We have developed recombinant mosquito-specific virus platforms for the manufacture of chimeric virus particles for major One Health viral diseases such as Japanese encephalitis and West Nile. One platform (ISVac), based on an Australian insect-specific flavivirus, is remarkably versatile, facilitating the production of vaccine and diagnostic antigens for a multitude of flaviviruses. The chimeric virions are structurally and antigenically indistinguishable from pathogenic flaviviruses, are replication-deficient in vertebrate cells, but replicate efficiency in mosquito cells.
As vaccine candidates, the chimeric viruses afforded protection against numerous flaviviruses in murine models. However, our recent vaccine trials have extended beyond the lab, providing protection against disease in livestock species, following successful tech transfer to a veterinary vaccine manufacturer. To progress the ISVac platform towards application as human vaccines, we have transitioned the upstream and downstream vaccine manufacture bioprocesses towards industry-standard techniques. To this end, we have adapted the vaccine production mosquito cell line to suspension culture in commercially available, serum-free, chemically-defined media and streamlined chromatography purification processes, to demonstrate proof-of-concept, scalable manufacture.
As diagnostic antigens, the chimeric particles have been applied to a variety of platforms, including rapid lateral flow assays, the design of which will form a blueprint for the optimisation of similar point-of-care tests for flavivirus infection detection in both humans and animals.