A Bacterially Expressed SARS-CoV-2 Receptor Binding Domain Fused With Cross-Reacting Material 197 A-Domain Elicits High Level of Neutralizing Antibodies in Mice
The Coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented public health crisis worldwide. Although several vaccines are available, the global supply of vaccines, particularly within developing countries, is inadequate, and this necessitates a need for the development of less expensi...
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2022.854630/full |
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| author | Liqin Liu Liqin Liu Tingting Chen Tingting Chen Lizhi Zhou Lizhi Zhou Jie Sun Jie Sun Yuqian Li Yuqian Li Meifeng Nie Meifeng Nie Hualong Xiong Hualong Xiong Yuhe Zhu Yuhe Zhu Wenhui Xue Wenhui Xue Yangtao Wu Yangtao Wu Tingting Li Tingting Li Tianying Zhang Tianying Zhang Zhibo Kong Zhibo Kong Hai Yu Hai Yu Jun Zhang Jun Zhang Ying Gu Ying Gu Qingbing Zheng Qingbing Zheng Qinjian Zhao Qinjian Zhao Ningshao Xia Ningshao Xia Shaowei Li Shaowei Li |
| author_facet | Liqin Liu Liqin Liu Tingting Chen Tingting Chen Lizhi Zhou Lizhi Zhou Jie Sun Jie Sun Yuqian Li Yuqian Li Meifeng Nie Meifeng Nie Hualong Xiong Hualong Xiong Yuhe Zhu Yuhe Zhu Wenhui Xue Wenhui Xue Yangtao Wu Yangtao Wu Tingting Li Tingting Li Tianying Zhang Tianying Zhang Zhibo Kong Zhibo Kong Hai Yu Hai Yu Jun Zhang Jun Zhang Ying Gu Ying Gu Qingbing Zheng Qingbing Zheng Qinjian Zhao Qinjian Zhao Ningshao Xia Ningshao Xia Shaowei Li Shaowei Li |
| author_sort | Liqin Liu |
| collection | DOAJ |
| description | The Coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented public health crisis worldwide. Although several vaccines are available, the global supply of vaccines, particularly within developing countries, is inadequate, and this necessitates a need for the development of less expensive, accessible vaccine options. To this end, here, we used the Escherichia coli expression system to produce a recombinant fusion protein comprising the receptor binding domain (RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; residues 319–541) and the fragment A domain of Cross-Reacting Material 197 (CRM197); hereafter, CRMA-RBD. We show that this CRMA-RBD fusion protein has excellent physicochemical properties and strong reactivity with COVID-19 convalescent sera and representative neutralizing antibodies (nAbs). Furthermore, compared with the use of a traditional aluminum adjuvant, we find that combining the CRMA-RBD protein with a nitrogen bisphosphonate-modified zinc-aluminum hybrid adjuvant (FH-002C-Ac) leads to stronger humoral immune responses in mice, with 4-log neutralizing antibody titers. Overall, our study highlights the value of this E. coli-expressed fusion protein as an alternative vaccine candidate strategy against COVID-19. |
| first_indexed | 2024-12-10T09:52:17Z |
| format | Article |
| id | doaj.art-51a2abad0eee44b1bf5241b66035a219 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-10T09:52:17Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-51a2abad0eee44b1bf5241b66035a2192022-12-22T01:53:38ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-04-011310.3389/fmicb.2022.854630854630A Bacterially Expressed SARS-CoV-2 Receptor Binding Domain Fused With Cross-Reacting Material 197 A-Domain Elicits High Level of Neutralizing Antibodies in MiceLiqin Liu0Liqin Liu1Tingting Chen2Tingting Chen3Lizhi Zhou4Lizhi Zhou5Jie Sun6Jie Sun7Yuqian Li8Yuqian Li9Meifeng Nie10Meifeng Nie11Hualong Xiong12Hualong Xiong13Yuhe Zhu14Yuhe Zhu15Wenhui Xue16Wenhui Xue17Yangtao Wu18Yangtao Wu19Tingting Li20Tingting Li21Tianying Zhang22Tianying Zhang23Zhibo Kong24Zhibo Kong25Hai Yu26Hai Yu27Jun Zhang28Jun Zhang29Ying Gu30Ying Gu31Qingbing Zheng32Qingbing Zheng33Qinjian Zhao34Qinjian Zhao35Ningshao Xia36Ningshao Xia37Shaowei Li38Shaowei Li39State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, ChinaNational Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, ChinaNational Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, ChinaNational Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, ChinaNational Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, ChinaNational Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, ChinaNational Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, ChinaNational Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, ChinaNational Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, ChinaNational Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, ChinaNational Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, ChinaNational Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, ChinaNational Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, ChinaNational Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, ChinaNational Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, ChinaNational Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, ChinaNational Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, ChinaNational Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, ChinaNational Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, ChinaNational Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, ChinaNational Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, ChinaThe Coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented public health crisis worldwide. Although several vaccines are available, the global supply of vaccines, particularly within developing countries, is inadequate, and this necessitates a need for the development of less expensive, accessible vaccine options. To this end, here, we used the Escherichia coli expression system to produce a recombinant fusion protein comprising the receptor binding domain (RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; residues 319–541) and the fragment A domain of Cross-Reacting Material 197 (CRM197); hereafter, CRMA-RBD. We show that this CRMA-RBD fusion protein has excellent physicochemical properties and strong reactivity with COVID-19 convalescent sera and representative neutralizing antibodies (nAbs). Furthermore, compared with the use of a traditional aluminum adjuvant, we find that combining the CRMA-RBD protein with a nitrogen bisphosphonate-modified zinc-aluminum hybrid adjuvant (FH-002C-Ac) leads to stronger humoral immune responses in mice, with 4-log neutralizing antibody titers. Overall, our study highlights the value of this E. coli-expressed fusion protein as an alternative vaccine candidate strategy against COVID-19.https://www.frontiersin.org/articles/10.3389/fmicb.2022.854630/fullSARS-CoV-2receptor binding domainCRM197 A domainEscherichia coli expression systemadjuvantvaccine |
| spellingShingle | Liqin Liu Liqin Liu Tingting Chen Tingting Chen Lizhi Zhou Lizhi Zhou Jie Sun Jie Sun Yuqian Li Yuqian Li Meifeng Nie Meifeng Nie Hualong Xiong Hualong Xiong Yuhe Zhu Yuhe Zhu Wenhui Xue Wenhui Xue Yangtao Wu Yangtao Wu Tingting Li Tingting Li Tianying Zhang Tianying Zhang Zhibo Kong Zhibo Kong Hai Yu Hai Yu Jun Zhang Jun Zhang Ying Gu Ying Gu Qingbing Zheng Qingbing Zheng Qinjian Zhao Qinjian Zhao Ningshao Xia Ningshao Xia Shaowei Li Shaowei Li A Bacterially Expressed SARS-CoV-2 Receptor Binding Domain Fused With Cross-Reacting Material 197 A-Domain Elicits High Level of Neutralizing Antibodies in Mice Frontiers in Microbiology SARS-CoV-2 receptor binding domain CRM197 A domain Escherichia coli expression system adjuvant vaccine |
| title | A Bacterially Expressed SARS-CoV-2 Receptor Binding Domain Fused With Cross-Reacting Material 197 A-Domain Elicits High Level of Neutralizing Antibodies in Mice |
| title_full | A Bacterially Expressed SARS-CoV-2 Receptor Binding Domain Fused With Cross-Reacting Material 197 A-Domain Elicits High Level of Neutralizing Antibodies in Mice |
| title_fullStr | A Bacterially Expressed SARS-CoV-2 Receptor Binding Domain Fused With Cross-Reacting Material 197 A-Domain Elicits High Level of Neutralizing Antibodies in Mice |
| title_full_unstemmed | A Bacterially Expressed SARS-CoV-2 Receptor Binding Domain Fused With Cross-Reacting Material 197 A-Domain Elicits High Level of Neutralizing Antibodies in Mice |
| title_short | A Bacterially Expressed SARS-CoV-2 Receptor Binding Domain Fused With Cross-Reacting Material 197 A-Domain Elicits High Level of Neutralizing Antibodies in Mice |
| title_sort | bacterially expressed sars cov 2 receptor binding domain fused with cross reacting material 197 a domain elicits high level of neutralizing antibodies in mice |
| topic | SARS-CoV-2 receptor binding domain CRM197 A domain Escherichia coli expression system adjuvant vaccine |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2022.854630/full |
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