Heterogeneous antibodies against SARS-CoV-2 spike receptor binding domain and nucleocapsid with implications for COVID-19 immunity
Heterogeneous antibodies against SARS-CoV-2 spike receptor binding domain and nucleocapsid with implications for COVID-19 immunity
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DOI：
10.1172/jci.insight.142386
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发表时间：
2020-09-17
期刊：
影响因子：
8
通讯作者：
Kalluri, Raghu
中科院分区：
文献类型：
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作者：
McAndrews, Kathleen M.;Dowlatshahi, Dara P.;Kalluri, Raghu
评估对2019年出现的新型严重急性呼吸综合征(SARS)冠状病毒(SARS-CoV-2)的潜在免疫力对于健康以及社会和经济复苏至关重要。SARS-CoV-2抗体应答(血清转换)的产生可能与先前接触过的获得性免疫有关，而针对SARS-CoV-2刺突蛋白受体结合域(S-RBD)的抗体被推测能中和病毒感染。一些血清学检测完全依赖SARS-CoV-2核衣壳蛋白(N蛋白)作为抗体检测抗原，但这种免疫反应是否与S-RBD反应和新冠肺炎免疫相关尚不清楚。在这里，我们建立了重组S-RBD和N蛋白的定量血清学ELISA，用于检测30例逆转录聚合酶链式反应确诊的SARS-CoV-2住院患者的138份血清样本中的循环抗体，以及2017年6月至2020年6月收集的464份健康和非新冠肺炎患者的血清样本。对两种不同病毒蛋白的免疫球蛋白抗体的定量检测显示出中等程度的相关性。在2020年新冠肺炎流行期间采集的健康人群和非支原体血清中，N蛋白抗体阳性率为3.6%，而S血型抗体阳性率为1.9%。在S-RBD结合抗体阳性个体中，约有86%具有中和能力，而在N蛋白阳性个体中，仅有74%具有中和能力。总之，我们的研究表明，N蛋白结合抗体的检测并不总是与S RBD中和抗体的存在相关，并警告不要广泛使用基于N蛋白的血清学检测来确定潜在的新冠肺炎免疫。
Evaluation of potential immunity against the novel severe acute respiratory syndrome (SARS) coronavirus that emerged in 2019 (SARS-CoV-2) is essential for health, as well as social and economic recovery. Generation of antibody response to SARS-CoV-2 (seroconversion) may inform on acquired immunity from prior exposure, and antibodies against the SARS-CoV-2 spike protein receptor binding domain (S-RBD) are speculated to neutralize virus infection. Some serology assays rely solely on SARS-CoV-2 nucleocapsid protein (N-protein) as the antibody detection antigen; however, whether such immune responses correlate with S-RBD response and COVID-19 immunity remains unknown. Here, we generated a quantitative serological ELISA using recombinant S-RBD and N-protein for the detection of circulating antibodies in 138 serial serum samples from 30 reverse transcription PCR-confirmed, SARS-CoV-2-hospitalized patients, as well as 464 healthy and non-COVID-19 serum samples that were collected between June 2017 and June 2020. Quantitative detection of IgG antibodies against the 2 different viral proteins showed a moderate correlation. Antibodies against N-protein were detected at a rate of 3.6% in healthy and non-COVID-19 sera collected during the pandemic in 2020, whereas 1.9% of these sera were positive for S-RBD. Approximately 86% of individuals positive for S-RBD-binding antibodies exhibited neutralizing capacity, but only 74% of N-protein-positive individuals exhibited neutralizing capacity. Collectively, our studies show that detection of N-protein-binding antibodies does not always correlate with presence of S-RBD-neutralizing antibodies and caution against the extensive use of N-protein-based serology testing for determination of potential COVID-19 immunity.