Semi-perfusion cultures of suspension MDCK cells enable high cell concentrations and efficient influenza A virus production.

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  • Additional Information
    • Source:
      Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 8406899 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2518 (Electronic) Linking ISSN: 0264410X NLM ISO Abbreviation: Vaccine Subsets: MEDLINE
    • Publication Information:
      Publication: Amsterdam, The Netherlands : Elsevier Science
      Original Publication: [Guildford, Surrey, UK] : Butterworths, [c1983-
    • Subject Terms:
      Influenza A virus/*growth & development ; Influenza A virus/*immunology ; Influenza Vaccines/*immunology; Animals ; Batch Cell Culture Techniques/methods ; Bioreactors/virology ; Cell Line ; Dogs ; Madin Darby Canine Kidney Cells ; Orthomyxoviridae Infections/immunology ; Virion/growth & development ; Virus Cultivation/methods ; Virus Replication/immunology
    • Abstract:
      Control and prevention of rapid influenza spread among humans depend on the availability of efficient and safe seasonal and pandemic vaccines, made primarily from inactivated influenza virus particles. Current influenza virus production processes rely heavily on embryonated chicken eggs or on cell culture as substrate for virus propagation. Today's efforts towards process intensification in animal cell culture could innovate viral vaccine manufacturing using high-yield suspension cells in high cell density perfusion processes. In this work, we present a MDCK cell line adapted to grow as single cell suspension with a doubling time of less than 20 h, achieving cell concentrations over 1 × 10 7  cells/mL in batch mode. Influenza A virus titer obtained in batch infections were 3.6 log 10 (HAU/100 µL) for total- and 10 9  virions/mL for infectious virus particles (TCID 50 ), respectively. In semi-perfusion mode concentrations up to 6 × 10 7  cells/mL, accumulated virus titer of 4.5 log 10 (HAU/100 µL) and infectious titer of almost 10 10  virions/mL (TCID 50 ) were possible. This exceeds results reported previously for cell culture-based influenza virus propagation by far and suggests perfusion cultures as the preferred method in viral vaccine manufacturing.
      (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
    • Contributed Indexing:
      Keywords: Cell culture-based vaccine manufacturing; High cell density; Influenza A virus production; MDCK suspension; Process intensification; Semi-perfusion
    • Accession Number:
      0 (Influenza Vaccines)
    • Publication Date:
      Date Created: 20190504 Date Completed: 20200929 Latest Revision: 20200929
    • Publication Date:
      20240829
    • Accession Number:
      10.1016/j.vaccine.2019.04.054
    • Accession Number:
      31047676