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A recombinant platform for flavivirus vaccines and diagnostics using chimeras of a new insect-specific virus.
Hobson-Peters, Jody; Harrison, Jessica J; Watterson, Daniel; Hazlewood, Jessamine E; Vet, Laura J; Newton, Natalee D; Warrilow, David; Colmant, Agathe M G; Taylor, Carmel; Huang, Bixing; Piyasena, Thisun B H; Chow, Weng Kong; Setoh, Yin Xiang; Tang, Bing; Nakayama, Eri; Yan, Kexin; Amarilla, Alberto A; Wheatley, Sarah; Moore, Peter R; Finger, Mitchell; Kurucz, Nina; Modhiran, Naphak; Young, Paul R; Khromykh, Alexander A; Bielefeldt-Ohmann, Helle; Suhrbier, Andreas; Hall, Roy A.
Afiliação
  • Hobson-Peters J; 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.
  • Harrison JJ; Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Queensland, Australia.
  • Watterson D; Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Queensland, Australia.
  • Hazlewood JE; Inflammation Biology Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia.
  • Vet LJ; Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Queensland, Australia.
  • Newton ND; Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Queensland, Australia.
  • Warrilow D; Public Health Virology Laboratory, Department of Health, Queensland Government, PO Box 594, Archerfield, Queensland, Australia.
  • Colmant AMG; Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Queensland, Australia.
  • Taylor C; Public Health Virology Laboratory, Department of Health, Queensland Government, PO Box 594, Archerfield, Queensland, Australia.
  • Huang B; Public Health Virology Laboratory, Department of Health, Queensland Government, PO Box 594, Archerfield, Queensland, Australia.
  • Piyasena TBH; Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Queensland, Australia.
  • Chow WK; Australian Defence Force Malaria and Infectious Disease Institute, Gallipoli Barracks, Queensland, Australia.
  • Setoh YX; Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Queensland, Australia.
  • Tang B; Inflammation Biology Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia.
  • Nakayama E; Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan.
  • Yan K; Inflammation Biology Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia.
  • Amarilla AA; Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Queensland, Australia.
  • Wheatley S; Public Health Virology Laboratory, Department of Health, Queensland Government, PO Box 594, Archerfield, Queensland, Australia.
  • Moore PR; Public Health Virology Laboratory, Department of Health, Queensland Government, PO Box 594, Archerfield, Queensland, Australia.
  • Finger M; Public Health Virology Laboratory, Department of Health, Queensland Government, PO Box 594, Archerfield, Queensland, Australia.
  • Kurucz N; Centre for Disease Control, Health Protection Division, Northern Territory Department of Health, Darwin, Northern Territory, Australia.
  • Modhiran N; Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Queensland, Australia.
  • Young PR; Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Queensland, Australia.
  • Khromykh AA; Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Queensland, Australia.
  • Bielefeldt-Ohmann H; Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Queensland, Australia.
  • Suhrbier A; School of Veterinary Science, University of Queensland Gatton Campus, Queensland 4343, Australia.
  • Hall RA; Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Queensland, Australia.
Sci Transl Med ; 11(522)2019 12 11.
Article em En | MEDLINE | ID: mdl-31826984
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Recombinação Genética / Vacinas Virais / Quimera / Infecções por Flavivirus / Flavivirus / Vírus de Insetos Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Animals / Humans / Male Idioma: En Revista: Sci Transl Med Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Recombinação Genética / Vacinas Virais / Quimera / Infecções por Flavivirus / Flavivirus / Vírus de Insetos Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Animals / Humans / Male Idioma: En Revista: Sci Transl Med Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2019 Tipo de documento: Article