7WUH

SARS-CoV-2 Spike in complex with Fab of m31A7

Summary for 7WUH

• Entry DOI: 10.2210/pdb7wuh/pdb
• EMDB information: 32832
• Descriptor: Spike glycoprotein, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (14 entities in total)
• Functional Keywords: sars-cov-2, monoclonal antibody, broad neutralization, m31a7, mono-glcnac-decorated s vaccine, memory b cells, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 9
• Total formula weight: 588377.94

Authors

Chen, X.,Wu, Y.-M. (deposition date: 2022-02-08, release date: 2022-03-23, Last modification date: 2024-11-06)

Primary citation

Huang, H.Y.,Liao, H.Y.,Chen, X.,Wang, S.W.,Cheng, C.W.,Shahed-Al-Mahmud, M.,Liu, Y.M.,Mohapatra, A.,Chen, T.H.,Lo, J.M.,Wu, Y.M.,Ma, H.H.,Chang, Y.H.,Tsai, H.Y.,Chou, Y.C.,Hsueh, Y.P.,Tsai, C.Y.,Huang, P.Y.,Chang, S.Y.,Chao, T.L.,Kao, H.C.,Tsai, Y.M.,Chen, Y.H.,Wu, C.Y.,Jan, J.T.,Cheng, T.R.,Lin, K.I.,Ma, C.,Wong, C.H.
Vaccination with SARS-CoV-2 spike protein lacking glycan shields elicits enhanced protective responses in animal models.
Sci Transl Med, 14:eabm0899-eabm0899, 2022

PubMed Abstract: 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.

PubMed: 35230146
DOI: 10.1126/scitranslmed.abm0899

Experimental method

ELECTRON MICROSCOPY (4.7 Å)