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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-11-01
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| Series: | Cell Reports Medicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666379121003165 |
| _version_ | 1798033169821204480 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T20:24:51Z |
| format | Article |
| id | doaj.art-6677d99468274bcea69009e391b42d59 |
| institution | Directory Open Access Journal |
| issn | 2666-3791 |
| language | English |
| last_indexed | 2024-04-11T20:24:51Z |
| publishDate | 2021-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports Medicine |
| spelling | doaj.art-6677d99468274bcea69009e391b42d592022-12-22T04:04:41ZengElsevierCell Reports Medicine2666-37912021-11-01211100448A pathogen-like antigen-based vaccine confers immune protection against SARS-CoV-2 in non-human primatesChang Guo0Yanan Peng1Lin Lin2Xiaoyan Pan3Mengqi Fang4Yun Zhao5Keyan Bao6Runhan Li7Jianbao Han8Jiaorong Chen9Tian-Zhang Song10Xiao-Li Feng11Yahong Zhou12Gan Zhao13Leike Zhang14Yongtang Zheng15Ping Zhu16Haiying Hang17Linqi Zhang18Zhaolin Hua19Hongyu Deng20Baidong Hou21CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaCAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, ChinaCAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, ChinaState Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei 430071, ChinaComprehensive AIDS Research Center, Beijing Advanced Innovation Center for Structural Biology, School of Medicine and Vanke School of Public Health, Tsinghua University, Beijing 100084, ChinaKey Laboratory for Protein and Peptide Pharmaceuticals, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, ChinaCAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, ChinaCAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaNational High-level Bio-safety Research Center for Non-human Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650107, ChinaCAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaNational High-level Bio-safety Research Center for Non-human Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650107, ChinaNational High-level Bio-safety Research Center for Non-human Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650107, ChinaCAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, ChinaAdvaccine Biopharmaceuticals (Suzhou), Suzhou 215000, ChinaState Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei 430071, ChinaNational High-level Bio-safety Research Center for Non-human Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650107, ChinaCAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaUniversity of Chinese Academy of Sciences, Beijing 100049, China; Key Laboratory for Protein and Peptide Pharmaceuticals, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, ChinaComprehensive AIDS Research Center, Beijing Advanced Innovation Center for Structural Biology, School of Medicine and Vanke School of Public Health, Tsinghua University, Beijing 100084, ChinaCAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Corresponding authorCAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Corresponding authorCAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2666379121003165COVID-19SARS-CoV-2RBDvaccineB cellsToll-like receptor |
| spellingShingle | 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 Cell Reports Medicine COVID-19 SARS-CoV-2 RBD vaccine B cells Toll-like receptor |
| title | 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_short | 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 |
| topic | COVID-19 SARS-CoV-2 RBD vaccine B cells Toll-like receptor |
| url | http://www.sciencedirect.com/science/article/pii/S2666379121003165 |
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