新冠肺炎目前呈现世界范围的大流行，有效的预防性疫苗亟待研发。新冠病毒表面spike蛋白是病毒感染细胞的关键蛋白，也是免疫系统识别并攻击病毒的重要蛋白。本实验室前期从新冠康复者体内分离到了针对病毒受体ACE2结合的RBD区域的高效中和单抗，提示RBD可能是保护性抗体的关键识别位点；同时发现新冠感染者血清对SARS-Cov和MERS-Cov spike具有交叉活性，且呈现出不同的识别模式。为了合理的疫苗设计，进一步认识自然感染中的体液免疫反应，我们需要在抗体识别位点层面拆分抗体反应。我们将利用酵母展示的三种冠状病毒spike蛋白片段文库筛选血清识别的表位，并进行血清吸附前后的中和活性检测，研究轻重症感染者中针对spike蛋白的抗体识别与交叉识别表位、保护性抗体的特征以及感染后长期存有的抗体识别情况。这将为合理的疫苗设计，疫苗有效性的评估以及设计潜在的广谱冠状病毒疫苗，提供重要的参考价值。

COVID-19 is now showing a worldwide pandemic. Effective preventive vaccines are urgently needed. Spike protein on the surface of SARS-Cov-2 is the key protein for virus infection, and it is also an important protein for immune system to recognize and attack the virus. In our lab, we have isolated highly effective neutralizing monoclonal antibodies targeting the RBD region that bound to the virus receptor ACE2, suggesting that RBD may be the key recognition site of protective antibody. At the same time, we found that the serum of the SARS-Cov-2 infected patients had cross activity to SARS-CoV and MERS-Cov spike, and showed different recognition patterns. In order to design a protective vaccine and further understand the humoral immune response in natural infection, we need to split the antibody response at the antibody recognition site level. We will use the three kinds of coronavirus spike protein fragment library displayed by yeast to screen the epitopes recognized by serum. And we will detect the neutralization activity before and after serum adsorption. After that we will look into the characteristics of antibody recognition and cross-recognition epitopes, protective antibodies and the long-term existence of antibody recognition. It will play a guiding role for the rational vaccine design, the evaluation of vaccine effectiveness and the design of potential broad-spectrum coronavirus vaccines.