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Abstract

A method of producing an influenza virus and vaccines derived from the virus utilizes cultured vertebrate biomass aggregates comprising a plurality of cell types derived from a plurality of vertebrate tissues and is particularly suitable for use with chicken embryo cultures. The method both eliminates the necessity to use costly methods requiring whole chicken embryos and provides proteases suitable for the activation of a wide variety of viruses. After infecting the cells of the culture with an influenza virus, which is preferably modified to create a cleavage site in the hemagglutinin of the virus, a substance such as a protease is introduced that cleaves the hemagglutinin. The culture then is incubated under conditions that permit growth of the virus. The method provides also for the augmentation of virus activation in the culture by the continuous or batchwise removal of culture media, treatment of the media with substances such as proteases which increase cellular activation, attenuation of any undesired effects of the augmentation and return of the augmented media to the culture. The vaccines produced from the harvested virus therefore are free of egg proteins and are much more economical to produce. The methodology of the present invention allows the large scale continuous production of many viruses to a high titre.

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First Claim