Construction and efficacy of a new live chimeric C-strain vaccine with DIVA characteristics against classical swine fever |
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| Affiliation: | 1. State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China;2. World Organisation for Animal Health Reference Laboratory for Classical Swine Fever, China Institute of Veterinary Drug Control, Beijing 100081, China;3. Key Laboratory of Prevention and Control Agents for Animal Bacteriosis (Ministry of Agriculture and Rural Affairs), Hubei Provincial Key Laboratory of Animal Pathogenic Microbiology, Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Sciences, Wuhan 430064, China;4. Laboratory, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430015, China;1. National University Health System, 1E Kent Ridge Road, Singapore 119228;2. London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, United Kingdom;3. Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, 12 Science Drive 2, #10-01, Singapore 117549, Singapore;4. University of North Carolina Project-China, 2 Lujing Road, Guangzhou 510095, Guangdong, China;1. Institut für Geschichte und Ethik der Medizin, Medizinische Fakultät, Universität Heidelberg, Heidelberg, Germany;2. Department of Health Sciences - University of Genoa, Genoa, Italy;1. Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India;2. Center for Human Genetics, Universitatsklinikum Giessen und Marburg - Standort Marburg, 35055 Marburg, Germany;3. Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, University Côte d’Azur, 30 avenue de la voie romaine, 06002 Nice, France;4. Institute for Research on Cancer and Ageing, Nice (IRCAN), INSERM U1081 and UMR CNRS 7284, Team 4, Nice, France;5. Hospital-Integrated Biobank BB-0033-00025, Pasteur Hospital, Nice, France;6. University Hospital Federation OncoAge, CHU de Nice, University Côte d’Azur, Nice, France;1. Department of Paediatric Infectious Diseases and Immunology Children''s Health Ireland at Crumlin & Temple Street, Dublin, Ireland;2. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA;3. School of Medicine, University College Dublin, Dublin, Ireland;4. Children’s Hospital of Philadelphia Global Health Center, USA;5. Niños Primeros en Salud, Consuelo, Dominican Republic;6. Hospital Materno Infantil San Lorenzo de Los Mina, Santo Domingo, Dominican Republic;7. Clinical Innovation Unit, The Rotunda Hospital, Dublin, Ireland;8. Irish Meningitis and Sepsis Reference Laboratory, Children’s Health Ireland at Temple Street, Dublin, Ireland;9. Department of Microbiology, Royal College of Surgeons in Ireland, Dublin, Ireland;10. Division of Obstetrics & Gynaecology, The Rotunda Hospital, Dublin, Ireland;11. Division of Pediatric Infectious Diseases, Grossman School of Medicine, New York University, New York, NY, USA;12. Global Medical and Scientific Affairs, Merck Research Laboratories, Merck & Co., Inc, Upper Gwynedd, PA, USA;1. Department of Health Law, Policy, & Management, Boston University, School of Public Health, United States;2. Network Science Institute at Northeastern University, and Shorenstein Center on Media, Politics, and Policy at Harvard University, United States;3. Program in Health Policy (Political Analysis), Harvard University, United States;1. Children’s Hospital of Philadelphia, Vaccine Education Center, Philadelphia, United States;2. Leonard Davis Institute, University of Pennsylvania, Philadelphia, United States;3. University of Pennsylvania, Perelman School of Medicine, Department of Medical Bioethics and Health Policy, Philadelphia, United States;4. University of Pennsylvania, Perelman School of Medicine, Department of Biostatistics, Epidemiology and Informatics, Philadelphia, United States;5. University of Pennsylvania, School of Nursing, Department of Family and Community Health, United States;6. University of Pennsylvania, Perelman School of Medicine, Department of Pediatrics, Division of Adolescent Medicine, United States;7. University of Pennsylvania, Annenberg School for Communication, United States |
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| Abstract: | To develop the new classical swine fever (CSF) vaccine candidate with differentiating infected vaccinated animals (DIVA) characteristics, a chimeric CSF virus (CSFV) was constructed based on an infectious cDNA clone of the CSF vaccine C-strain. The 5’- and 3’-untranslated regions (UTRs) and partial E2 region (residues 690-860) of the C-strain were substituted with the corresponding regions of bovine viral diarrhoea virus (BVDV) to construct the chimeric cDNA clone pC/bUTRs-tE2. The chimeric virus rC/bUTRs-tE2 was generated by several passages of pC/bUTRs-tE2-transfected PK15 cells. Stable growth and genetic properties of rC/bUTRs-tE2 were obtained after 30 serial passages. Compared to parental rC/bUTRs-tE2 (1st passage), two residue mutations (M834K and M979K) located in E2 in rC/bUTRs-tE2 P30 were observed. Compared to the C-strain, rC/bUTRs-tE2 exhibited unchanged cell tropism and decreased plaque-forming ability. Substituting the C-strain UTRs with the BVDV UTRs resulted in significantly increased viral replication in PK15 cells. Compared to CSFV Erns-positive and BVDV tE2-negative antibody responses induced by the CSF vaccine C-strain, immunization of rabbits and piglets with rC/bUTRs-tE2 resulted in serological profiles of CSFV Erns- and BVDV tE2-positive antibodies, which are used to serologically discriminate pigs that are clinically infected and vaccinated. Vaccination of piglets with rC/bUTRs-tE2 conferred complete protection against lethal CSFV challenge. Our results suggest that rC/bUTRs-tE2 is a promising new CSF marker vaccine candidate. |
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| Keywords: | Classical swine fever virus Chimeric virus Marker vaccine E2 UTR DIVA |
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