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-Structure paper
タイトル | Vaccination with SARS-CoV-2 spike protein lacking glycan shields elicits enhanced protective responses in animal models. |
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ジャーナル・号・ページ | Sci Transl Med, Vol. 14, Issue 639, Page eabm0899, Year 2022 |
掲載日 | 2022年4月6日 |
![]() | Han-Yi Huang / Hsin-Yu Liao / Xiaorui Chen / Szu-Wen Wang / Cheng-Wei Cheng / Md Shahed-Al-Mahmud / Yo-Min Liu / Arpita Mohapatra / Ting-Hua Chen / Jennifer M Lo / Yi-Min Wu / Hsiu-Hua Ma / Yi-Hsuan Chang / Ho-Yang Tsai / Yu-Chi Chou / Yi-Ping Hsueh / Ching-Yen Tsai / Pau-Yi Huang / Sui-Yuan Chang / Tai-Ling Chao / Han-Chieh Kao / Ya-Min Tsai / Yen-Hui Chen / Chung-Yi Wu / Jia-Tsrong Jan / Ting-Jen Rachel Cheng / Kuo-I Lin / Che Ma / Chi-Huey Wong / ![]() ![]() |
PubMed 要旨 | 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 ...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 (S) 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 S-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. |
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手法 | EM (単粒子) / X線回折 |
解像度 | 3.2 - 14.5 Å |
構造データ | ![]() EMDB-32825: EMDB-32832, PDB-7wuh: ![]() PDB-7wue: |
化合物 | ![]() ChemComp-NAG: |
由来 |
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![]() | VIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 / Spike / receptor binding domain / m31A7 / monoclonal antibody / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex / broad neutralization / mono-GlcNAc-decorated S vaccine / memory B cells |