Liang Qingtai, Wang Yifeng, Zhang Shuyuan, Sun Jing, Sun Wenbo, Li Jizhou, Liu Yaping, Li Mingxi, Cheng Lin, Jiang Yuhang, Wang Ruoke, Zhang Rui, Yang Zihan, Ren Yifei, Chen Peng, Gao Peng, Yan Huayuan, Zhang Zheng, Zhang Qi, Shi Xuanling, Wang Jianbin, Liu Wanli, Wang Xinquan, Ying Bo, Zhao Jincun, Qi Hai, Zhang Linqi
Comprehensive AIDS Research Center, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
NexVac Research Center, School of Medicine, Tsinghua University, Beijing 100084, China.
iScience. 2022 Apr 15;25(4):104043. doi: 10.1016/j.isci.2022.104043. Epub 2022 Mar 11.
With the rapid emergence and spread of SARS-CoV-2 variants, development of vaccines with broad and potent protectivity has become a global priority. Here, we designed a lipid nanoparticle-encapsulated, nucleoside-unmodified mRNA (mRNA-LNP) vaccine encoding the trimerized receptor-binding domain (RBD trimer) and showed its robust capability in inducing broad and protective immune responses against wild-type and major variants of concern (VOCs) in the mouse model of SARS-CoV-2 infection. The protectivity was correlated with RBD-specific B cell responses especially the long-lived plasma B cells in bone marrow, strong ability in triggering BCR clustering, and downstream signaling. Monoclonal antibodies isolated from vaccinated animals demonstrated broad and potent neutralizing activity against VOCs tested. Structure analysis of one representative antibody identified a novel epitope with a high degree of conservation among different variants. Collectively, these results demonstrate that the RBD trimer mRNA vaccine serves as a promising vaccine candidate against SARS-CoV-2 variants and beyond.
随着严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变体的迅速出现和传播，开发具有广泛强效保护力的疫苗已成为全球优先事项。在此，我们设计了一种脂质纳米颗粒包裹的、未修饰核苷的信使核糖核酸（mRNA-LNP）疫苗，该疫苗编码三聚化受体结合域（RBD三聚体），并在SARS-CoV-2感染小鼠模型中展示了其在诱导针对野生型和主要关注变体（VOCs）的广泛保护性免疫反应方面的强大能力。这种保护力与RBD特异性B细胞反应相关，特别是骨髓中的长寿浆细胞B细胞，其触发BCR聚集和下游信号传导的能力很强。从接种疫苗的动物中分离出的单克隆抗体对测试的VOCs表现出广泛强效的中和活性。对一种代表性抗体的结构分析确定了一个在不同变体中具有高度保守性的新表位。总体而言，这些结果表明，RBD三聚体mRNA疫苗是一种有前景的针对SARS-CoV-2变体及其他毒株的候选疫苗。
