_21

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-660-3

  • Online ISBN: 978-1-59745-399-8

  • eBook Packages: Springer Protocols

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