5K9Q

Crystal structure of multidonor HV1-18-class broadly neutralizing Influenza A antibody 16.a.26 in complex with A/Hong Kong/1-4-MA21-1/1968 (H3N2) Hemagglutinin

Summary for 5K9Q

• Entry DOI: 10.2210/pdb5k9q/pdb
• Related: 5K9J 5K9K 5K9O
• Descriptor: Hemagglutinin HA1, Hemagglutinin HA2, 16.a.26 Heavy chain, ... (6 entities in total)
• Functional Keywords: hv1-18 (qxxv), multidonor, h5, universal influenza vaccine, immune system
• Biological source: Influenza A virus; More
• Cellular location: Virion membrane ; Single-pass type I membrane protein : Q91MA7 Q91MA7
• Total number of polymer chains: 24
• Total formula weight: 626606.30

Authors

Joyce, M.G.,Thomas, P.V.,Wheatley, A.K.,McDermott, A.B.,Mascola, J.R.,Kwong, P.D. (deposition date: 2016-06-01, release date: 2016-11-30, Last modification date: 2024-10-23)

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(Cambridge,Mass.), 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 (2.503 Å)