Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Division of Experimental Medicine, Department of Medicine, Zuckerberg San Francisco General Hospital, University of California, San Francisco, San Francisco, CA, USA.
Cell Rep Med. 2020 Oct 20;1(7):100123. doi: 10.1016/j.xcrm.2020.100123. Epub 2020 Sep 24.
Comprehensive understanding of the serological response to SARS-CoV-2 infection is important for both pathophysiologic insight and diagnostic development. Here, we generate a pan-human coronavirus programmable phage display assay to perform proteome-wide profiling of coronavirus antigens enriched by 98 COVID-19 patient sera. Next, we use ReScan, a method to efficiently sequester phage expressing the most immunogenic peptides and print them onto paper-based microarrays using acoustic liquid handling, which isolates and identifies nine candidate antigens, eight of which are derived from the two proteins used for SARS-CoV-2 serologic assays: spike and nucleocapsid proteins. After deployment in a high-throughput assay amenable to clinical lab settings, these antigens show improved specificity over a whole protein panel. This proof-of-concept study demonstrates that ReScan will have broad applicability for other emerging infectious diseases or autoimmune diseases that lack a valid biomarker, enabling a seamless pipeline from antigen discovery to diagnostic using one recombinant protein source.
全面了解 SARS-CoV-2 感染的血清学反应对于病理生理学的认识和诊断的发展都很重要。在这里，我们生成了一种泛人种冠状病毒可编程噬菌体展示分析，以对 98 例 COVID-19 患者血清中富集的冠状病毒抗原进行蛋白质组范围的分析。接下来，我们使用 ReScan，这是一种利用声控液体处理将表达最免疫原性肽的噬菌体分离并打印到基于纸张的微阵列上的方法，从而分离和鉴定出九个候选抗原，其中八个来自用于 SARS-CoV-2 血清学检测的两种蛋白质：刺突蛋白和核衣壳蛋白。在适用于临床实验室环境的高通量检测中部署后，这些抗原在特异性方面优于整个蛋白质组面板。这项概念验证研究表明，ReScan 将广泛适用于其他缺乏有效生物标志物的新发传染病或自身免疫性疾病，从而能够在使用一种重组蛋白源的情况下从抗原发现到诊断无缝连接。
