Development of a downstream process for the production of an inactivated whole hepatitis C virus vaccine

Keven Lothert, Anna F Offersgaard, Anne F Pihl, Christian K Mathiesen, Tanja B Jensen, Garazi Peña Alzua, Ulrik Fahnøe, Jens Bukh, Judith M Gottwein, Michael W Wolff

23 Citations (Scopus)


There is a large unmet need for a prophylactic hepatitis C virus (HCV) vaccine to control the ongoing epidemic with this deadly pathogen. Many antiviral vaccines employ whole viruses as antigens. For HCV, this approach became feasible following the development of infectious cell culture systems for virus production. However, the lack of efficient downstream processes (DSP) for HCV purification poses a roadblock for the development of a whole virus vaccine. Using cell culture-derived genotype 1a HCV we developed a scalable and efficient DSP train, employing commonly used clarification and ultrafiltration techniques, followed by two membrane-based chromatography steps. For virus capture, steric exclusion chromatography using cellulose membranes was established, resulting in a virtually complete virus recovery with > 99% protein and 84% DNA depletion. Virus polishing was achieved by sulphated cellulose membrane adsorbers with ~ 50% virus recovery and > 99% protein and 90% DNA depletion. Additional nuclease digestion resulted in 99% overall DNA depletion with final DNA concentrations of 2 ng/mL. Process results were comparable for cell culture-derived HCV of another major genotype (5a). This study provides proof-of-concept for establishment of an efficient and economically attractive DSP with potential application for production of an inactivated whole virus vaccine against HCV for human use.

Original languageEnglish
Article number16261
JournalScientific Reports
Issue number1
Pages (from-to)16261
Publication statusPublished - 1 Oct 2020


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