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

被引:31
作者
Liang, Yu [1 ,2 ]
Zhang, Jing [1 ,2 ]
Yuan, Run Yu [3 ]
Wang, Mei Yu [4 ]
He, Peng [4 ]
Su, Ji Guo [1 ,2 ]
Han, Zi Bo [1 ,2 ]
Jin, Yu Qin [1 ,2 ]
Hou, Jun Wei [1 ,2 ]
Zhang, Hao [1 ,2 ]
Zhang, Xue Feng [1 ,2 ]
Shao, Shuai [1 ,2 ]
Hou, Ya Nan [1 ,2 ]
Liu, Zhao Ming [1 ,2 ]
Du, Li Fang [1 ,2 ]
Shen, Fu Jie [1 ,2 ]
Zhou, Wei Min [5 ]
Xu, Ke [5 ]
Gao, Ru Qin [6 ]
Tang, Fang [1 ,2 ]
Lei, Ze Hua [1 ,2 ]
Liu, Shuo [4 ]
Zhen, Wei [5 ]
Wu, Jin Juan [1 ,2 ]
Zheng, Xiang [1 ,2 ]
Liu, Ning [1 ,2 ]
Chen, Shi [1 ,2 ]
Ma, Zhi Jing [1 ,2 ]
Zheng, Fan [1 ,2 ]
Ren, Si Yu [1 ,2 ]
Hu, Zhong Yu [4 ]
Huang, Wei Jin [4 ]
Wu, Gui Zhen [5 ]
Ke, Chang Wen [3 ]
Li, Qi Ming [1 ,2 ]
机构
[1] Natl Vaccine & Serum Inst NVSI, Lab 6, Beijing, Peoples R China
[2] Natl Engn Ctr New Vaccine Res, Beijing, Peoples R China
[3] Guangdong Prov Ctr Dis Control & Prevent, Guangdong Prov Inst Publ Hlth, Guangzhou, Peoples R China
[4] Natl Inst Food & Drug Control NIFDC, Beijing, Peoples R China
[5] Chinese Ctr Dis Control & Prevent China CDC, Natl Inst Viral Dis Control & Prevent, Beijing, Peoples R China
[6] Qingdao Ctr Dis Control & Prevent, Qingdao, Shandong, Peoples R China
关键词
RECEPTOR-BINDING DOMAIN; VACCINES; NEUTRALIZATION; SPIKE; RECOGNITION; VARIANTS; COVID-19; ANTIBODY;
D O I
10.1038/s41421-022-00383-5
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
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页数:17
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