PF-D-Trimer, a protective SARS-CoV-2 subunit vaccine: immunogenicity and application
Abstract The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had and continues to have a significant impact on global public health. One of the characteristics of SARS-CoV-2 is a surface homotrimeric spike protein, which is primarily responsible for the host immune response upon infection. He...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-03-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-023-00636-8 |
| _version_ | 1827608177191944192 |
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| author | Zhihao Zhang Jinhu Zhou Peng Ni Bing Hu Normand Jolicoeur Shuang Deng Qian Xiao Qian He Gai Li Yan Xia Mei Liu Cong Wang Zhizheng Fang Nan Xia Zhe-Rui Zhang Bo Zhang Kun Cai Yan Xu Binlei Liu |
| author_facet | Zhihao Zhang Jinhu Zhou Peng Ni Bing Hu Normand Jolicoeur Shuang Deng Qian Xiao Qian He Gai Li Yan Xia Mei Liu Cong Wang Zhizheng Fang Nan Xia Zhe-Rui Zhang Bo Zhang Kun Cai Yan Xu Binlei Liu |
| author_sort | Zhihao Zhang |
| collection | DOAJ |
| description | Abstract The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had and continues to have a significant impact on global public health. One of the characteristics of SARS-CoV-2 is a surface homotrimeric spike protein, which is primarily responsible for the host immune response upon infection. Here we present the preclinical studies of a broadly protective SARS-CoV-2 subunit vaccine developed from our trimer domain platform using the Delta spike protein, from antigen design through purification, vaccine evaluation and manufacturability. The pre-fusion trimerized Delta spike protein, PF-D-Trimer, was highly expressed in Chinese hamster ovary (CHO) cells, purified by a rapid one-step anti-Trimer Domain monoclonal antibody immunoaffinity process and prepared as a vaccine formulation with an adjuvant. Immunogenicity studies have shown that this vaccine candidate induces robust immune responses in mouse, rat and Syrian hamster models. It also protects K18-hACE2 transgenic mice in a homologous viral challenge. Neutralizing antibodies induced by this vaccine show cross-reactivity against the ancestral WA1, Delta and several Omicrons, including BA.5.2. The formulated PF-D Trimer is stable for up to six months without refrigeration. The Trimer Domain platform was proven to be a key technology in the rapid production of PF-D-Trimer vaccine and may be crucial to accelerate the development and accessibility of updated versions of SARS-CoV-2 vaccines. |
| first_indexed | 2024-03-09T07:07:18Z |
| format | Article |
| id | doaj.art-6acfff514dc147d08a313a0fae3fb0b5 |
| institution | Directory Open Access Journal |
| issn | 2059-0105 |
| language | English |
| last_indexed | 2024-03-09T07:07:18Z |
| publishDate | 2023-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj.art-6acfff514dc147d08a313a0fae3fb0b52023-12-03T09:27:38ZengNature Portfolionpj Vaccines2059-01052023-03-018111310.1038/s41541-023-00636-8PF-D-Trimer, a protective SARS-CoV-2 subunit vaccine: immunogenicity and applicationZhihao Zhang0Jinhu Zhou1Peng Ni2Bing Hu3Normand Jolicoeur4Shuang Deng5Qian Xiao6Qian He7Gai Li8Yan Xia9Mei Liu10Cong Wang11Zhizheng Fang12Nan Xia13Zhe-Rui Zhang14Bo Zhang15Kun Cai16Yan Xu17Binlei Liu18National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei Key Laboratory of Industrial Microbiology, Hubei University of TechnologyWuhan Binhui Biopharmaceutical Co., LtdWuhan Binhui Biopharmaceutical Co., LtdInstitute of Health Inspection and Testing, Hubei Provincial Centre for Disease Control and Prevention (Hubei CDC)Wuhan Binhui Biopharmaceutical Co., LtdNova Biologiques Inc. MontréalWuhan Binhui Biopharmaceutical Co., LtdWuhan Binhui Biopharmaceutical Co., LtdNova Biologiques Inc. MontréalNova Biologiques Inc. MontréalNational “111” Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei Key Laboratory of Industrial Microbiology, Hubei University of TechnologyWuhan Binhui Biopharmaceutical Co., LtdWuhan Binhui Biopharmaceutical Co., LtdWuhan Binhui Biopharmaceutical Co., LtdWuhan Institute of Virology, Chinese Academy of SciencesWuhan Binhui Biopharmaceutical Co., LtdInstitute of Health Inspection and Testing, Hubei Provincial Centre for Disease Control and Prevention (Hubei CDC)Wuhan Binhui Biopharmaceutical Co., LtdNational “111” Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei Key Laboratory of Industrial Microbiology, Hubei University of TechnologyAbstract The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had and continues to have a significant impact on global public health. One of the characteristics of SARS-CoV-2 is a surface homotrimeric spike protein, which is primarily responsible for the host immune response upon infection. Here we present the preclinical studies of a broadly protective SARS-CoV-2 subunit vaccine developed from our trimer domain platform using the Delta spike protein, from antigen design through purification, vaccine evaluation and manufacturability. The pre-fusion trimerized Delta spike protein, PF-D-Trimer, was highly expressed in Chinese hamster ovary (CHO) cells, purified by a rapid one-step anti-Trimer Domain monoclonal antibody immunoaffinity process and prepared as a vaccine formulation with an adjuvant. Immunogenicity studies have shown that this vaccine candidate induces robust immune responses in mouse, rat and Syrian hamster models. It also protects K18-hACE2 transgenic mice in a homologous viral challenge. Neutralizing antibodies induced by this vaccine show cross-reactivity against the ancestral WA1, Delta and several Omicrons, including BA.5.2. The formulated PF-D Trimer is stable for up to six months without refrigeration. The Trimer Domain platform was proven to be a key technology in the rapid production of PF-D-Trimer vaccine and may be crucial to accelerate the development and accessibility of updated versions of SARS-CoV-2 vaccines.https://doi.org/10.1038/s41541-023-00636-8 |
| spellingShingle | Zhihao Zhang Jinhu Zhou Peng Ni Bing Hu Normand Jolicoeur Shuang Deng Qian Xiao Qian He Gai Li Yan Xia Mei Liu Cong Wang Zhizheng Fang Nan Xia Zhe-Rui Zhang Bo Zhang Kun Cai Yan Xu Binlei Liu PF-D-Trimer, a protective SARS-CoV-2 subunit vaccine: immunogenicity and application npj Vaccines |
| title | PF-D-Trimer, a protective SARS-CoV-2 subunit vaccine: immunogenicity and application |
| title_full | PF-D-Trimer, a protective SARS-CoV-2 subunit vaccine: immunogenicity and application |
| title_fullStr | PF-D-Trimer, a protective SARS-CoV-2 subunit vaccine: immunogenicity and application |
| title_full_unstemmed | PF-D-Trimer, a protective SARS-CoV-2 subunit vaccine: immunogenicity and application |
| title_short | PF-D-Trimer, a protective SARS-CoV-2 subunit vaccine: immunogenicity and application |
| title_sort | pf d trimer a protective sars cov 2 subunit vaccine immunogenicity and application |
| url | https://doi.org/10.1038/s41541-023-00636-8 |
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