8TP5

H1 hemagglutinin (NC99) in complex with RBS-targeting Fab 1-1-1E04

8TP5 の概要

• エントリーDOI: 10.2210/pdb8tp5/pdb
• EMDBエントリー: 41467
• 分子名称: Hemagglutinin HA1 chain, Hemagglutinin HA2 chain, Heavy chain of Fab 1-1-1E04, ... (6 entities in total)
• 機能のキーワード: influenza, hemagglutinin, monoclonal antibody, immune complex, viral protein, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Influenza A virus (A/New Caledonia/20/1999(H1N1)); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 249114.63

構造登録者

Yang, Y.R.,Han, J.,Perrett, H.R.,Ward, A.B. (登録日: 2023-08-04, 公開日: 2023-10-11, 最終更新日: 2025-05-14)

主引用文献

Yang, Y.R.,Han, J.,Perrett, H.R.,Richey, S.T.,Rodriguez, A.J.,Jackson, A.M.,Gillespie, R.A.,O'Connell, S.,Raab, J.E.,Cominsky, L.Y.,Chopde, A.,Kanekiyo, M.,Houser, K.V.,Chen, G.L.,McDermott, A.B.,Andrews, S.F.,Ward, A.B.
Immune memory shapes human polyclonal antibody responses to H2N2 vaccination.
Cell Rep, 43:114171-114171, 2024

PubMed Abstract: Influenza A virus subtype H2N2, which caused the 1957 influenza pandemic, remains a global threat. A recent phase 1 clinical trial investigating a ferritin nanoparticle vaccine displaying H2 hemagglutinin (HA) in H2-naive and H2-exposed adults enabled us to perform comprehensive structural and biochemical characterization of immune memory on the breadth and diversity of the polyclonal serum antibody response elicited. We temporally map the epitopes targeted by serum antibodies after vaccine prime and boost, revealing that previous H2 exposure results in higher responses to the variable HA head domain. In contrast, initial responses in H2-naive participants are dominated by antibodies targeting conserved epitopes. We use cryoelectron microscopy and monoclonal B cell isolation to describe the molecular details of cross-reactive antibodies targeting conserved epitopes on the HA head, including the receptor-binding site and a new site of vulnerability deemed the medial junction. Our findings accentuate the impact of pre-existing influenza exposure on serum antibody responses post-vaccination.

PubMed: 38717904
DOI: 10.1016/j.celrep.2024.114171

実験手法

ELECTRON MICROSCOPY (2.9 Å)