Design of a mutation-integrated trimeric RBD with broad protection against SARS-CoV-2

The continuous emergence of SARS-CoV-2 variants highlights the need of developing vaccines with broad protection. Here, according to the immune-escape capability and evolutionary convergence, the representative SARS-CoV-2 strains carrying the hotspot mutations were selected. Then, guided by structur...

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Bibliographic Details
Published in:Cell discovery 2022-02, Vol.8 (1), p.17-17, Article 17
Main Authors: Liang, Yu, Zhang, Jing, Yuan, Run Yu, Wang, Mei Yu, He, Peng, Su, Ji Guo, Han, Zi Bo, Jin, Yu Qin, Hou, Jun Wei, Zhang, Hao, Zhang, Xue Feng, Shao, Shuai, Hou, Ya Nan, Liu, Zhao Ming, Du, Li Fang, Shen, Fu Jie, Zhou, Wei Min, Xu, Ke, Gao, Ru Qin, Tang, Fang, Lei, Ze Hua, Liu, Shuo, Zhen, Wei, Wu, Jin Juan, Zheng, Xiang, Liu, Ning, Chen, Shi, Ma, Zhi Jing, Zheng, Fan, Ren, Si Yu, Hu, Zhong Yu, Huang, Wei Jin, Wu, Gui Zhen, Ke, Chang Wen, Li, Qi Ming
Format: Article
Language:English
Subjects:
631/1647
631/250
Biomedical and Life Sciences
Cell Biology
Cell Culture
Cell Cycle Analysis
Cell Physiology
Combined vaccines
Computer applications
Immune response
Life Sciences
Mutation
Mutation hot spots
Severe acute respiratory syndrome coronavirus 2
Stem Cells
Strains (organisms)
Transgenic mice
Vaccines
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Summary:The continuous emergence of SARS-CoV-2 variants highlights the need of developing vaccines with broad protection. Here, according to the immune-escape capability and evolutionary convergence, the representative SARS-CoV-2 strains carrying the hotspot mutations were selected. Then, guided by structural and computational analyses, we present a mutation-integrated trimeric form of spike receptor-binding domain (mutI-tri-RBD) as a broadly protective vaccine candidate, which combined heterologous RBDs from different representative strains into a hybrid immunogen and integrated immune-escape hotspots into a single antigen. When compared with a homo-tri-RBD vaccine candidate in the stage of phase II trial, of which all three RBDs are derived from the SARS-CoV-2 prototype strain, mutI-tri-RBD induced significantly higher neutralizing antibody titers against the Delta and Beta variants, and maintained a similar immune response against the prototype strain. Pseudo-virus neutralization assay demonstrated that mutI-tri-RBD also induced broadly strong neutralizing activities against all tested 23 SARS-CoV-2 variants. The in vivo protective capability of mutI-tri-RBD was further validated in hACE2-transgenic mice challenged by the live virus, and the results showed that mutI-tri-RBD provided potent protection not only against the SARS-CoV-2 prototype strain but also against the Delta and Beta variants.
ISSN:2056-5968
2056-5968
DOI:10.1038/s41421-022-00383-5