Display of receptor-binding domain of SARS-CoV-2 Spike protein variants on the Saccharomyces cerevisiae cell surface
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a significant global human health threat. The most effective way to end the pandemic is through timely vaccination. In this study, the receptor-binding domains (RBDs)...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.935573/full |
| _version_ | 1811310594219835392 |
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| author | Hongguan Xing Hongguan Xing Liyan Zhu Liyan Zhu Pingping Wang Guoping Zhao Guoping Zhao Zhihua Zhou Yi Yang Hong Zou Xing Yan Xing Yan |
| author_facet | Hongguan Xing Hongguan Xing Liyan Zhu Liyan Zhu Pingping Wang Guoping Zhao Guoping Zhao Zhihua Zhou Yi Yang Hong Zou Xing Yan Xing Yan |
| author_sort | Hongguan Xing |
| collection | DOAJ |
| description | Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a significant global human health threat. The most effective way to end the pandemic is through timely vaccination. In this study, the receptor-binding domains (RBDs) of Spike protein of the initial strain of SARS-CoV-2 and its variants, B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.1 (Kappa), were successfully displayed on the surface of a Saccharomyces cerevisiae strain for development as a vaccine candidate. To rapidly express the recombinant protein and avoid the need for expensive galactose as an inducer, the gal80 gene of S. cerevisiae was knocked out, and the conventional 72-h culture period was thus successfully shortened to 24 h. Mice vaccinated against variant B.1.617.1 showed robust humoral and cellular immune responses. Moreover, the antiserum in the B.1.671.1 group had neutralizing activity against wild-type RBD and high binding titers against RBD mutants of variants B.1.351 and B.1.1.7. Double deglycosylation at N331Q and N343Q resulted in marked reduction of the affinity of RBD binding to angiotensin converting enzyme 2 (ACE2) and escaped antibody neutralization. This study demonstrates that yeast surface display technology can provide an alternative approach to rapid large-scale preparation of promising SARS-CoV-2 vaccine candidates at low cost. |
| first_indexed | 2024-04-13T10:01:38Z |
| format | Article |
| id | doaj.art-412fbe00641e4b208bd508b66f0f63b8 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T10:01:38Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-412fbe00641e4b208bd508b66f0f63b82022-12-22T02:51:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.935573935573Display of receptor-binding domain of SARS-CoV-2 Spike protein variants on the Saccharomyces cerevisiae cell surfaceHongguan Xing0Hongguan Xing1Liyan Zhu2Liyan Zhu3Pingping Wang4Guoping Zhao5Guoping Zhao6Zhihua Zhou7Yi Yang8Hong Zou9Xing Yan10Xing Yan11Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, ChinaChinese Academy of Science-Key Laboratory of Synthetic Biology, Chinese Academy of Science Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, ChinaKey Laboratory of Medical Molecular Virology of Ministry of Education/National Health Commission, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Process Technology, Zhejiang Hongguan Bio-pharma Co., Ltd., Jiaxing, ChinaChinese Academy of Science-Key Laboratory of Synthetic Biology, Chinese Academy of Science Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, ChinaChinese Academy of Science-Key Laboratory of Synthetic Biology, Chinese Academy of Science Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, ChinaKey Laboratory of Medical Molecular Virology of Ministry of Education/National Health Commission, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, ChinaChinese Academy of Science-Key Laboratory of Synthetic Biology, Chinese Academy of Science Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, ChinaShanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, ChinaChinese Academy of Sciences Engineering Laboratory for Nutrition, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, ChinaShanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, ChinaChinese Academy of Science-Key Laboratory of Synthetic Biology, Chinese Academy of Science Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, ChinaSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a significant global human health threat. The most effective way to end the pandemic is through timely vaccination. In this study, the receptor-binding domains (RBDs) of Spike protein of the initial strain of SARS-CoV-2 and its variants, B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.1 (Kappa), were successfully displayed on the surface of a Saccharomyces cerevisiae strain for development as a vaccine candidate. To rapidly express the recombinant protein and avoid the need for expensive galactose as an inducer, the gal80 gene of S. cerevisiae was knocked out, and the conventional 72-h culture period was thus successfully shortened to 24 h. Mice vaccinated against variant B.1.617.1 showed robust humoral and cellular immune responses. Moreover, the antiserum in the B.1.671.1 group had neutralizing activity against wild-type RBD and high binding titers against RBD mutants of variants B.1.351 and B.1.1.7. Double deglycosylation at N331Q and N343Q resulted in marked reduction of the affinity of RBD binding to angiotensin converting enzyme 2 (ACE2) and escaped antibody neutralization. This study demonstrates that yeast surface display technology can provide an alternative approach to rapid large-scale preparation of promising SARS-CoV-2 vaccine candidates at low cost.https://www.frontiersin.org/articles/10.3389/fimmu.2022.935573/fullSARS-CoV-2receptor-binding domainyeast surface displayvaccineB.1.671.1 |
| spellingShingle | Hongguan Xing Hongguan Xing Liyan Zhu Liyan Zhu Pingping Wang Guoping Zhao Guoping Zhao Zhihua Zhou Yi Yang Hong Zou Xing Yan Xing Yan Display of receptor-binding domain of SARS-CoV-2 Spike protein variants on the Saccharomyces cerevisiae cell surface Frontiers in Immunology SARS-CoV-2 receptor-binding domain yeast surface display vaccine B.1.671.1 |
| title | Display of receptor-binding domain of SARS-CoV-2 Spike protein variants on the Saccharomyces cerevisiae cell surface |
| title_full | Display of receptor-binding domain of SARS-CoV-2 Spike protein variants on the Saccharomyces cerevisiae cell surface |
| title_fullStr | Display of receptor-binding domain of SARS-CoV-2 Spike protein variants on the Saccharomyces cerevisiae cell surface |
| title_full_unstemmed | Display of receptor-binding domain of SARS-CoV-2 Spike protein variants on the Saccharomyces cerevisiae cell surface |
| title_short | Display of receptor-binding domain of SARS-CoV-2 Spike protein variants on the Saccharomyces cerevisiae cell surface |
| title_sort | display of receptor binding domain of sars cov 2 spike protein variants on the saccharomyces cerevisiae cell surface |
| topic | SARS-CoV-2 receptor-binding domain yeast surface display vaccine B.1.671.1 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.935573/full |
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