This is accomplished by the switch between negative and positive air pressure, which submerges the matrices where the cells attach

This is accomplished by the switch between negative and positive air pressure, which submerges the matrices where the cells attach. 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 g/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 PTGER2 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. Introduction Since the avian influenza H5N1 outbreak of 2003, the H5N1 virus has caused over 450 deaths [1]. In addition, the avian influenza H7N9 virus has caused outbreak in China. The flu vaccine for unmatched strains of the virus is not expected to be cross-protective confirmed by data relating to the H5N1 pandemic strain. Many animal and clinical-trial studies have shown that the 2004 H5N1 influenza vaccine virus strain, which belongs to the first H5N1 genotype (clade I), does not provide cross-protection for the most recently isolated H5N1 virus from the Chinese mainland and Hong Kong, which belongs to the second H5N1 virus genotype (clade II) [2, 3]. To prevent influenza outbreaks from spreading, the most effective public health measure is vaccination [4]. Currently, influenza vaccine production heavily relies on traditional embryonated egg technology [5]. This process requires long and logistic planning that would severely delay the vaccine production to meet the surge demand in the event of a pandemic. Cell-based technology is considered as an alternative platform for influenza vaccine production, and it has piqued the interest of many in recent years [6, 7]. The common cell lines used for cell-based influenza vaccine production are MDCK (derived from Madin-Darby canine kidney) and Vero (derived from African green monkey kidney) cells, which are anchorage-dependent cells [8, 9]. For influenza vaccine production, it SB 258585 HCl is crucial to choose a system, which is simple and robust, can produce high viral titers from a wide variety of influenza virus strains [10]. A number SB 258585 HCl of cell culture systems were already used for their large-scale vaccine production potential, such as roller bottles and cell factories. These systems were originally designed for adherent cells; however, large-scale production with these systems is challenge to increase surface to volume ratio for cell proliferation. A solution to overcome this problem would be to use a microcarrier cell-lift bioreactor (New Brunswick Scientific, USA), by providing good mixing of the oxygen supply and a high concentration of microcarrier for more surface area. Other traditional bioreactors such as hollow-fiber bioreactors [11], the Celligen Plus bioreactor, [12] or bioreactors supplemented with microcarriers were already used for large-scale production [13]. However, all of these SB 258585 HCl bioreactors involve complicated operations and are labor intensive. Since single-use (disposable) bioreactors were introduced, the traditional stainless-steel bioreactors slowly became obsolete in small-scale biotechnology and contract manufacturing companies [14]. Single-use bioreactors offer lower capital cost, easier operations, faster turn-around times, and fewer requirements for cleaning validation. Two novel bioreactors, BelloCell (bench-top scale) and TideCell002 (industrial scale), have recently been developed by Cesco Bioengineering, Taiwan. The BelloCell bioreactors have been successfully used to cultivate mammalian cells for the production of HDV-like particles [15], Japanese encephalitis virus [16], and insect cells for baculovirus [17]. In these studies, the bioreactors.