An In-Depth Analysis of Original Antigenic Sin in Dengue Virus Infection
An In-Depth Analysis of Original Antigenic Sin in Dengue Virus Infection
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DOI：
10.1128/jvi.01826-10
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发表时间：
2011-01-01
影响因子：
5.4
通讯作者：
Screaton, Gavin R.
中科院分区：
文献类型：
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作者：
Midgley, Claire M.;Bajwa-Joseph, Martha;Screaton, Gavin R.
登革病毒的进化产生了四种抗原性相似但又不同的血清型。感染一种血清型可能会引发对该血清型的终身免疫，但通常对其他三种血清型没有免疫力。二次感染或连续感染很常见，因为多种病毒血清型经常共同传播。登革热感染虽然通常症状较轻，但可能导致登革出血热（DHF），这可能会危及生命。登革出血热在二次登革热感染中更为常见，这意味着适应性免疫反应在该疾病中起作用。目前，人们在大力设计和实施登革热疫苗，但由于要诱导对所有四种病毒产生持久的中和免疫这一挑战，这些努力变得更加困难。登革病毒包膜蛋白的结构域3（ED3）被认为是一个这样的候选对象，因为它包含中和表位，并且最初认为针对该结构域的交叉反应抗体相对较少。在这项研究中，我们对一组原发性或继发性登革热感染患者的抗 - ED3反应进行了详细分析。结果显示，在二次感染中，无论是结合活性还是增强活性方面，都有明显的原始抗原痕迹的证据。这对登革热疫苗的设计具有重要意义，因为异源加强免疫可能会保留首次接种的免疫印记。基于这些发现，我们提出一种简单的体外酶联免疫吸附测定（ELISA）方法，用于诊断二次登革热病例中的初次登革热感染。
The evolution of dengue viruses has resulted in four antigenically similar yet distinct serotypes. Infection with one serotype likely elicits lifelong immunity to that serotype, but generally not against the other three. Secondary or sequential infections are common, as multiple viral serotypes frequently cocirculate. Dengue infection, although frequently mild, can lead to dengue hemorrhagic fever (DHF) which can be life threatening. DHF is more common in secondary dengue infections, implying a role for the adaptive immune response in the disease. There is currently much effort toward the design and implementation of a dengue vaccine but these efforts are made more difficult by the challenge of inducing durable neutralizing immunity to all four viruses. Domain 3 of the dengue virus envelope protein (ED3) has been suggested as one such candidate because it contains neutralizing epitopes and it was originally thought that relatively few cross-reactive antibodies are directed to this domain. In this study, we performed a detailed analysis of the anti-ED3 response in a cohort of patients suffering either primary or secondary dengue infections. The results show dramatic evidence of original antigenic sin in secondary infections both in terms of binding and enhancement activity. This has important implications for dengue vaccine design because heterologous boosting is likely to maintain the immunological footprint of the first vaccination. On the basis of these findings, we propose a simple in vitro enzyme-linked immunosorbent assay (ELISA) to diagnose the original dengue infection in secondary dengue cases.