5k9k
Crystal structure of multidonor HV6-1-class broadly neutralizing Influenza A antibody 56.a.09 in complex with Hemagglutinin Hong Kong 1968.
Structural highlights
FunctionHEMA_I68A4 Binds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. This attachment induces virion internalization of about two third of the virus particles through clathrin-dependent endocytosis and about one third through a clathrin- and caveolin-independent pathway. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in HA2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore (By similarity). Publication Abstract from PubMedAntibodies 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. Vaccine-Induced Antibodies that Neutralize Group 1 and Group 2 Influenza A Viruses.,Joyce MG, Wheatley AK, Thomas PV, Chuang GY, Soto C, Bailer RT, Druz A, Georgiev IS, Gillespie RA, Kanekiyo M, Kong WP, Leung K, Narpala SN, Prabhakaran MS, Yang ES, Zhang B, Zhang Y, Asokan M, Boyington JC, Bylund T, Darko S, Lees CR, Ransier A, Shen CH, Wang L, Whittle JR, Wu X, Yassine HM, Santos C, Matsuoka Y, Tsybovsky Y, Baxa U, Mullikin JC, Subbarao K, Douek DC, Graham BS, Koup RA, Ledgerwood JE, Roederer M, Shapiro L, Kwong PD, Mascola JR, McDermott AB Cell. 2016 Jul 28;166(3):609-23. doi: 10.1016/j.cell.2016.06.043. Epub 2016 Jul, 21. PMID:27453470[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
