Research ArticleFLAVIVIRUSES

A recombinant platform for flavivirus vaccines and diagnostics using chimeras of a new insect-specific virus

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Science Translational Medicine  11 Dec 2019:
Vol. 11, Issue 522, eaax7888
DOI: 10.1126/scitranslmed.aax7888

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Fighting flavi with flavi

Insect-transmitted flaviviruses can cause hemorrhagic fever in humans and contribute to morbidity and mortality worldwide. Hobson-Peters et al. isolated a new flavivirus from mosquitoes in Australia that can only infect insect cells. Binjari virus permits swapping of structural proteins from other flaviviruses such as dengue or Zika virus. The chimeric viruses grow to high titers in insect cells but do not infect human cells. They can be used to efficiently produce vaccines or antigens for diagnostics, overcoming safety and manufacturing hurdles of other approaches. A chimeric Binjari virus platform could facilitate and possibly accelerate development of much needed diagnostics and interventions for flaviviruses.

Abstract

Flaviviruses such as dengue, yellow fever, Zika, West Nile, and Japanese encephalitis virus present substantial global health burdens. New vaccines are being sought to address safety and manufacturing issues associated with current live attenuated vaccines. Here, we describe a new insect-specific flavivirus, Binjari virus, which was found to be remarkably tolerant for exchange of its structural protein genes (prME) with those of the aforementioned pathogenic vertebrate-infecting flaviviruses (VIFs). Chimeric BinJ/VIF-prME viruses remained replication defective in vertebrate cells but replicated with high efficiency in mosquito cells. Cryo–electron microscopy and monoclonal antibody binding studies illustrated that the chimeric BinJ/VIF-prME virus particles were structurally and immunologically similar to their parental VIFs. Pilot manufacturing in C6/36 cells suggests that high yields can be reached up to 109.5 cell culture infectious dose/ml or ≈7 mg/liter. BinJ/VIF-prME viruses showed utility in diagnostic (microsphere immunoassays and ELISAs using panels of human and equine sera) and vaccine applications (illustrating protection against Zika virus challenge in murine IFNAR−/− mouse models). BinJ/VIF-prME viruses thus represent a versatile, noninfectious (for vertebrate cells), high-yield technology for generating chimeric flavivirus particles with low biocontainment requirements.

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