Stochastic population balance modeling of influenza virus replication in vaccine production processes. II. Detailed description of the replication mechanism

Abstract

In a recent paper a segregated stochastic model was proposed for influenza virus replication in vaccine production processes [Sidorenko, Y., Schulze-Horsel, J., Voigt, A., Reichl, U., Kienle, A., 2008. Stochastic population balance modeling of influenza virus replication in vaccine production processes. Chemical Engineering Science 63, 157–169]. The model used a simple segregated, unstructured approach for the description of the virus replication. In particular, effects arising from limited internal cellular resources and detailed cell physiology were not taken into account. The degree of infection—corresponding to the number of virus equivalents per cell—was used as the only internal coordinate. The model was successful in describing the integral dynamics of the process, however, revealed some discrepancies with respect to the “internal dynamics” of the virus replication. Therefore, in a second step, a much more detailed description of the virus replication process is considered in this paper. Again, cell physiology is described in terms of global growth and death events. Limitations of the intracellular resources are not taken into account. It is shown that this type of model does not contribute significantly to an improvement of the prediction of the internal dynamics. Hence, it is concluded that limited intracellular resources or a detailed description of the cell physiology is required for a more realistic modeling of virus replication dynamics.