5K9O

Crystal structure of multidonor HV1-18+HD3-9 class broadly neutralizing Influenza A antibody 31.b.09 in complex with Hemagglutinin H1 A/California/04/2009

5K9O の概要

• エントリーDOI: 10.2210/pdb5k9o/pdb
• 分子名称: 31.b.09 Heavy Fv, 31.b.09 Light Fv, Hemagglutinin, ... (4 entities in total)
• 機能のキーワード: hv1-18, multidonor, h5, universal influenza vaccine, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 210813.38

構造登録者

Joyce, M.G.,Thomas, P.V.,Wheatley, A.K.,McDermott, A.B.,Mascola, J.R.,Kwong, P.D. (登録日: 2016-06-01, 公開日: 2016-12-28, 最終更新日: 2024-10-09)

主引用文献

Joyce, M.G.,Wheatley, A.K.,Thomas, P.V.,Chuang, G.Y.,Soto, C.,Bailer, R.T.,Druz, A.,Georgiev, I.S.,Gillespie, R.A.,Kanekiyo, M.,Kong, W.P.,Leung, K.,Narpala, S.N.,Prabhakaran, M.S.,Yang, E.S.,Zhang, B.,Zhang, Y.,Asokan, M.,Boyington, J.C.,Bylund, T.,Darko, S.,Lees, C.R.,Ransier, A.,Shen, C.H.,Wang, L.,Whittle, J.R.,Wu, X.,Yassine, H.M.,Santos, C.,Matsuoka, Y.,Tsybovsky, Y.,Baxa, U.,Mullikin, J.C.,Subbarao, K.,Douek, D.C.,Graham, B.S.,Koup, R.A.,Ledgerwood, J.E.,Roederer, M.,Shapiro, L.,Kwong, P.D.,Mascola, J.R.,McDermott, A.B.
Vaccine-Induced Antibodies that Neutralize Group 1 and Group 2 Influenza A Viruses.
Cell, 166:609-623, 2016

PubMed Abstract: Antibodies capable of neutralizing divergent influenza A viruses could form the basis of a universal vaccine. Here, from subjects enrolled in an H5N1 DNA/MIV-prime-boost influenza vaccine trial, we sorted hemagglutinin cross-reactive memory B cells and identified three antibody classes, each capable of neutralizing diverse subtypes of group 1 and group 2 influenza A viruses. Co-crystal structures with hemagglutinin revealed that each class utilized characteristic germline genes and convergent sequence motifs to recognize overlapping epitopes in the hemagglutinin stem. All six analyzed subjects had sequences from at least one multidonor class, and-in half the subjects-multidonor-class sequences were recovered from >40% of cross-reactive B cells. By contrast, these multidonor-class sequences were rare in published antibody datasets. Vaccination with a divergent hemagglutinin can thus increase the frequency of B cells encoding broad influenza A-neutralizing antibodies. We propose the sequence signature-quantified prevalence of these B cells as a metric to guide universal influenza A immunization strategies.

PubMed: 27453470
DOI: 10.1016/j.cell.2016.06.043

実験手法

X-RAY DIFFRACTION (3.387 Å)