Augmentation of cellular immune responses to bovine herpesvirus-1 glycoprotein D by vaccination with CpG-enhanced plasmid vectors.
The potential of CpG-enhanced plasmid DNA vectors encoding a truncated secreted form of bovine herpesvirus-1 (BHV-1) glycoprotein D (tgD) to induce enhanced immune responses in cattle was investigated. We created tgD expression plasmids containing 0, 40 or 88 copies of the hexamer 5' GTCGTT 3', a known pan-activating CpG motif in several species. The total tgD-specific IgG titre of calves immunized with these plasmids did not correlate with the CpG content of the plasmid backbone. However, the pBISIA88-tgD-vaccinated group showed a significantly lower IgG1:IgG2 ratio than calves immunized with pBISIA40-tgD or pMASIA-tgD, which has no CpG motifs inserted. Antigen-specific lymphocyte proliferation and IFN-gamma secretion by peripheral blood mononuclear cells correlated positively with the CpG content of the vectors. In contrast, calves that received a killed BHV-1 vaccine had an IgG1-predominant isotype and low lymphocyte proliferation and IFN-gamma levels. Following challenge, the pBISIA88-tgD-immunized group developed the greatest anamnestic response, the highest BHV-1 neutralization titres in serum and a significantly lower level of virus shedding than the saline control group. However, there were no significant differences in clinical symptoms of infection between the DNA-immunized groups and the saline control group. These data indicate that CpG-enhanced plasmids induce augmented immune responses and could be used to vaccinate against pathogens requiring a strong cellular response for protection.
Pontarollo
R A
RA
Veterinary Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, CanadaS7N 5E31.
Babiuk
L A
LA
Veterinary Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, CanadaS7N 5E31.
Hecker
R
R
Qiagen GmbH, 40724 Hilden, Germany2.
van Drunen Littel-van den Hurk
S
S
Veterinary Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, CanadaS7N 5E31.
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001483:Base Sequence; D002417:Cattle; D002418:Cattle Diseases / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D018899:CpG Islands / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors / Q000276:immunology*; D006566:Herpesviridae Infections / Q000276:immunology / Q000517:prevention & control; D007242:Herpesvirus 1, Bovine / Q000276:immunology*; D022283:Herpesvirus Vaccines / Q000235:genetics / Q000276:immunology*; D007114:Immunization / Q000662:veterinary; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D010957:Plasmids / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D022283:Herpesvirus Vaccines; D019444:Vaccines, DNA; D014764:Viral Proteins; C046998:bovine herpesvirus type-1 glycoproteins; D007371:Interferon-gamma