The insect cell-baculovirus expression vector system (IC-BEVS) has been an asset to produce biologics for over 30 years. With the current trend in biotechnology shifting toward process intensification and integration, developing intensified processes such as continuous production is crucial to hold this platform as a suitable alternative to others. However, the implementation of continuous production has been hindered by the lytic nature of this expression system and the process-detrimental virus passage effect. In this study, we implemented a multi-stage bioreactor setup for continuous production of influenza hemagglutinin-displaying virus-like particles (HA-VLPs) using IC-BEVS. A setup consisting of one Cell Growth Bioreactor simultaneously feeding non-infected insect cells to three parallel Production Bioreactors operated at different residence times (RT) (18, 36, and 54 h) was implemented
Production Bioreactors were continuously harvested. Two insect cell lines (neutral pH-adapted High Five and Sf9) and two recombinant baculovirus (rBAC) constructs (one that originates from a bacmid, rBAC