Kallewaard, Nicole L. Corti, Davide Collins, Patrick J. Neu, Ursula McAuliffe, Josephine M. Benjamin, Ebony Wachter-Rosati, Leslie Palmer-Hill, Frances J. Yuan, Andy Q. Walker, Philip A. Vorlaender, Matthias K. Bianchi, Siro Guarino, Barbara De Marco, Anna Vanzetta, Fabrizia Agatic, Gloria Foglierini, Mathilde Pinna, Debora Fernandez-Rodriguez, Blanca Fruehwirth, Alexander Silacci, Chiara Ogrodowicz, Roksana W. Martin, Stephen R. Sallusto, Federica Suzich, JoAnn A. Lanzavecchia, Antonio Zhu, Qing Gamblin, Steven J. Skehel, John J. 2016-07-21 Influenza virus remains a threat because of its ability to evade vaccine-induced immune responses due to antigenic drift. Here, we describe the isolation, evolution, and structure of a broad-spectrum human monoclonal antibody (mAb), MEDI8852, effectively reacting with all influenza A hemagglutinin (HA) subtypes. MEDI8852 uses the heavy-chain VH6-1 gene and has higher potency and breadth when compared to other anti-stem antibodies. MEDI8852 is effective in mice and ferrets with a therapeutic window superior to that of oseltamivir. Crystallographic analysis of Fab alone or in complex with H5 or H7 HA proteins reveals that MEDI8852 binds through a coordinated movement of CDRs to a highly conserved epitope encompassing a hydrophobic groove in the fusion domain and a large portion of the fusion peptide, distinguishing it from other structurally characterized cross- reactive antibodies. The unprecedented breadth and potency of neutralization by MEDI8852 support its development as immunotherapy for influenza virus-infected humans. application/pdf https://n2t.net/ark:/12658/srd1319400 https://susi.usi.ch/global/documents/319400 https://susi.usi.ch/documents/319400/files/Foglierini_2020_cell.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cell.2016.05.073 info:eu-repo/semantics/altIdentifier/ark/12658/srd1319400 info:eu-repo/semantics/openAccess CC BY Cell. - 2016, vol. 166, no. 3, p. 596-608 info:eu-repo/classification/udc/61 Structure and function analysis of an antibody recognizing all influenza A subtypes http://purl.org/coar/resource_type/c_6501