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一种多变量替代中和试验可识别原发性SARS-CoV-2奥密克戎感染中特定变异株的中和抗体谱。

A Multivariant Surrogate Neutralization Assay Identifies Variant-Specific Neutralizing Antibody Profiles in Primary SARS-CoV-2 Omicron Infection.

作者信息

Springer David Niklas, Traugott Marianna, Reuberger Elisabeth, Kothbauer Klaus Benjamin, Borsodi Christian, Nägeli Michelle, Oelschlägel Theresa, Kelani Hasan, Lammel Oliver, Deutsch Josef, Puchhammer-Stöckl Elisabeth, Höltl Eva, Aberle Judith Helene, Stiasny Karin, Weseslindtner Lukas

机构信息

Center for Virology, Medical University of Vienna, 1090 Vienna, Austria.

4th Medical Department, Clinic Favoriten, Kaiser-Franz-Josef Hospital, 1100 Vienna, Austria.

出版信息

Diagnostics (Basel). 2023 Jul 5;13(13):2278. doi: 10.3390/diagnostics13132278.

DOI:10.3390/diagnostics13132278
PMID:37443672
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10341213/
Abstract

Primary infection with the Omicron variant of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) can be serologically identified with distinct profiles of neutralizing antibodies (nAbs), as indicated by high titers against the Omicron variant and low titers against the ancestral wild-type (WT). Here, we evaluated whether a novel surrogate virus neutralization assay (sVNT) that simultaneously quantifies the binding inhibition of angiotensin-converting enzyme 2 (ACE2) to the proteins of the WT- and Omicron-specific receptor-binding domains (RBDs) can identify nAb profiles after primary Omicron infection with accuracy similar to that of variant-specific live-virus neutralization tests (NTs). Therefore, we comparatively tested 205 samples from individuals after primary infection with the Omicron variant and the WT, and vaccinated subjects with or without Omicron breakthrough infections. Indeed, variant-specific RBD-ACE2 binding inhibition levels significantly correlated with respective NT titers ( < 0.0001, Spearman's r = 0.92 and r = 0.80 for WT and Omicron, respectively). In addition, samples from individuals after primary Omicron infection were securely identified with the sVNT according to their distinctive nAb profiles (area under the curve = 0.99; sensitivity: 97.2%; specificity: 97.84%). Thus, when laborious live-virus NTs are not feasible, the novel sVNT we evaluated in this study may serve as an acceptable substitute for the serological identification of individuals with primary Omicron infection.

摘要

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)奥密克戎变异株的初次感染可以通过中和抗体(nAbs)的不同特征进行血清学鉴定,表现为针对奥密克戎变异株的高滴度和针对原始野生型(WT)的低滴度。在此,我们评估了一种新型替代病毒中和试验(sVNT),该试验同时定量血管紧张素转换酶2(ACE2)与野生型和奥密克戎特异性受体结合域(RBDs)蛋白的结合抑制,能否准确识别奥密克戎初次感染后的nAb特征,其准确性与变异株特异性活病毒中和试验(NTs)相似。因此,我们对205份来自奥密克戎变异株和野生型初次感染个体以及有或无奥密克戎突破性感染的接种疫苗个体的样本进行了比较测试。事实上,变异株特异性RBD-ACE2结合抑制水平与各自的中和试验滴度显著相关(<0.0001,野生型和奥密克戎的Spearman's r分别为0.92和0.80)。此外,根据其独特的nAb特征,通过sVNT可以可靠地识别奥密克戎初次感染个体的样本(曲线下面积=0.99;敏感性:97.2%;特异性:97.84%)。因此,当费力的活病毒中和试验不可行时,我们在本研究中评估的新型sVNT可作为血清学鉴定奥密克戎初次感染个体的可接受替代方法。

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