LONG-TERM SEMICONTINUOUS PRODUCTION OF RECOMBINANT BACULOVIRUS PROTEIN IN A REPEATED (FED-)BATCH 2-STAGE REACTOR SYSTEM

The baculovirus expression system is commonly used in the research and development area and in the production of diagnostics and vaccines. B ecause the infection of insect-cell cultures with a (recombinant) bacu lovirus is a lytic process, the running time of an infected batch inse ct-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. Th ree 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 perf ormance with respect to long-term operation was obtained with a repeat ed batch system. Twelve consecutive productive runs, consisting of inf ections during 5 days, could be performed. The titers of an infectious extracellular virus could be described well with an infection model p reviously developed in our laboratory.