Comparison of immunogenicity of cell-and egg-passaged viruses for manufacturing MDCK cell culture-based influenza vaccines.

While cell culture-based technology has been recently used for manufacturing influenza vaccines, currently available seed viruses are mostly egg-derived reassortants that are egg-adapted to achieve high virus growth in eggs. For use as viruses for cell culture-based influenza vaccine manufacturing, egg-adapted viral seeds may undergo several passages in manufacturing cell lines. However, the suitability of such cell-passaged viruses for vaccine production remains largely unelucidated. In this study, influenza viruses produced in suspension Madin-Darby canine kidney (MDCK) cell cultures were compared to those produced in embryonated hen's eggs for manufacturing MDCK cell culture-based influenza vaccines through comparability studies of virus productivity and vaccine immunogenicity. The results indicate no change in the amino acid sequence of the main antigens, including hemagglutinin (HA) and neuraminidase (NA), of cell-passaged viruses after three passages in suspension MDCK cells. In lab-scale (3-L) single-use bioreactors, suspension MDCK culture supernatants inoculated with cell-passaged viruses were found to show higher virus productivity, suspension MDCK culture supernatants inoculated with egg-passaged viruses, in respect to the HA titers and HA contents determined by single radial immunodiffusion. Finally, comparable hemagglutination inhibition and influenza-specific IgG titers were determined in the mice immunized with cell culture-based vaccines produced with cell- or egg-passaged viruses. These results indicate that MDCK cell-passaged viruses from egg-adapted viruses, as well as egg-derived seed virus, are suitable for MDCK cell culture-based influenza vaccine production.