Antibody-dependent enhancement of severe dengue disease in humans.

Antibody-dependent enhancement of severe dengue disease in humans.
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DOI:
10.1126/science.aan6836
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发表时间:
2017-11-17
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Harris E
Harris E
中科院分区:
其他
文献类型:
--
作者:
Katzelnick LC;Gresh L;Halloran ME;Mercado JC;Kuan G;Gordon A;Balmaseda A;Harris E

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对于登革病毒1至4(DENV 1 -4),已显示特定范围的抗体滴度在体外增强病毒复制和在动物模型中增强严重疾病。虽然怀疑,但这种严重疾病的抗体依赖性增强尚未显示在人类中发生。使用多种统计方法来研究尼加拉瓜的长期儿科队列,我们发现在预先存在的抗DENV抗体滴度的狭窄范围内,严重登革热疾病的风险最高。相比之下,我们观察到在高抗体滴度下对所有症状性登革热疾病的保护。因此,严重登革热的免疫相关性必须与针对症状性疾病的保护相关性分开评估。这些结果对登革热发病机制的研究和疫苗的开发具有重要意义,因为增强,而不仅仅是缺乏保护,是值得关注的。
For dengue viruses 1 to 4 (DENV1-4), a specific range of antibody titer has been shown to enhance viral replication in vitro and severe disease in animal models. Although suspected, such antibody-dependent enhancement of severe disease has not been shown to occur in humans. Using multiple statistical approaches to study a long-term pediatric cohort in Nicaragua, we show that risk of severe dengue disease is highest within a narrow range of preexisting anti-DENV antibody titers. By contrast, we observe protection from all symptomatic dengue disease at high antibody titers. Thus, immune correlates of severe dengue must be evaluated separately from correlates of protection against symptomatic disease. These results have implications for studies of dengue pathogenesis and for vaccine development, because enhancement, not just lack of protection, is of concern.
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