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.

Details

Title
The self-assembled nanoparticle-based trimeric RBD mRNA vaccine elicits robust and durable protective immunity against SARS-CoV-2 in mice
Author
Sun Wenqiang 1 ; He, Lihong 2 ; Zhang, He 3 ; Tian Xiaodong 4 ; Bai Zhihua 2 ; Sun, Lei 2   VIAFID ORCID Logo  ; Yang, Limin 4   VIAFID ORCID Logo  ; Jia Xiaojuan 4 ; Bi Yuhai 2   VIAFID ORCID Logo  ; Luo Tingrong 5 ; Gong, Cheng 6 ; Fan Wenhui 4 ; Liu, Wenjun 7 ; Li, Jing 2   VIAFID ORCID Logo 

1  CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China (GRID:grid.458488.d) (ISNI:0000 0004 0627 1442); Institute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, China (GRID:grid.510951.9) (ISNI:0000 0004 7775 6738); Guangxi University, State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources & Laboratory of Animal Infectious Diseases, College of Animal Sciences and Veterinary Medicine, Nanning, China (GRID:grid.256609.e) (ISNI:0000 0001 2254 5798) 
2  CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China (GRID:grid.458488.d) (ISNI:0000 0004 0627 1442); University of Chinese Academy of Sciences, Beijing, China (GRID:grid.410726.6) (ISNI:0000 0004 1797 8419) 
3  CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China (GRID:grid.458488.d) (ISNI:0000 0004 0627 1442); Institute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, China (GRID:grid.510951.9) (ISNI:0000 0004 7775 6738) 
4  CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China (GRID:grid.458488.d) (ISNI:0000 0004 0627 1442) 
5  Guangxi University, State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources & Laboratory of Animal Infectious Diseases, College of Animal Sciences and Veterinary Medicine, Nanning, China (GRID:grid.256609.e) (ISNI:0000 0001 2254 5798) 
6  Institute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, China (GRID:grid.510951.9) (ISNI:0000 0004 7775 6738); Tsinghua University, Tsinghua-Peking Center for Life Sciences, School of Medicine, Beijing, China (GRID:grid.12527.33) (ISNI:0000 0001 0662 3178) 
7  CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China (GRID:grid.458488.d) (ISNI:0000 0004 0627 1442); Institute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, China (GRID:grid.510951.9) (ISNI:0000 0004 7775 6738); Guangxi University, State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources & Laboratory of Animal Infectious Diseases, College of Animal Sciences and Veterinary Medicine, Nanning, China (GRID:grid.256609.e) (ISNI:0000 0001 2254 5798); University of Chinese Academy of Sciences, Beijing, China (GRID:grid.410726.6) (ISNI:0000 0004 1797 8419); Institute of Microbiology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Beijing, China (GRID:grid.458488.d) (ISNI:0000 0004 0627 1442) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
ISSN
20959907
e-ISSN
20593635
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41392-021-00750-w
ProQuest document ID
2570657761
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.