A Rapid and Specific Diagnostic for Immunoglobulin Response to Zika Virus Exposure Based on De novo Designed Low Cost Hyper-stable Mini-Protein Epitopes

项目摘要 寨卡病毒是一种由蚊子传播的病原体，已与许多坟墓有关 受感染的妇女所怀胎儿的并发症。最近，寨卡病毒与一种 格林-巴利综合征和小头畸形症病例数量激增 婴儿严重阻碍了大脑发育，出生时头部较小。鉴于此， 可能与这些严重的出生缺陷有关，迫切需要一种方法来确定 诊断一名妇女是否接触过该病毒。当前测试的方法 寨卡病毒的存在错过了感染后病毒清除身体之前的狭窄时间窗口 而血清学测试经常受到与其他流行于 和寨卡病毒一样的地区。这里描述的研究建议开发一种 仅针对宿主多克隆反应中结合到的抗体的免疫分析 寨卡病毒外壳蛋白中的那些与其他黄病毒不同的表位。这样的化验 可能导致对所讨论的病毒进行更具临床特异性的免疫分析。首先，我们会 开发新型计算设计的寨卡病毒超稳定表位模拟(VEM) 具有能与人抗寨卡病毒免疫球蛋白特异性结合的结构的包膜蛋白。 其次，这些VEM将在一种快速、低成本的纸质三明治中实施 临床相关人群血浆中抗寨卡病毒抗体的免疫检测 浓度。

PROJECT ABSTRACT The Zika virus is a mosquito-borne pathogen that has been implicated in a number of grave complications to fetuses carried by infected women. More recently, Zika has been linked to a spike in the number of cases of Guillain-Barre syndrome and microcephaly, a condition in which babies have severely hindered brain development and are born with smaller heads. Given this possible link to these serious birth defects, there is a pressing need for a way to definitively diagnose whether a woman has been exposed to the virus. Current methods to test for the presence of Zika miss the narrow time window before the virus clears the body after infection and serological tests are often hindered by cross-reactivity to other flaviviruses endemic in the same regions as Zika. The studies described here propose the development of an immunoassay targeting only those antibodies in the host’s polyclonal response that bind to those epitopes in the Zika coat protein that are not shared by other Flaviviruses. Such an assay could lead to more clinically specific immunoassays for the viruses in question. First we will develop novel computationally designed hyperstable viral epitope mimetics (VEMs) of the Zika envelope protein with structures that can specifically bind human anti-Zika immunoglobulins. Second these VEMs will be implemented in a rapid, low-cost paper-based sandwich immunoassay capable of detecting anti-Zika antibodies in human plasma at clinically relevant concentrations.