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

J Gen Virol. 2002 Dec;83(Pt 12):2973-2981. doi: 10.1099/0022-1317-83-12-2973.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / blood
  • Base Sequence
  • Cattle
  • Cattle Diseases / immunology
  • Cattle Diseases / prevention & control
  • Cattle Diseases / virology
  • CpG Islands / genetics
  • CpG Islands / immunology*
  • Genetic Vectors / immunology*
  • Herpesviridae Infections / immunology
  • Herpesviridae Infections / prevention & control
  • Herpesvirus 1, Bovine / immunology*
  • Herpesvirus Vaccines / genetics
  • Herpesvirus Vaccines / immunology*
  • Immunization / veterinary
  • Interferon-gamma / biosynthesis
  • Lymphocyte Activation / immunology*
  • Plasmids / genetics
  • Plasmids / immunology
  • Vaccines, DNA / immunology
  • Viral Proteins / genetics
  • Viral Proteins / immunology*

Substances

  • Antibodies, Viral
  • Herpesvirus Vaccines
  • Vaccines, DNA
  • Viral Proteins
  • bovine herpesvirus type-1 glycoproteins
  • Interferon-gamma