Replicative advantage in tissue culture of egg-adapted influenza virus over tissue-culture derived virus: implications for vaccine manufacture.

Influenza virus derived from clinical material on MDCK cells has been shown to possess haemagglutinin (HA) indistinguishable from that of the natural, uncultivated virus. In contrast, viurs derived in embryonated hens' eggs are variants with substitutions in their HA in the vicinity of the receptor binding site. We report here the superior growth of egg-adapted virus over cell-derived virus on MDCK cells in studies in which MDCK-derived virus was spiked with small amounts of egg-adapted virus and the mixture sequentially passaged on MDCK cells. Such egg-derived variants bind to and are internalized by MDCK cells with a much higher efficiency than cell-derived virus. These data imply that the natural virus, whilst able to replicate on MDCK cells, is by no means the best fit for the MDCK receptor and variants with appropriate substitutions around the receptor binding site can readily displace the natural virus. Vaccine manufacturers who are investigating the use of tissue culture for vaccine production should minimize passage levels of cell-derived virus and beware of the displacement of the original virus with variants similar to those derived in eggs, which are often antigenically distinct.