Datensatz

Zusammenfassung

The pressure to innovate in cell-based production systems is weighting particularly strong on the manufacturers of vaccines, as the currently used manufacturing systems do encounter severe problems. In the case of currently used egg-based vaccine manufacturing technology an average production campaign of e.g. influenza vaccines takes up to 6 months. In contrast to the egg-based production technology, cell culture-based systems show the potential to drastically shorten production cycles and improve quality of the vaccine regarding e.g. glycosylation of immunogenic antigens and risk of animal contaminants. CEVECs Amniocyte Production (CAP) cell technology is a versatile production platform to generate difficult-to-express and manufacture therapeutic proteins. The generation and development of the CAP human cell system has been fully documented according to all relevant regulatory standards. During the past years CAP cells have been broadly used for production of complex proteins and antibodies and thus have proved its strong potential as new technology platform for proteins in high yields and with authentic human glycosylation pattern. Addressing the needs of vaccine manufacturers, we have tested the suitability of CAP cells for the production of influenza vaccines. CAP cells growing in suspension in serum-free medium were evaluated for their potential as host cells for different human and animal influenza strains. The studies included extracellular metabolite concentrations during growth and virus production in different cultivation systems, test of different commercial serum-free media and evaluation of process conditions (trypsin concentration, multiplicity of infection, media feeding). In addition, time-course of infection and virus adaptation was characterized, and virus yields obtained with CAP cells were compared to those with MDCK cells. Favorable robust process parameters and high virus yields obtained with different influenza strains demonstrated that CAP cells are very promising candidates for large-scale manufacturing of vaccines in serum-free medium.