Augmentation of cellular immune responses to bovine herpesvirus-1 glycoprotein D by vaccination with CpG-enhanced plasmid vectors

• Published in: Journal of general virology 2002-12, Vol.83 (12), p.2973-2981
• Main Authors: Pontarollo, R.A, Babiuk, L.A, Hecker, R, Van Drunen Littel-Van den Hurk, A
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Viral - blood; Base Sequence; blood serum; Bovine herpesvirus 1; calves; Cattle; Cattle Diseases - immunology; Cattle Diseases - prevention & control; Cattle Diseases - virology; CpG Islands - genetics; CpG Islands - immunology; Genetic Vectors - immunology; glycoproteins; Herpesviridae Infections - immunology; Herpesviridae Infections - prevention & control; Herpesvirus 1, Bovine - immunology; Herpesvirus Vaccines - genetics; Herpesvirus Vaccines - immunology; immune response; Immunization - veterinary; immunoglobulin G; interferon-gamma; Interferon-gamma - biosynthesis; Lymphocyte Activation - immunology; lymphocyte proliferation; mononuclear leukocytes; neutralization; pathogens; plasmid vectors; plasmids; Plasmids - genetics; Plasmids - immunology; secretion; vaccination; vaccines; Vaccines, DNA - immunology; Viral Proteins - genetics; Viral Proteins - immunology; viral shedding
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/0022-1317-83-12-2973

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 pBISIA4O-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.