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.

Nucleocapsid protein-based vaccine provides protection in mice against lethal Crimean-Congo hemorrhagic fever virus challenge

“…In this study, IFNAR -/mice vaccinated with Ad-N developed IgG responses to CCHFV N (S1 Fig) and were partially protected from CCHFV challenge (Figs 1-3; S2 Fig). Due to a lack of GPC antigen in the vaccine preparations protection is unlikely to be mediated by neutralizing antibodies but rather due to priming of CD4+ and CD8+ T-cells and/or non-neutralizing antibody responses as has been previously reported for the Ad platform in other IFNAR -/vaccine studies [38]. Additional experiments are required to demonstrate which of the CD4+, CD8+ T cell and/or antibody responses after vaccination/infection are responsible for protection.…”

Recall T cell responses to bluetongue virus produce a narrowing of the T cell repertoire

“…Viral RNA loads were determined by amplification of segment 5 as described [12, 22] using the QIAGEN OneStep RT-PCR kit (QIAGEN) or the Ambion AgPath-ID One-Step RT-PCR (Thermo Fisher Scientific).…”

Vaccination with recombinant adenovirus expressing peste des petits ruminants virus-F or -H proteins elicits T cell responses to epitopes that arises during PPRV infection

“…Recombinant adenovirus vaccines can also be manipulated to alter epitope hierarchy and favor the CD8 + T cell response to subdominant epitopes [ 62 ]. This strategy could be used in sheep to broaden the T cell repertoire in viral infections that narrowly focus the T cell response [ 63 , 64 ]. Importantly, adenovirus vaccines can also produce inflationary CD8 + T cell memory to some epitopes [ 65 – 67 ].…”