A Universal Design of Betacoronavirus Vaccines against COVID-19, MERS, and SARS

被引：478

作者：

Dai, Lianpan ^{[1
,2
,3
]}

Zheng, Tianyi ^{[1
,2
]}

Xu, Kun ^{[3
]}

Han, Yuxuan ^{[2
]}

Xu, Lili ^{[4
,5
]}

Huang, Enqi ^{[6
]}

An, Yaling ^{[1
]}

Cheng, Yingjie ^{[6
]}

Li, Shihua ^{[7
]}

Liu, Mei ^{[8
]}

Yang, Mi ^{[8
]}

Li, Yan ^{[7
]}

Cheng, Huijun ^{[1
]}

Yuan, Yuan ^{[7
]}

Zhang, Wei ^{[7
]}

Ke, Changwen ^{[9
]}

Wong, Gary ^{[10
,11
]}

Qi, Jianxun ^{[2
,7
]}

Qin, Chuan ^{[4
,5
]}

Yan, Jinghua ^{[7
,8
]}

Gao, George F. ^{[1
,2
,7
,12
]}

机构：

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

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

[3] Hainan Med Univ, Affiliated Hosp 1, Sch Trop Med & Lab Med, Key Lab Trop Translat Med,Minist Educ, Haikou 571199, Hainan, Peoples R China

[4] Chinese Acad Med Sci, Inst Lab Anim Sci, Key Lab Anim Models Emerging & Remerging Infect D, Beijing 100032, Peoples R China

[5] Peking Union Med Coll, Comparat Med Ctr, Beijing 100032, Peoples R China

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

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

[8] Chinese Acad Sci, Inst Microbiol, CAS Key Lab Microbial Physiol & Metab Engn, Beijing 100101, Peoples R China

[9] Guangdong Prov Ctr Dis Control & Prevent, Guangzhou 511430, Peoples R China

[10] Chinese Acad Sci, Inst Pasteur Shanghai, Shanghai 200031, Peoples R China

[11] Laval Univ, Dept Microbiol Infectiol & Immunol, Quebec City, PQ G1V 4G2, Canada

[12] Chinese Ctr Dis Control & Prevent China CDC, Beijing 102206, Peoples R China

来源：

CELL | 2020年 / 182卷 / 03期

基金：

中国国家自然科学基金;

关键词：

RECEPTOR-BINDING DOMAIN; ANTIBODY-DEPENDENT ENHANCEMENT; DIPEPTIDYL PEPTIDASE 4; HUMAN CORONAVIRUS; SPIKE PROTEIN; NEUTRALIZING ANTIBODIES; STRUCTURAL DEFINITION; FUNCTIONAL RECEPTOR; SUBUNIT VACCINE; S-GLYCOPROTEIN;

D O I：

10.1016/j.cell.2020.06.035

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Vaccines are urgently needed to control the ongoing pandemic COVID-19 and previously emerging MERS/ SARS caused by coronavirus (CoV) infections. The CoV spike receptor-binding domain (RBD) is an attractive vaccine target but is undermined by limited immunogenicity. We describe a dimeric form of MERS-CoV RBD that overcomes this limitation. The RBD-dimer significantly increased neutralizing antibody (NAb) titers compared to conventional monomeric form and protected mice against MERS-CoV infection. Crystal structure showed RBD-dimer fully exposed dual receptor-binding motifs, the major target for NAbs. Structureguided design further yielded a stable version of RBD-dimer as a tandem repeat single-chain (RBD-sc-dimer) which retained the vaccine potency. We generalized this strategy to design vaccines against COVID-19 and SARS, achieving 10- to 100-fold enhancement of NAb titers. RBD-sc-dimers in pilot scale production yielded high yields, supporting their scalability for further clinical development. The framework of immunogen design can be universally applied to other beta-CoV vaccines to counter emerging threats.

引用

页码：722 / +

页数：23

共 74 条

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