Influenza pandemics: can we prepare for the unpredictable?

Although no viruses are better understood or more intensively studied than the viruses of influenza, if the next influenza pandemic occurs within the next 5-10 years its control will depend on innovations in vaccine production developed more than 40 years ago, but not yet applied to the full extent demanded by our present hard-won knowledge of the epidemiology of the disease. We have become so enamored of the brilliant advances made in the interim in understanding the molecular biology of both virus and host that common sense and inexpensive implementation of proven and older methods of control have been neglected as an interim barricade. In this review, I have advocated a return to first principles, while embracing the promise and returns of contemporary research. With the assumption that the next pandemic virus will contain one of the 13 influenza A virus hemagglutinin subtypes not currently causing epidemic human disease, high-yield reassortant viruses of each of these subtypes should be produced with all dispatch and, in collaboration with industry, tested for production stability and immunogenicity in humans. From this archive, an appropriate reassortant could be selected within days or weeks, and production could ensue. If not a perfect match with the imminent pandemic virus, this "barricade vaccine" could stand as a first line of defense until supplanted by a definitive "rampart vaccine," matching better the emergent, potentially pandemic virus.