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A mathematical description of the infection of insect cells with baculovirus in a continuously operated reactor configuration is presented. The reactor configuration consists of one bioreactor in which insect cells (Spodoptera frugiperda) are grown followed by one or two bioreactors in which cells are infected by a baculovirus (Autographa californica nuclear polyhedrosis virus). It was demonstrated that the so-called passage effect is responsible for the observed difference in run time between a configuration with one or with two infection vessels. Furthermore, a model is presented based on the hypothesis that the limited run time of series of continuously operated bioreactors is associated with the occurrence of a virus particle (so-called virion) that is defective and has interfering properties. With the assumption that not all nonoccluded virions are capable of establishing a correct infection leading to new virus production, infection levels in continuously operated reactor configurations could be described well with the model.

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Insect cells (Spodoptera frugiperda) were cultured in a continuous stirred-tank reactor. The effluent was led to a cascade of another two reactors, each containing half the volume of the cell-growth reactor, where the cells were infected with Autographa californica nuclear polyhedrosis virus. For about 10 days production of 10(7) polyhedra (virus particles embedded in a protein capsule) per cm3 was achieved. This short production time compared to previous experiments involving an analogous system with a single infection vessel of equal volume to the cell-growth vessel is ascribed to the accelerated occurrence of the so-called passage effect (a decrease of infectious virus with time). From the results of a computer model it was concluded that this passage effect was accelerated by the change in residence time distribution as compared to the earlier experiments.

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