The humoral immune response to SARS-CoV-2 results in antibodies against spike (S) and nucleoprotein (N). However, whilst there are widely available neutralization assays for S antibodies, there is no assay for N-antibody activity. Here, we present a simple in vitro method called EDNA (electroporated-antibody-dependent neutralization assay) that provides a quantitative measure of N-antibody activity in unpurified serum from SARS-CoV-2 convalescents. We show that N antibodies neutralize SARS-CoV-2 intracellularly and cell-autonomously but require the cytosolic Fc receptor TRIM21. Using EDNA, we show that low N-antibody titres can be neutralizing, whilst some convalescents possess serum with high titres but weak activity. N-antibody and N-specific T-cell activity correlates within individuals, suggesting N antibodies may protect against SARS-CoV-2 by promoting antigen presentation. This work highlights the potential benefits of N-based vaccines and provides an in vitro assay to allow the antibodies they induce to be tested.

中文翻译：

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血清检测 SARS-CoV-2 核蛋白抗体的功能测定

对 SARS-CoV-2 的体液免疫反应会产生针对刺突 (S) 和核蛋白 (N) 的抗体。然而，虽然有广泛可用的 S 抗体中和测定法，但没有针对 N 抗体活性的测定法。在这里，我们提出了一种简单的体外方法，称为 EDNA（电穿孔抗体依赖性中和测定），该方法可定量测量 SARS-CoV-2 康复者未纯化血清中的 N 抗体活性。我们发现 N 抗体可以在细胞内和细胞自主中和 SARS-CoV-2，但需要胞质 Fc 受体 TRIM21。使用EDNA，我们发现低N-抗体滴度可以被中和，而一些康复者拥有滴度高但活性弱的血清。N 抗体和 N 特异性 T 细胞活性在个体内相关，表明 N 抗体可能通过促进抗原呈递来预防 SARS-CoV-2。这项工作强调了基于 N 的疫苗的潜在好处，并提供了一种体外测定方法，可以测试它们诱导的抗体。