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从合成噬菌体文库中分离出一种人 SARS-CoV-2 中和抗体及其转化为荧光生物传感器。

Isolation of a human SARS-CoV-2 neutralizing antibody from a synthetic phage library and its conversion to fluorescent biosensors.

机构信息

Weifang Key Laboratory for Antibodies Medicine, School of Life Science and Technology, Weifang Medical University, Weifang, China.

Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama, Japan.

出版信息

Sci Rep. 2022 Sep 15;12(1):15496. doi: 10.1038/s41598-022-19699-z.

DOI:10.1038/s41598-022-19699-z
PMID:36109569
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9476436/
Abstract

Since late 2019, the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resultant spread of COVID-19 have given rise to a worldwide health crisis that is posing great challenges to public health and clinical treatment, in addition to serving as a formidable threat to the global economy. To obtain an effective tool to prevent and diagnose viral infections, we attempted to obtain human antibody fragments that can effectively neutralize viral infection and be utilized for rapid virus detection. To this end, several human monoclonal antibodies were isolated by bio-panning a phage-displayed human antibody library, Tomlinson I. The selected clones were demonstrated to bind to the S1 domain of the spike glycoprotein of SARS-CoV-2. Moreover, clone A7 in Fab and IgG formats were found to effectively neutralize the binding of S protein to angiotensin-converting enzyme 2 in the low nM range. In addition, this clone was successfully converted to quench-based fluorescent immunosensors (Quenchbodies) that allowed antigen detection within a few minutes, with the help of a handy fluorometer.

摘要

自 2019 年末以来，严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的爆发以及由此导致的 COVID-19 的传播引发了一场全球卫生危机，除了对全球经济构成巨大威胁外，还对公共卫生和临床治疗构成了巨大挑战。为了获得预防和诊断病毒感染的有效工具，我们试图获得能够有效中和病毒感染并可用于快速病毒检测的人源抗体片段。为此，我们通过噬菌体展示的人源抗体库 Tomlinson I 进行生物淘选，分离出了几种人源单克隆抗体。所选克隆被证明可与 SARS-CoV-2 的刺突糖蛋白 S1 结构域结合。此外，Fab 和 IgG 两种形式的克隆 A7 被发现可在纳摩尔级别的低浓度范围内有效中和 S 蛋白与血管紧张素转化酶 2 的结合。此外，在便捷荧光计的帮助下，该克隆成功转化为基于淬灭的荧光免疫传感器（Quenchbody），可在几分钟内检测抗原。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b477/9478140/9006454936be/41598_2022_19699_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b477/9478140/4e134a4d63b6/41598_2022_19699_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b477/9478140/7a541fec5cf2/41598_2022_19699_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b477/9478140/aa601b636295/41598_2022_19699_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b477/9478140/cdf8cbb48cd2/41598_2022_19699_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b477/9478140/13e238a18e4d/41598_2022_19699_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b477/9478140/d6f2965f3236/41598_2022_19699_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b477/9478140/3c01632f9357/41598_2022_19699_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b477/9478140/a5451453b26e/41598_2022_19699_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b477/9478140/9006454936be/41598_2022_19699_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b477/9478140/4e134a4d63b6/41598_2022_19699_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b477/9478140/7a541fec5cf2/41598_2022_19699_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b477/9478140/aa601b636295/41598_2022_19699_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b477/9478140/cdf8cbb48cd2/41598_2022_19699_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b477/9478140/13e238a18e4d/41598_2022_19699_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b477/9478140/d6f2965f3236/41598_2022_19699_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b477/9478140/3c01632f9357/41598_2022_19699_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b477/9478140/a5451453b26e/41598_2022_19699_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b477/9478140/9006454936be/41598_2022_19699_Fig9_HTML.jpg

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