Long-term semi-continuous production of recombinant baculovirus protein in a repeated (fed-)batch two-stage reactor system

Abstract

The baculovirus expression system is commonly used in the research and development area and in the production of diagnostics and vaccines. Because the infection of insect-cell cultures with a (recombinant) baculovirus is a lytic process, the running time of an infected batch insect-cell reactor is limited. Another disadvantage of the system is the instability of the virus. In this study a two-stage reactor system was tested for its suitability for long-term semicontinuous operation. Three experimental setups were tested involving repeated infections in a reactor fed with cell suspension from a separate cell-growth reactor. Part of a previous infection was used as the virus inoculum. Best performance with respect to long-term operation was obtained with a repeated batch system. Twelve consecutive productive runs, consisting of infections during 5 days, could be performed. The titers of an infectious extracellular virus could be described well with an infection model previously developed in our laboratory.