7MEM

CryoEM structure of monoclonal Fab 045-09 2B05 binding the lateral patch of influenza virus H1 HA

7MEM の概要

• エントリーDOI: 10.2210/pdb7mem/pdb
• EMDBエントリー: 23792 23793 23794 23795 23796 23797 23798
• 分子名称: Hemagglutinin HA1 chain, Light chain of monoclonal antibody 045-09 2B05, Heavy chain of monoclonal antibody 045-09 2B05, ... (7 entities in total)
• 機能のキーワード: hemagglutinin, monoclonal antibody, influenza virus, immune system, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Influenza A virus (strain swl A/California/04/2009 H1N1); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 247328.77

構造登録者

Han, J.,Ward, A. (登録日: 2021-04-06, 公開日: 2021-07-28, 最終更新日: 2024-11-20)

主引用文献

Guthmiller, J.J.,Han, J.,Li, L.,Freyn, A.W.,Liu, S.T.H.,Stovicek, O.,Stamper, C.T.,Dugan, H.L.,Tepora, M.E.,Utset, H.A.,Bitar, D.J.,Hamel, N.J.,Changrob, S.,Zheng, N.Y.,Huang, M.,Krammer, F.,Nachbagauer, R.,Palese, P.,Ward, A.B.,Wilson, P.C.
First exposure to the pandemic H1N1 virus induced broadly neutralizing antibodies targeting hemagglutinin head epitopes.
Sci Transl Med, 13:-, 2021

PubMed Abstract: Broadly neutralizing antibodies are critical for protection against both drifted and shifted influenza viruses. Here, we reveal that first exposure to the 2009 pandemic H1N1 influenza virus recalls memory B cells that are specific to the conserved receptor-binding site (RBS) or lateral patch epitopes of the hemagglutinin (HA) head domain. Monoclonal antibodies (mAbs) generated against these epitopes are broadly neutralizing against H1N1 viruses spanning 40 years of viral evolution and provide potent protection in vivo. Lateral patch-targeting antibodies demonstrated near universal binding to H1 viruses, and RBS-binding antibodies commonly cross-reacted with H3N2 viruses and influenza B viruses. Lateral patch-targeting mAbs were restricted to expressing the variable heavy-chain gene VH3-23 with or without the variable kappa-chain gene VK1-33 and often had a Y-x-R motif within the heavy-chain complementarity determining region 3 to make key contacts with HA. Moreover, lateral patch antibodies that used both VH3-23 and VK1-33 maintained neutralizing capability with recent pH1N1 strains that acquired mutations near the lateral patch. RBS-binding mAbs used a diverse repertoire but targeted the RBS epitope similarly and made extensive contacts with the major antigenic site Sb. Together, our data indicate that RBS- and lateral patch-targeting clones are abundant within the human memory B cell pool, and universal vaccine strategies should aim to drive antibodies against both conserved head and stalk epitopes.

PubMed: 34078743
DOI: 10.1126/scitranslmed.abg4535

実験手法

ELECTRON MICROSCOPY (3.2 Å)