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A simplified roller bottle platform for the production of a new generation VLPs rabies vaccine for veterinary applications
Institution:1. UNL, Biotechnological Development Laboratory, FBCB, Edificio FBCB-Ciudad Universitaria UNL, C.C. 242. (S3000ZAA), Santa Fe, Argentina;2. UNL, CONICET, Cell Culture Laboratory, FBCB, Edificio FBCB-Ciudad Universitaria UNL, C.C. 242. (S3000ZAA), Santa Fe, Argentina;3. Cellargen Biotech S.R.L. Antonia Godoy 6369, C.C. 242. (S3000ZAA), Santa Fe, Argentina;1. Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran;2. Department of Urology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran;1. The Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian, UK;2. The Roslin Institute, Division of Genetics and Genomics, Easter Bush Veterinary Centre, Roslin, Midlothian, UK;3. The Royal (Dick) School of Veterinary Studies, Division of Veterinary Clinical Studies, The University of Edinburgh, Hospital for Small Animals, Easter Bush Veterinary Centre, Roslin, Midlothian, UK;4. Mission Rabies, Cranborne, Dorset, UK;5. School of Veterinary Medicine, College of Veterinary Medicine, Animal Resources and Bio-security, Makerere University, Kampala, Uganda;6. The Big Fix Uganda, Gulu, Uganda;1. Department of Small Animal Clinical Sciences, University of Florida, Gainesville, FL, USA;2. Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, FL, USA;1. Centro de Desenvolvimento Tecnológico, Núcleo de Biotecnologia Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil;2. Laboratório de Bacteriologia Veterinária, Departamento de Microbiologia e Parasitologia, Universidade Federal Fluminense, Niterói, Rio de Janeiro, Brazil;1. Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran;2. Department of Parasitology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran;3. Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran;4. Department of Medical Parasitology and Mycology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran;5. Department of Infectious Diseases, Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran;6. Social determinants of Health Research Center and Department of Community Medicine, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran;7. Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran;1. Program of Immunology, Institute of Biomedical Sciences ICBM, Faculty of Medicine, Universidad de Chile, Santiago, Chile;2. Periodontal Biology Laboratory, Faculty of Dentistry, Universidad de Chile, Santiago, Chile;3. Laboratory of Veterinary Bacteriology, Department of Animal Preventive Medicine, Faculty of Veterinary Sciences, Universidad de Chile, Santiago, Chile;4. Centro de Investigaciones Biológicas (CIB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain;5. Dentistry Unit, Faculty of Health Sciences, Universidad Autónoma de Chile, Santiago, Chile
Abstract:Rabies is a neglected disease with an estimated annual mortality of 55,000 human deaths, affecting mainly low-income countries. Over 95% of these cases result from virus transmission through the bite of infected dogs and for this reason there is a real need for a cheap and effective rabies veterinary vaccine to be used in mass vaccination campaigns. In this work, we describe the establishment of a simple platform for the production of a virus-like particles based rabies vaccine using mammalian cells and roller bottles as culture system. Adherent cells were cultured during more than 15 days and VLPs were continuously produced and secreted to the culture supernatant. Immunogenicity and protective efficacy of VLPs were tested through rabies virus neutralizing antibody test and NIH potency test. These viral particles induced high titer of long lasting neutralizing antibodies and protected mice against active virus challenge. Therefore, this development represents a promising platform for the production of a new generation and virus-free rabies vaccine candidate for veterinary applications.
Keywords:Rabies  Veterinary vaccine  Virus-like particles  Roller bottle
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