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Cell Immobilization for the Production of Viral Vaccines

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Animal Cell Culture

Part of the book series: Cell Engineering ((CEEN,volume 9))

Abstract

Innovative vaccine production platforms are needed to efficiently generate countermeasures against (re)emerging diseases or pandemic outbreaks such as the Influenza pandemic H1N1 in 2009. Traditional viral vaccines manufacturing platforms such as embryonated eggs and conventional/classical cell substrates no longer satisfy the needs in terms of production capacity and speed to market and therefore require urgent replacement (Hess et al. 2012).

Well-established mammalian cell substrates such as MRC-5, MDCK or VERO have been used for many years for viral vaccine production. However, there is a major limitation in using these cells; they are anchorage-dependent and require a matrix to adhere and grow in stirred tank bioreactors, often used for large scale vaccine manufacturing. Moreover, the majority of the virus production processes are lytic to the host cells posing extra challenges, namely to preserve as much as possible cell viability (i.e. cell adherence) during virus replication phase; their tumorigenic and/or oncogenic nature are also of concern.

Microcarrier technology or cell aggregation strategies are the most common approaches for mass production of anchorage-dependent cells in large-scale bioreactors. Hollow fibers and cell encapsulation in biocompatible polymers are also alternatives. Efforts were made during the last two decades to adapt some of these cells to grow as single cells in suspension, but often this approach compromise cell specific productivities and product quality.

These and other issues related with viral vaccine production, e.g. the selection of the cell line, type of bioreactor and culture mode, the use of adherent or suspension cultures, and cell immobilization techniques are presented in this chapter. In addition, alternative cell substrates for vaccine production, namely insect cells, and an overview of the viral vaccine production market are discussed.

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Acknowledgments

The authors acknowledge the financial support received from Fundação para a Ciência e Tecnologia (FCT), Portugal (project PTDC/EBB-BIO/119501/2010) and the European Project EDUFLUVAC (FP7-HEALTH-2013-INNOVATION-1). Ana Carina Silva and Paulo Fernandes acknowledge FCT for their Ph.D. grants (SFRH/BD/45786/2008 and SFRH/BD/70810/2010, respectively).

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Authors and Affiliations

  1. Animal Cell Technology Unit, iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901, Oeiras, Portugal

    Ana Carina Silva, António Roldão, Ana Teixeira, Paulo Fernandes, Marcos F. Q. Sousa & Paula M. Alves

  2. Animal Cell Technology Unit, Instituto de Tecnologia Química e Biológica – Universidade Nova de Lisboa, Av. da República, 2780-157, Oeiras, Portugal

    Ana Carina Silva, António Roldão, Ana Teixeira, Paulo Fernandes, Marcos F. Q. Sousa & Paula M. Alves

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  1. Ana Carina Silva
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  2. António Roldão
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  3. Ana Teixeira
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  4. Paulo Fernandes
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  5. Marcos F. Q. Sousa
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  6. Paula M. Alves
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Correspondence to Paula M. Alves .

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  1. University College Dublin, Dublin, Ireland

    Mohamed Al-Rubeai

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Silva, A.C., Roldão, A., Teixeira, A., Fernandes, P., Sousa, M.F.Q., Alves, P.M. (2015). Cell Immobilization for the Production of Viral Vaccines. In: Al-Rubeai, M. (eds) Animal Cell Culture. Cell Engineering, vol 9. Springer, Cham. https://doi.org/10.1007/978-3-319-10320-4_17

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