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-Structure paper
タイトル | Structural insights into broadly neutralizing antibodies elicited by hybrid immunity against SARS-CoV-2. |
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ジャーナル・号・ページ | Emerg Microbes Infect, Vol. 12, Issue 1, Page 2146538, Year 2023 |
掲載日 | 2023年1月5日 |
著者 | Mengxiao Luo / Biao Zhou / Eswar R Reddem / Bingjie Tang / Bohao Chen / Runhong Zhou / Hang Liu / Lihong Liu / Phinikoula S Katsamba / Ka-Kit Au / Hiu-On Man / Kelvin Kai-Wang To / Kwok-Yung Yuen / Lawrence Shapiro / Shangyu Dang / David D Ho / Zhiwei Chen / |
PubMed 要旨 | Increasing spread by SARS-CoV-2 Omicron variants challenges existing vaccines and broadly reactive neutralizing antibodies (bNAbs) against COVID-19. Here we determine the diversity, potency, breadth ...Increasing spread by SARS-CoV-2 Omicron variants challenges existing vaccines and broadly reactive neutralizing antibodies (bNAbs) against COVID-19. Here we determine the diversity, potency, breadth and structural insights of bNAbs derived from memory B cells of BNT162b2-vaccinee after homogeneous Omicron BA.1 breakthrough infection. The infection activates diverse memory B cell clonotypes for generating potent class I/II and III bNAbs with new epitopes mapped to the receptor-binding domain (RBD). The top eight bNAbs neutralize wildtype and BA.1 potently but display divergent IgH/IgL sequences and neuralization profiles against other variants of concern (VOCs). Two of them (P2D9 and P3E6) belonging to class III NAbs display comparable potency against BA.4/BA.5, although structural analysis reveals distinct modes of action. P3E6 neutralizes all variants tested through a unique bivalent interaction with two RBDs. Our findings provide new insights into hybrid immunity on BNT162b2-induced diverse memory B cells in response to Omicron breakthrough infection for generating diverse bNAbs with distinct structural basis. |
リンク | Emerg Microbes Infect / PubMed:36354024 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 3.2 - 4 Å |
構造データ | EMDB-27775, PDB-8dxs: EMDB-33892: Omicron spike trimer bound with P3E6 (Local Refinement) EMDB-33893: Omicron Spike trimer bound with up P3E6 Fab (2 RBDs up and 1 RBD down) EMDB-33894: Omicron Spike trimer bound with side P3E6 Fab (1 RBD up and 2 RBDs down) PDB-8dw9: PDB-8dwa: |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | VIRAL PROTEIN/IMMUNE SYSTEM / COVID-19 / P3E6 / Omicron / spike protein / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex / SarbecoVirus / WIV1 RBD / Spike glycoprotein / Receptor Binding Protein / Neutralizing antibody / potent / 10-40 / Fab / SARS-CoV-2 / RBD / 10-28 / Fusion protein / RBD-directed antibody / P2B4 / IMMUNE SYSTEM |