Method for producing viruses and vaccines in serum-free culture

Abstract

A method for producing Influenza and other viruses and vaccines derived therefrom utilizes serum-free cultured vertebrate cells or vertebrate biomass aggregates to both eliminate the necessity to use costly methods requiring whole chicken embryos and, optionally, to provide proteases suitable for the activation of a wide variety of viruses. In one aspect, the method comprises the periodic or continuous removal of 'treatment portions' of virus-containing culture medium into an 'augmentation loop' for treatment with a broad range of substances, such as proteases that augment the activation of the virus. Use of the loop allows utilization of such substances at high concentrations while eliminating their cell toxic effects. Another aspect of the invention provides for the alteration of cleavage sites in virus proteins to thereby render them more susceptible to activation in culture. Thus, the method provides for the high yield production of many viruses that can be easily scaled up to continuous large scale production volumes and for resultant vaccines which are free of egg proteins and are much more economical to produce.