Intradermal immunization with a bovine herpesvirus-1 DNA vaccine induces protective immunity in cattle.

Abstract

Although intramuscular (i.m.) injection of DNA encoding glycoprotein D (gD) of bovine herpesvirus-1 (BHV-1) induces immune responses in cattle, this route of delivery is inefficient. Here we assessed three parameters that may enhance the efficacy of a gD DNA vaccine in cattle. First, the immune response generated by i.m. injected plasmid expressing a secreted form of gD (tgD) was determined and found to be very similar in magnitude to the response induced by gD-expressing plasmid. Secondly, 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 IgG1 to IgG2 being approximately 4:1. Finally, the effect of promoter strength was assessed by replacing the Rous sarcoma virus (RSV) promoter, which was used in the original experiments, with the human cytomegalovirus immediate early promoter and first intron A (HCMV/IA). Although upon transfection in vitro the HCMV/IA promoter appeared to be stronger than the RSV promoter, there was only a 2-fold higher antibody response 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 excretion, temperature response and clinical disease. No significant protection was observed in the animals vaccinated i.d. with the gD-expressing plasmid, which correlates with the lower level of immunity pre-challenge.

Genetic immunisation of cattle against Bovine herpesvirus 1: glycoprotein gD confers higher protection than glycoprotein gC or tegument protein VP8

“…To our knowledge, this phenomenon had not been further explained or studied for other antigens of BoHV-1. Here, we first confirmed that the intradermal administration of a construct encoding secreted gD induced significantly higher IgG and virus neutralising titres in cattle than a construct encoding full-length gD but we failed to confirm that truncated gD also elicited enhanced cellular immunity [54]. Although the deletion of the transmembranous anchor of gC also induced secretion of the truncated protein, it had a slight adverse effect on both IgG and virus neutralising titres.…”

“…In the present study, we describe the characterisation and the evaluation of several DNA vaccines in cattle in similar conditions. Although these DNA vaccines conferred an immune response comparable to that described by other groups [17,54], they induced weaker immune response and virological protection than the best protocol developed previously with conventional marker vaccine [20]. Therefore, a further experiment will aim at optimising some of the parameters known to modulate the efficacy of DNA vaccines such as the adjuvancy of immunostimulatory CpG motifs in the plasmid backbone [43].…”

“…Previous studies had shown that plasmid DNA encoding a secreted form of the glycoprotein gD elicited higher immune response than the same plasmid vector encoding membrane-anchored gD [27][28][29]54]. Two hypotheses, which are not mutually exclusive had been proposed to explain this observation: the highest immunocompetency of the skin for antigens secreted extracellularly [28,29,54] and/or the decreased toxicity of secreted gD as compared to full-length gD [47]. To our knowledge, this phenomenon had not been further explained or studied for other antigens of BoHV-1.…”

“…Immunisation with plasmid vaccines expressing BoHV-1 glycoproteins has been studied extensively since a first experiment indicated that a plasmid encoding BoHV-1 gD was immunogenic in mice and cattle [10]. Further DNA vaccination experiments performed in mice and cattle have shown that a construct encoding a secreted form of BoHV-1 gD induces a higher immune response than membrane-associated full-length gD [4,54]. Different routes of DNA administration to cattle have been tested such as intradermic or intramuscular injection [10,17,54] and biolistic delivery (gene-gun) of gold particles coated with DNA vaccines [6,33,34].…”

“…Further DNA vaccination experiments performed in mice and cattle have shown that a construct encoding a secreted form of BoHV-1 gD induces a higher immune response than membrane-associated full-length gD [4,54]. Different routes of DNA administration to cattle have been tested such as intradermic or intramuscular injection [10,17,54] and biolistic delivery (gene-gun) of gold particles coated with DNA vaccines [6,33,34]. Mucosal administration of plasmid DNA via a gene-gun [34] or into suppositories [35] has also been shown to induce systemic as well as mucosal immunity.…”