A synthetic biology approach for a vaccine platform against known and newly emerging serotypes of bluetongue virus.
A synthetic biology approach for a vaccine platform against known and newly emerging serotypes of bluetongue virus.
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DOI：
10.1128/jvi.02183-14
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发表时间：
2014-11
影响因子：
5.4
通讯作者：
Palmarini M
中科院分区：
文献类型：
--
作者：
Nunes SF;Hamers C;Ratinier M;Shaw A;Brunet S;Hudelet P;Palmarini M
蓝舌病是反刍动物的主要传染病之一，由蓝舌病病毒（BTV）引起，BTV是一种存在于自然界中的至少26种不同血清型的虫媒病毒。在这里，我们描述了BTV疫苗平台的开发。合成生物学方法的出现和反向遗传学系统的发展使得能够快速可靠地设计和生产病原体基因组，随后可以操纵这些基因组用于疫苗生产。我们描述了基于“合成”病毒的BTV疫苗，其中不同BTV血清型的外核心蛋白被并入共同的组织培养适应性骨架中。作为验证这种方法的一种手段，我们选择了两种BTV-8合成抑制剂，并证明了它们保护绵羊免受BTV-8强毒攻击的能力。除了进一步强调基因组操作用于疫苗生产的可能性外，我们还设计并拯救了含有VP 2蛋白的合成BTV嵌合体，包括来自BTV-1和BTV-8的区域。有趣的是，虽然亲本病毒仅被同源抗血清中和，但嵌合蛋白可以被BTV-1和BTV-8抗血清中和。这些数据表明，中和表位存在于BTV VP 2的不同区域中，并且可以获得可能的“二价”毒株，其引发针对多种毒株的中和抗体。总体而言，该疫苗平台可以显著缩短从鉴定新BTV毒株到开发和生产新疫苗所需的时间，因为这些病毒的病毒基因组可以在体外完全合成。此外，这些疫苗可以迅速进入市场，因为它们改变了现有商业产品的方法，但不是最终产品。
Bluetongue is one of the major infectious diseases of ruminants and is caused by bluetongue virus (BTV), an arbovirus existing in nature in at least 26 distinct serotypes. Here, we describe the development of a vaccine platform for BTV. The advent of synthetic biology approaches and the development of reverse genetics systems has allowed the rapid and reliable design and production of pathogen genomes which can be subsequently manipulated for vaccine production. We describe BTV vaccines based on “synthetic” viruses in which the outer core proteins of different BTV serotypes are incorporated into a common tissue-culture-adapted backbone. As a means of validation for this approach, we selected two BTV-8 synthetic reassortants and demonstrated their ability to protect sheep against virulent BTV-8 challenge. In addition to further highlight the possibilities of genome manipulation for vaccine production, we also designed and rescued a synthetic BTV chimera containing a VP2 protein, including regions derived from both BTV-1 and BTV-8. Interestingly, while the parental viruses were neutralized only by homologous antisera, the chimeric proteins could be neutralized by both BTV-1 and BTV-8 antisera. These data suggest that neutralizing epitopes are present in different areas of the BTV VP2 and likely “bivalent” strains eliciting neutralizing antibodies for multiple strains can be obtained. IMPORTANCE Overall, this vaccine platform can significantly reduce the time taken from the identification of new BTV strains to the development and production of new vaccines, since the viral genomes of these viruses can be entirely synthesized in vitro. In addition, these vaccines can be brought quickly into the market because they alter the approach, but not the final product, of existing commercial products.