The University Grants Committee, Research Grants Council (RGC)
香港
引用
ジャーナル: Nat Commun / 年: 2022 タイトル: A broadly neutralizing antibody protects Syrian hamsters against SARS-CoV-2 Omicron challenge. 著者: Biao Zhou / Runhong Zhou / Bingjie Tang / Jasper Fuk-Woo Chan / Mengxiao Luo / Qiaoli Peng / Shuofeng Yuan / Hang Liu / Bobo Wing-Yee Mok / Bohao Chen / Pui Wang / Vincent Kwok-Man Poon / Hin ...著者: Biao Zhou / Runhong Zhou / Bingjie Tang / Jasper Fuk-Woo Chan / Mengxiao Luo / Qiaoli Peng / Shuofeng Yuan / Hang Liu / Bobo Wing-Yee Mok / Bohao Chen / Pui Wang / Vincent Kwok-Man Poon / Hin Chu / Chris Chung-Sing Chan / Jessica Oi-Ling Tsang / Chris Chun-Yiu Chan / Ka-Kit Au / Hiu-On Man / Lu Lu / Kelvin Kai-Wang To / Honglin Chen / Kwok-Yung Yuen / Shangyu Dang / Zhiwei Chen / 要旨: The strikingly high transmissibility and antibody evasion of SARS-CoV-2 Omicron variants have posed great challenges to the efficacy of current vaccines and antibody immunotherapy. Here, we screen 34 ...The strikingly high transmissibility and antibody evasion of SARS-CoV-2 Omicron variants have posed great challenges to the efficacy of current vaccines and antibody immunotherapy. Here, we screen 34 BNT162b2-vaccinees and isolate a public broadly neutralizing antibody ZCB11 derived from the IGHV1-58 family. ZCB11 targets viral receptor-binding domain specifically and neutralizes all SARS-CoV-2 variants of concern, especially with great potency against authentic Omicron and Delta variants. Pseudovirus-based mapping of 57 naturally occurred spike mutations or deletions reveals that S371L results in 11-fold neutralization resistance, but it is rescued by compensating mutations in Omicron variants. Cryo-EM analysis demonstrates that ZCB11 heavy chain predominantly interacts with Omicron spike trimer with receptor-binding domain in up conformation blocking ACE2 binding. In addition, prophylactic or therapeutic ZCB11 administration protects lung infection against Omicron viral challenge in golden Syrian hamsters. These results suggest that vaccine-induced ZCB11 is a promising broadly neutralizing antibody for biomedical interventions against pandemic SARS-CoV-2.
全体 : The complex of ZCB11 against Fab SARS-CoV-2 Omicron Spike
全体
名称: The complex of ZCB11 against Fab SARS-CoV-2 Omicron Spike
要素
複合体: The complex of ZCB11 against Fab SARS-CoV-2 Omicron Spike
複合体: The ZCB11 fab
複合体: The spike protein of SARS-CoV-2 Omicron variant
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超分子 #1: The complex of ZCB11 against Fab SARS-CoV-2 Omicron Spike
超分子
名称: The complex of ZCB11 against Fab SARS-CoV-2 Omicron Spike タイプ: complex / キメラ: Yes / ID: 1 / 親要素: 0 / 含まれる分子: #1-#3 詳細: the formation of Spike-Fab complex, the Omicron Spike trimer (2.2mg/ml) was mixed with Fab (2.9mg/ml) in 1x PBS buffer at a molar ratio of 1:1.2 (Spike monomer:Fab) and incubated on ice for 40 minutes.
由来(天然)
生物種: Homo sapiens (ヒト)
組換発現
生物種: Homo sapiens (ヒト)
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超分子 #2: The ZCB11 fab
超分子
名称: The ZCB11 fab / タイプ: complex / キメラ: Yes / ID: 2 / 親要素: 1 / 含まれる分子: #2-#3
由来(天然)
生物種: Severe acute respiratory syndrome coronavirus 2 (ウイルス)
組換発現
生物種: Homo sapiens (ヒト)
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超分子 #3: The spike protein of SARS-CoV-2 Omicron variant
超分子
名称: The spike protein of SARS-CoV-2 Omicron variant / タイプ: complex / キメラ: Yes / ID: 3 / 親要素: 1 / 含まれる分子: #1
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実験情報
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構造解析
手法
クライオ電子顕微鏡法
解析
単粒子再構成法
試料の集合状態
particle
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試料調製
緩衝液
pH: 7.4
凍結
凍結剤: ETHANE / チャンバー内湿度: 100 %
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電子顕微鏡法
顕微鏡
FEI TITAN KRIOS
撮影
フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均露光時間: 4.5 sec. / 平均電子線量: 50.0 e/Å2