7T3D

CryoEM map of anchor 222-1C06 Fab and lateral patch 2B05 Fab binding H1 HA

Summary for 7T3D

• Entry DOI: 10.2210/pdb7t3d/pdb
• EMDB information: 25634 25635 25636 25637 25638 25639 25640 25641 25642 25643 25644 25645 25646 25655
• Descriptor: Hemagglutinin HA1 chain, Hemagglutinin HA2 chain, 2B05 mAb light chain, ... (8 entities in total)
• Functional Keywords: anchor, antibodies, influenza a virus, hemagglutinin, immune system, viral protein-immune system complex, viral protein/immune system
• Biological source: Influenza A virus (A/California/04/2009(H1N1)); More
• Total number of polymer chains: 18
• Total formula weight: 323989.03

Authors

Han, J.,Ward, A.B. (deposition date: 2021-12-07, release date: 2022-01-12, Last modification date: 2024-10-30)

Primary citation

Guthmiller, J.J.,Han, J.,Utset, H.A.,Li, L.,Lan, L.Y.,Henry, C.,Stamper, C.T.,McMahon, M.,O'Dell, G.,Fernandez-Quintero, M.L.,Freyn, A.W.,Amanat, F.,Stovicek, O.,Gentles, L.,Richey, S.T.,de la Pena, A.T.,Rosado, V.,Dugan, H.L.,Zheng, N.Y.,Tepora, M.E.,Bitar, D.J.,Changrob, S.,Strohmeier, S.,Huang, M.,Garcia-Sastre, A.,Liedl, K.R.,Bloom, J.D.,Nachbagauer, R.,Palese, P.,Krammer, F.,Coughlan, L.,Ward, A.B.,Wilson, P.C.
Broadly neutralizing antibodies target a haemagglutinin anchor epitope.
Nature, 602:314-320, 2022

PubMed Abstract: Broadly neutralizing antibodies that target epitopes of haemagglutinin on the influenza virus have the potential to provide near universal protection against influenza virus infection. However, viral mutants that escape broadly neutralizing antibodies have been reported. The identification of broadly neutralizing antibody classes that can neutralize viral escape mutants is critical for universal influenza virus vaccine design. Here we report a distinct class of broadly neutralizing antibodies that target a discrete membrane-proximal anchor epitope of the haemagglutinin stalk domain. Anchor epitope-targeting antibodies are broadly neutralizing across H1 viruses and can cross-react with H2 and H5 viruses that are a pandemic threat. Antibodies that target this anchor epitope utilize a highly restricted repertoire, which encodes two public binding motifs that make extensive contacts with conserved residues in the fusion peptide. Moreover, anchor epitope-targeting B cells are common in the human memory B cell repertoire and were recalled in humans by an oil-in-water adjuvanted chimeric haemagglutinin vaccine, which is a potential universal influenza virus vaccine. To maximize protection against seasonal and pandemic influenza viruses, vaccines should aim to boost this previously untapped source of broadly neutralizing antibodies that are widespread in the human memory B cell pool.

PubMed: 34942633
DOI: 10.1038/s41586-021-04356-8

Experimental method

ELECTRON MICROSCOPY (3.38 Å)