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利用无细胞核糖体展示技术生成和筛选泛丝状病毒单链抗体

Generation and Selection of a Panel of Pan-Filovirus Single-Chain Antibodies using Cell-Free Ribosome Display.

机构信息

Department of Medicine, Loyola University Medical Center, Chicago, Illinois.

Department of Internal Medicine, Center for Global Health, University of New Mexico, Albuquerque, New Mexico.

出版信息

Am J Trop Med Hyg. 2019 Jul;101(1):198-206. doi: 10.4269/ajtmh.18-0658.

Abstract

Filoviruses, which include ebolaviruses and marburgvirus, can cause outbreaks of highly lethal hemorrhagic fever. This disease causes significant morbidity and mortality in humans and non-human primates, with human fatality rates reaching 90% during some outbreaks. Currently, there is lack of licensed vaccines or antivirals for these viruses. Since early symptoms of filovirus infection mimic more common diseases, there is a strong unmet public health and biodefense need for broad-spectrum filovirus rapid diagnostics. We have generated a panel of mouse single-chain Fv-antibodies (scFvs) to filovirus glycoproteins (GPs) using cell-free ribosome display and determined their cross-reactivity profiles to all known filovirus species. Two scFvs (4-2 and 22-1) were able to detect all known and species. This is the first report on ribosome display scFvs that can detect a broad set of filovirus GPs, which demonstrates the potential for use in diagnostics.

摘要

丝状病毒,包括埃博拉病毒和马尔堡病毒,可引起高致死性出血热的爆发。这种疾病在人类和非人类灵长类动物中引起严重的发病率和死亡率,在某些爆发期间,人类死亡率达到 90%。目前,这些病毒缺乏许可的疫苗或抗病毒药物。由于丝状病毒感染的早期症状类似于更常见的疾病,因此迫切需要广谱丝状病毒快速诊断技术来满足公共卫生和生物防御的需求。我们使用无细胞核糖体展示技术生成了一组针对丝状病毒糖蛋白(GP)的小鼠单链 Fv 抗体(scFv),并确定了它们对所有已知丝状病毒物种的交叉反应谱。两种 scFv(4-2 和 22-1)能够检测到所有已知的 和 物种。这是首次报道能够检测广泛的丝状病毒 GP 的核糖体展示 scFv,这表明其在诊断中的应用潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a66/6609206/b09db8ff19c8/tpmd180658f1.jpg

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