5JW4

Structure of MEDI8852 Fab Fragment in Complex with H5 HA

Summary for 5JW4

• Entry DOI: 10.2210/pdb5jw4/pdb
• Descriptor: Hemagglutinin, MEDI8852 heavy chain, MEDI8852 light chain, ... (8 entities in total)
• Functional Keywords: antibody influenza broadly neutralizing, immune system
• Biological source: Influenza A virus (A/Vietnam/1194/2004(H5N1)); More
• Total number of polymer chains: 24
• Total formula weight: 618414.55

Authors

Neu, U.,Collins, P.J.,Walker, P.A.,Vorlaender, M.K.,Ogrodowicz, R.W.,Martin, S.R.,Gamblin, S.J.,Skehel, J.J. (deposition date: 2016-05-11, release date: 2016-08-03, Last modification date: 2024-11-06)

Primary citation

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.
Structure and Function Analysis of an Antibody Recognizing All Influenza A Subtypes.
Cell, 166:596-608, 2016

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.

PubMed: 27453466
DOI: 10.1016/j.cell.2016.05.073

Experimental method

X-RAY DIFFRACTION (3.7 Å)