The bright and the dark side of human antibody responses to flaviviruses: lessons for vaccine design.
The bright and the dark side of human antibody responses to flaviviruses: lessons for vaccine design.
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DOI：
10.15252/embr.201745302
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发表时间：
2018-03
期刊：
影响因子：
7.7
通讯作者：
Heinz FX
中科院分区：
文献类型：
--
作者：
Rey FA;Stiasny K;Vaney MC;Dellarole M;Heinz FX
寨卡病毒和登革热病毒属于黄病毒属，这是一组抗原性相关的病毒，在全球范围内引起重要的节肢动物传播疾病。虽然被一种黄病毒感染被认为可以获得终身保护，但患者的一些抗体与其他黄病毒发生交叉反应而没有交叉中和。在随后的异源黄病毒感染中，原始抗原现象可能会扩增这些抗体，从而通过抗体依赖性增强（ADE）潜在地加重疾病。最显著的例子是四种不同的登革热病毒，其中一种血清型的感染似乎在感染第二种血清型后易患更严重的疾病。寨卡病毒和登革热病毒的连续感染也有类似的效果。在这篇综述中，我们分析了人类对黄病毒感染或疫苗接种的双重抗体反应的分子决定因素。我们强调了保守的部分隐蔽性表位的作用，引起交叉反应和低中和，ADE易感抗体。最后，我们提出了一种开发表位聚焦疫苗的策略，以避免引起不需要的抗体，同时使免疫系统只产生保护性抗体。
Zika and dengue viruses belong to the Flavivirus genus, a close group of antigenically related viruses that cause significant arthropod‐transmitted diseases throughout the globe. Although infection by a given flavivirus is thought to confer lifelong protection, some of the patient's antibodies cross‐react with other flaviviruses without cross‐neutralizing. The original antigenic sin phenomenon may amplify such antibodies upon subsequent heterologous flavivirus infection, potentially aggravating disease by antibody‐dependent enhancement (ADE). The most striking example is provided by the four different dengue viruses, where infection by one serotype appears to predispose to more severe disease upon infection by a second one. A similar effect was postulated for sequential infections with Zika and dengue viruses. In this review, we analyze the molecular determinants of the dual antibody response to flavivirus infection or vaccination in humans. We highlight the role of conserved partially cryptic epitopes giving rise to cross‐reacting and poorly neutralizing, ADE‐prone antibodies. We end by proposing a strategy for developing an epitope‐focused vaccine approach to avoid eliciting undesirable antibodies while focusing the immune system on producing protective antibodies only.