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Title: A recombinant platform for flavivirus vaccines and diagnostics using chimeras of a new insect-specific virus.
Authors: Hobson-Peters J
Harrison JJ
Watterson D
Hazlewood JE
Vet LJ
Newton ND
Warrilow D
Colmant AMG
Taylor C
Huang B
Piyasena TBH
Chow WK
Setoh YX
Tang B
Nakayama E
Yan K
Amarilla AA
Wheatley S
Moore PR
Finger M
Kurucz N
Modhiran N
Young PR
Khromykh AA
Bielefeldt-Ohmann H
Suhrbier A
Hall RA
Citation: Science translational medicine 2019-12-11; 11(522)
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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Journal title: Science translational medicine
Publication Date: 2019-12-11
Type: Journal Article
DOI: 10.1126/scitranslmed.aax7888
Appears in Collections:(a) NT Health Research Collection

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