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A common solution to group 2 influenza virus neutralization

2013; National Academy of Sciences; Volume: 111; Issue: 1 Linguagem: Inglês

10.1073/pnas.1319058110

1091-6490

Robert H. Friesen, Peter S. Lee, Esther J. M. Stoop, Ryan M. B. Hoffman, Damian C. Ekiert, Gira Bhabha, Wenli Yu, Jarek Juraszek, Wouter Koudstaal, Mandy Jongeneelen, Hans J. W. M. Korse, C. Ophorst, Els C.M. Brinkman-Van der Linden, Mark Throsby, Mark J. Kwakkenbos, Arjen Q. Bakker, Tim Beaumont, Hergen Spits, Ted Kwaks, Ronald Vogels, Andrew B. Ward, Jaap Goudsmit, Ian A. Wilson,

Respiratory viral infections research

The discovery and characterization of broadly neutralizing antibodies (bnAbs) against influenza viruses have raised hopes for the development of monoclonal antibody (mAb)-based immunotherapy and the design of universal influenza vaccines. Only one human bnAb (CR8020) specifically recognizing group 2 influenza A viruses has been previously characterized that binds to a highly conserved epitope at the base of the hemagglutinin (HA) stem and has neutralizing activity against H3, H7, and H10 viruses. Here, we report a second group 2 bnAb, CR8043, which was derived from a different germ-line gene encoding a highly divergent amino acid sequence. CR8043 has in vitro neutralizing activity against H3 and H10 viruses and protects mice against challenge with a lethal dose of H3N2 and H7N7 viruses. The crystal structure and EM reconstructions of the CR8043-H3 HA complex revealed that CR8043 binds to a site similar to the CR8020 epitope but uses an alternative angle of approach and a distinct set of interactions. The identification of another antibody against the group 2 stem epitope suggests that this conserved site of vulnerability has great potential for design of therapeutics and vaccines.