Bissinger T, Wu Y, Marichal-Gallardo P, Riedel D,. Towards integrated production of an influenza A vaccine candidate with MDCK suspension cells. Biotechnol Bioeng. 2021 Jul 5
Seasonal influenza epidemics occur both in northern and southern hemispheres every year. Despite the differences in influenza virus surface antigens and virulence of seasonal subtypes, manufacturers are well-adapted to respond to this periodical vaccine demand. Due to decades of influenza virus research, the development of new influenza vaccines is relatively straight-forward. In similarity with the ongoing COVID-19 pandemic, vaccine manufacturing is a major bottleneck for a rapid supply of the billions of doses required worldwide. In particular, egg-based vaccine production would be difficult to schedule and shortages of other egg-based vaccines with high demands also have to be anticipated. Cell culture-based production systems enable manufacturing of large amounts of vaccines within a short time frame and expand significantly our options to respond to pandemics and emerging viral diseases. In this work, we present an integrated process for the production of inactivated influenza A virus vaccines based on a MDCK suspension cell line cultivated in a chemically defined medium. Very high titers of 3.6 log10 (HAU/100 μL) were achieved using fast growing MDCK cells at concentrations up to 9.5 × 106 cells/mL infected with influenza A/PR/8/34 H1N1 virus in 1 L stirred tank bioreactors. A combination of membrane-based steric-exclusion chromatography followed by pseudo-affinity chromatography with a sulfated cellulose membrane adsorber enabled full recovery for the virus capture step and up to 80 % recovery for the virus polishing step. Purified virus particles showed a homogenous size distribution with a mean diameter of 80 nm. Based on a monovalent dose of 15 μg hemagglutinin (SRID assay), the level of total protein and host cell DNA was 58 μg and 10 ng, respectively. Furthermore, all process steps can be fully scaled up to industrial quantities for commercial manufacturing of either seasonal or pandemic influenza virus vaccines. Fast production of up to 300 vaccine doses per liter within 4 to 5 days makes this process competitive not only to other cell-based processes, but to egg-based processes as well.
See Also:
Latest articles in those days:
- Birth cohort effects in adults associated with influenza A(H1N1)pdm09 vaccine effectiveness 5 hours ago
- Genetic Characterization of Swine Influenza Viruses in Thailand in 2019-2025 Reveals Novel Reassortants 5 hours ago
- Outbreak dynamics of high pathogenicity avian influenza virus H5N1, clade 2.3.4.4b euBB, in black-headed gulls and common terns in Germany in 2023 6 hours ago
- [preprint]The canine respiratory epithelium is a permissive ecosystem for influenza interspecies transmission and emergence 6 hours ago
- [preprint]Explainable and Calibrated AI for Decoding Host-Adaptive Changes in Influenza A Virus 6 hours ago
[Go Top] [Close Window]


