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

Abstract

-Bovine herpesvirus 1 (BoHV-1) has frequently been used as a model for testing parameters affecting DNA immunisation in large animals like cattle. However, the selection of target antigens has been poorly studied, and most of the experiments have been conducted in mice. In the present study, we demonstrated in cattle that a DNA vaccine encoding BoHV-1 glycoprotein gD induces higher neutralising antibody titres than vaccines encoding BoHV-1 gC. Additionally, we show that a DNA vaccine encoding a secreted form of gD induces a higher immune response than a vaccine encoding full-length gD. However, the enhanced immunogenicity associated with the secretion of gD could not be extended to the glycoprotein gC. The current study also describes for the first time the development and the evaluation of a DNA vaccine encoding the major tegument protein VP8. This construct, which is the first BoHV-1 plasmid vaccine candidate that is not directed against a surface glycoprotein, induced a high BoHV-1 specific cellular immunity but no humoral immune response. The calves vaccinated with the constructs encoding full-length and truncated gD showed a non-significant tenfold reduction of virus excretion after challenge. Those calves also excreted virus for significantly (p < 0.05) shorter periods (1.5 days) than the nonvaccinated controls. The other constructs encoding gC and VP8 antigens induced no virological protection as compared to controls. Altogether the DNA vaccines induced weaker immunity and protection than conventional marker vaccines tested previously, confirming the difficulty to develop efficient DNA vaccines in large species.BoHV-1 / DNA immunisation / gC / gD / VP8

Sequence-optimised E2 constructs from BVDV-1b and BVDV-2 for DNA immunisation in cattle

“…In this research group, the results of investigations on the localisation of cloned BoHV-1 structural proteins using a modified IPMA were consistent with confocal microscopy [54]. Therefore, we considered the former as a reliable approach.…”

“…Therefore, we considered the former as a reliable approach. COS cells in 24-well plates were transiently transfected with plasmid constructs expressing gD (pCI-gD) [54], protein N (pNsyn) [8] and our new constructs pCMVLPsynE2.1 and pCMVL-PsynE2.2. After 48 h, half the culture plates were first dried then frozen at -20 • C and finally fixed with 4% formaldehyde, leading to permeabilisation of membranes (permeabilised condition).…”

Bovine herpesvirus 1 infection and infectious bovine rhinotracheitis

“…The latest vaccine approaches consist of plasmid DNA vaccines containing sequences encoding for the three major immunodominant BoHV-1 glycoproteins gC [64], gB [117] or gD [153,199,200]. These constructs raised the putative vaccination of cattle by needle free delivery methods which would be advantageous to avoid losses due to tissue damage encountered by classical vaccine delivery methods [83,206].…”

Use of Adjuvants to Enhance the Immune Response Induced by a DNA Vaccine Against Bovine Herpesvirus-1

“…It has been highlighted as the best antigen for a DNA vaccine against BoHV-1 (18). A construct encoding the secreted form of the protein was able to induce a higher immune response than the complete gD sequence (9,10).…”