INTRADERMAL IMMUNIZATION WITH A BOVINE HERPESVIRUS-1 DNA VACCINE INDUCES PROTECTIVE IMMUNITY IN CATTLE

Although intramuscular (i.m.) injection of DNA encoding glycoprotein D (gD) of bovine herpesvirus-1 (BHV-1) induces immune responses in catt le, this route of delivery is inefficient, Here we assessed three para meters that may enhance the efficacy of a gD DNA vaccine in cattle, Fi rst, the immune response generated by i.m. injected plasmid expressing a secreted form of gD (tgD) was determined and found to be very simil ar in magnitude to the response induced by gD-expressing plasmid, Seco ndly, gD- and tgD-expressing plasmids were administered by intradermal (i.d.) immunization, which resulted in a superior immune response to the secreted form, but no improvement in the response to the membrane- associated form, However, the form of gD used for immunization did not influence the immunoglobulin subtype, the ratio of antigen-specific I gG1 to IgG2 being approximately 4:1. Finally, the effect of promoter s trength was assessed by replacing the Rous sarcoma virus (RSV) promote r, which was used in the original experiments, with the human cytomega lovirus immediate early promoter and first intron A (HCMV/IA), Althoug h upon transfection in vitro the HCMV/IA promoter appeared to be stron ger than the RSV promoter, there was only a 2-fold higher antibody res ponse in vivo upon i.d. injection of cattle, Protection against virus challenge was obtained in the calves immunized i.d. with tgD-encoding plasmid, as shown by a significant reduction in weight loss, virus exc retion, temperature response and clinical disease, No significant prot ection was observed in the animals vaccinated i.d. with the gD-express ing plasmid, which correlates with the lower level of immunity pre-cha llenge.