The self-assembled nanoparticle-based trimeric RBD mRNA vaccine elicits robust and durable protective immunity against SARS-CoV-2 in mice

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 fe...

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Bibliographic Details
Published in:Signal transduction and targeted therapy 2021-09, Vol.6 (1), p.340-11, Article 340
Main Authors: Sun, Wenqiang, He, Lihong, Zhang, He, Tian, Xiaodong, Bai, Zhihua, Sun, Lei, Yang, Limin, Jia, Xiaojuan, Bi, Yuhai, Luo, Tingrong, Cheng, Gong, Fan, Wenhui, Liu, Wenjun, Li, Jing
Format: Article
Language:English
Subjects:
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631/326/590
Animals
Cancer Research
Cell Biology
Chlorocebus aethiops
COVID-19
COVID-19 - immunology
COVID-19 - pathology
COVID-19 - prevention & control
COVID-19 Vaccines - chemistry
COVID-19 Vaccines - pharmacology
Female
Ferritin
HEK293 Cells
Humans
Humoral immunity
Immunization
Internal Medicine
Lymphocytes T
Medicine
Medicine & Public Health
Mice
Mice, Transgenic
mRNA
mRNA Vaccines
Nanoparticles
Nanoparticles - chemistry
Nanoparticles - therapeutic use
Oncology
Pathology
SARS-CoV-2 - immunology
Severe acute respiratory syndrome coronavirus 2
Th1 Cells - immunology
Th1 Cells - pathology
Trimers
Vaccines, Synthetic - chemistry
Vaccines, Synthetic - immunology
Vero Cells
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Summary: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.
ISSN:2059-3635
2095-9907
2059-3635
DOI:10.1038/s41392-021-00750-w