Model-based Investigation of Influenza Virus Replication in Mammalian Cell Culture

Motivation

The composition of human influenza vaccines changes frequently to target the three most representative virus strains in circulation. Vaccine production has to rapidly respond to these changes while aiming for maximum virus yields. This, however, requires a detailed understanding of how the virus infects the host cell population used for production in bioreactors. To support process design and to further optimize cell culture-based influenza vaccine manufacturing our group investigates key aspects of the infection dynamics of prevalent vaccination strains.

Influenza virus-infected MDCK cells on microcarrier

Aim of the project

In this project, we aim at elucidating strain-specific factors that limit the replication of influenza viruses in mammalian cell culture. Such knowledge could reduce the development time of new vaccines and may facilitate tailor-made process design.

Replication performance of two influenza strains [1]. Time courses of infected cells (red), uninfected cells (blue) and virus titer (black).

Modeling approach

In the past, delay differential equation models have proven successful in describing influenza virus infection [1]. Through a close collaboration with experimental biologists, we refine these models to reflect the replication dynamics of different influenza strains. Subsequently, we apply model analysis techniques to infer the origin of strain-specific differences in replication performance. This knowledge may lead to new optimization strategies, which facilitates an early evaluation of the yield of new virus strains and allows targeting the weaknesses of each strain.

References

[1] J. Schulze-Horsel, M. Schulze, G. Agalaridis, Y. Genzel, and U. Reichl. Infection dynamics and virus-induced apoptosis in cell culture-based influenza vaccine production-Flow cytometry and mathematical modeling. Vaccine, 2009, 27(20):2712-22.

Related projects

Flow Cytometric Analysis of Virus-induced Apoptosis and Virus Replication
Influenza Vaccine Production in Microcarrier Systems and Suspension Cells
Modeling the Dynamics of Influenza Virus Replication in Mammalian Cells
Vaccine Production with Mammalian Cell Cultures (Process Systems Engineering Group)
Virus Replication during Vaccine Production (Process Synthesis and Process Dynamics Group)

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