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-Structure paper
タイトル | Discovery and characterization of potent pan-variant SARS-CoV-2 neutralizing antibodies from individuals with Omicron breakthrough infection. |
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ジャーナル・号・ページ | Nat Commun, Vol. 14, Issue 1, Page 3537, Year 2023 |
掲載日 | 2023年6月15日 |
著者 | Yu Guo / Guangshun Zhang / Qi Yang / Xiaowei Xie / Yang Lu / Xuelian Cheng / Hui Wang / Jingxi Liang / Jielin Tang / Yuxin Gao / Hang Shang / Jun Dai / Yongxia Shi / Jiaxi Zhou / Jun Zhou / Hangtian Guo / Haitao Yang / Jianwei Qi / Lijun Liu / Shihui Ma / Biao Zhang / Qianyu Huo / Yi Xie / Junping Wu / Fang Dong / Song Zhang / Zhiyong Lou / Yan Gao / Zidan Song / Wenming Wang / Zixian Sun / Xiaoming Yang / Dongsheng Xiong / Fengjiang Liu / Xinwen Chen / Ping Zhu / Ximo Wang / Tao Cheng / Zihe Rao / |
PubMed 要旨 | The SARS-CoV-2 Omicron variant evades most currently approved neutralizing antibodies (nAbs) and caused drastic decrease of plasma neutralizing activity elicited by vaccination or prior infection, ...The SARS-CoV-2 Omicron variant evades most currently approved neutralizing antibodies (nAbs) and caused drastic decrease of plasma neutralizing activity elicited by vaccination or prior infection, urging the need for the development of pan-variant antivirals. Breakthrough infection induces a hybrid immunological response with potentially broad, potent and durable protection against variants, therefore, convalescent plasma from breakthrough infection may provide a broadened repertoire for identifying elite nAbs. We performed single-cell RNA sequencing (scRNA-seq) and BCR sequencing (scBCR-seq) of B cells from BA.1 breakthrough-infected patients who received 2 or 3 previous doses of inactivated vaccine. Elite nAbs, mainly derived from the IGHV2-5 and IGHV3-66/53 germlines, showed potent neutralizing activity across Wuhan-Hu-1, Delta, Omicron sublineages BA.1 and BA.2 at picomolar NT values. Cryo-EM analysis revealed diverse modes of spike recognition and guides the design of cocktail therapy. A single injection of paired antibodies cocktail provided potent protection in the K18-hACE2 transgenic female mouse model of SARS-CoV-2 infection. |
リンク | Nat Commun / PubMed:37322000 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 2.51 - 3.8 Å |
構造データ | EMDB-34124, PDB-7yve: EMDB-34125, PDB-7yvf: EMDB-34126, PDB-7yvg: EMDB-34127, PDB-7yvh: EMDB-34128, PDB-7yvi: EMDB-34129, PDB-7yvj: EMDB-34130, PDB-7yvk: EMDB-34131, PDB-7yvl: EMDB-34132, PDB-7yvm: EMDB-34133, PDB-7yvn: EMDB-34134, PDB-7yvo: EMDB-34135, PDB-7yvp: EMDB-34181, PDB-8gou: PDB-8gpy: |
化合物 | ChemComp-NAG: ChemComp-HOH: |
由来 |
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キーワード | VIRAL PROTEIN/ANTIVIRAL PROTEIN / COVID-19 / spike glycoprotein / virus / VIRAL PROTEIN / VIRAL PROTEIN-ANTIVIRAL PROTEIN complex / ANTIVIRAL PROTEIN/VIRAL PROTEIN / ANTIVIRAL PROTEIN-VIRAL PROTEIN complex / Omicron / crystal strcture / neutralizing antibody / scFV |