8HQ7

Cryo-EM structure of SARS-CoV-2 Omicron Prototype RBD in complex with fab L4.65 and L5.34

8HQ7 の概要

• エントリーDOI: 10.2210/pdb8hq7/pdb
• EMDBエントリー: 34946
• 分子名称: Spike protein S1, fab L5.34, fab L4.65, ... (6 entities in total)
• 機能のキーワード: sars-cov-2, omicron prototype rbd, cryo-em structure, fab, immune system/viral protein, immune system-viral protein complex
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 117909.36

構造登録者

Gao, G.F.,Liu, S. (登録日: 2022-12-13, 公開日: 2023-12-20, 最終更新日: 2024-10-30)

主引用文献

Guo, S.,Zheng, Y.,Gao, Z.,Duan, M.,Liu, S.,Du, P.,Xu, X.,Xu, K.,Zhao, X.,Chai, Y.,Wang, P.,Zhao, Q.,Gao, G.F.,Dai, L.
Dosing interval regimen shapes potency and breadth of antibody repertoire after vaccination of SARS-CoV-2 RBD protein subunit vaccine.
Cell Discov, 9:79-79, 2023

PubMed Abstract: Vaccination with different vaccines has been implemented globally to counter the continuous COVID-19 pandemic. However, the vaccine-elicited antibodies have reduced efficiency against the highly mutated Omicron sub-variants. Previously, we developed a protein subunit COVID-19 vaccine called ZF2001, based on the dimeric receptor-binding domain (RBD). This vaccine has been administered using different dosing intervals in real-world setting. Some individuals received three doses of ZF2001, with a one-month interval between each dose, due to urgent clinical requirements. Others had an extended dosing interval of up to five months between the second and third dose, a standard vaccination regimen for the protein subunit vaccine against hepatitis B. In this study, we profile B cell responses in individuals who received three doses of ZF2001, and compared those with long or short dosing intervals. We observed that the long-interval group exhibited higher and broader serologic antibody responses. These responses were associated with the increased size and evolution of vaccine-elicited B-cell receptor repertoires, characterized by the elevation of expanded clonotypes and somatic hypermutations. Both groups of individuals generated substantial amounts of broadly neutralizing antibodies (bnAbs) against various SARS-CoV-2 variants, including Omicron sub-variants such as XBB. These bnAbs target four antigenic sites within the RBD. To determine the vulnerable site of SARS-CoV-2, we employed cryo-electron microscopy to identify the epitopes of highly potent bnAbs that targeted two major sites. Our findings provide immunological insights into the B cell responses elicited by RBD-based vaccine, and suggest that a vaccination regimen of prolonging time interval should be used in practice.

PubMed: 37507370
DOI: 10.1038/s41421-023-00585-5

実験手法

ELECTRON MICROSCOPY (2.7 Å)