Production of high-titer human influenza A virus with adherent and suspension MDCK cells cultured in a single-use hollow fiber bioreactor

Tapia, Felipe; Vogel, Thomas; Genzel, Yvonne; Behrendt, Ilona; Hirschel, Mark; Gangemi, J. David; Reichl, Udo

doi:10.1016/j.vaccine.2013.11.044

Cited by 47 publications

(40 citation statements)

References 39 publications

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“…The harvesting strategy has a significant influence on the virus particle yield, so the bioreactor system must achieve the rapid and continuous collection of virus particles while ensuring total host cell retention. The best systems for this purpose are fixed-bed or hollow fiber bioreactors [17,58]. Both systems immobilize cells to ensure complete cell retention.…”

Section: Bioreactor Selection For Continuous Retrovirus Productionmentioning

confidence: 99%

“…Typically online, these data are collected by indirect inline measurement, e.g. by estimating the cell number based on the oxygen demand or glucose consumption rate of adherent cells growing in semi-dynamic cultivation systems [58,84,85]. In a fixed-bed bioreactor, this is realized by the simultaneous measurement of oxygen concentrations at the inlet and outlet.…”

Section: Process Controlmentioning

confidence: 99%

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Concepts for the Production of Viruses and Viral Vectors in Cell Cultures

Grein¹,

Weidner²,

Czermak³

2017

New Insights Into Cell Culture Technology

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The industrial-scale manufacturing of viruses or virus-like particles in cell culture is necessary for gene therapy and the treatment of cancer with oncolytic viruses. Complex multistep processes are required in both cases, but the low virus titers in batch cultures and the temperature sensitivity of the virus particles limit the production scale. To meet commercial and regulatory requirements, each process must be scalable and reproducible and must yield high virus titers. These requirements are met by establishing a cell culture process that matches the properties of the virus/host-cell system and by using serum-free cell culture medium. This chapter focuses on two case studies to consider the different aspects of process design, such as the reactor configuration and operational mode: the continuous production of retroviral pseudotype vectors in a retroviral packaging cell line and the production of oncolytic measles virus vectors for cancer therapy.

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Section: Bioreactor Selection For Continuous Retrovirus Productionmentioning

confidence: 99%

Section: Process Controlmentioning

confidence: 99%

Concepts for the Production of Viruses and Viral Vectors in Cell Cultures

Grein¹,

Weidner²,

Czermak³

2017

New Insights Into Cell Culture Technology

View full text Add to dashboard Cite

show abstract

“…The potential of adherent Madin Darby Canine Kidney (MDCK) cell lines for the production of influenza vaccines has been intensively investigated in the past decades Hu et al 2011;Liu et al 2009;Merten et al 1996;Tapia et al 2014). Indeed, Optaflu ® produced in MDCK cells by Novartis Vaccines was recently commercialized (Doroshenko and Halperin 2009).…”

Section: Introductionmentioning

confidence: 99%

Production of canine adenovirus type 2 in serum-free suspension cultures of MDCK cells

Fernandes

Laske

Sousa

et al. 2015

Appl Microbiol Biotechnol

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The potential of adherent Madin Darby Canine Kidney (MDCK) cells for the production of influenza viruses and canine adenovirus type 2 (CAV-2) for vaccines or gene therapy approaches has been shown. Recently, a new MDCK cell line (MDCK.SUS2) that was able to grow in suspension in a fully defined system was established. In this work, we investigated whether the new MDCK.SUS2 suspension cell line is suitable for the amplification of CAV-2 under serum-free culture conditions. Cell growth performance and CAV-2 production were evaluated in three serum-free media: AEM, SMIF8, and EXCELL MDCK. CAV-2 production in shake flasks was maximal when AEM medium was used, resulting in an amplification ratio of infectious particles (IP) of 142 IP out/IP in and volumetric and cell-specific productivities of 2.1 × 10(8) IP/mL and 482 IP/cell, respectively. CAV-2 production was further improved when cells were cultivated in a 0.5-L stirred tank bioreactor. To monitor infection and virus production, cells were analyzed by flow cytometry. A correlation between the side scatter measurement and CAV-2 productivity was found, which represents a key feature to determine the best harvesting time during process development of gene therapy vectors that do not express reporter genes. This work demonstrates that MDCK.SUS2 is a suitable cell substrate for CAV-2 production, constituting a step forward in developing a production process transferable to industrial scales. This could allow for the production of high CAV-2 titers either for vaccination or for gene therapy purposes.

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“…The cells can be easily adapted to and be grown in serum-free media, and in suspension, as well as on various microcarriers maintained under various bioreactor conditions. 93,[101][102][103][104][105][106][107][108] Subclones of MDCK cells adopted to grow in suspension and support robust virus production have also been described, 91,108,109 although adherent MDCK cells appear to support more robust virus production than suspension MDCK cells. 110 Influenza vaccines derived from MDCK cells are also safe and immunogenic.…”

Section: Mdck Cell-derived Influenza Vaccines: the Final Joust?mentioning

confidence: 99%

Cell culture-based influenza vaccines: A necessary and indispensable investment for the future

Hegde

2015

Human Vaccines & Immunotherapeutics

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Production of high-titer human influenza A virus with adherent and suspension MDCK cells cultured in a single-use hollow fiber bioreactor

Cited by 47 publications

References 39 publications

Concepts for the Production of Viruses and Viral Vectors in Cell Cultures

Concepts for the Production of Viruses and Viral Vectors in Cell Cultures

Production of canine adenovirus type 2 in serum-free suspension cultures of MDCK cells

Cell culture-based influenza vaccines: A necessary and indispensable investment for the future

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