RBD trimer mRNA vaccine elicits broad and protective immune responses against SARS-CoV-2 variants
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 do...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-04-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222003133 |
| _version_ | 1818289327689433088 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Qingtai Liang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T02:10:31Z |
| format | Article |
| id | doaj.art-825edf0730eb4410b98c681d97cf8898 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-13T02:10:31Z |
| publishDate | 2022-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-825edf0730eb4410b98c681d97cf88982022-12-22T00:03:02ZengElsevieriScience2589-00422022-04-01254104043RBD trimer mRNA vaccine elicits broad and protective immune responses against SARS-CoV-2 variantsQingtai Liang0Yifeng Wang1Shuyuan Zhang2Jing Sun3Wenbo Sun4Jizhou Li5Yaping Liu6Mingxi Li7Lin Cheng8Yuhang Jiang9Ruoke Wang10Rui Zhang11Zihan Yang12Yifei Ren13Peng Chen14Peng Gao15Huayuan Yan16Zheng Zhang17Qi Zhang18Xuanling Shi19Jianbin Wang20Wanli Liu21Xinquan Wang22Bo Ying23Jincun Zhao24Hai Qi25Linqi Zhang26Comprehensive 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, ChinaNexVac 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, ChinaThe 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, ChinaState 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, ChinaTsinghua-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, ChinaSchool of Life Sciences, Tsinghua University, Beijing 100084, ChinaComprehensive 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, ChinaComprehensive 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, ChinaInstitute 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, ChinaSuzhou Abogen Biosciences Co., Ltd., Suzhou 215123, ChinaComprehensive 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, ChinaComprehensive 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, ChinaSchool of Life Sciences, Tsinghua University, Beijing 100084, ChinaThe 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, ChinaComprehensive 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, ChinaSuzhou Abogen Biosciences Co., Ltd., Suzhou 215123, ChinaSuzhou Abogen Biosciences Co., Ltd., Suzhou 215123, ChinaInstitute 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, ChinaComprehensive 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, ChinaComprehensive 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, ChinaSchool 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, ChinaTsinghua-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 authorThe 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 authorSuzhou Abogen Biosciences Co., Ltd., Suzhou 215123, China; Corresponding authorState 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 authorNexVac 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 authorComprehensive 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 authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004222003133Health sciencesVirologyImmunology |
| spellingShingle | 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 RBD trimer mRNA vaccine elicits broad and protective immune responses against SARS-CoV-2 variants iScience Health sciences Virology Immunology |
| title | RBD trimer mRNA vaccine elicits broad and protective immune responses against SARS-CoV-2 variants |
| title_full | RBD trimer mRNA vaccine elicits broad and protective immune responses against SARS-CoV-2 variants |
| title_fullStr | RBD trimer mRNA vaccine elicits broad and protective immune responses against SARS-CoV-2 variants |
| title_full_unstemmed | RBD trimer mRNA vaccine elicits broad and protective immune responses against SARS-CoV-2 variants |
| title_short | RBD trimer mRNA vaccine elicits broad and protective immune responses against SARS-CoV-2 variants |
| title_sort | rbd trimer mrna vaccine elicits broad and protective immune responses against sars cov 2 variants |
| topic | Health sciences Virology Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222003133 |
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