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

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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.