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

Summary: 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) const...

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Autores principales: Chang Guo, Yanan Peng, Lin Lin, Xiaoyan Pan, Mengqi Fang, Yun Zhao, Keyan Bao, Runhan Li, Jianbao Han, Jiaorong Chen, Tian-Zhang Song, Xiao-Li Feng, Yahong Zhou, Gan Zhao, Leike Zhang, Yongtang Zheng, Ping Zhu, Haiying Hang, Linqi Zhang, Zhaolin Hua, Hongyu Deng, Baidong Hou
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Publicado: Elsevier 2021
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Acceso en línea:https://doaj.org/article/6677d99468274bcea69009e391b42d59
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spelling oai:doaj.org-article:6677d99468274bcea69009e391b42d592021-11-18T04:52:16ZA pathogen-like antigen-based vaccine confers immune protection against SARS-CoV-2 in non-human primates2666-379110.1016/j.xcrm.2021.100448https://doaj.org/article/6677d99468274bcea69009e391b42d592021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2666379121003165https://doaj.org/toc/2666-3791Summary: 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.Chang GuoYanan PengLin LinXiaoyan PanMengqi FangYun ZhaoKeyan BaoRunhan LiJianbao HanJiaorong ChenTian-Zhang SongXiao-Li FengYahong ZhouGan ZhaoLeike ZhangYongtang ZhengPing ZhuHaiying HangLinqi ZhangZhaolin HuaHongyu DengBaidong HouElsevierarticleCOVID-19SARS-CoV-2RBDvaccineB cellsToll-like receptorMedicine (General)R5-920ENCell Reports Medicine, Vol 2, Iss 11, Pp 100448- (2021)
institution DOAJ
collection DOAJ
language EN
topic COVID-19
SARS-CoV-2
RBD
vaccine
B cells
Toll-like receptor
Medicine (General)
R5-920
spellingShingle COVID-19
SARS-CoV-2
RBD
vaccine
B cells
Toll-like receptor
Medicine (General)
R5-920
Chang Guo
Yanan Peng
Lin Lin
Xiaoyan Pan
Mengqi Fang
Yun Zhao
Keyan Bao
Runhan Li
Jianbao Han
Jiaorong Chen
Tian-Zhang Song
Xiao-Li Feng
Yahong Zhou
Gan Zhao
Leike Zhang
Yongtang Zheng
Ping Zhu
Haiying Hang
Linqi Zhang
Zhaolin Hua
Hongyu Deng
Baidong Hou
A pathogen-like antigen-based vaccine confers immune protection against SARS-CoV-2 in non-human primates
description Summary: 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.
format article
author Chang Guo
Yanan Peng
Lin Lin
Xiaoyan Pan
Mengqi Fang
Yun Zhao
Keyan Bao
Runhan Li
Jianbao Han
Jiaorong Chen
Tian-Zhang Song
Xiao-Li Feng
Yahong Zhou
Gan Zhao
Leike Zhang
Yongtang Zheng
Ping Zhu
Haiying Hang
Linqi Zhang
Zhaolin Hua
Hongyu Deng
Baidong Hou
author_facet Chang Guo
Yanan Peng
Lin Lin
Xiaoyan Pan
Mengqi Fang
Yun Zhao
Keyan Bao
Runhan Li
Jianbao Han
Jiaorong Chen
Tian-Zhang Song
Xiao-Li Feng
Yahong Zhou
Gan Zhao
Leike Zhang
Yongtang Zheng
Ping Zhu
Haiying Hang
Linqi Zhang
Zhaolin Hua
Hongyu Deng
Baidong Hou
author_sort Chang Guo
title A pathogen-like antigen-based vaccine confers immune protection against SARS-CoV-2 in non-human primates
title_short A pathogen-like antigen-based vaccine confers immune protection against SARS-CoV-2 in non-human primates
title_full A pathogen-like antigen-based vaccine confers immune protection against SARS-CoV-2 in non-human primates
title_fullStr A pathogen-like antigen-based vaccine confers immune protection against SARS-CoV-2 in non-human primates
title_full_unstemmed A pathogen-like antigen-based vaccine confers immune protection against SARS-CoV-2 in non-human primates
title_sort pathogen-like antigen-based vaccine confers immune protection against sars-cov-2 in non-human primates
publisher Elsevier
publishDate 2021
url https://doaj.org/article/6677d99468274bcea69009e391b42d59
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