Avian influenza viruses pose a significant health threat for both humans and chickens in developing and developed countries. Chickens and aquatic avian species also provide a reservoir of influenza viruses that have increasingly in the last several years crossed the avian-human barrier and caused fatal disease in humans across several continents. This reservoir is of major concern as a potential source of pandemic influenza virus strains. Inactivated vaccines are currently available for protection against some of the circulating strains, and for these strains the vaccines are effective in preventing disease. However, these vaccines do not completely prevent viral shedding. Another significant problem with existing killed vaccines is that they confer minimal cross-protection to divergent influenza strains. Protection induced by inactivated vaccines is mediated by antibody to the viral hemagglutinin and neuraminidase. Minor changes in antigenic epitopes of these proteins, termed """"""""antigenic drift"""""""" can severely reduce vaccine efficacy. Encouraging efforts have been made in mammals to induce T cytotoxic and Th 1 type responses using killed vaccines supplemented with cytokines, since these responses are more efficacious against homotypic and heterotypic strains of influenza. However, these efforts are not easily translated to the production of commercially feasible avian vaccines. To address this problem, we are proposing a molecular approach that will anchor chicken immunomodulatory cytokines and chemokines to the envelope glycoproteins of influenza virus. The viruses will be completely inactivated with a protocol that leaves the bioactivity of the attached molecule intact. Our hypothesis is that cytokine- or chemokine-modified virus particles will induce an efficacious Th1 and/or T cytotoxic responses in addition to a protective humoral response and thus, provide better protection against homotypic and heterotypic influenza strains. ? ? ?
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