A recombinant DNA vaccine protects mice deficient in the alpha/beta interferon receptor against lethal challenge with Usutu virus |
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| Affiliation: | 1. Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Madrid, Spain;2. Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM), Madrid, Spain;1. Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Madrid, Spain;2. Scientific Veterinary Institute “Novi Sad”, Novi Sad, Serbia;1. Institut Pasteur, URE ERI/CIBU, Paris, France;2. French Agency for Food, Environmental and Occupational Health & Safety (ANSES), Animal Health Laboratory, UMR1161 Virology, INRA, ANSES, ENVA, Maisons-Alfort, France;3. Arbovirus & Imported Viral Diseases, Centro Nacional de Microbiología, Ctra. Pozuelo, Madrid, Spain;4. University of La Réunion Island, UM134 PIMIT, INSERM U1187, CNRS UMR9192, IRD UMR249, Technology Platform CYROI, 97490 Saint-Clotilde, La Réunion, France;1. Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Institute of Novel and Emerging Infectious Diseases, Südufer 10, 17493 Greifswald-Insel Riems, Germany;2. Berlin-Brandenburg, State Laboratory, Gerhard-Neumann-Str. 2, 15236 Frankfurt (Oder), Germany;3. Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Institute of Diagnostic Virology, Südufer 10, 17493 Greifswald-Insel Riems, Germany;4. Zoological Garden Berlin AG, Hardenbergplatz 8, 10787 Berlin, Germany;5. Bernhard-Nocht-Institute for Tropical Medicine, WHO Collaborating Centre for Arbovirus and Hemorrhagic Fever Reference and Research, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany;6. Leibniz-Centre for Agricultural Landscape Research (ZALF), Institute of Land Use Systems, Eberswalder Straße 84, 15374 Müncheberg, Germany;7. German Centre for Infection Research (DZIF), Partner Site Hamburg-Luebeck-Borstel, Hamburg, Germany;1. Unit of Clinical Microbiology, Regional Reference Centre for Microbiological Emergencies (CRREM), St Orsola-Malpighi University Hospital;2. U.O.C. Idoneità Biologica Donatori Sangue ed Emocomponenti;3. Emilia-Romagna Regional Blood Center;4. Public Health Authority Emilia-Romagna, Bologna;5. Unit of Microbiology, ‘AVR – Greater Romagna’ Central Laboratory, Pievesestina, Cesena, Italy;1. Division of Molecular Pathobiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Hokkaido, 001-0020, Japan;2. Shionogi & Co., Ltd., Osaka, 541-0045, Japan;3. Laboratory of Biomolecular Science, Faculty of Pharmaceutical Science, Hokkaido University, Sapporo, 060-0812, Japan;4. International Collaboration Unit, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Hokkaido, 001-0020, Japan;5. Global Virus Network, Baltimore, MD, 21201, USA;6. National Virus Reference Laboratory, School of Medicine, University College Dublin, Belfield, Dublin, 4, Ireland;7. Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, Queensland, Australia;8. One Health Research Center, Hokkaido University, Sapporo, Hokkaido, 001-0020, Japan |
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| Abstract: | Usutu virus (USUV) is a mosquito-borne flavivirus whose circulation had been confined to Africa since it was first detected in 1959. However, in the last decade USUV has emerged in Europe causing episodes of avian mortality and sporadic severe neuroinvasive infections in humans. Remarkably, adult laboratory mice exhibit limited susceptibility to USUV infection, which has impaired the analysis of the immune responses, thus complicating the evaluation of virus–host interactions and of vaccine candidates against this pathogen. In this work, we showed that mice deficient in the alpha/beta interferon receptor (IFNAR (−/−) mice) were highly susceptible to USUV infection and provided a lethal challenge model for vaccine testing. To validate this infection model, a plasmid DNA vaccine candidate encoding the precursor of membrane (prM) and envelope (E) proteins of USUV was engineered. Transfection of cultured cells with this plasmid resulted in expression of USUV antigens and the assembly and secretion of small virus-like particles also known as recombinant subviral particles (RSPs). A single intramuscular immunization with this plasmid was sufficient to elicit a significant level of protection against challenge with USUV in IFNAR (−/−) mice. The characterization of the humoral response induced revealed that DNA vaccination primed anti-USUV antibodies, including neutralizing antibodies. Overall, these results probe the suitability of IFNAR (−/−) mice as an amenable small animal model for the study of USUV host virus interactions and vaccine testing, as well as the feasibility of DNA-based vaccine strategies for the control of this pathogen. |
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| Keywords: | Flavivirus Usutu virus DNA vaccine IFNAR mice Antibodies |
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