Vaccination strategies for an influenza pandemic.

An influenza pandemic represents one of the greatest acute infectious threats to health. The 1918–1919 influenza pandemic caused an estimated 500,000 deaths in the United States, making it the most fatal event in all of US history. The spread of highly pathogenic avian H5N1 influenza across much of Asia creates a substantial risk of igniting the next pandemic. In 2004, 44 human cases caused by this strain were documented and resulted in 32 deaths. The evolution of a strain that is effectively transmitted between people may be a single reassortment event away or could occur through continuing mutation. Vaccination offers the best opportunity to prevent disease and death in a pandemic , but there will be limitations on the timeliness and availability of vaccine [1]. Optimistic projections are that it could take at least 6 months for the first pandemic vaccine doses to be prooduced after the identification of a pandemic strain. Global influenza-vaccine production capacity has nearly doubled over the preceding decade, and increased demand for annual influenza vaccine will continue to encourage an expansion of production capacity. However, current industrial capacity for a monovalent pandemic influenza vaccine formulated with 15 mg of hem-agglutinin antigen would be far lower than the amount needed worldwide [1]. Under the assumption that a 2-dose schedule would be recommended for vaccination to a novel influenza strain and that the entire population would be susceptible, US-based production for 1 year would be sufficient for full vaccination of only about one-half the American population. Efforts to expand the global industrial base and to optimize the amount of vaccine antigen that can be produced are urgently needed. Extraordinary threats call for consideration of innovative strategies that, in less-threatening circumstances, might be dismissed. Although it has been assumed that pandemic vaccine cannot be stockpiled or that vaccination cannot occur before the start of a pandemic, might these approaches actually be possible? Major barriers to stockpiling or preemptive vaccination are uncertainty over when the next pandemic might occur, whether it will be caused by H5 or some other influenza subtype, and whether the stockpiled vaccine would be a match for the pandemic strain. Production of an H5N1 or other potential pandemic vaccine would need to occur without an interruption in the production of the annual influenza vaccine, which is a substantial challenge given the delays or shortages in influenza vaccine that have occurred in recent years. In addition, …