title: Protective Efficacy in Sheep of Adenovirus-Vectored Vaccines against Bluetongue Virus Is Associated with Specific T Cell Responses.
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.
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Instituto Nacional de Investigación Agraria y Alimentaria, Valdeolmos, Madrid, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Martín
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Instituto Nacional de Investigación Agraria y Alimentaria, Valdeolmos, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Pascual
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Instituto Nacional de Investigación Agraria y Alimentaria, Valdeolmos, Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Avia
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Instituto Nacional de Investigación Agraria y Alimentaria, Valdeolmos, Madrid, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Peña
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Instituto Nacional de Investigación Agraria y Alimentaria, Valdeolmos, Madrid, Spain.
authors.forename: Félix
authors.initials: F
authors.lastname: Valcárcel
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Instituto Nacional de Investigación Agraria y Alimentaria, Valdeolmos, Madrid, Spain.
authors.forename: Noemí
authors.initials: N
authors.lastname: Sevilla
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001819:Bluetongue / Q000276:immunology* / Q000517:prevention & control; D036022:Capsid Proteins / Q000276:immunology*; D002522:Chlorocebus aethiops; D006224:Cricetinae; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D012756:Sheep; D013601:T-Lymphocytes / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology*; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000276:immunology*; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
chemical_list: D036022:Capsid Proteins; C075080:S10 protein, Bluetongue virus; C442520:VP2 protein, Bluetongue virus; D014614:Vaccines, Synthetic; D017361:Viral Nonstructural Proteins; D014765:Viral Vaccines