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标题：RBD trimer mRNA vaccine elicits broad and protective immune responses against SARS-CoV-2 variants
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作者：Qingtai Liang ; Yifeng Wang ; Shuyuan Zhang 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：4
页码：1-29
DOI：10.1016/j.isci.2022.104043
语种：English
出版社：Elsevier
摘要：SummaryWith 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.Graphical abstractDisplay OmittedHighlights•A mRNA vaccine encoding the RBD trimer of wild-type SARS-CoV-2 was designed and studied•The vaccine elicited strong RBD-specific memory and plasma B cell responses•The vaccine induced broadly serum and monoclonal neutralizing antibodies in mice•The vaccine induced strong and protective immunity against major SARS-CoV-2 variantsHealth sciences; Virology; Immunology