Rapid production of synthetic influenza vaccines.

The strain composition of influenza vaccines must be changed regularly to track influenza virus antigenic evolution. During outbreaks with pandemic potential, strain changes are urgent. The systems for accomplishing vaccine strain changes have required the shipment of viruses and other biological materials around the globe, with delays in vaccine availability, and have used legacy techniques of egg-based virus cultivation, resulting in vaccine mismatches. In collaboration with Synthetic Genomics Vaccines Inc. and the US Biomedical Advanced Research and Development Authority, Novartis has developed a synthetic approach to influenza vaccine virus generation. Synthetic influenza vaccine viruses and mammalian cell culture technology promise influenza vaccines that match circulating influenza strains more closely and are delivered in greater quantities, more rapidly than vaccines produced by conventional technologies. These new technologies could yield an improved influenza vaccine response system in which viral sequence data from many sources are posted on the Internet, are downloaded by vaccine manufacturers, and are used to rescue multiple, attenuated vaccine viruses directly on high yielding backbones. Elements of this system were deployed in the response to the 2013 H7N9 influenza outbreak in China. The result was the production, clinical testing, and stockpiling of an H7N9 vaccine before the second wave of the outbreak struck at the end of 2013. Future directions in synthetic influenza vaccine technology include the automation of influenza virus rescue from sequence data and the merger of synthetic and self-amplifying mRNA vaccine technologies. The result could be a more robust and effective influenza vaccine system.