9O8Q

Cryo-EM structure of NI06063_d30_103 Fab in complex with influenza virus hemagglutinin from A/Hong Kong/485197/2014 (H3N2)

Summary for 9O8Q

• Entry DOI: 10.2210/pdb9o8q/pdb
• EMDB information: 70233
• Descriptor: NI06063_d30_103 Fab heavy chain, NI06063_d30_103 Fab light chain, Hemagglutinin HA1, ... (7 entities in total)
• Functional Keywords: influenza, hemagglutinin, antibody complex, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 12
• Total formula weight: 281418.66

Authors

Jo, G.,Ward, A.B. (deposition date: 2025-04-16, release date: 2026-02-04, Last modification date: 2026-04-08)

Primary citation

Sun, J.,Jo, G.,Troxell, C.A.,Fu, Y.,Hoezl, R.,Lv, H.,Abozeid, H.H.,Teo, Q.W.,Pholcharee, T.,McGrath, J.J.C.,Changrob, S.,Nelson, S.A.,Yasuhara, A.,Huang, M.,Zheng, N.Y.,Chervin, J.C.,Li, L.,Fernandez-Quintero, M.L.,Loeffler, J.R.,Rodriguez, A.J.,Huang, J.,Swanson, O.M.,Balmaseda, A.,Kuan, G.,Campredon, L.,Kaitlynn Allen, E.,Neumann, G.,Wu, N.C.,Kawaoka, Y.,Krammer, F.,Mejias, A.,Ramilo, O.,Thomas, P.G.,Gordon, A.,Ward, A.B.,Han, J.,Wilson, P.C.
B cell imprinting in children impairs antibodies to the haemagglutinin stalk.
Nature, 2026

PubMed Abstract: Immune imprinting or original antigenic sin is a phenomenon whereby the immune system preferentially recalls its initial response to a related, often evolving pathogen after subsequent exposure. Despite its important implications for vaccine development, the causes of imprinting remain unclear. Here, to understand the basis and impact of imprinting by influenza A viruses, we characterized the B cell responses of young children after consecutive first infections with divergent H1N1 and H3N2 strains of influenza. Children had a primary but otherwise similar B cell response to that of adults. Adult B cells commonly cross-reacted with past strains using more stereotyped and mutated immunoglobulin genes, indicating substantial homosubtypic imprinting. In children, after consecutive heterosubtypic primary infections, up to 6% of memory B cells are H1/H3 cross-reactive and bind to the highly conserved central stalk epitope-a lead target for broadly protective vaccine candidates. Over 90% of these B cells had a higher affinity for the imprinting H3N2 strain, resulting in reduced breadth and neutralization potency against H1N1 strains. Mechanistically, the imprinting H3 strains and affected H1 strains shared a residue change in the stalk epitope (D46N) that was central to the nearly universal shift in reactivity, despite differing by only a single atomic group. In conclusion, imprinting by influenza viruses can cause a deleterious shift of nearly the entire memory recall response against key, conserved epitopes.

PubMed: 41813896
DOI: 10.1038/s41586-026-10248-6

Experimental method

ELECTRON MICROSCOPY (2.62 Å)