Year: 2016
Type: article
Abstract: 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.
Source: Cell
Authors: Nicole L. Kallewaard, Davide Corti, Patrick J. Collins, Ursula Neu, Josephine M. McAuliffe, Ebony Benjamin, Leslie Wachter-Rosati, Frances J. Palmer-Hill, Andy Q. Yuan, Philip A. Walker, Matthias K. Vorlaender, Siro Bianchi, Barbara Guarino, Anna De Marco, Fabrizia Vanzetta, Gloria Agatic, Mathilde Foglierini, Debora Pinna, Blanca Fernandez-Rodriguez, Alexander Fruehwirth, Chiara Silacci, Roksana W. Ogrodowicz, Stephen R. Martin, Federica Sallusto, JoAnn A. Suzich, Antonio Lanzavecchia, Qing Zhu, Steven J. Gamblin, John J. Skehel
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $11,400
OpenAlex ID: W2491163602