Expression of VP7, a Bluetongue Virus Group Specific Antigen by Viral Vectors: Analysis of the Induced Immune Responses and Evaluation of Protective Potential in Sheep

Abstract

Bluetongue virus (BTV) is an economically important Orbivirus transmitted by biting midges to domestic and wild ruminants. The need for new vaccines has been highlighted by the occurrence of repeated outbreaks caused by different BTV serotypes since 1998. The major group-reactive antigen of BTV, VP7, is conserved in the 26 serotypes described so far, and its role in the induction of protective immunity has been proposed. Viral-based vectors as antigen delivery systems display considerable promise as veterinary vaccine candidates. In this paper we have evaluated the capacity of the BTV-2 serotype VP7 core protein expressed by either a non-replicative canine adenovirus type 2 (Cav-VP7 R0) or a leporipoxvirus (SG33-VP7), to induce immune responses in sheep. Humoral responses were elicited against VP7 in almost all animals that received the recombinant vectors. Both Cav-VP7 R0 and SG33-VP7 stimulated an antigen-specific CD4+ response and Cav-VP7 R0 stimulated substantial proliferation of antigen-specific CD8+ lymphocytes. Encouraged by the results obtained with the Cav-VP7 R0 vaccine vector, immunized animals were challenged with either the homologous BTV-2 or the heterologous BTV-8 serotype and viral burden in plasma was followed by real-time RT-PCR. The immune responses triggered by Cav-VP7 R0 were insufficient to afford protective immunity against BTV infection, despite partial protection obtained against homologous challenge. This work underscores the need to further characterize the role of BTV proteins in cross-protective immunity.

Analysis of Conserved, Computationally Predicted Epitope Regions for VP5 and VP7 Across three Orbiviruses

“…Investigations into BTV VP7 have shown that VP7 has regions that are exposed on the virion surface and are able to act as epitopes, 65 and vectors presenting VP7 are capable to produce an immune response that is at least partially protective. 76 , 77 This, along with evidence that VP6, the middle layer protein in Rotavirus, which is also a member of the Reoviridae family, has shown to be involved in B-cell immunity which suggests that VP7 of the orbiviruses is a good candidate for B-cell activation as numerous papers point out the similarity of BTV VP7 and Rotavirus VP6. 78 , 79 , 80 In addition to this, in BTV, VP7 is seen to be a major group reactive antigen that has been seen to contain CD8 + and CD4 + T-cell epitopes that are conserved among different serotypes.…”

Protective Efficacy in Sheep of Adenovirus-Vectored Vaccines against Bluetongue Virus Is Associated with Specific T Cell Responses

“…Among BTV proteins, VP7 is a major BTV group reactive antigen that contains CD8 + and CD4 + T cell epitopes [ 27 , 28 ] that are conserved among different serotypes. Vaccination with recombinant capripox virus encoding VP7 [ 27 ] and recombinant canine adenovirus type 2 expressing VP7 [ 29 ] showed clinical protection against heterologous challenge, although the virus still replicated. In general, BTV NS proteins have mostly been associated with cellular immune responses [ 15 , 16 , 30 ].…”

Bluetongue virus vaccine: conventional to modern approach

“…Sheep vaccinated with Ad5-BTV-VP7 elicited sufficient BTV-specific CD8+ T cell response but no neutralizing antibodies response. In other study, the VP7 core protein of BTV2 was expressed either in a non-replicative canine adenovirus type 2 (Cav-VP7 R 0 ) or a leporipoxvirus (SG33-VP7) to elicit immune response in sheep (Bouet-Cararo et al, 2014). Both of the recombinant antigens elicited the humoral immune response in sheep.…”

“…Later on, Cav-VP7 R 0 vaccine-immunized sheep were challenged with either homologous serotype BTV2 or the heterologous BTV8. The viremia estimation by real-time PCR in plasma showed that the immune response triggered by Cav-VP7 R 0 was insufficient to provide protective immunity against BTV (Bouet-Cararo et al, 2014). It only generated partial protection against homologous serotype.…”