Oral Presentation 9th Australasian Vaccines & Immunotherapeutics Development Meeting 2022

Chimeric viruses based on the novel insect-specific flavivirus, Binjari virus, provide a new generation of vaccines for mosquito borne viral diseases. (#16)

Jody Hobson-Peters 1 , Jessica Harrison 1 , Jessamine Hazlewood 2 , Laura Vet 1 , Jovin J.Y. Choo 1 , Henry de Malmanche 1 , Daniel Watterson 1 , David Muller 1 , Helle Bielefeldt-Ohmann 1 , Andreas Suhrbier 2 , Roy Hall 1
  1. The University of Queensland, St Lucia, Qld, Australia
  2. QIMR Berghofer Medical Research Institute, Herston

Mosquito-borne flaviviruses cause a significant global health burden and have potential for pandemic emergence. Upscaling of vaccine and diagnostic capabilities during outbreaks can be slow and expensive. Here we describe a recombinant platform for the rapid manufacture of chimeric virus particles for a spectrum of major pathogenic flaviviruses using a new Australian insect-specific flavivirus, named Binjari virus (BinJV).  BinJV was found to be remarkably tolerant for exchange of its structural protein genes (prME) with those of pathogenic vertebrate-infecting flaviviruses (VIFs), including Zika, (ZIKV), dengue (DENV), Japanese encephalitis and West Nile (WNV) viruses.  We have successfully produced BinJV chimeras displaying the structural proteins of >35 flavivirus pathogens. The chimeric BinJ/VIF-prME virus particles are structurally and antigenically indistinguishable from wild type pathogens, are completely replication-deficient in vertebrate cells, but replicate with very high efficiency in mosquito cells (up to 109.5 CCID50/mL) or ~7 mg/L.  Recent advances in conversion of the cell matrix to shaker culture has further increased chimera production by up to 5-fold. Thus, they provide a safe, simple and efficient means of antigen production. As vaccine candidates, BinJ/VIF-prME viruses afforded protection against DENV, ZIKV, WNV and yellow fever virus in pre-clinical models of disease, in most cases administered as a single unadjuvanted dose. While neutralising antibody titres were significantly reduced when the chimeric vaccine was inactivated by UV-C (to remove GMO status), it remained protective and could be further enhanced using a delta inulin-based adjuvant (AdVax). BinJ/VIF-prME viruses thus represent a simple, non-infectious (to vertebrate cells), high-yield technology for generating chimeric flavivirus particles with low biocontainment requirements.