Intensifying Animal Cell Culture for Virus Vaccine Manufacturing

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Past challenges of vaccine manufacturing have arguably been related to scale-up, and for the most part the challenge has been met. Today, the unmet challenges, which have dogged the vaccine industry for the past 30 years, are the lack of manufacturing flexibility, especially in cases of sudden virus outbreaks, and the failure to intensify the production of viruses. Three major intensification strategies include: the use of cell lines for virus propagation instead of embryonated eggs or mouse brains; the adaptation of cell lines to suspension that can enable high density cultures; and the move from batch to continuous modes of operating the process. In this project, Profs Aucoin and Kamen, who have a long history of working collaboratively together, are partnering with Sanofi, a leading international vaccine manufacturer, to transform the Vero cell culture platform into a leading edge technology amenable to intensification. There is a clear need and demand for efficient, large scale production of vaccines to prevent disease related to viral infection in the world, evidenced by the fact that today's vaccine market is worth ~25 billion dollars and is expected to more than double by 2020. In the last two decades, four viruses have been the documented cause of global epidemics: SARS coronavirus; avian and swine influenza viruses; Ebola virus; and recently, Zika virus. Cell culture is the most attractive manufacturing platform for rapid, scalable and controlled production of viral vaccines - and Vero is the most widely accepted platform for viral vaccine manufacturing. Despite reaching significant intensification in Chinese Hamster Ovary cultures for the production of monoclonal antibodies, productive infections at high cell densities in cell culture for recombinant protein production or virus manufacture remains elusive. The goals of this work are to enhance the genetic understanding of the Vero cell line; determine the genetic and metabolic underpinnings of the peak cell density effect and the phenotypic transformation from adherent to suspension cell state; and develop a (semi)-continuous mode of operation that enables higher volumetric productivity.