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.
This research is directly related to inhouse objective 2 - Identify genetic and biological determinants of virulence, tissue tropism and host range of avian influenza virus; and inhouse objective 3 - Identify genetic and biological determinants of avian influenza virus susceptibility and resistance in avian species.
For FY2013, avian influenza virus strains previously attenuated by genetic engineer or reverse genetics (rg) by CDC 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. Two rg candidate H7N9 vaccine viruses were tested. The rg vaccine viruses were attenuated in chickens based on the inability to cause clinical signs or death in chickens after intravenous inoculation. In addition, both viruses were unable to infect the birds by lack of AI specific antibodies and lack of virus recovery after intranasal inoculation. The rg vaccine virus would have negligible negative impact on animal agriculture and can be pursued as potential human pandemic influenza vaccine strain.