RBD trimer mRNA vaccine elicits broad and protective immune responses against SARS-CoV-2 variants

Liang，Qingtai1,2; Wang，Yifeng2,3,4,5; Zhang，Shuyuan6; Sun，Jing7; Sun，Wenbo3,18; Li，Jizhou8; Liu，Yaping1,2; Li，Mingxi1,2; Cheng，Lin9,10; Jiang，Yuhang13; Wang，Ruoke1,2; Zhang，Rui1,2; Yang，Zihan8; Ren，Yifei6; Chen，Peng1,2; Gao，Peng13; Yan，Huayuan13; Zhang，Zheng9,10; Zhang，Qi1,2; Shi，Xuanling1,2; Wang，Jianbin8,11,12; Liu，Wanli3,18; Wang，Xinquan6; Ying，Bo13; Zhao，Jincun7; Qi，Hai2,3,4,5,14,15; Zhang，Linqi1,2,16,17

2022-04-15

10.1016/j.isci.2022.104043

iScience   影响因子和分区

2589-0042

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.

Health sciences Immunology Virology

SCI

英语

其他

Science, Technology and Innovation Commission of Shenzhen Municipality[202002073000002];Tsinghua University[20201080053];China Postdoctoral Science Foundation[2020T130062ZX];Tsinghua University[2020Z99CFG004];National Natural Science Foundation of China[32000661];National Natural Science Foundation of China[81530065];National Science Fund for Distinguished Young Scholars[82025022];National Natural Science Foundation of China[91442127];National Natural Science Foundation of China[92169205];Beijing Municipal Science and Technology Commission[D171100000517];Beijing Municipal Science and Technology Commission[Z201100005420019];

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000819870200003

CELL PRESS

2-s2.0-85126849696

Scopus

1.Comprehensive AIDS Research Center,Department of Basic Medical Sciences,School of Medicine,Tsinghua University,Beijing,100084,China
2.NexVac Research Center,School of Medicine,Tsinghua University,Beijing,100084,China
3.Tsinghua-Peking Center for Life Sciences,Tsinghua University,Beijing,100084,China
4.Laboratory of Dynamic Immunobiology,Institute for Immunology,Tsinghua University,Beijing,100084,China
5.Department of Basic Medical Sciences,School of Medicine,Tsinghua University,Beijing,100084,China
6.The Ministry of Education Key Laboratory of Protein Science,Beijing Advanced Innovation Center for Structural Biology,Beijing Frontier Research Center for Biological Structure,School of Life Sciences,Tsinghua University,Beijing,100084,China
7.State Key Laboratory of Respiratory Disease,National Clinical Research Center for Respiratory Disease,Guangzhou Institute of Respiratory Health,The First Affiliated Hospital of Guangzhou Medical University,Guangzhou,Guangdong,510182,China
8.School of Life Sciences,Tsinghua University,Beijing,100084,China
9.Institute for Hepatology,National Clinical Research Center for Infectious Disease,Shenzhen Third People's Hospital,Shenzhen,Guangdong Province,China
10.The Second Affiliated Hospital,School of Medicine,Southern University of Science and Technology,Shenzhen,Guangdong Province,China
11.Chinese Institute for Brain Research (CIBR),Beijing,102206,China
12.Beijing Advanced Innovation Center for Structural Biology (ICSB),Tsinghua University,Beijing,100084,China
13.Suzhou Abogen Biosciences Co.,Ltd.,Suzhou,215123,China
14.Beijing Key Laboratory for Immunological Research on Chronic Diseases,Tsinghua University,Beijing,100084,China
15.Beijing Frontier Research Center for Biological Structure,Tsinghua University,Beijing,100084,China
16.Institute of Biopharmaceutical and Health Engineering,Tsinghua Shenzhen International Graduate School,Tsinghua University,Shenzhen,518055,China
17.Institute of Biomedical Health Technology and Engineering,Shenzhen Bay Laboratory,Shenzhen,518132,China
18.School of Life Sciences,Institute for Immunology,MOE Key Laboratory of Protein Sciences,Center for Life Sciences,Advanced Innovation Center for Structural Biology,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,Beijing Key Lab for Immunological Research on Chronic Diseases,Tsinghua University,Beijing,100084,China

Liang，Qingtai,Wang，Yifeng,Zhang，Shuyuan,et al. RBD trimer mRNA vaccine elicits broad and protective immune responses against SARS-CoV-2 variants[J]. iScience,2022,25(4).

Liang，Qingtai.,Wang，Yifeng.,Zhang，Shuyuan.,Sun，Jing.,Sun，Wenbo.,...&Zhang，Linqi.(2022).RBD trimer mRNA vaccine elicits broad and protective immune responses against SARS-CoV-2 variants.iScience,25(4).

Liang，Qingtai,et al."RBD trimer mRNA vaccine elicits broad and protective immune responses against SARS-CoV-2 variants".iScience 25.4(2022).