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Development of an APC-targeted multivalent E2-based vaccine against Bovine Viral Diarrhea Virus types 1 and 2
Affiliation:1. Virology Institute, Veterinary and Agricultural Science Research Centre, INTA Castelar, Buenos Aires, Argentina;2. Vetanco SA, Buenos Aires, Argentina;3. Algenex SL, Madrid, Spain;4. Departamento de Biotecnología, INIA, Madrid, Spain;1. VIDO-Intervac, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E3;2. Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E3;1. Pathology & Pathogen Biology, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield AL9 7TA, Hertfordshire, UK;2. Nature Technology Corporation, 4701 Innovation Drive, Lincoln, NE 68521, USA;1. University of Adelaide, School of Animal and Veterinary Sciences, Roseworthy Campus, Roseworthy, South Australia 5371, Australia;2. Gribbles Veterinary, 840 Tremaine Ave, Palmerston North 4440, New Zealand;3. Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire AL97TA, United Kingdom;1. College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA;2. Wisconsin Veterinary Diagnostic Laboratory and Department of Pathobiological Sciences, University of Wisconsin, Madison, WI 53706, USA;3. Animal Disease Diagnostic Laboratory, Ohio Department of Agriculture, Reynoldsburg, OH 43068, USA;4. Nebraska Veterinary Diagnostic Laboratory System, University of Nebraska, Lincoln, NE 68501, USA;1. Virology Institute, Veterinary and Agricultural Science Research Centre, INTA Castelar, Buenos Aires, Argentina;2. Ruminant Diseases and Immunology Research Unit USDA, Ames, USA;3. Laboratorio Azul Diagnóstico, Buenos Aires, Argentina;4. Laboratorio de Sanidad Animal, INTA Balcarce, Buenos Aires, Argentina;5. Departamento de Virología, Facultad de Farmacia y Bioquímica UBA, Buenos Aires, Argentina;1. Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843, USA;2. Ruminant Diseases and Immunology Research Unit, National Animal Disease Center, USDA, Agricultural Research Services, 1920 Dayton Avenue, P.O. Box 70, Ames, IA 50010, USA;3. Department of Animal Science, Texas A&M University & Texas A&M AgriLife Research, College Station, TX 77843, USA
Abstract:The aim of this study was to develop and test a multivalent subunit vaccine against Bovine Viral Diarrhea Virus (BVDV) based on the E2 virus glycoprotein belonging to genotypes 1a, 1b and 2a, immunopotentiated by targeting these antigens to antigen-presenting cells. The E2 antigens were expressed in insect cells by a baculovirus vector as fusion proteins with a single chain antibody, named APCH I, which recognizes the β-chain of the MHC Class II antigen. The three chimeric proteins were evaluated for their immunogenicity in a guinea pig model as well as in colostrum-deprived calves. Once the immune response in experimentally vaccinated calves was evaluated, immunized animals were challenged with type 1b or type 2b BVDV in order to study the protection conferred by the experimental vaccine.The recombinant APCH I-tE21a-1b-2a vaccine was immunogenic both in guinea pigs and calves, inducing neutralizing antibodies. After BVDV type 1b and type 2 challenge of vaccinated calves in a proof of concept, the type 1b virus could not be isolated in any animal; meanwhile it was detected in all challenged non-vaccinated control animals. However, the type 2 BVDV was isolated to a lesser extent compared to unvaccinated animals challenged with type 2 BVDV. Clinical signs associated to BVDV, hyperthermia and leukopenia were reduced with respect to controls in all vaccinated calves. Given these results, this multivalent vaccine holds promise for a safe and effective tool to control BVDV in herds.
Keywords:BVDV  E2 glycoprotein  Pestivirus  Subunit vaccine
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