SARS-CoV-2与MERS-CoV病毒通用疫苗的研究

建立有效的新冠（COVID-19）疫情应急控制体系，最直接的方式就是疫苗研制和评价的快速反应，建立针对新型冠状病毒（nCoVs）的通用疫苗的应急开发技术储备。基于nCoVs 的S蛋白结构特征和N衣壳蛋白的的保守性,及其在新冠病毒-宿主相互作用的生命周期中所展现的优质抗原潜能,本研究将以幽门螺杆菌转铁蛋白（Ferritin）为载体，在真核表达系统中以嵌合表达技术的形式呈递SARS-CoV-2和MERS-CoV-2病毒的S-RBD-N串联蛋白的，生成可以展示各个抗原的自组装抗原颗粒，从实际应用层面形成新型冠状病毒通用疫苗的应急疫苗技术手段。同时，本项目拟利用高等级生物安全灵长类动物实验平台，对SARS-CoV2与MERS-CoV通用疫苗的免疫有效性和进行恒河猴攻毒保护性研究，同时观察分析低中和抗体是否会引起ADE效应，获得新型冠状病毒疫苗安全性和有效性系统评价的临床前数据。

The most direct way to establish an effective emergency system for the Coronavirus disease 2019 (COVID-19) epidemic is rapid response to vaccine development and evaluation. In this case, an emergency development technology reserve for universal vaccines against new coronaviruses (nCoVs) is becoming an urgent need. Based on the structural characteristics of the S protein and conservatism of the N-capsid protein of nCoVs, and its high-quality antigen potential in the life cycle of the new coronavirus-host interaction, this study will use Helicobacter pylori transferrin (Ferritin) as a vector, the S-RBD-N tandem proteins of SARS-CoV-2 and MERS-CoV-2 viruses are presented in the form of chimeric expression technology in a eukaryotic expression system to generate self-assembled antigen particles that can display antigens. This emergency vaccine technical means of a new universal coronavirus vaccine will be practiced. Of note, our proposal intends to use the high-level biosafety primate experimental platform to conduct an immunological effectiveness and protective research on this universal vaccines against challenge of rhesus monkeys against SARS-CoV2 and MERS-CoV, and analyze whether low-neutralizing antibodies will cause the ADE effect . These preclinical data for the systematic review of the safety and effectiveness can be the supportive for the new coronavirus vaccine.