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Abstract

Various cell lines are currently being evaluated for influenza virus production and process performance to find alternatives to the egg-based vaccine manufacturing. Choosing between suspension and adherent cell lines is not easy and requires evaluation of different process concepts. Here, we present a comparison of adherent cell lines (MDCK, Vero) and suspension cell lines (MDCK.SUS2, AGE1.CR, HEK293, CAP) to give insights into the complexity of this choice. The cells were cultivated in various cultivation systems including roller bottles, shaker flasks, small scale stirred tank reactors, and wave bioreactors. Different cultivation strategies were investigated (batch (with or without medium exchange), perfusion), cultivating each cell line in its appropriate medium. Infection with several influenza virus strains using different infection conditions (MOI (multiplicity of infection), trypsin activity) helped to improve virus yields. Data on metabolism, cell growth and virus titer will be discussed for several bioreactor cultivations. It can be seen that a simple screening of cell lines would not lead to satisfactory results concerning the choice of adherent versus suspension cell-based processes and optimum cultivation conditions. In particular, each of the cell lines investigated can produce most influenza strains in acceptable titers after careful adaptation and selection of appropriate process conditions. It remains however unclear, why some virus strains cannot be produced by specific cell lines. Because of this it seems advisable, to have several alternatives for influenza vaccine manufacturing in case of a pandemic threat.