https://scholars.lib.ntu.edu.tw/handle/123456789/610518
標題: | Vaccination with SARS-CoV-2 spike protein lacking glycan shields elicits enhanced protective responses in animal models | 作者: | Huang, Han-Yi Liao, Hsin-Yu Chen, Xiaorui Wang, Szu-Wen Cheng, Cheng-Wei Shahed-Al-Mahmud, Md Liu, Yo-Min Mohapatra, Arpita Chen, Ting-Hua Lo, Jennifer M Wu, Yi-Min Ma, Hsiu-Hua Chang, Yi-Hsuan Tsai, Ho-Yang Chou, Yu-Chi Hsueh, Yi-Ping Tsai, Ching-Yen Huang, Pau-Yi SUI-YUAN CHANG TAI-LING CHAO Kao, Han-Chieh Tsai, Ya-Min Chen, Yen-Hui Wu, Chung-Yi Jan, Jia-Tsrong Cheng, Ting-Jen Rachel Lin, Kuo-I Ma, Che Wong, Chi-Huey |
關鍵字: | CRYO-EM STRUCTURE; PATTERN-RECOGNITION; SECONDARY STRUCTURE; COVID-19 | 公開日期: | 6-四月-2022 | 出版社: | AMER ASSOC ADVANCEMENT SCIENCE | 卷: | 14 | 期: | 639 | 來源出版物: | Science translational medicine | 摘要: | A major challenge to end the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is to develop a broadly protective vaccine that elicits long-term immunity. As the key immunogen, the viral surface spike (S) protein is frequently mutated, and conserved epitopes are shielded by glycans. Here, we revealed that S protein glycosylation has site-differential effects on viral infectivity. We found that S protein generated by lung epithelial cells has glycoforms associated with increased infectivity. Compared to the fully glycosylated S protein, immunization of S protein with N-glycans trimmed to the mono-GlcNAc-decorated state (SMG) elicited stronger immune responses and better protection for human angiotensin-converting enzyme 2 (hACE2) transgenic mice against variants of concern (VOCs). In addition, a broadly neutralizing monoclonal antibody was identified from SMG-immunized mice that could neutralize wild-type SARS-CoV-2 and VOCs with subpicomolar potency. Together, these results demonstrate that removal of glycan shields to better expose the conserved sequences has the potential to be an effective and simple approach for developing a broadly protective SARS-CoV-2 vaccine. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/610518 | ISSN: | 1946-6234 | DOI: | 10.1126/scitranslmed.abm0899 |
顯示於: | 醫學檢驗暨生物技術學系 |
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