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<OL> <LI> Characterize mucosal immunity induced by natural infection and vaccination with both high and low pathogenicity AIV to identify innate and adaptive immune indicators of protection.</li> <LI> Characterize the cellular and humoral immune responses to mucosal vaccination, and develop improved methods for identifying cells, cytokines and antibody from mucosal sites.</li> <LI>Assess immune variability of the host, both in different poultry species and lines, and non-poultry avian species, by examining the frequency of genetic polymorphism in host genes related to innate and adaptive immunity (toll-like receptors, cytokines, chemokines). </li><LI> Using reverse genetics approaches for avian influenza and Newcastle Disease Virus, examine the role of individual viral genes in host gene response. </li></ol>
APPROACH: New vaccine approaches for controlling avian influenza virus (AIV) in poultry will be developed following application of antigen via different routes of exposure to the mucosal system. Characterization of the mucosal immune response following vaccination and challenge will be used to extend the understating of the role of local immunity against AIV. Novel mucosal vaccines will be developed and tested with and without adjuvants to enhance immunological response to vaccination. The protective role of serum and mucosal antibodies will be ascertained by passive administration of antibodies to naive birds followed by challenge. The role of cell mediated immunity against avian influenza will be determined following adaptive transfer of isolated lymphocyte fractions from birds previously exposed to live avian influenza and provided to na?ve birds prior to challenge. The pathogenomic basis of protection will be delineated by genomic characterization through sequence analysis of immune regulatory factors, including cytokines and toll-like receptors, from immunologically competent and na?ve birds. Reverse genetics will be used for vaccine development and pathogenesis studies with AIV by replacement or inactivation of genes involved in virulence and evasion of the host immune response. A comparison of pathogenesis from recombinant viruses will allow characterization of proteins and motifs involved with establishment of viral infection on mucosal surfaces which may be targets for vaccine development.