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.

中文翻译：

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抗体依赖性增强人类严重登革热疾病

对于登革热病毒1至4（DENV1-4），已显示特定范围的抗体滴度可增强体外病毒复制和动物模型中的严重疾病。尽管被怀疑，但尚未证明这种抗体依赖性严重疾病的增强在人类中发生。使用多种统计方法研究尼加拉瓜的长期儿科队列，我们​​显示严重登革热疾病的风险在预先存在的抗DENV抗体滴度的狭窄范围内最高。相比之下，我们在高抗体滴度下观察到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疾病的保护相关性分开评估。这些结果对登革热致病机理的研究和疫苗开发具有重要意义，因为增强作用不仅是缺乏保护，