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

PLoS One. 2014 Nov 3;9(11):e111605. doi: 10.1371/journal.pone.0111605. eCollection 2014.

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.

MeSH terms

  • Animals
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Antigens, Viral / genetics*
  • Antigens, Viral / immunology
  • Bluetongue / immunology*
  • Bluetongue / prevention & control
  • Bluetongue / virology
  • Bluetongue virus / genetics*
  • Bluetongue virus / immunology
  • Cell Line
  • Cricetinae
  • Cross Reactions / immunology
  • Dogs
  • Female
  • Gene Expression*
  • Genetic Vectors / genetics*
  • Immunity, Cellular
  • Immunization
  • Male
  • Rabbits
  • Sheep
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Viral Core Proteins / genetics*
  • Viral Core Proteins / immunology
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology

Substances

  • Antibodies, Viral
  • Antigens, Viral
  • Viral Core Proteins
  • Viral Vaccines
  • VP7 protein, orbivirus

Grants and funding

This work was supported by the FP7 project ORBIVAC (contract N °. 245266) and the UE Network of Excellence, EPIZONE (Contract N °. FOOD-CT-2006-016236). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.