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Enhancing viral vaccine production using engineered knockout vero cell lines – A second look
Institution:1. Batavia Biosciences, Leiden, The Netherlands;2. Independent Researcher, Athens, GA, USA;3. Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA;4. Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA
Abstract:The global adoption of vaccines to combat disease is hampered by the high cost of vaccine manufacturing. The work described herein follows two previous publications (van der Sanden et al., 2016; Wu et al., 2017) that report a strategy to enhance poliovirus and rotavirus vaccine production through genetic modification of the Vero cell lines used in large-scale vaccine manufacturing. CRISPR/Cas9 gene editing tools were used to knockout Vero target genes previously shown to play a role in polio- and rotavirus production. Subsequently, small-scale models of current industry manufacturing systems were developed and adopted to assess the increases in polio- and rotavirus output by multiple stable knockout cell lines. Unlike previous studies, the Vero knockout cell lines failed to achieve desired target yield increases. These findings suggest that additional research will be required before implementing the genetically engineered Vero cell lines in the manufacturing process for polio- and rotavirus vaccines to be able to supply vaccines at reduced prices.
Keywords:Vero cell  Cell substrate  Chlorocebus sabaeus  Manufacturing cell line  Gene editing  CRISPR  Gene knockout  Vaccine production  Poliovirus  Rotavirus  Microcarriers  Poliomyelitis  Costs and cost analysis  Virus cultivation  RNA viruses  Reoviridae  Picornaviridae
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