@article{f69523a7d0b04c8a920d747099a865a9,
title = "A multifunctional human monoclonal neutralizing antibody that targets a unique conserved epitope on influenza HA",
abstract = "The high rate of antigenic drift in seasonal influenza viruses necessitates frequent changes in vaccine composition. Recent seasonal H3 vaccines do not protect against swine-origin H3N2 variant (H3N2v) strains that recently have caused severe human infections. Here, we report a human V H 1-69 gene-encoded monoclonal antibody (mAb) designated H3v-47 that exhibits potent cross-reactive neutralization activity against human and swine H3N2 viruses that circulated since 1989. The crystal structure and electron microscopy reconstruction of H3v-47 Fab with the H3N2v hemagglutinin (HA) identify a unique epitope spanning the vestigial esterase and receptor-binding subdomains that is distinct from that of any known neutralizing antibody for influenza A H3 viruses. MAb H3v-47 functions largely by blocking viral egress from infected cells. Interestingly, H3v-47 also engages Fcγ receptor and mediates antibody dependent cellular cytotoxicity (ADCC). This newly identified conserved epitope can be used in design of novel immunogens for development of broadly protective H3 vaccines.",
author = "Sandhya Bangaru and Heng Zhang and Gilchuk, {Iuliia M.} and Voss, {Thomas G.} and Irving, {Ryan P.} and Pavlo Gilchuk and Pranathi Matta and Xueyong Zhu and Shanshan Lang and Travis Nieusma and Richt, {Juergen A.} and Albrecht, {Randy A.} and Vanderven, {Hillary A.} and Robin Bombardi and Kent, {Stephen J.} and Ward, {Andrew B.} and Wilson, {Ian A.} and Crowe, {James E.}",
note = "Funding Information: This work was supported by a grant from the National Institutes of Health (NIH) U19 AI117905 and NIH contract NIH HHSN272201400024C. We thank Janice Williams of the Vanderbilt-Ingram Cancer Center for excellent technical support in TEM imaging. We thank Drs. Bruce Wines and Mark Hogarth (Burnet Institute) for kindly providing the Fc dimer reagent used in these studies. This project was supported in part by the NCI Cancer Center Support Grant number P30 CA068485 using the Cell Imaging Shared Resource (CISR) Shared Resource, which provided TEM services and by CTSA award number UL1 TR000445 from the National Center for Advancing Translational Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NCI, NCATS, or the NIH. Publisher Copyright: {\textcopyright} 2018 The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41467-018-04704-9",
language = "English",
volume = "9",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}