title: Modulation of immune responses to bovine herpesvirus-1 in cattle by immunization with a DNA vaccine encoding glycoprotein D as a fusion protein with bovine CD154.
abstract: The objective of this study was to determine whether a DNA vaccine encoding bovine CD154 linked to a truncated version of bovine herpesvirus-1 (BHV-1) glycoprotein D (tgD-CD154) induces enhanced tgD-specific immune responses in cattle. In vitro characterization demonstrated that tgD and tgD-CD154 both bind to cultured bovine B cells, whereas only tgD-CD154 induces interleukin-4-dependent proliferation, suggesting that tgD-CD154 specifically binds the CD40 receptor and induces receptor signalling. Calves were immunized with plasmid encoding either tgD or tgD-CD154 by intradermal injection with a needle-free device. After two immunizations, tgD-specific immune responses were observed in both vaccinated groups and after challenge with BHV-1 these responses further increased. Animals immunized with plasmid encoding tgD-CD154 had significantly higher tgD-specific serum titres of immunoglobulins G and A but significantly lower numbers of tgD-specific interferon-gamma-secreting cells than animals immunized with plasmid encoding tgD after BHV-1 challenge. This suggests that the expression of an antigen as a chimeric protein with CD154 can qualitatively alter immune responses in cattle. Since we previously showed that plasmid encoding tgD-CD154 induces significantly enhanced secondary tgD-specific antibody responses in sheep, there appear to be interspecies differences in the immune responses induced by tgD-CD154, which suggests that both proteins in the chimeric molecule may influence protein targeting and the induction of an immune response.
authors.affiliation: Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: Sharmila
authors.initials: S
authors.lastname: Manoj
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Griebel
authors.forename: Lorne A
authors.initials: LA
authors.lastname: Babiuk
authors.forename: Sylvia
authors.initials: S
authors.lastname: van Drunen Littel-van den Hurk
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000956:Antigens, Viral / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology; D002417:Cattle / Q000276:immunology*; D002418:Cattle Diseases / Q000517:prevention & control; D002478:Cells, Cultured; D006566:Herpesviridae Infections / Q000517:prevention & control / Q000662:veterinary; D007242:Herpesvirus 1, Bovine / Q000276:immunology*; D022283:Herpesvirus Vaccines / Q000276:immunology*; D007111:Immunity, Cellular; D007114:Immunization; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014162:Transfection; D019444:Vaccines, DNA / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D022283:Herpesvirus Vaccines; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D014764:Viral Proteins; C046998:bovine herpesvirus type-1 glycoproteins; D023201:CD40 Ligand