A recombinant platform for flavivirus vaccines and diagnostics using chimeras of a new insect-specific virus
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 fl...
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| Published in | Science translational medicine Vol. 11; no. 522 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
11.12.2019
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| Online Access | Get more information |
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| 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 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. |
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| AbstractList | 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. |
| Author | Warrilow, David Chow, Weng Kong Suhrbier, Andreas Hazlewood, Jessamine E Bielefeldt-Ohmann, Helle Harrison, Jessica J Watterson, Daniel Colmant, Agathe M G Hobson-Peters, Jody Kurucz, Nina Setoh, Yin Xiang Hall, Roy A Newton, Natalee D Piyasena, Thisun B H Finger, Mitchell Taylor, Carmel Yan, Kexin Vet, Laura J Khromykh, Alexander A Moore, Peter R Modhiran, Naphak Huang, Bixing Tang, Bing Nakayama, Eri Amarilla, Alberto A Young, Paul R Wheatley, Sarah |
| Author_xml | – sequence: 1 givenname: Jody orcidid: 0000-0003-0139-9829 surname: Hobson-Peters fullname: Hobson-Peters, Jody email: roy.hall@uq.edu.au, j.peters2@uq.edu.au organization: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Queensland, Australia. roy.hall@uq.edu.au j.peters2@uq.edu.au – sequence: 2 givenname: Jessica J orcidid: 0000-0002-3577-9910 surname: Harrison fullname: Harrison, Jessica J organization: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Queensland, Australia – sequence: 3 givenname: Daniel orcidid: 0000-0001-5957-2853 surname: Watterson fullname: Watterson, Daniel organization: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Queensland, Australia – sequence: 4 givenname: Jessamine E orcidid: 0000-0001-6104-4531 surname: Hazlewood fullname: Hazlewood, Jessamine E organization: Inflammation Biology Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia – sequence: 5 givenname: Laura J orcidid: 0000-0001-7587-2936 surname: Vet fullname: Vet, Laura J organization: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Queensland, Australia – sequence: 6 givenname: Natalee D orcidid: 0000-0002-5617-8639 surname: Newton fullname: Newton, Natalee D organization: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Queensland, Australia – sequence: 7 givenname: David orcidid: 0000-0002-3221-7605 surname: Warrilow fullname: Warrilow, David organization: Public Health Virology Laboratory, Department of Health, Queensland Government, PO Box 594, Archerfield, Queensland, Australia – sequence: 8 givenname: Agathe M G orcidid: 0000-0002-2004-4073 surname: Colmant fullname: Colmant, Agathe M G organization: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Queensland, Australia – sequence: 9 givenname: Carmel surname: Taylor fullname: Taylor, Carmel organization: Public Health Virology Laboratory, Department of Health, Queensland Government, PO Box 594, Archerfield, Queensland, Australia – sequence: 10 givenname: Bixing orcidid: 0000-0002-7025-2292 surname: Huang fullname: Huang, Bixing organization: Public Health Virology Laboratory, Department of Health, Queensland Government, PO Box 594, Archerfield, Queensland, Australia – sequence: 11 givenname: Thisun B H orcidid: 0000-0002-1657-8558 surname: Piyasena fullname: Piyasena, Thisun B H organization: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Queensland, Australia – sequence: 12 givenname: Weng Kong orcidid: 0000-0003-3609-2499 surname: Chow fullname: Chow, Weng Kong organization: Australian Defence Force Malaria and Infectious Disease Institute, Gallipoli Barracks, Queensland, Australia – sequence: 13 givenname: Yin Xiang orcidid: 0000-0002-1683-3555 surname: Setoh fullname: Setoh, Yin Xiang organization: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Queensland, Australia – sequence: 14 givenname: Bing orcidid: 0000-0003-0281-2160 surname: Tang fullname: Tang, Bing organization: Inflammation Biology Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia – sequence: 15 givenname: Eri orcidid: 0000-0002-0826-3513 surname: Nakayama fullname: Nakayama, Eri organization: Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan – sequence: 16 givenname: Kexin orcidid: 0000-0003-2203-217X surname: Yan fullname: Yan, Kexin organization: Inflammation Biology Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia – sequence: 17 givenname: Alberto A orcidid: 0000-0002-6640-3377 surname: Amarilla fullname: Amarilla, Alberto A organization: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Queensland, Australia – sequence: 18 givenname: Sarah surname: Wheatley fullname: Wheatley, Sarah organization: Public Health Virology Laboratory, Department of Health, Queensland Government, PO Box 594, Archerfield, Queensland, Australia – sequence: 19 givenname: Peter R surname: Moore fullname: Moore, Peter R organization: Public Health Virology Laboratory, Department of Health, Queensland Government, PO Box 594, Archerfield, Queensland, Australia – sequence: 20 givenname: Mitchell orcidid: 0000-0002-3861-1443 surname: Finger fullname: Finger, Mitchell organization: Public Health Virology Laboratory, Department of Health, Queensland Government, PO Box 594, Archerfield, Queensland, Australia – sequence: 21 givenname: Nina surname: Kurucz fullname: Kurucz, Nina organization: Centre for Disease Control, Health Protection Division, Northern Territory Department of Health, Darwin, Northern Territory, Australia – sequence: 22 givenname: Naphak orcidid: 0000-0003-3205-4970 surname: Modhiran fullname: Modhiran, Naphak organization: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Queensland, Australia – sequence: 23 givenname: Paul R surname: Young fullname: Young, Paul R organization: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Queensland, Australia – sequence: 24 givenname: Alexander A surname: Khromykh fullname: Khromykh, Alexander A organization: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Queensland, Australia – sequence: 25 givenname: Helle surname: Bielefeldt-Ohmann fullname: Bielefeldt-Ohmann, Helle organization: School of Veterinary Science, University of Queensland Gatton Campus, Queensland 4343, Australia – sequence: 26 givenname: Andreas surname: Suhrbier fullname: Suhrbier, Andreas organization: Inflammation Biology Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia – sequence: 27 givenname: Roy A orcidid: 0000-0001-5778-1387 surname: Hall fullname: Hall, Roy A email: roy.hall@uq.edu.au, j.peters2@uq.edu.au organization: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Queensland, Australia. roy.hall@uq.edu.au j.peters2@uq.edu.au |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31826984$$D View this record in MEDLINE/PubMed |
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| Copyright | Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. |
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