【摘要】 目的：对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)广谱中和抗体XMA09进行性质鉴定，探究其广谱中和突变株的潜在机制，为SARS-CoV-2的疫苗设计与广谱中和抗体筛选提供参考。方法：通过ExpiCHO真核表达系统与Protein A层析柱表达纯化XMA09蛋白；冷冻电镜技术确定XMA09识别的受体结构域（RBD）上的关键氨基酸位点；间接ELISA与表面等离子共振（SPR）技术检测XMA09对SARS-CoV-2及其突变株Spike蛋白的亲和力；采用基于水疱性口炎病毒（VSV）的假病毒系统检测XMA09对SARS-CoV-2野生型及突变株的中和能力。结果：本研究发现XMA09识别的表位较为保守，对多种突变株Spike蛋白均具有强结合能力，能广谱中和关切突变株（VOCs），包括广泛流行的Omicron亚突变株BA.4/5。结论：XMA09是SARS-CoV-2广谱中和抗体，具有作为SARS-CoV-2治疗性抗体的潜力，并可为SARS-CoV-2的广谱疫苗设计与抗体药物开发提供参考意义。更多还原

【Abstract】 Objective:To identify XMA09, a broadly neutralizing antibody against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), and to explore the potential mechanism of XMA09 to broadly neutralize variants of SARS-CoV-2, so as to provide a reference for vaccine design and broadly neutralizing antibody screening against SARS-CoV-2. Methods:XMA09 protein was expressed and purified by ExpiCHO expression system and Protein A chromatography column. The key amino acid sites on receptor binding domain(RBD) recognized by XMA09 were identified by Cryo-EM, and the affinity of XMA09 to Spike protein of SARS-CoV-2and its variants was detected by indirect ELISA and Surface Plasmon Resonance(SPR). The pseudovirus neutralization assay based on vesicular stomatitis virus(VSV) was used to detect the neutralization ability of XMA09 to wild-type and variants of SARS-CoV-2.Results:In this study, it was found that the epitopes recognized by XMA09 were conservative, who has an excellent binding ability to Spike protein of many kinds of variants, and could neutralize the variants of concern(VOCs), including the widespread BA.4/5.Conclusion:XMA09 is a broadly neutralizing antibody, which has the potential to be used as a therapeutic antibody against SARSCoV-2, and can provide reference for broad-spectrum vaccine design and antibody drug development against SARS-CoV-2.更多还原