Bat influenza virus chimeras as basis for the development of a new type of vaccine backbone

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Influenza A viruses (IAV) are important pathogens for animals and spillover of IAV from farm animals to humans is a major risk factor for new pandemics. Vaccination could be an option for controlling IAV-infections in both livestock and companion animals. However, effective and safe IAV live vaccines to protect poultry are missing. This is mainly due to the risk of reassortment events between vaccine strains and wild type IAV-strains, and partly to the pathogenicity associated with vaccine strains e.g. in very young animals. However, we recently succeeded to generate chimeric viruses containing six out of the eight bat H17N10 virus genes, with the remaining two genes encoding the haemagglutinin (HA) and neuraminidase (NA) proteins of a prototypic influenza A virus (IAV). These viruses grow in mammalian cells but show limited replication in avian cells and chicken. Most importantly, these bat chimeric viruses fail to reassort with other IAV. Thus bat chimeric viruses might represent ideal viral backbones to develop novel and safe live vaccines for poultry. To achieve this, we want to study the capacity of these bat chimeric viruses to replicate in chickens of different age classes after several rounds of adaptation in chicken embryos in more detail. We also want to equip these viruses with HA and NA of high (H5, H7) and low (H1, H5, H7, H9) pathogenic avian IAV and determine the growth properties and associated immune responses in chicken. As a novel strategy to prevent species transmission of the vaccine strain, species-specific siRNA target sequences will be embedded in the viral genome. Finally, we want to obtain proof of principal that vaccination with bat chimeras can protect from IAV-infection with highly pathogenic avian influenza viruses. From these studies we expect the development of novel and safe viral vectors for livestock vaccination.