新型冠状病毒疫苗标准化的体内和体外有效性评价技术研究

目前，新型冠状病毒（SARS-CoV-2）疫情仍在全球大流行，预防性疫苗是一种最经济有效的防控措施。本项目计划建立不同SARS-CoV-2流行株的假病毒库和标准化的假病毒体外中和抗体检测方法；评价不同疫苗免疫后小鼠、人体和自然感染人群的中和抗体滴度和中和广谱性；利用假病毒感染hACE2小鼠等动物，建立体内有效性评价模型；比较SARS-CoV-2活病毒和假病毒体内和体外方法的相关性，验证假病毒方法；利用假病毒和活病毒小鼠感染模型验证分析SARS-CoV-2疫苗免疫保护机制，确定最低保护性中和抗体水平，以及细胞免疫等是否存在保护作用，最终建立反应疫苗有效性的免疫学评价方法与标准。本项目对SARS-CoV-2疫苗保护机制和保护水平的研究以及相应标准化评价方法，将直接用于候选疫苗临床前和临床试验的免疫原性评价，推动我国SARS-CoV-2疫苗的研发进程，提升应对SARS-CoV-2的防控能力。

The recent global pandemic of a novel coronavirus (SARS-CoV-2) highlights the urgent need for screening and evaluation of a promising candidate vaccine, which is a key step of preventing and controlling the current situation.The project plans to establish pseudovirus libraries of different SARS-CoV-2 epidemic strains and standardized methods of neutralizing antibody assay in vitro; to evaluate the neutralizing antibody titer and neutralizing broad spectrum of mice, human body and natural infected population after immunization with different vaccines；The pseudovirus infection will be established in susceptible transgenic mice with human angiotensin-converting enzyme 2 (hACE2). In vivo and in vitro infection of wild-type live virus will also be used for comparison, validation and standardization of the pseudovirus infection model. Moreover, in order to investigate the lowest protective level of the neutralizing antibodies and whether cellular immunity has protective effect, titers of antibodies against SARS-CoV-2 in convalescent patients and the immunized individuals will be analyzed and subsequently validated by pseudovirus and live virus-infected hACE2 mice. The successful implementation of this project will guide and promote the development of effective candidate vaccine that can specifically induce potent immune response to complete the pre-clinical evaluation and enter the clinical trials, and then promote the research and development process of SARS-CoV-2 vaccine in China.