Frontiers in Microbiology (Apr 2022)
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
- 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
Affiliations
- Liqin Liu
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
- Liqin Liu
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, China
- Tingting Chen
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
- Tingting Chen
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, China
- Lizhi Zhou
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
- Lizhi Zhou
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, China
- Jie Sun
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
- Jie Sun
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, China
- Yuqian Li
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
- Yuqian Li
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, China
- Meifeng Nie
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
- Meifeng Nie
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, China
- Hualong Xiong
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
- Hualong Xiong
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, China
- Yuhe Zhu
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
- Yuhe Zhu
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, China
- Wenhui Xue
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
- Wenhui Xue
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, China
- Yangtao Wu
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
- Yangtao Wu
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, China
- Tingting Li
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
- Tingting Li
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, China
- Tianying Zhang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
- Tianying Zhang
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, China
- Zhibo Kong
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
- Zhibo Kong
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, China
- Hai Yu
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
- Hai Yu
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, China
- Jun Zhang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
- Jun Zhang
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, China
- Ying Gu
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
- Ying Gu
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, China
- Qingbing Zheng
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
- Qingbing Zheng
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, China
- Qinjian Zhao
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
- Qinjian Zhao
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, China
- Ningshao Xia
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
- Ningshao Xia
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, China
- Shaowei Li
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
- Shaowei Li
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, China
- DOI
- https://doi.org/10.3389/fmicb.2022.854630
- Journal volume & issue
-
Vol. 13
Abstract
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.
Keywords
- SARS-CoV-2
- receptor binding domain
- CRM197 A domain
- Escherichia coli expression system
- adjuvant
- vaccine
