5K9J

Crystal structure of multidonor HV6-1-class broadly neutralizing Influenza A antibody 56.a.09 isolated following H5 immunization.

Summary for 5K9J

• Entry DOI: 10.2210/pdb5k9j/pdb
• Related: 5K9K 5K9O 5K9Q
• Descriptor: 56.a.09 heavy chain, 56.a.09 light chain, POLYETHYLENE GLYCOL (N=34), ... (4 entities in total)
• Functional Keywords: influenza, multidonor, h5, universal influenza vaccine, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 50714.97

Authors

Joyce, M.G.,Thomas, P.V.,Wheatley, A.K.,McDermott, A.B.,Mascola, J.R.,Kwong, P.D. (deposition date: 2016-05-31, release date: 2016-07-27, Last modification date: 2024-10-16)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.904 Å)