Download MendeleyStructure and Function Analysis of an Antibody Recognizing All Influenza A Subtypes.
Kallewaard, N.L., Corti, D., Collins, P.J., Neu, U., McAuliffe, J.M., Benjamin, E., Wachter-Rosati, L., Palmer-Hill, F.J., Yuan, A.Q., Walker, P.A., Vorlaender, M.K., Bianchi, S., Guarino, B., De Marco, A., Vanzetta, F., Agatic, G., Foglierini, M., Pinna, D., Fernandez-Rodriguez, B., Fruehwirth, A., Silacci, C., Ogrodowicz, R.W., Martin, S.R., Sallusto, F., Suzich, J.A., Lanzavecchia, A., Zhu, Q., Gamblin, S.J., Skehel, J.J.(2016) Cell 166: 596-608
- PubMed: 27453466
- DOI: https://doi.org/10.1016/j.cell.2016.05.073
- Primary Citation of Related Structures:
5JW3, 5JW4, 5JW5 - PubMed 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.
Organizational Affiliation:
Department of Infectious Disease and Vaccines, MedImmune LLC, One MedImmune Way, Gaithersburg, MD 20878, USA.
