Multiserotype protection elicited by a combinatorial prime-boost vaccination strategy against bluetongue virus.

Multiserotype protection elicited by a combinatorial prime-boost vaccination strategy against bluetongue virus.
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DOI:
10.1371/journal.pone.0034735
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Ortego J
Ortego J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Calvo-Pinilla E;Navasa N;Anguita J;Ortego J

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蓝舌病毒(BTV)属于呼肠孤病毒科(Reoviridae)中的环状病毒属。表达保守保护性抗原的基于载体的疫苗的开发导致增加的免疫激活,并且可以减少所需的多血清型疫苗接种的数量,因此提供了具有成本效益的产品。最近的重组DNA技术允许开发新的策略来开发针对BTV的标记和安全疫苗。我们现在已经设计了裸DNA和重组修饰的牛痘病毒安卡拉(rMVA)表达来自BTV-4的VP 2,VP 7和NS 1蛋白。在异源初免加强免疫接种策略中用DNA/rMVA-VP 2,-VP 7-NS 1接种的IFNAR(−/−)小鼠产生显著水平的VP 2、VP 7和NS 1特异性抗体,包括对BTV-4具有中和活性的抗体。此外,疫苗接种刺激针对这三种BTV蛋白的特异性CD 8 + T细胞应答。重要的是,表达BTV-4的NS 1、VP 2和VP 7蛋白的疫苗组合引起针对致死剂量的同源BTV-4感染的无菌保护。值得注意的是,该疫苗诱导了针对致死剂量的异源BTV-8和BTV-1的交叉保护,这表明DNA/rMVA-VP 2、-VP 7、-NS 1标记疫苗是一种有希望的针对BTV的多血清型疫苗。
Bluetongue virus (BTV) belongs to the genus Orbivirus within the family Reoviridae. The development of vector-based vaccines expressing conserved protective antigens results in increased immune activation and could reduce the number of multiserotype vaccinations required, therefore providing a cost-effective product. Recent recombinant DNA technology has allowed the development of novel strategies to develop marker and safe vaccines against BTV. We have now engineered naked DNAs and recombinant modified vaccinia virus Ankara (rMVA) expressing VP2, VP7 and NS1 proteins from BTV-4. IFNAR(−/−) mice inoculated with DNA/rMVA-VP2,-VP7-NS1 in an heterologous prime boost vaccination strategy generated significant levels of antibodies specific of VP2, VP7, and NS1, including those with neutralizing activity against BTV-4. In addition, vaccination stimulated specific CD8+ T cell responses against these three BTV proteins. Importantly, the vaccine combination expressing NS1, VP2 and VP7 proteins of BTV-4, elicited sterile protection against a lethal dose of homologous BTV-4 infection. Remarkably, the vaccine induced cross-protection against lethal doses of heterologous BTV-8 and BTV-1 suggesting that the DNA/rMVA-VP2,-VP7,-NS1 marker vaccine is a promising multiserotype vaccine against BTV.
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