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

F.L.J. van Lier, J.P.T.W. van den Hombergh, C.D. de Gooijer, M.M. den Boer, J.M. Vlak, J. Tramper

Research output: Contribution to journalArticleAcademicpeer-review

18 Citations (Scopus)

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. 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.
Original languageEnglish
Pages (from-to)460-466
JournalEnzyme and Microbial Technology
Volume18
DOIs
Publication statusPublished - 1996

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