The self-assembled nanoparticle-based trimeric RBD mRNA vaccine elicits robust and durable protective immunity against SARS-CoV-2 in mice
Abstract As COVID-19 continues to spread rapidly worldwide and variants continue to emerge, the development and deployment of safe and effective vaccines are urgently needed. Here, we developed an mRNA vaccine based on the trimeric receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein fu...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2021-09-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-021-00750-w |
| _version_ | 1818728710242566144 |
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| author | Wenqiang Sun Lihong He He Zhang Xiaodong Tian Zhihua Bai Lei Sun Limin Yang Xiaojuan Jia Yuhai Bi Tingrong Luo Gong Cheng Wenhui Fan Wenjun Liu Jing Li |
| author_facet | Wenqiang Sun Lihong He He Zhang Xiaodong Tian Zhihua Bai Lei Sun Limin Yang Xiaojuan Jia Yuhai Bi Tingrong Luo Gong Cheng Wenhui Fan Wenjun Liu Jing Li |
| author_sort | Wenqiang Sun |
| collection | DOAJ |
| description | Abstract As COVID-19 continues to spread rapidly worldwide and variants continue to emerge, the development and deployment of safe and effective vaccines are urgently needed. Here, we developed an mRNA vaccine based on the trimeric receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein fused to ferritin-formed nanoparticles (TF-RBD). Compared to the trimeric form of the RBD mRNA vaccine (T-RBD), TF-RBD delivered intramuscularly elicited robust and durable humoral immunity as well as a Th1-biased cellular response. After further challenge with live SARS-CoV-2, immunization with a two-shot low-dose regimen of TF-RBD provided adequate protection in hACE2-transduced mice. In addition, the mRNA template of TF-RBD was easily and quickly engineered into a variant vaccine to address SARS-CoV-2 mutations. The TF-RBD multivalent vaccine produced broad-spectrum neutralizing antibodies against Alpha (B.1.1.7) and Beta (B.1.351) variants. This mRNA vaccine based on the encoded self-assembled nanoparticle-based trimer RBD provides a reference for the design of mRNA vaccines targeting SARS-CoV-2. |
| first_indexed | 2024-12-17T22:34:19Z |
| format | Article |
| id | doaj.art-aa4958ddb0da4bfcb1eadc517a56d063 |
| institution | Directory Open Access Journal |
| issn | 2059-3635 |
| language | English |
| last_indexed | 2024-12-17T22:34:19Z |
| publishDate | 2021-09-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj.art-aa4958ddb0da4bfcb1eadc517a56d0632022-12-21T21:30:08ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352021-09-016111110.1038/s41392-021-00750-wThe self-assembled nanoparticle-based trimeric RBD mRNA vaccine elicits robust and durable protective immunity against SARS-CoV-2 in miceWenqiang Sun0Lihong He1He Zhang2Xiaodong Tian3Zhihua Bai4Lei Sun5Limin Yang6Xiaojuan Jia7Yuhai Bi8Tingrong Luo9Gong Cheng10Wenhui Fan11Wenjun Liu12Jing Li13CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of SciencesCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of SciencesCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of SciencesCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of SciencesCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of SciencesCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of SciencesCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of SciencesCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of SciencesCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of SciencesState Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources & Laboratory of Animal Infectious Diseases, College of Animal Sciences and Veterinary Medicine, Guangxi UniversityInstitute of Infectious Diseases, Shenzhen Bay LaboratoryCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of SciencesCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of SciencesCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of SciencesAbstract As COVID-19 continues to spread rapidly worldwide and variants continue to emerge, the development and deployment of safe and effective vaccines are urgently needed. Here, we developed an mRNA vaccine based on the trimeric receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein fused to ferritin-formed nanoparticles (TF-RBD). Compared to the trimeric form of the RBD mRNA vaccine (T-RBD), TF-RBD delivered intramuscularly elicited robust and durable humoral immunity as well as a Th1-biased cellular response. After further challenge with live SARS-CoV-2, immunization with a two-shot low-dose regimen of TF-RBD provided adequate protection in hACE2-transduced mice. In addition, the mRNA template of TF-RBD was easily and quickly engineered into a variant vaccine to address SARS-CoV-2 mutations. The TF-RBD multivalent vaccine produced broad-spectrum neutralizing antibodies against Alpha (B.1.1.7) and Beta (B.1.351) variants. This mRNA vaccine based on the encoded self-assembled nanoparticle-based trimer RBD provides a reference for the design of mRNA vaccines targeting SARS-CoV-2.https://doi.org/10.1038/s41392-021-00750-w |
| spellingShingle | Wenqiang Sun Lihong He He Zhang Xiaodong Tian Zhihua Bai Lei Sun Limin Yang Xiaojuan Jia Yuhai Bi Tingrong Luo Gong Cheng Wenhui Fan Wenjun Liu Jing Li The self-assembled nanoparticle-based trimeric RBD mRNA vaccine elicits robust and durable protective immunity against SARS-CoV-2 in mice Signal Transduction and Targeted Therapy |
| title | The self-assembled nanoparticle-based trimeric RBD mRNA vaccine elicits robust and durable protective immunity against SARS-CoV-2 in mice |
| title_full | The self-assembled nanoparticle-based trimeric RBD mRNA vaccine elicits robust and durable protective immunity against SARS-CoV-2 in mice |
| title_fullStr | The self-assembled nanoparticle-based trimeric RBD mRNA vaccine elicits robust and durable protective immunity against SARS-CoV-2 in mice |
| title_full_unstemmed | The self-assembled nanoparticle-based trimeric RBD mRNA vaccine elicits robust and durable protective immunity against SARS-CoV-2 in mice |
| title_short | The self-assembled nanoparticle-based trimeric RBD mRNA vaccine elicits robust and durable protective immunity against SARS-CoV-2 in mice |
| title_sort | self assembled nanoparticle based trimeric rbd mrna vaccine elicits robust and durable protective immunity against sars cov 2 in mice |
| url | https://doi.org/10.1038/s41392-021-00750-w |
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