Protective prototype-Beta and Delta-Omicron chimeric RBD-dimer vaccines against SARS-CoV-2

被引：118

作者：

Xu, Kun ^{[1
]}

Gao, Ping ^{[2
,3
]}

Liu, Sheng ^{[4
]}

Lu, Shuaiyao ^{[5
]}

Lei, Wenwen ^{[6
]}

Zheng, Tianyi ^{[7
]}

Liu, Xueyuan ^{[8
]}

Xie, Yufeng ^{[9
]}

Zhao, Zhennan ^{[2
,3
]}

Guo, Shuxin ^{[10
]}

Tang, Cong ^{[5
]}

Yang, Yun ^{[5
]}

Yu, Wenhai ^{[5
]}

Wang, Junbin ^{[5
]}

Zhou, Yanan ^{[5
]}

Huang, Qing ^{[5
]}

Liu, Chuanyu ^{[11
]}

An, Yaling ^{[12
]}

Zhang, Rong ^{[11
]}

Han, Yuxuan ^{[12
]}

Duan, Minrun ^{[13
]}

Wang, Shaofeng ^{[2
,3
]}

Yang, Chenxi ^{[2
,3
]}

Wu, Changwei ^{[14
]}

Liu, Xiaoya ^{[14
]}

She, Guangbiao ^{[14
]}

Liu, Yan ^{[15
]}

Zhao, Xin ^{[2
]}

Xu, Ke ^{[6
]}

Qi, Jianxun ^{[2
]}

Wu, Guizhen ^{[6
]}

Peng, Xiaozhong ^{[5
,16
]}

Dai, Lianpan ^{[2
,3
]}

Wang, Peiyi ^{[4
]}

Gao, George F. ^{[1
,2
,3
,12
]}

机构：

[1] Chinese Acad Sci, Beijing Inst Life Sci, Res Network Immun & Hlth RNIH, Beijing 100101, Peoples R China

[2] Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing 100101, Peoples R China

[3] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[4] Southern Univ Sci & Technol, Cryo EM Ctr, Shenzhen 518055, Peoples R China

[5] Chinese Acad Med Sci & Peking Union Med Coll, Inst Med Biol, Natl Kunming High Level Biosafety Primate Res Ctr, Kunming 650031, Yunnan, Peoples R China

[6] Chinese Ctr Dis Control & Prevent, Natl Inst Viral Dis Control & Prevent, NHC Key Lab Biosafety, Beijing 102206, Peoples R China

[7] Zhejiang Univ, Sch Med, Hangzhou 310058, Peoples R China

[8] Shandong Univ, Cheeloo Coll Med, Sch Publ Hlth, Jinan 250012, Peoples R China

[9] Tsinghua Univ, Sch Med, Dept Basic Med Sci, Beijing 100084, Peoples R China

[10] Univ Macau, Fac Hlth Sci, Taipa 999078, Macau, Peoples R China

[11] Guangxi Univ, State Key Lab Conservat & Utilizat Subtrop Agrobi, Nanning 530004, Peoples R China

[12] Univ Chinese Acad Sci, Savaid Med Sch, Beijing 101408, Peoples R China

[13] Yunnan Univ, Sch Life Sci, Kunming 650091, Yunnan, Peoples R China

[14] Anhui Zhifei Longcom Biopharmaceut Co Ltd, Hefei 230088, Peoples R China

[15] Chongqing Medleader Biopharm, Chongqing 401338, Peoples R China

[16] Chinese Acad Med Sci, Peking Union Med Coll,Dept Mol Biol & Biochem, Sch Basic Med,State Key Lab Med Mol Biol, Med Primate Res Ctr,Neurosci Ctr,Inst Basic Med S, Beijing 100005, Peoples R China

来源：

CELL | 2022年 / 185卷 / 13期

基金：

中国国家自然科学基金; 比尔及梅琳达.盖茨基金会; 国家重点研发计划; 中国博士后科学基金;

关键词：

NEUTRALIZATION; MUTATIONS; COVID-19; CHINA;

D O I：

10.1016/j.cell.2022.04.029

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Breakthrough infections by SARS-CoV-2 variants become the global challenge for pandemic control. Previously, we developed the protein subunit vaccine ZF2001 based on the dimeric receptor-binding domain (RBD) of prototype SARS-CoV-2. Here, we developed a chimeric RBD-dimer vaccine approach to adapt SARS-CoV-2 variants. A prototype-Beta chimeric RBD-dimer was first designed to adapt the resistant Beta variant. Compared with its homotypic forms, the chimeric vaccine elicited broader sera neutralization of variants and conferred better protection in mice. The protection of the chimeric vaccine was further verified in macaques. This approach was generalized to develop Delta-Omicron chimeric RBD-dimer to adapt the currently prevalent variants. Again, the chimeric vaccine elicited broader sera neutralization of SARS-CoV-2 variants and conferred better protection against challenge by either Delta or Omicron SARS-CoV-2 in mice. The chimeric approach is applicable for rapid updating of immunogens, and our data supported the use of variant-adapted multivalent vaccine against circulating and emerging variants.

引用

页码：2265 / +

页数：29

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