Martín Verónica, Pascual Elena, Avia Miguel, Peña Lourdes, Valcárcel Félix, Sevilla Noemí
Centro de Investigación en Sanidad Animal (CISA-INIA), Instituto Nacional de Investigación Agraria y Alimentaria, Valdeolmos, Madrid, Spain.
PLoS One. 2015 Nov 30;10(11):e0143273. doi: 10.1371/journal.pone.0143273. eCollection 2015.
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.
蓝舌病病毒（BTV）是呼肠孤病毒科一种具有重要经济意义的环状病毒，可在反刍动物中引发出血性疾病。通过灭活疫苗已实现对该病毒的控制，尽管这些疫苗无法诱导长期免疫，但已证明能有效抵御同源BTV攻击。因此，需要研发更有效的防控策略。重组腺病毒载体是多种疾病疫苗的主要候选者，主要因其具有诱导强效T细胞免疫的能力。在此，我们报告了通过表达BTV的VP7、VP2或NS3蛋白的重组复制缺陷型人5型腺病毒（Ad5）诱导体液免疫和T细胞介导的免疫反应，从而使动物免受BTV攻击。首先，我们利用IFNAR（-/-）小鼠模型系统建立原理验证，随后在BTV的天然宿主绵羊中检测其保护效果。通过接种不同的rAd5，小鼠完全免受BTV攻击，并产生体液免疫以及BTV特异性CD8 +和CD4 + T细胞反应。接种Ad5-BTV-VP2和Ad5-BTV-VP7或仅接种Ad5-BTV-VP7并接受BTV攻击的绵羊表现出轻微的疾病症状且病毒血症减轻。这种部分保护是在没有中和抗体的情况下实现的，但在接种Ad5-BTV-VP7的绵羊中产生了强烈的BTV特异性CD8 + T细胞反应。这些数据表明，rAd5是BTV疫苗接种期间诱导T细胞免疫的合适疫苗载体，并提供了关于T细胞反应在BTV感染期间保护作用相关性的新数据。
