Oral Presentation Lorne Infection and Immunity 2020

A novel Binjari virus chimeric vaccine platform protects against West Nile, Zika and dengue viruses in mice (#29)

Laura J Vet 1 , Jovin JY Choo 1 , Jessamine EG Hazlewood 2 , Helle Bielefeldt-Ohmann 1 , Willy W Suen 1 , Jessica J Harrison 1 , Jody Hobson-Peters 1 , Bing Tang 2 , Paul R Young 1 , Andreas Suhrbier 2 , David A Muller 1 , Roy A Hall 1
  1. University of Queensland, Brisbane, QUEENSLAND, Australia
  2. QIMR Berghofer medical research institute, Brisbane, Queensland

Mosquito-borne flaviviruses like West Nile (WNV), Zika (ZIKV) and dengue viruses (DENV) continue to pose a significant global health threat. Despite the disease burden of these viruses few vaccines are currently licensed and none available for WNV and ZIKV, illustrating the need for development new vaccines. This study describes a new chimeric vaccine platform that is based on the novel insect-specific flavivirus (ISF) Binjari virus (BinJV). Despite the genetic similarity of this ISF to traditional vertebrate-infecting flaviviruses (VIF), BinJV is unable to replicate in vertebrate cells. Using the circular polymerase extension reaction to rapidly construct infectious virus clones, we replaced the structural prME genes of BinJV for those of the WNV, DENV-2 and ZIKV, to generate the chimeric viruses BinJV/WNV-prME, BinJV/DENV-2-prME and BinJV/ZIKV-prME. These chimeric viruses were shown to be antigenically indistinguishable from the parental VIF, while still lacking the ability to replicate in vertebrate cells. Immuno-competent CD1 mice that were immunised with as little as 1-5 mg of purified BinJV/WNV-prME, produced high neutralising antibody titres that were detected in the blood for at least 6 months after vaccination. We thereafter determined whether a BinJV/VIF-prME chimeric vaccine could protect against a subsequent virus infection and found 100% protection in IFNAR KO mice after ZIKV challenge when immunised with a single, non-adjuvanted dose of 1 mg BinJV/ZIKV-prME. Similarly, three doses of 1 mg BinJV/DENV-2-prME provided 80-100% protection against viremia and weight-loss in immuno-deficient AG129 mice after challenge with a lethal dose of DENV-2. These results suggest this chimeric vaccine platform is effective across the different flaviviruses tested. The highly flexibly nature of the system allows for rapid response to outbreaks while the BinJV backbone provides an additional safety aspect due to its inability to replicate or revert to virulence in the vaccinated individual.