2011 Annual Report 1a.Objectives (from AD-416) To assess the pathogenicity and infectivity of influenza vaccine reassortants and their respective parental wild type viruses for chickens. This includes:. 1)determining in vivo pathotype of wild type and reassortant vaccine candidate strains in chickens, and. 2)assess in vivo infectivity and pathogenicity in chickens using simulated natural route of exposure (intranasal). 1b.Approach (from AD-416) The challenge studies will be conducted in BSL-3 Enhanced facilities. Four vaccine candidates will be tested per year using the below study design:. 1)conducting in vivo pathotype of virus strains by intravenous testing in chickens using intravenous pathogenicity index, and. 2)conducting in vivo infectivity and pathogenicity testing by intranasal inoculation of chickens and determining the ability for the virus to grow as evident by virus shedding for oropharynx and cloaca, and ability to cause disease by assessing clinical features, serological reaction and histopathological changes to various organs. 3.Progress Report This research is related to inhouse objective 2: Develop vaccines that effectively stop outbreaks, allow differentiation from natural infection and can be administered in a cost effective manner. Development of vaccines for potential human pandemics from avian influenza virus is an important public health project. Avian influenza virus strains previously attenuated by genetic engineer by Centers for Disease Control (CDC) or Institute for Experimental Medicine (IEM) were inoculated into chickens by intranasal and intravenous routes, aiming to test if the attenuation process was successful and if the vaccine viruses would not have a negative impact on animal agriculture. Seven candidate vaccine viruses were tested had shown to be attenuated in chickens based on the inability of causing clinical signs or death in chickens after intravenous inoculation. Some of the birds developed antibodies after intranasal inoculation, and presented very mild lesions in the respiratory tract. These 7 vaccine viruses would have negligible negative impact on animal agriculture and can be pursued as potential human pandemic influenza vaccine strains.