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首页> 外文期刊>Vaccine >Development of a novel DNA SynConTM tetravalent dengue vaccine that elicits immune responses against four serotypes. (Special Issue: Advances in vaccine technology II 2008.)
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Development of a novel DNA SynConTM tetravalent dengue vaccine that elicits immune responses against four serotypes. (Special Issue: Advances in vaccine technology II 2008.)

机译：新型DNA SynCon TM 四价登革热疫苗的开发，该疫苗可引发针对四种血清型的免疫反应。 （特刊：疫苗技术的进步II，2008年。）

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The increased transmission and geographic spread of dengue fever (DF) and its most severe presentations, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), make it one of the most important mosquito-borne viral disease of humans. Four distinct serotypes of dengue viruses are transmitted to humans through the bites of the mosquitoes. Currently there is no vaccine or antiviral drug against DV infections. Cross-protection between dengue virus serotypes is limited and antibody dependent enhancement (ADE) contributes significantly to the severity of the disease. The major challenge is to induce a broad durable immune response against all four serotypes of dengue virus simultaneously while avoiding the possible exacerbation of risk of developing the severe forms of disease through incomplete or modified responses. In order to address this worldwide concern, we present a synthetic consensus (SynConTM) human codon optimized DNA vaccine that elicits immunity against all four dengue serotypes. We cloned consensus DIII domain of E protein from all serotypes and expressed them as a single open reading frame in a mammalian expression vector, called pDV-U-DIII (dengue-vaccine universal). In mice, this dengue-universal construct elicits significant level of anti-DIII antibody that neutralizes all four dengue subtypes and prevents cell death induced by dengue infection. This is the first SynConTM DNA vaccine that provides tetravalent immunity against all four serotypes of dengue virus.
机译：登革热（DF）及其最严重的表现，登革出血热（DHF）和登革热休克综合征（DSS）的传播和地理分布增加，使其成为人类最重要的蚊媒病毒性疾病之一。四种不同的登革热病毒血清型通过蚊子叮咬传播给人类。当前没有针对DV感染的疫苗或抗病毒药。登革热病毒血清型之间的交叉保护受到限制，抗体依赖性增强（ADE）对该疾病的严重程度做出了重要贡献。主要的挑战是如何同时针对所有四种血清型的登革热病毒诱导广泛的持久免疫应答，同时避免由于不完全或修饰的应答而加剧患上严重疾病的风险。为了解决这一全球关注的问题，我们提出了一种合成共识（SynCon TM ）人类密码子优化的DNA疫苗，该疫苗可引发针对所有四种登革热血清型的免疫力。我们从所有血清型中克隆了E蛋白的共有DIII结构域，并在称为pDV-U-DIII（登革热疫苗通用）的哺乳动物表达载体中将其表达为单个开放阅读框。在小鼠中，这种登革热通用构建体引发显着水平的抗DIII抗体，该抗体可中和所有四种登革热亚型并防止登革热感染诱导的细胞死亡。这是第一款可对所有四种血清型登革热病毒提供四价免疫力的SynCon TM DNA疫苗。

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