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PDBsum entry 5jw3
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Immune system
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PDB id
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5jw3
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Contents |
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316 a.a.
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170 a.a.
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222 a.a.
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206 a.a.
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References listed in PDB file
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Key reference
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Title
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Structure and function analysis of an antibody recognizing all influenza a subtypes.
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Authors
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N.L.Kallewaard,
D.Corti,
P.J.Collins,
U.Neu,
J.M.Mcauliffe,
E.Benjamin,
L.Wachter-Rosati,
F.J.Palmer-Hill,
A.Q.Yuan,
P.A.Walker,
M.K.Vorlaender,
S.Bianchi,
B.Guarino,
A.De marco,
F.Vanzetta,
G.Agatic,
M.Foglierini,
D.Pinna,
B.Fernandez-Rodriguez,
A.Fruehwirth,
C.Silacci,
R.W.Ogrodowicz,
S.R.Martin,
F.Sallusto,
J.A.Suzich,
A.Lanzavecchia,
Q.Zhu,
S.J.Gamblin,
J.J.Skehel.
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Ref.
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Cell, 2016,
166,
596-608.
[DOI no: ]
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PubMed id
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Abstract
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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.
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