Circular RNA vaccines against SARS-CoV-2 and emerging variants

被引：414

作者：

Qu, Liang ^{[1
]}

Yi, Zongyi ^{[1
,2
]}

Shen, Yong ^{[1
,2
]}

Lin, Liangru ^{[1
]}

Chen, Feng ^{[1
,2
]}

Xu, Yiyuan ^{[1
]}

Wu, Zeguang ^{[1
]}

Tang, Huixian ^{[1
]}

Zhang, Xiaoxue ^{[1
,2
]}

Tian, Feng ^{[1
]}

Wang, Chunhui ^{[1
]}

Xiao, Xia ^{[3
,4
,10
]}

Dong, Xiaojing ^{[3
,4
,10
]}

Guo, Li ^{[3
,4
,10
]}

Lu, Shuaiyao ^{[5
]}

Yang, Chengyun ^{[2
]}

Tang, Cong ^{[5
]}

Yang, Yun ^{[5
]}

Yu, Wenhai ^{[5
]}

Wang, Junbin ^{[5
]}

Zhou, Yanan ^{[5
]}

Huang, Qing ^{[5
]}

Yisimayi, Ayijiang ^{[6
]}

Liu, Shuo ^{[7
,8
]}

Huang, Weijin ^{[7
,8
]}

Cao, Yunlong ^{[6
]}

Wang, Youchun ^{[1
]}

Zhou, Zhuo ^{[1
]}

Peng, Xiaozhong ^{[5
,9
]}

Wang, Jianwei ^{[3
,4
,10
]}

Xie, Xiaoliang Sunney ^{[6
]}

Wei, Wensheng ^{[1
]}

机构：

[1] Peking Univ, Peking Univ Genome Editing Res Ctr,Peking Tsinghu, Sch Life Sci,Beijing Adv Innovat Ctr Genom, State Key Lab Prot & Plant Gene Res,Biomed Pionee, Beijing 100871, Peoples R China

[2] Peking Univ, Acad Adv Interdisciplinary Studies, Beijing 100871, Peoples R China

[3] Chinese Acad Med Sci & Peking Union Med Coll, Inst Pathogen Biol, NHC Key Lab Syst Biol Pathogens, Beijing 100730, Peoples R China

[4] Chinese Acad Med Sci & Peking Union Med Coll, Inst Pathogen Biol, Christophe Merieux Lab, Beijing 100730, Peoples R China

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

[6] Peking Univ, Biomed Pioneering Innovat Ctr, Beijing Adv Innovat Ctr Genom, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China

[7] Natl Inst Food & Drug Control NIFDC, Inst Biol Prod Control, Div HIV AIDS & Sex Transmitted Virus Vaccines, Beijing 102629, Peoples R China

[8] WHO Collaborating Ctr Standardizat & Evaluat Biol, Beijing 102629, Peoples R China

[9] Chinese Acad Med Sci, Sch Basic Med,Dept Mol Biol & Biochem, Peking Union Med Coll,State Key Lab Med Mol Biol, Med Primate Res Ctr,Neurosci Ctr,Inst Basic Med S, Beijing 100730, Peoples R China

[10] Chinese Acad Med Sci & Peking Union Med Coll, Key Lab Resp Dis Pathogen, Beijing 100730, Peoples R China

来源：

CELL | 2022年 / 185卷 / 10期

基金：

美国国家科学基金会; 国家重点研发计划;

关键词：

ANTIBODY-DEPENDENT ENHANCEMENT; POTENT; INFECTION; IMMUNOGENICITY; COVID-19; DESIGN; DRIVEN; SAFETY; ACE2;

D O I：

10.1016/j.cell.2022.03.044

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：

As the emerging variants of SARS-CoV-2 continue to drive the worldwide pandemic, there is a constant demand for vaccines that offer more effective and broad-spectrum protection. Here, we report a circular RNA (circRNA) vaccine that elicited potent neutralizing antibodies and T cell responses by expressing the trimeric RBD of the spike protein, providing robust protection against SARS-CoV-2 in both mice and rhesus macaques. Notably, the circRNA vaccine enabled higher and more durable antigen production than the 1m Psi-modified mRNA vaccine and elicited a higher proportion of neutralizing antibodies and distinct Th1-skewed immune responses. Importantly, we found that the circRNA(RBD)(-Omicron) vaccine induced effective neutralizing antibodies against the Omicron but not the Delta variant. In contrast, the circRNA(RBD)(-Delta) vaccine protected against both Delta and Omicron or functioned as a booster after two doses of either native-or Delta-specific vaccination, making it a favorable choice against the current variants of concern (VOCs) of SARS-CoV-2.

引用

页码：1728 / +

页数：34

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