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TitleA recombinant platform for flavivirus vaccines and diagnostics using chimeras of a new insect-specific virus.
Journal, issue, pagesSci Transl Med, Vol. 11, Issue 522, Year 2019
Publish dateDec 11, 2019
AuthorsJody Hobson-Peters / Jessica J Harrison / Daniel Watterson / Jessamine E Hazlewood / Laura J Vet / Natalee D Newton / David Warrilow / Agathe M G Colmant / Carmel Taylor / Bixing Huang / Thisun B H Piyasena / Weng Kong Chow / Yin Xiang Setoh / Bing Tang / Eri Nakayama / Kexin Yan / Alberto A Amarilla / Sarah Wheatley / Peter R Moore / Mitchell Finger / Nina Kurucz / Naphak Modhiran / Paul R Young / Alexander A Khromykh / Helle Bielefeldt-Ohmann / Andreas Suhrbier / Roy A Hall /
PubMed AbstractFlaviviruses 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 ...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 10 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.
External linksSci Transl Med / PubMed:31826984
MethodsEM (single particle)
Resolution7.1 - 12.2 Å
Structure data

EMDB-20417:
Cryo-EM reconstruction of the mature chimeric BinJV/ZIKV-prME virion
Method: EM (single particle) / Resolution: 7.1 Å

EMDB-20438:
Cryo-EM reconstruction of the mature chimeric BinJV/ZIKV-prME virion in complex with Fab C8
Method: EM (single particle) / Resolution: 12.2 Å

EMDB-20439:
Cryo-EM reconstruction of the immature chimeric BinJV/ZIKV-prME virion
Method: EM (single particle) / Resolution: 12.2 Å

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