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

PLoS One. 2015 Nov 30;10(11):e0143273. doi: 10.1371/journal.pone.0143273. eCollection 2015.

Abstract

Bluetongue virus (BTV) is an economically important Orbivirus of the Reoviridae family that causes a hemorrhagic disease in ruminants. Its control has been achieved by inactivated-vaccines that have proven to protect against homologous BTV challenge although unable to induce long-term immunity. Therefore, a more efficient control strategy needs to be developed. Recombinant adenovirus vectors are lead vaccine candidates for protection of several diseases, mainly because of their potency to induce potent T cell immunity. Here we report the induction of humoral and T-cell mediated responses able to protect animals against BTV challenge by recombinant replication-defective human adenovirus serotype 5 (Ad5) expressing either VP7, VP2 or NS3 BTV proteins. First we used the IFNAR(-/-) mouse model system to establish a proof of principle, and afterwards we assayed the protective efficacy in sheep, the natural host of BTV. Mice were completely protected against BTV challenge, developing humoral and BTV-specific CD8+- and CD4+-T cell responses by vaccination with the different rAd5. Sheep vaccinated with Ad5-BTV-VP2 and Ad5-BTV-VP7 or only with Ad5-BTV-VP7 and challenged with BTV showed mild disease symptoms and reduced viremia. This partial protection was achieved in the absence of neutralizing antibodies but strong BTV-specific CD8+ T cell responses in those sheep vaccinated with Ad5-BTV-VP7. These data indicate that rAd5 is a suitable vaccine vector to induce T cell immunity during BTV vaccination and provide new data regarding the relevance of T cell responses in protection during BTV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Bluetongue / immunology*
  • Bluetongue / prevention & control
  • Capsid Proteins / immunology*
  • Chlorocebus aethiops
  • Cricetinae
  • Female
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Sheep
  • T-Lymphocytes / immunology*
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology*
  • Vero Cells
  • Viral Nonstructural Proteins / immunology*
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology*

Substances

  • Capsid Proteins
  • S10 protein, Bluetongue virus
  • VP2 protein, Bluetongue virus
  • Vaccines, Synthetic
  • Viral Nonstructural Proteins
  • Viral Vaccines

Grants and funding

This work was supported by AGL212-33289 (NS) and AGL2011-25025 (VM) from Ministerio de Economía y Competitividad. PLATESA (S2013/ABI-2906) from Comunidad Autómoma de Madrid (NS). RyC2010-06516 from Ministerio de Ciencia e Innovación (VM). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.