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

基于从头设计的低成本超稳定微型蛋白表位，对寨卡病毒暴露后的免疫球蛋白反应进行快速、特异性诊断

• 批准号: 9334100
• 负责人: DAVID BAKER
• 金额: $ 18.87万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-20 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9334100
• 关键词: Alpha Cell; Antibodies; Binding; Binding Proteins; Biological Assay; Blood; Brain; Brazil; Capsid Proteins; Cellular Phone; Chemicals; Clinical; Color; Congenital Abnormality; Coupled; Culicidae; Dengue; Dengue Virus; Detection; Development; Diagnosis; Diagnostic; Diagnostic Reagent; Disease; Enzyme-Linked Immunosorbent Assay; Epidemic; Epitopes; Event; Fc Immunoglobulins; Fetus; Flavivirus; Genetic; Goals; Gold; Guillain-Barré Syndrome; Head; Horseradish Peroxidase; Hospitals; Human; Immune response; Immunoassay; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Infection; Label; Lateral; Lead; Link; Location; Methods; Microcephaly; Modification; Optics; Paper; Patients; Phase; Plasma; Pregnancy; Production; Protein Engineering; Proteins; Pyroxylin; RNA; Recombinants; Resources; Reverse Transcriptase Polymerase Chain Reaction; Sampling; Scheme; Serologic tests; Specificity; Structure; Surface; System; Tertiary Protein Structure; Testing; Tick-Borne Encephalitis; Time; Universities; Viral; Viral Proteins; Virus; Washington; West Nile virus; Woman; Work; Yellow Fever; Zika Virus; base; clinically relevant; cost; cross reactivity; design; env Gene Products; flavivirus envelope protein E; instrument; mimetics; nanoparticle; novel; optical imaging; pathogen; pathogen genome; point of care; programs; response; two-dimensional

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.

项目摘要