ABSTRACT Influenza A virus is a prominent viral pathogen that infects between 5-20% of the U.S. population annually, and is a major contributor to life-threatening respiratory illness in the young, old, and immunocompromised. In addition, sporadic outbreaks of highly virulent avian H5N1 influenza and the recent outbreak of a pandemic H1N1 virus have heightened concerns about the eventual emergence of a particularly lethal pandemic virus. Although commercial influenza vaccines have been available since the mid-1900s, a number of key challenges continue to limit the efficacy of these vaccines. Foremost, current strain-specific vaccines must be revised annually due to the rapid mutation rate of immunodominant viral proteins. Despite this drawback, some recent research investigations have indicated the potential for developing universally protective immune responses against influenza viruses. Over the past decade, an array of conserved influenza virus epitopes have been identified, and the ability of both cell-mediated and humoral immune components to elicit cross-protective immunity to heterologous influenza A viruses has been documented. Moreover, improvements in influenza vaccine immunogenicity via novel delivery methods, molecular adjuvants, and modification of vaccine modality have also been widely reported, and will likely contribute to further progress on the development of a maximally efficacious universal influenza vaccine. This report reviews some of the literature on universal influenza A viral vaccine development and provides a comprehensive account of recent progress that has been made in this field.
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