iScience (Apr 2022)
RBD trimer mRNA vaccine elicits broad and protective immune responses against SARS-CoV-2 variants
- Qingtai Liang,
- Yifeng Wang,
- Shuyuan Zhang,
- Jing Sun,
- Wenbo Sun,
- Jizhou Li,
- Yaping Liu,
- Mingxi Li,
- Lin Cheng,
- Yuhang Jiang,
- Ruoke Wang,
- Rui Zhang,
- Zihan Yang,
- Yifei Ren,
- Peng Chen,
- Peng Gao,
- Huayuan Yan,
- Zheng Zhang,
- Qi Zhang,
- Xuanling Shi,
- Jianbin Wang,
- Wanli Liu,
- Xinquan Wang,
- Bo Ying,
- Jincun Zhao,
- Hai Qi,
- Linqi Zhang
Affiliations
- Qingtai Liang
- 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
- Yifeng Wang
- NexVac Research Center, School of Medicine, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China; Laboratory of Dynamic Immunobiology, Institute for Immunology, Tsinghua University, Beijing 100084, China; Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China
- Shuyuan Zhang
- 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
- Jing Sun
- 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
- Wenbo Sun
- Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China; 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
- Jizhou Li
- School of Life Sciences, Tsinghua University, Beijing 100084, China
- Yaping Liu
- 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
- Mingxi Li
- 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
- Lin Cheng
- Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Shenzhen, Guangdong Province, China; The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong Province, China
- Yuhang Jiang
- Suzhou Abogen Biosciences Co., Ltd., Suzhou 215123, China
- Ruoke Wang
- 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
- Rui Zhang
- 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
- Zihan Yang
- School of Life Sciences, Tsinghua University, Beijing 100084, China
- Yifei Ren
- 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
- Peng Chen
- 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
- Peng Gao
- Suzhou Abogen Biosciences Co., Ltd., Suzhou 215123, China
- Huayuan Yan
- Suzhou Abogen Biosciences Co., Ltd., Suzhou 215123, China
- Zheng Zhang
- Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Shenzhen, Guangdong Province, China; The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong Province, China
- Qi Zhang
- 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
- Xuanling Shi
- 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
- Jianbin Wang
- School of Life Sciences, Tsinghua University, Beijing 100084, China; Chinese Institute for Brain Research (CIBR), Beijing 102206, China; Beijing Advanced Innovation Center for Structural Biology (ICSB), Tsinghua University, Beijing 100084, China
- Wanli Liu
- Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China; 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; Corresponding author
- Xinquan Wang
- 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; Corresponding author
- Bo Ying
- Suzhou Abogen Biosciences Co., Ltd., Suzhou 215123, China; Corresponding author
- Jincun Zhao
- 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; Corresponding author
- Hai Qi
- NexVac Research Center, School of Medicine, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China; Laboratory of Dynamic Immunobiology, Institute for Immunology, Tsinghua University, Beijing 100084, China; Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China; Beijing Key Laboratory for Immunological Research on Chronic Diseases, Tsinghua University, Beijing 100084, China; Beijing Frontier Research Center for Biological Structure, Tsinghua University, Beijing 100084, China; Corresponding author
- Linqi Zhang
- 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; Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China; Institute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen 518132, China; Corresponding author
- Journal volume & issue
-
Vol. 25,
no. 4
p. 104043
Abstract
Summary: 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.
