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Our Project consists of four specific aims. Specific Aim 1: Generation of ca/ts/att (cold adapted, temperature sensitive, live attenuated) H5 and H7 avian influenza virus vaccine candidates. Specific Aim 2: Introduction of reassortment-incompetent traits and truncations into the NS1 gene of the ca/ts/att vaccine candidates. Specific Aim 3: To evaluate the efficacy of the NS1 truncated, reassortment-incompetent, ca/ts/att influenza virus vaccines in relevant domestic poultry species. Specific Aim 4: To develop a DIVA strategy based on the C-terminus of NS1.
NON-TECHNICAL SUMMARY: <p>Avian influenza (AI) is an infectious disease, which is both devastating to the poultry industry and of particular public health importance. Since 1997, many Asian countries have experienced frequent influenza outbreaks in chickens caused by H5N1 highly pathogenic avian influenza (HPAI) virus. The list of countries reporting the outbreaks continues to increase despite more than 160 million domestic poultry that have either died or been culled to control the spread of the disease. The estimated economic losses are around $10 billion, threatening the livelihood of millions of people. <p>This unprecedented outbreak has spread to migratory wild aquatic birds and to commercial poultry in a small number of Eastern European countries. The avian H5N1 influenza scare is also affecting consumer trust worldwide, leading to a decline in poultry consumption in international markets. <p>Culling of infected poultry is the best-known strategy to prevent transmission of HPAI; however, when the viruses are widely spread in multiple domestic and wild avian species such as in the case of the Asian epidemic, "stamping out" alone is unlikely to be successful. Reverse genetics provides an opportunity to develop modified live attenuated vaccines that are safe and more effective than killed or recombinant vaccines. We propose to demonstrate that modified live avian influenza vaccines can be prepared using reverse genetics that protect domestic poultry against wild type influenza virus infections, cannot reassort with other AI viruses, and will not interfere with diagnostic techniques.
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APPROACH: <p>We will use a combination of reverse genetics and other molecular tools to generate recombinant avian influenza viruses that can protect a wide variety of poultry species against highly pathogenic influenza. Our vaccines will be attenuated in poultry, non transmissible, reassortment incompetent and capable of being administered in multiple formats, including in ovo adminsitration.