ジャーナル: Proc Natl Acad Sci U S A / 年: 2014 タイトル: A common solution to group 2 influenza virus neutralization. 著者: Robert H E 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 / ...著者: Robert H E 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 / Carla 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 / 要旨: 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 ...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.
超分子 #1000: Influenza (A/Hong Kong/1/1968, H3N2) hemagglutinin bound to neutr...
超分子
名称: Influenza (A/Hong Kong/1/1968, H3N2) hemagglutinin bound to neutralizing antibody CR8043 タイプ: sample / ID: 1000 / 集合状態: One HA trimer bound to three Fabs / Number unique components: 2