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A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus

机译:从登革热病毒感染的病毒血症患者中分离出的一类新型高效,广泛中和抗体

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摘要

Dengue is a rapidly emerging, mosquito-borne viral infection, with an estimated 400 million infections occurring annually. To gain insight into dengue immunity, we characterized 145 human monoclonal antibodies (mAbs) and identified a previously unknown epitope, the envelope dimer epitope (EDE), that bridges two envelope protein subunits that make up the 90 repeating dimers on the mature virion. The mAbs to EDE were broadly reactive across the dengue serocomplex and fully neutralized virus produced in either insect cells or primary human cells, with 50% neutralization in the low picomolar range. Our results provide a path to a subunit vaccine against dengue virus and have implications for the design and monitoring of future vaccine trials in which the induction of antibody to the EDE should be prioritized.
机译:登革热是一种迅速出现的,由蚊子传播的病毒感染,估计每年发生4亿例感染。为了深入了解登革热免疫,我们对145种人类单克隆抗体(mAb)进行了鉴定,并鉴定了一个以前未知的表位,包膜二聚体表位(EDE),该表位桥接了两个包膜蛋白亚基,这些亚基构成了成熟病毒体上90个重复的二聚体。在昆虫细胞或原代人细胞中产生的登革热血清复合物和完全中和的病毒中,对EDE的单克隆抗体具有广泛的反应性,其中50%的中和在低皮摩尔范围内。我们的结果提供了一种抗登革热病毒亚单位疫苗的途径,并且对未来疫苗试验的设计和监控具有影响,在该试验中应优先诱导EDE抗体。

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