A pathogen-like antigen-based vaccine confers immune protection against SARS-CoV-2 in non-human primates

被引：11

作者：

Guo, Chang ^{[1
,2
,3
]}

Peng, Yanan ^{[1
,2
]}

Lin, Lin ^{[1
,2
]}

Pan, Xiaoyan ^{[4
]}

Fang, Mengqi ^{[5
,6
]}

Zhao, Yun ^{[6
,7
]}

Bao, Keyan ^{[2
]}

Li, Runhan ^{[1
,2
,3
]}

Han, Jianbao ^{[8
]}

Chen, Jiaorong ^{[1
,2
,3
]}

Song, Tian-Zhang ^{[8
]}

Feng, Xiao-Li ^{[8
]}

Zhou, Yahong ^{[1
,2
]}

Zhao, Gan ^{[9
]}

Zhang, Leike ^{[4
]}

Zheng, Yongtang ^{[8
]}

Zhu, Ping ^{[2
,3
]}

Hang, Haiying ^{[3
,6
,7
]}

Zhang, Linqi ^{[5
,6
]}

Hua, Zhaolin ^{[1
,2
,3
]}

Deng, Hongyu ^{[1
,2
,3
]}

Hou, Baidong ^{[1
,2
,3
]}

机构：

[1] Chinese Acad Sci, Inst Biophys, CAS Key Lab Infect & Immun, Beijing 100101, Peoples R China

[2] Chinese Acad Sci, Inst Biophys, CAS Ctr Excellence Biomacromol, Beijing 100101, Peoples R China

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

[4] Chinese Acad Sci, Ctr Biosafety Mega Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan 430071, Hubei, Peoples R China

[5] Tsinghua Univ, Sch Med, Beijing Adv Innovat Ctr Struct Biol, Comprehens AIDS Res Ctr, Beijing 100084, Peoples R China

[6] Tsinghua Univ, Vanke Sch Publ Hlth, Beijing 100084, Peoples R China

[7] Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Key Lab Prot & Peptide Pharmaceut, Beijing 100101, Peoples R China

[8] Chinese Acad Sci, Kunming Inst Zool, Ctr Biosafety Mega Sci, Natl High Level Biosafety Res Ctr Nonhuman Primat, Kunming 650107, Yunnan, Peoples R China

[9] Advaccine Biopharmaceut Suzhou, Suzhou 215000, Peoples R China

来源：

CELL REPORTS MEDICINE | 2021年 / 2卷 / 11期

基金：

中国国家自然科学基金;

关键词：

B-CELL RESPONSES; NEUTRALIZING ANTIBODY-RESPONSES; TOLL-LIKE RECEPTORS; NANOPARTICLE VACCINES; COVID-19; PROTEIN; DESIGN; DIFFERENTIATION; IMMUNOGENICITY; EFFICACY;

D O I：

10.1016/j.xcrm.2021.100448

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Activation of nucleic acid sensing Toll-like receptors (TLRs) in B cells is involved in antiviral responses by promoting B cell activation and germinal center responses. In order to take advantage of this natural pathway for vaccine development, synthetic pathogen-like antigens (PLAs) constructed of multivalent antigens with encapsulated TLR ligands can be used to activate B cell antigen receptors and TLRs in a synergistic manner. Here we report a PLA-based coronavirus disease 2019 (COVID-19) vaccine candidate designed by combining a phage-derived virus-like particle carrying bacterial RNA as TLR ligands with the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S protein as the target antigen. This PLA-based vaccine candidate induces robust neutralizing antibodies in both mice and non-human primates (NHPs). Using a NHP infection model, we demonstrate that the viral clearance is accelerated in vaccinated animals. In addition, the PLA-based vaccine induces a T helper 1 (Th1)-oriented response and a durable memory, supporting its potential for further clinical development.

引用

页数：20

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