Immunogenicity and protective efficacy of recombinant Modified Vaccinia virus Ankara candidate vaccines delivering West Nile virus envelope antigens |
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| Institution: | 1. German Centre for Infection Research (DZIF), Institute for Infectious Diseases and Zoonoses, LMU University of Munich, Veterinaerstrasse 13, D-80539 Munich, Germany;2. Viroscience Lab, Erasmus Medical Center, Rotterdam, The Netherlands;3. Artemis One Health Research Institute, Utrecht, The Netherlands;4. Institute for Animal Physiology, LMU University of Munich, Munich, Germany;5. Laboratory of Virology, Wageningen University, Wageningen, The Netherlands;1. Aix Marseille Université, Unité de Recherche en Maladies Infectieuses et Tropicales Emergentes (URMITE), UM 63, CNRS 7278, IRD 198, Inserm 1095, WHO Collaborative Center for Rickettsioses and Other Arthropod-Borne Bacterial Diseases, Faculté de Médecine, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 5, France;2. Institut de Recherche Biomédicale des Armées (Armed Forces Biomedical Research Institute, IRBA), antenne Marseille, Unité de Parasitologie, URMITE UM 63, GSBdD de Marseille Aubagne, 111 Avenue de la Corse BP 40026, 13568 Marseille Cedex 02, France;3. CIRE/ARS Océan indien, 2 bis Avenue Georges Brassens CS 60050, 97408 Saint Denis Cedex 9, Reunion;4. Groupe de Recherche “Borréliose de Lyme”, EA7290, Virulence bactérienne précoce, Université de Strasbourg, France;5. Marseille Proteomic (MaP), Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM CNRS, Aix-Marseille Université, Institut Paoli-Calmette, 27 Boulevard Leï Roure, BP 30059, 13273 Marseille Cedex 09, France;1. Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China;2. Graduate School, Anhui Medical University, Hefei, China;1. Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy;2. Department of Biology and Biotechnology “Charles Darwin”, Sapienza University of Rome 00185 Rome, Italy;3. Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, USA;4. Division of Virology, Department of Microbiology and Immunology, and International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Japan;5. Infection-Induced Host Responses Project, Exploratory Research for Advanced Technology, Saitama 332-0012, Japan |
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| Abstract: | West Nile virus (WNV) cycles between insects and wild birds, and is transmitted via mosquito vectors to horses and humans, potentially causing severe neuroinvasive disease. Modified Vaccinia virus Ankara (MVA) is an advanced viral vector for developing new recombinant vaccines against infectious diseases and cancer. Here, we generated and evaluated recombinant MVA candidate vaccines that deliver WNV envelope (E) antigens and fulfil all the requirements to proceed to clinical testing in humans. Infections of human and equine cell cultures with recombinant MVA demonstrated efficient synthesis and secretion of WNV envelope proteins in mammalian cells non-permissive for MVA replication. Prime-boost immunizations in BALB/c mice readily induced circulating serum antibodies binding to recombinant WNV E protein and neutralizing WNV in tissue culture infections. Vaccinations in HLA-A2.1-/HLA-DR1-transgenic H-2 class I-/class II-knockout mice elicited WNV E-specific CD8+ T cell responses. Moreover, the MVA–WNV candidate vaccines protected C57BL/6 mice against lineage 1 and lineage 2 WNV infection and induced heterologous neutralizing antibodies. Thus, further studies are warranted to evaluate these recombinant MVA–WNV vaccines in other preclinical models and use them as candidate vaccine in humans. |
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| Keywords: | West Nile fever Flavivirus Viral vaccine Poxvirus vector |
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