刺突蛋白（S蛋白）是新型冠状病毒入侵靶细胞的关键蛋白，也是中和抗体产生的重要免疫原，是疫苗设计和抗体药物的关键靶点。越来越多的研究显示，冠状病毒S蛋白IgG抗体（Anti-S-IgG）能通过介导炎性反应而引起严重组织损伤，这给疫苗和抗体药物的应用带来难以预计的“副作用”，非常值得关注。目前，Anti-S-IgG抗体介导细胞因子分泌的机制很大程度上是未知的。本项目拟利用前期获得的大量新冠状病毒Anti-S-IgG抗体，研究比较不同特性Anti-S-IgG抗体介导的细胞因子分泌作用的差异。并通过高通量单细胞测序的方法研究Anti-S-IgG抗体和假病毒对免疫细胞细胞增殖与分化、细胞基因表达差异、细胞内病毒核酸载量的影响，及对非免疫细胞（病毒感染细胞）细胞毒性作用和细胞因子分泌的影响，从而阐明Anti-S-IgG抗体介导细胞因子分泌的作用机制，揭示抑制“炎症风暴”可能的新靶点或新方法。

As a key protein for coronavirus to invade target cells, spikes protein (S protein) is also an important immunogen for neutralizing antibody production and a key target for vaccine design and antibody drugs. Previous studies have shown that anti-S protein antibodies (anti-S-IgG) can also cause severe lung injury by altering inflammatory responses. It may bring about unpredictable side effects to the use of vaccines and antibody drugs. However, the mechanism of anti-S-IgG-mediated SARS-CoV-2-induced cytokine secretion is still largely unknown. In previous study, we have obtained a large number of anti-S-IgG antibodies. This project intends to use them to compare the differences in cytokine secretion mediated by different affinity antibodies, different neutralizing active antibodies, different IgG subtype antibodies, different ADCC and CDC active antibodies. Furthermore, we will study the cell proliferation and differentiation, cell gene expression and the loads of the viral nucleic acid in cells on immune cells, and cell cytotoxicity and cytokine secretion on no- immune cells (virus-infected cells), after incubating with anti-S-IgG and SARS-CoV-2 Spike Pseudovirus. Our studies will reveal the mechanism of anti-S-IgG-mediated SARS-CoV-2-induced cytokine secretion, and showing possible new targets or new methods for inflammation "storm". It will provide a good foundation for vaccines and antibody drug development.