The ultimate goal of this research is to develop nonpathogenic replication-defective adenoviral vector-based vaccines that rapidly induce long-lasting and broad immunity against a number of pandemic strains of IFV. The genetic reassortment between human and avian IFVs can result in a virus with a novel HA, typically of avian origin, against which humans lack immunity. In the 20th century, the pandemics of 1918, 1957, and 1968 were the result of such antigenic shifts. The recent outbreaks of avian influenza caused by H5N1, H7N7 and H9N2 IFVs with infections of humans have created a new awareness of the pandemic potential of IFVs that circulate in domestic poultry. These events highlight the need for vaccines against influenza that confer cross-protection against pandemic strains, subtypes with pandemic potential, and new drift variants. The estimated economic impact of a pandemic would be up to $166.5 billion in the United States alone, with 200,000 deaths, 730,000 hospitalizations, 42 million outpatient visits, and 50 million additional illnesses. In the context of prevailing threats of global bioterrorism, terrorists deliberately infected with a highly virulent IFV preparation could act as difficult-to-detect biological weapons of mass destruction.
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