9B2M

Hemagglutinin H1 New Caledonia 1999 in complex with monoclonal antibody Fab 43_S0008

Summary for 9B2M

• Entry DOI: 10.2210/pdb9b2m/pdb
• EMDB information: 44112
• Descriptor: Hemagglutinin HA1 chain, Hemagglutinin HA2 chain, Heavy chain monoclonal antibody Fab 3_S0008, ... (5 entities in total)
• Functional Keywords: influenza virus; broadly neutralizing antibody; bnab; vh1-69; dh3-9; hemagglutinin; ha; stem; stalk; germline-targeting, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Influenza A virus (A/New Caledonia/20/1999(H1N1)); More
• Total number of polymer chains: 12
• Total formula weight: 340228.68

Authors

Torrents de la Pena, A.,de Paiva Froes Rocha, R.,Ward, A.B.,Ataca, S.,Kanekiyo, M. (deposition date: 2024-03-15, release date: 2024-12-11)

Primary citation

Ataca, S.,Sangesland, M.,de Paiva Froes Rocha, R.,Torrents de la Pena, A.,Ronsard, L.,Boyoglu-Barnum, S.,Gillespie, R.A.,Tsybovsky, Y.,Stephens, T.,Moin, S.M.,Lederhofer, J.,Creanga, A.,Andrews, S.F.,Barnes, R.M.,Rohrer, D.,Lonberg, N.,Graham, B.S.,Ward, A.B.,Lingwood, D.,Kanekiyo, M.
Modulating the immunodominance hierarchy of immunoglobulin germline-encoded structural motifs targeting the influenza hemagglutinin stem.
Cell Rep, 43:114990-114990, 2024

PubMed Abstract: Antibodies targeting epitopes through germline-encoded motifs can be found in different individuals. While these public antibodies are often beneficial, they also pose hurdles for subdominant antibodies to emerge. Here, we use transgenic mice that reproduce the human IGHV1-6901 germline-encoded antibody response to the conserved stem epitope on group 1 hemagglutinin (HA) of influenza A virus to show that this germline-endowed response can be overridden by a subdominant yet cross-group reactive public antibody response. Immunization with a non-cognate group 2 HA stem enriched B cells harboring the IGHD3-9 gene, thereby switching from IGHV1-69- to IGHD3-9-encoded motif-dependent epitope recognition. These IGHD3-9 antibodies bound, neutralized, and conferred cross-group protection in mice against influenza A viruses. A cryoelectron microscopy (cryo-EM) structure of an IGHD3-9 antibody resembled the human broadly neutralizing antibody FI6v3, which uses IGHD3-9. Together, our findings offer insights into vaccine regimens that engage an immunoglobulin repertoire with broader cross-reactivity to influenza A viruses.

PubMed: 39580804
DOI: 10.1016/j.celrep.2024.114990

Experimental method

ELECTRON MICROSCOPY (3.09 Å)