Epitope-resolved profiling of the SARS-CoV-2 antibody response identifies cross-reactivity with endemic human coronaviruses.
Epitope-resolved profiling of the SARS-CoV-2 antibody response identifies cross-reactivity with endemic human coronaviruses.
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DOI：
10.1016/j.xcrm.2020.100189
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发表时间：
2021-01-19
期刊：
影响因子：
--
通讯作者：
Altin JA
中科院分区：
文献类型：
--
作者：
Ladner JT;Henson SN;Boyle AS;Engelbrektson AL;Fink ZW;Rahee F;D'ambrozio J;Schaecher KE;Stone M;Dong W;Dadwal S;Yu J;Caligiuri MA;Cieplak P;Bjørås M;Fenstad MH;Nordbø SA;Kainov DE;Muranaka N;Chee MS;Shiryaev SA;Altin JA
SARS-CoV-2蛋白质组与地方性人类冠状病毒（CoV）共享保守区域，但仍不清楚这些区域在多大程度上可能被抗体反应交叉识别。在这里，我们使用高度多重肽测定（PepSeq）研究交叉反应性，以生成COVID-19恢复期和阴性供体中所有人类CoV的IgG反应性的表位解析视图。PepSeq解析SARS-CoV-2刺突蛋白和核衣壳蛋白的表位，这些表位通常在恢复期供体中靶向，包括在一些未感染对照中也识别的几个位点。通过比较冠状病毒之间的同源反应性模式，并使用靶向抗体耗竭实验，我们证明了SARS-CoV-2 eliminates抗体交叉识别大流行和地方性冠状病毒抗原的两个刺突S2亚单位表位。我们进一步表明，这些交叉反应性抗体优先结合地方性同源物。我们的研究结果突出了SARS-CoV-2反应似乎受到先前CoV暴露影响的部位，这些部位有可能引起广泛的中和反应。PepSeq可实现完全体外、高度多重的基于肽的抗体测定表位作图显示了对SARS-CoV-2抗原的预先存在的抗体反应性抗体交叉识别刺突S2亚基中的地方性和大流行性抗原由SARS-CoV-2产生的交叉反应性抗体优先结合地方性同源物拉德纳et al.使用完全体外、高度多重的方法，精细绘制所有感染人类的冠状病毒刺突蛋白和核衣壳蛋白的抗体表位。这表明SARS-CoV-2抗体在刺突的保守区域交叉识别地方性冠状病毒抗原，并且这些抗体优先结合地方性同源物。
The SARS-CoV-2 proteome shares regions of conservation with endemic human coronaviruses (CoVs), but it remains unknown to what extent these may be cross-recognized by the antibody response. Here, we study cross-reactivity using a highly multiplexed peptide assay (PepSeq) to generate an epitope-resolved view of IgG reactivity across all human CoVs in both COVID-19 convalescent and negative donors. PepSeq resolves epitopes across the SARS-CoV-2 Spike and Nucleocapsid proteins that are commonly targeted in convalescent donors, including several sites also recognized in some uninfected controls. By comparing patterns of homologous reactivity between CoVs and using targeted antibody-depletion experiments, we demonstrate that SARS-CoV-2 elicits antibodies that cross-recognize pandemic and endemic CoV antigens at two Spike S2 subunit epitopes. We further show that these cross-reactive antibodies preferentially bind endemic homologs. Our findings highlight sites at which the SARS-CoV-2 response appears to be shaped by previous CoV exposures and which have the potential to raise broadly neutralizing responses. PepSeq enables fully in vitro, highly multiplexed peptide-based antibody assays Epitope mapping shows preexisting antibody reactivity to SARS-CoV-2 antigens Antibodies cross-recognize endemic and pandemic antigens in the Spike S2 subunit Cross-reactive antibodies raised by SARS-CoV-2 preferentially bind endemic homologs Ladner et al. use a fully in vitro, highly multiplexed approach to finely map antibody epitopes across the Spike and Nucleocapsid proteins of all human-infecting coronaviruses. This demonstrates that SARS-CoV-2 elicits antibodies that cross-recognize endemic coronavirus antigens at conserved regions of Spike and that these antibodies preferentially bind endemic homologs.
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影响因子：
9.4
作者：
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通讯作者：
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DOI：
10.1073/pnas.1319058110
发表时间：
2014-01-07
影响因子：
11.1
作者：
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