title: DNA vaccination against bovine viral diarrhoea virus induces humoral and cellular responses in cattle with evidence for protection against viral challenge.
abstract: The immune response induced by a DNA construct expressing the E2 envelope glycoprotein of bovine viral diarrhoea virus (BVDV) was studied in cattle. Four groups of five calves, were immunised by intradermal injection with a total of 1mg of plasmid DNA on each of two occasions, with a 3-week dose interval. Group 1 received non-coding plasmid DNA only (control), group 2 received the E2 coding plasmid (0.5mg) plus non-coding plasmid DNA (0.5mg) and groups 3 and 4 received the E2 coding plasmid plus plasmid encoding either bovine interleukin 2 (IL-2) or granulocyte macrophage colony stimulating factor (GM-CSF) respectively. Two weeks after the final immunisation, all calves were challenged by intranasal inoculation with 5 x 10(6) TCID(50) of homologous virus. On the day of challenge, neutralising antibodies were detectable in 13 of 15 vaccinated calves (one animal in each of groups 3 and 4 remained seronegative at this point). Thereafter, a strong anamnestic serological response was evident in all vaccinated animals. Furthermore, T-cell proliferation following in vitro re-stimulation with BVDV antigen was significantly elevated in the cytokine adjuvanted groups. This enhancement of BVDV specific immune responses in vaccinated animals was reflected in the clinical responses observed post-challenge. In particular, reduced febrile responses provided evidence of a disease sparing effect of vaccination. Significantly, whilst a transient viraemia was detected in all control animals following challenge, no virus was isolated from the leucocytes from 8 out of the 15 vaccinated animals. In groups 2 and 4, three animals remained virus free, although virus was isolated from two animals in each group at a single time point, while in group 3, three out of five animals had detectable viraemia. In summary, the administration of a DNA vaccine encoding only the E2 glycoprotein of BVDV induced a disease sparing effect in vaccinated calves following challenge and protected more than half of the vaccinated animals from detectable viraemia.
authors.affiliation: Department of Pathology and Infectious Diseases, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire AL9 7TA, UK.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Nobiron
authors.forename: Ian
authors.initials: I
authors.lastname: Thompson
authors.forename: Joe
authors.initials: J
authors.lastname: Brownlie
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Collins
mesh_terms: D000818:Animals; D001483:Base Sequence; D001831:Body Temperature; D001912:Bovine Virus Diarrhea-Mucosal Disease / Q000276:immunology* / Q000523:psychology; D002417:Cattle; D003001:Cloning, Molecular; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D001908:Diarrhea Viruses, Bovine Viral / Q000276:immunology*; D007117:Immunization, Secondary; D008213:Lymphocyte Activation; D009500:Neutralization Tests; D013997:Time Factors; D019444:Vaccines, DNA / Q000627:therapeutic use*; D014765:Viral Vaccines / Q000627:therapeutic use*
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D019444:Vaccines, DNA; D014765:Viral Vaccines