High-Titer Hepatitis C Virus Production in a Scalable Single-Use High Cell Density Bioreactor

Anna Offersgaard, Carlos Rene Duarte Hernandez, Anne Finne Pihl, Nandini Prabhakar Venkatesan, Henrik Krarup, Xiangliang Lin, Udo Reichl, Jens Bukh, Yvonne Genzel, Judith Margarete Gottwein

1 Citation (Scopus)


Hepatitis C virus (HCV) infections pose a major public health burden due to high chronicity rates and associated morbidity and mortality. A vaccine protecting against chronic infection is not available but would be important for global control of HCV infections. In this study, cell culture-based HCV production was established in a packed-bed bioreactor (CelCradle™) aiming to further the development of an inactivated whole virus vaccine and to facilitate virological and immunological studies requiring large quantities of virus particles. HCV was produced in human hepatoma-derived Huh7.5 cells maintained in serum-free medium on days of virus harvesting. Highest virus yields were obtained when the culture was maintained with two medium exchanges per day. However, increasing the total number of cells in the culture vessel negatively impacted infectivity titers. Peak infectivity titers of up to 7.2 log10 focus forming units (FFU)/mL, accumulated virus yields of up to 5.9 × 1010 FFU, and a cell specific virus yield of up to 41 FFU/cell were obtained from one CelCradle™. CelCradle™-derived and T flask-derived virus had similar characteristics regarding neutralization sensitivity and buoyant density. This packed-bed tide-motion system is available with larger vessels and may thus be a promising platform for large-scale HCV production.

Original languageEnglish
Article number249
Issue number2
Pages (from-to)1-23
Number of pages23
Publication statusPublished - 7 Feb 2022


  • CelCradle™
  • HCV vaccine development
  • High cell density cell culture
  • High‐titer HCV production
  • Huh7.5 cells
  • Inactivated virus vaccine
  • Packed‐bed bioreactor
  • Whole virus vaccine


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