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

• Published in: Enzyme and microbial technology 1996, Vol.18 (6), p.460-466
• Main Authors: van Lier, Frank L.J., van den Hombergh, Johannes P.T.W., de Gooijer, Cornelis D., den Boer, Mirjam M., Vlak, Just M., Tramper, Johannes
• Format: Article
• Language: English
• Subjects: baculovirus; Baculovirus expression vector; Biological and medical sciences; Bioreactors; Biotechnology; Fundamental and applied biological sciences. Psychology; infection model; Laboratorium voor Virologie; Laboratory of Virology; long-term operation; Methods. Procedures. Technologies; PE&RC; Sectie Proceskunde; Sub-department of Food and Bioprocess Engineering; Various methods and equipments; β-galactosidase
• ISSN: 0141-0229; 1879-0909
• DOI: 10.1016/0141-0229(95)00129-8

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.