[Source: PLoS One, full page: (LINK). Abstract, edited.]
OPEN ACCESS / PEER-REVIEWED / RESEARCH ARTICLE
Evaluation of novel disposable bioreactors on pandemic influenza virus production
Chia-Chun Lai, Tsai-Chuan Weng, Yu-Fen Tseng, Jen-Ron Chiang, Min-Shi Lee, Alan Yung-Chih Hu
Published: August 12, 2019 / DOI: https://doi.org/10.1371/journal.pone.0220803
Since 1997, the highly pathogenic influenza H5N1 virus has spread from Hong Kong. According to the WHO bulletin report, the H5N1 virus is a zoonotic disease threat that has infected more than 850 humans, causing over 450 deaths. In addition, an outbreak of another new and highly pathogenic influenza virus (H7N9) occurred in 2013 in China. These highly pathogenic influenza viruses could potentially cause a worldwide pandemic. it is crucial to develop a rapid production platform to meet this surge demand against any possible influenza pandemic. A potential solution for this problem is the use of cell-based bioreactors for rapid vaccine production. These novel bioreactors, used for cell-based vaccine production, possess various advantages. For example, they enable a short production time, allow for the handling highly pathogenic influenza in closed environments, and can be easily scaled up. In this study, two novel disposable cell-based bioreactors, BelloCell and TideCell, were used to produce H5N1 clade II and H7N9 candidate vaccine viruses (CVVs). Madin-Darby canine kidney (MDCK) cells were used for the production of these influenza CVVs. A novel bench-scale bioreactor named BelloCell bioreactor was used in the study. All culturing conditions were tested and scaled to 10 L industrial-scale bioreactor known as TideCell002. The performances of between BelloCell and TideCell were similar in cell growth, the average MDCK cell doubling time was slightly decreased to 25 hours. The systems yielded approximately 39.2 and 18.0 μg/ml of HA protein with the 10-liter TideCell002 from the H5N1 clade II and H7N9 CVVs, respectively. The results of this study not only highlight the overall effectiveness of these bioreactors but also illustrate the potential of maintaining the same outcome when scaled up to industrial production, which has many implications for faster vaccine production. Although additional studies are required for process optimization, the results of this study are promising and show that oscillating bioreactors may be a suitable platform for pandemic influenza virus production.
Citation: Lai C-C, Weng T-C, Tseng Y-F, Chiang J-R, Lee M-S, Hu AY-C (2019) Evaluation of novel disposable bioreactors on pandemic influenza virus production. PLoS ONE 14(8): e0220803. https://doi.org/10.1371/journal.pone.0220803
Editor: Balaji Manicassamy, University of Iowa, UNITED STATES
Received: February 20, 2019; Accepted: July 23, 2019; Published: August 12, 2019
Copyright: © 2019 Lai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the manuscript and its Supporting Information files.
Funding: The authors would like to thank Mr. Anthony Chang for English editing, and the US CDC for supplying the egg-derived vaccine strains. The authors would also like to thank the funding support from the Ministry of Science and Technology (R.O.C. 102-2622-B-400-001-CC2; 103-2622-B-400-001-CC2). Mr. Chia-Chun Lai is currently pursuing his Ph.D. studies under the Graduate Program of Biotechnology in Medicine, National Tsing Hua University and the National Health Research Institutes. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Keywords: Avian Influenza; H5N1; H7N9; Vaccines; Pandemic preparedness.