Priming Cross-Protective Bovine Viral Diarrhea Virus-Specific Immunity Using Live-Vectored Mosaic Antigens

Autor: Christopher C. L. Chase, Shehnaz Lokhandwala, Suryakant D. Waghela, Andy D. Herring, Jocelyn Bray, Karim W. Abdelsalam, Waithaka Mwangi, Leo M. Njongmeta, Xin Fang
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Adenoviruses
Heredity
Physiology
animal diseases
viruses
Cross Protection
T-Lymphocytes
lcsh:Medicine
Pathology and Laboratory Medicine
Antibodies
Viral
Biochemistry
0403 veterinary science
White Blood Cells
Animal Cells
Immune Physiology
Medicine and Health Sciences
Diarrhea Virus 2
Bovine Viral
Public and Occupational Health
Neutralizing antibody
lcsh:Science
Immune Response
Antigens
Viral
Mammals
Vaccines
Multidisciplinary
Immune System Proteins
biology
T Cells
Viral Vaccine
Diarrhea Virus 1
Bovine Viral
Vaccination
Agriculture
04 agricultural and veterinary sciences
Ruminants
Vaccination and Immunization
Genetic Mapping
Medical Microbiology
Mutant Genotypes
Viral Pathogens
Viruses
Vertebrates
Vaccines
Subunit
Bovine Virus Diarrhea-Mucosal Disease
Antibody
Pathogens
Cellular Types
Research Article
Livestock
040301 veterinary sciences
medicine.drug_class
Immune Cells
Immunology
Monoclonal antibody
Microbiology
Virus
Antibodies
Cell Line
03 medical and health sciences
Interferon-gamma
Immune system
Cross-Priming
Antigen
Bovines
Virology
medicine
Genetics
Animals
Humans
Microbial Pathogens
Blood Cells
Biology and life sciences
Chimera
lcsh:R
Organisms
Proteins
Viral Vaccines
Cell Biology
biochemical phenomena
metabolism
and nutrition
Antibodies
Neutralizing
030104 developmental biology
HEK293 Cells
Amniotes
biology.protein
lcsh:Q
Cattle
Preventive Medicine
DNA viruses
Zdroj: PLoS ONE
PLoS ONE, Vol 12, Iss 1, p e0170425 (2017)
ISSN: 1932-6203
Popis: Bovine viral diarrhea virus (BVDV) plays a key role in bovine respiratory disease complex, which can lead to pneumonia, diarrhea and death of calves. Current vaccines are not very effective due, in part, to immunosuppressive traits and failure to induce broad protection. There are diverse BVDV strains and thus, current vaccines contain representative genotype 1 and 2 viruses (BVDV-1 & 2) to broaden coverage. BVDV modified live virus (MLV) vaccines are superior to killed virus vaccines, but they are susceptible to neutralization and complement-mediated destruction triggered by passively acquired antibodies, thus limiting their efficacy. We generated three novel mosaic polypeptide chimeras, designated NproE2123; NS231; and NS232, which incorporate protective determinants that are highly conserved among BVDV-1a, 1b, and BVDV-2 genotypes. In addition, strain-specific protective antigens from disparate BVDV strains were included to broaden coverage. We confirmed that adenovirus constructs expressing these antigens were strongly recognized by monoclonal antibodies, polyclonal sera, and IFN-γ-secreting T cells generated against diverse BVDV strains. In a proof-of-concept efficacy study, the multi-antigen proto-type vaccine induced higher, but not significantly different, IFN-γ spot forming cells and T-cell proliferation compared to a commercial MLV vaccine. In regards to the humoral response, the prototype vaccine induced higher BVDV-1 specific neutralizing antibody titers, whereas the MLV vaccine induced higher BVDV-2 specific neutralizing antibody titers. Following BVDV type 2a (1373) challenge, calves immunized with the proto-type or the MLV vaccine had lower clinical scores compared to naive controls. These results support the hypothesis that a broadly protective subunit vaccine can be generated using mosaic polypeptides that incorporate rationally selected and validated protective determinants from diverse BVDV strains. Furthermore, regarding biosafety of using a live vector in cattle, we showed that recombinant human adenovirus-5 was cleared within one week following intradermal inoculation.
Databáze: OpenAIRE
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