中东呼吸综合征（Middle East Respiratory Syndrome, MERS）是由新型冠状病毒MERS-coronavirus（CoV）引起的急性重症肺炎。MERS病人来源的单克隆应急救治抗体是防控重要手段。本团队前期研发了国际首个MERS小鼠动物模型（PNAS 2014）和MERS病人来源单克隆保护性抗体（PNAS 2015）。然而此抗体识别MERS-CoV Spike蛋白N端S1结构域，易于受病毒变异影响。C端S2结构域在多种冠状病毒中保守，也可诱导中和抗体产生，而识别MERS-CoV S2的保护性抗体在国际上仍空白；不同呼吸道冠状病毒感染后，S2是否诱导产生抗MERS交叉保护性抗体也不明。本项目拟基于前期研究，改良EB病毒转化人外周血记忆性B细胞技术；研发识别MERS-CoV S2应急救治抗体；阐明不同呼吸道冠状病毒感染后抗体的交叉反应性；填补国内外空白并协助疫情防控

The newly discovered Middle East Respiratory Syndrome coronavirus (MERS-CoV) is the causative agent for MERS. Administration of protective monoclonal antibodies derived from convalescent MERS patients is a potent prophylactic and therapeutic treatment against lethal MERS-CoV infection. Our group generated the first MERS mouse model (PNAS 2014) and developed the first patient derived MERS protective monoclonal antibody (PNAS 2015) previously. However, most of these antibodies target the S1 domain to the N terminal of MERS-CoV spike protein, which is prone to mutation. The S2 domain to the C terminal is relatively stable and conserved among coronaviruses. No protective antibody is developed targeting S2 domain and the possibility of S2 domain to induce cross-protective antibodies against different human respiratory coronaviruses remains unknown. Our group will optimize the EBV transformation platform and immortalize human memory B cells from periphery blood and generate novel protective monoclonal antibodies targeting S2 domain of MERS-CoV spike protein; further we will decipher the mechanism that these antibodies using to protect from lethal MERS-CoV infection, and will investigate whether S2 domain could induce cross-protective antibodies after different human respiratory coronavirus infections. These studies will help prevent and control MERS epidemic in China.