Poster Presentation 9th Australasian Virology Society Meeting 2017

Exploring the use of chimeric insect-specific viruses to develop safe and efficient vaccines against flavivirus pathogens (#174)

Laura J Vet 1 , Thisun BH Piyasena 1 , Jessica J Harrison 1 , Natalee D Newton 1 , Jody Hobson-Peters 1 , Helle Bielefeldt-Ohmann 1 , Roy A Hall 1
  1. University of Queensland, Brisbane, QUEENSLAND, Australia

Mosquito-borne flaviviruses such as West Nile virus, Zika virus, Dengue virus and Japanese encephalitis virus continue to be a worldwide threat to human and animal health. Despite increasing understanding about these viruses and their replication mechanisms, safe and effective human antivirals and vaccines are still lacking. In contrast to these viruses, insect-specific flaviviruses (ISFs) are incapable of replicating in vertebrates and have been shown to inhibit pathogenic flavivirus replication in the mosquito. Using the novel Circular Polymerase Extension Cloning (CPEC) method, a set of chimeras, containing an ISF backbone with the structural proteins of a vertebrate-infecting flavivirus (VIF), was generated. The focus of this study is on the use of these chimeras for developing vaccines against a range of pathogenic flaviviruses. Due to their inability to replicate in vertebrates, these chimeras provide a safe platform to present antigens to the immune system. The chimeras contain either the Palm Creek virus (Lineage I ISF) or Binjari virus (Lineage II ISF) backbone in order to select the most suitable vaccine candidate. The different chimeras will be assessed and compared with regards to efficiency of growth in culture, virus purification yield, stability, safety, antigenicity and immunogenicity - notably the ability to induce neutralising antibodies to the VIF-parent in vivo. Antigenic assessment has shown the structural proteins of the chimeras to be antigenically similar to their parental VIFs, providing promising results for further in vivo testing.