An Assessment of Serological Assays for SARS-CoV-2 as Surrogates for Authentic Virus Neutralization.

An Assessment of Serological Assays for SARS-CoV-2 as Surrogates for Authentic Virus Neutralization.
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SARS-CoV-2血清学试验作为真实病毒中和替代物的评估。

DOI:
10.1128/spectrum.01059-21
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发表时间:
2021-10-31
影响因子:
3.7
通讯作者:
Schultz-Cherry S
Schultz-Cherry S
中科院分区:
生物学1区
文献类型:
--
作者:
Wohlgemuth N;Whitt K;Cherry S;Kirkpatrick Roubidoux E;Lin CY;Allison KJ;Gowen A;Freiden P;Allen EK;St. Jude Investigative Team,;Gaur AH;Estepp JH;Tang L;Mori T;Hijano DR;Hakim H;McGargill MA;Krammer F;Whitt MA;Wolf J;Thomas PG;Schultz-Cherry S

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严重急性呼吸综合征冠状病毒2(SARS-CoV-2)于2019年底出现,此后引发了一场全球大流行,导致数百万病例和死亡。诊断工具和血清学分析对于控制疫情至关重要,特别是被认为是最佳保护相关性的中和抗体水平的量化分析。随着疫苗的可获得性越来越高,重要的是确定可靠的方法来测量中和抗体反应,这些方法与真正的病毒中和相关,但可以在生物安全3级(BSL3)实验室之外进行。虽然已经开发了许多使用伪型病毒的中和试验,但很少有研究将不同的中和试验作为真正的病毒中和的替代品。在这里,我们鉴定了三种酶联免疫吸附试验(ELISA)和三种假型水疱性口炎病毒(VSV)中和试验,并评估了它们与正宗病毒中和试验的一致性。预测真实病毒中和的最准确的方法是荧光素酶和分泌型胚胎碱性磷酸酶(SEAP)表达的假型病毒中和,其次是绿色荧光蛋白(GFP)表达的假型病毒中和,然后是ELISA。重要性正在进行的新冠肺炎大流行是由感染严重急性呼吸综合征病毒2型(SARS-CoV-2)引起的。以前的感染或疫苗接种可以通过血液中抗体的存在来检测。血液中的抗体也被认为对未来感染同一病毒具有保护作用。检测SARS-CoV-2保护性抗体的“金标准”是中和真正的SARS-CoV-2病毒。然而,这种分析只能在高度限制性的生物遏制条件下进行。因此,我们确定了六种抗体检测方法与正宗病毒中和的相关性。本研究的意义在于总结不同检测方法的优缺点,并找出中和病毒的最佳替代方法。这将使对感染和接种疫苗后对SARS-CoV-2的保护性免疫进行更准确的评估。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and has since caused a global pandemic resulting in millions of cases and deaths. Diagnostic tools and serological assays are critical for controlling the outbreak, especially assays designed to quantitate neutralizing antibody levels, considered the best correlate of protection. As vaccines become increasingly available, it is important to identify reliable methods for measuring neutralizing antibody responses that correlate with authentic virus neutralization but can be performed outside biosafety level 3 (BSL3) laboratories. While many neutralizing assays using pseudotyped virus have been developed, there have been few studies comparing the different assays to each other as surrogates for authentic virus neutralization. Here, we characterized three enzyme-linked immunosorbent assays (ELISAs) and three pseudotyped vesicular stomatitis virus (VSV) neutralization assays and assessed their concordance with authentic virus neutralization. The most accurate assays for predicting authentic virus neutralization were luciferase- and secreted embryonic alkaline phosphatase (SEAP)-expressing pseudotyped virus neutralizations, followed by green fluorescent protein (GFP)-expressing pseudotyped virus neutralization, and then the ELISAs. IMPORTANCE The ongoing COVID-19 pandemic is caused by infection with severe acute respiratory syndrome virus 2 (SARS-CoV-2). Prior infection or vaccination can be detected by the presence of antibodies in the blood. Antibodies in the blood are also considered to be protective against future infections from the same virus. The “gold standard” assay for detecting protective antibodies against SARS-CoV-2 is neutralization of authentic SARS-CoV-2 virus. However, this assay can only be performed under highly restrictive biocontainment conditions. We therefore characterized six antibody-detecting assays for their correlation with authentic virus neutralization. The significance of our research is in outlining the advantages and disadvantages of the different assays and identifying the optimal surrogate assay for authentic virus neutralization. This will allow for more accurate assessments of protective immunity against SARS-CoV-2 following infection and vaccination.