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The main goal of this research is to develop effective influenza virus A vaccines which induce long-lasting and broad immunity against multiple strains of influenza. Nonpathogenic replication-defective adenoviral vectors expressing hemagglutinin (HA), nucleoprotein (NP), or matrix 1 (M1) proteins of highly pathogenic avian influenza viruses will be tested for their efficacy related to long-lasting and broad immunity in suitable animal models. This project will be undertaken with the following objectives: <ol>
<li>Generation and characterization of adenoviral vectors expressing HA, NP, or M1 proteins of avian influenza viruses.
<li>Evaluation of immune responses to and protection efficacy of adenoviral vector-based vaccines in suitable animal models.
<li>Evaluation of the duration and breadth of influenza-specific immunity in experimental animals. </ul>
NON-TECHNICAL SUMMARY: The recent emergence of avian H5N1, H7N7 and H9N2 influenza viruses in humans has highlighted the ability of at least some avian subtypes to cross the species barrier into humans. Such events can cause pandemic outbreaks of influenza by the emergence of an avian-human reassortant virus with the ability to spread rapidly in a nave human and animal populations. The proposed research explores the utility of adenoviral vectors for the construction of vaccines that provide protection against pandemic influenza.
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APPROACH: Nonpathogenic replication-defective adenoviral vectors will be used for expressing HA, NP, or M1 proteins of highly pathogenic avian influenza viruses. These adenoviral vector-based vaccines will be tested to evaluate their efficacy related to long-lasting and broad immunity in suitable animal models.