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

Martín V, Pascual E, Avia M, Peña L, Valcárcel F, Sevilla N - PLoS ONE (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Instituto Nacional de Investigación Agraria y Alimentaria, Valdeolmos, Madrid, Spain.

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.

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Related in: MedlinePlus

Serum IgG and neutralizing antibodies response in sheep following immunization with recombinant adenovirus.(A) Antibody responses elicited against VP7 protein assessed by ELISA. Data are expressed as the mean ± SD of antibody titers of individual values obtained for each animal. Titers are expressed as the reciprocal of the highest dilution of serum (log10) that gives an ODA450 of twice the value obtained with the pre-immune serum of the corresponding animal. (B) Neutralizing antibody response after vaccination and after challenge of the vaccinated and control sheep. The neutralizing antibodies titers are given in log10. The detection limit of the assay is 0.3.
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pone.0143273.g006: Serum IgG and neutralizing antibodies response in sheep following immunization with recombinant adenovirus.(A) Antibody responses elicited against VP7 protein assessed by ELISA. Data are expressed as the mean ± SD of antibody titers of individual values obtained for each animal. Titers are expressed as the reciprocal of the highest dilution of serum (log10) that gives an ODA450 of twice the value obtained with the pre-immune serum of the corresponding animal. (B) Neutralizing antibody response after vaccination and after challenge of the vaccinated and control sheep. The neutralizing antibodies titers are given in log10. The detection limit of the assay is 0.3.

Mentions: BTV-specific antibodies were quantitated by ELISA in serum of sheep vaccinated with recombinant adenovirus. IgG levels increased from day 15 post-vaccination in those animals vaccinated with Ad5-BTV-VP7 or Ad5-BTV-VP7 + Ad5-BTV-VP2 (Fig 6A), to D7pc, while sheep treated with PBS or vaccinated with Ad5-DsRed remained negative before challenge. This data indicates that all recombinant antigens were immunogenic, inducing the production of BTV-8-specific antibodies.


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

Martín V, Pascual E, Avia M, Peña L, Valcárcel F, Sevilla N - PLoS ONE (2015)

Serum IgG and neutralizing antibodies response in sheep following immunization with recombinant adenovirus.(A) Antibody responses elicited against VP7 protein assessed by ELISA. Data are expressed as the mean ± SD of antibody titers of individual values obtained for each animal. Titers are expressed as the reciprocal of the highest dilution of serum (log10) that gives an ODA450 of twice the value obtained with the pre-immune serum of the corresponding animal. (B) Neutralizing antibody response after vaccination and after challenge of the vaccinated and control sheep. The neutralizing antibodies titers are given in log10. The detection limit of the assay is 0.3.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4664254&req=5

pone.0143273.g006: Serum IgG and neutralizing antibodies response in sheep following immunization with recombinant adenovirus.(A) Antibody responses elicited against VP7 protein assessed by ELISA. Data are expressed as the mean ± SD of antibody titers of individual values obtained for each animal. Titers are expressed as the reciprocal of the highest dilution of serum (log10) that gives an ODA450 of twice the value obtained with the pre-immune serum of the corresponding animal. (B) Neutralizing antibody response after vaccination and after challenge of the vaccinated and control sheep. The neutralizing antibodies titers are given in log10. The detection limit of the assay is 0.3.
Mentions: BTV-specific antibodies were quantitated by ELISA in serum of sheep vaccinated with recombinant adenovirus. IgG levels increased from day 15 post-vaccination in those animals vaccinated with Ad5-BTV-VP7 or Ad5-BTV-VP7 + Ad5-BTV-VP2 (Fig 6A), to D7pc, while sheep treated with PBS or vaccinated with Ad5-DsRed remained negative before challenge. This data indicates that all recombinant antigens were immunogenic, inducing the production of BTV-8-specific antibodies.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Instituto Nacional de Investigación Agraria y Alimentaria, Valdeolmos, Madrid, Spain.

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.

Show MeSH
Related in: MedlinePlus