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PDBsum entry 4mmt
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Viral protein
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PDB id
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4mmt
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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-Based design of a fusion glycoprotein vaccine for respiratory syncytial virus.
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Authors
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J.S.Mclellan,
M.Chen,
M.G.Joyce,
M.Sastry,
G.B.Stewart-Jones,
Y.Yang,
B.Zhang,
L.Chen,
S.Srivatsan,
A.Zheng,
T.Zhou,
K.W.Graepel,
A.Kumar,
S.Moin,
J.C.Boyington,
G.Y.Chuang,
C.Soto,
U.Baxa,
A.Q.Bakker,
H.Spits,
T.Beaumont,
Z.Zheng,
N.Xia,
S.Y.Ko,
J.P.Todd,
S.Rao,
B.S.Graham,
P.D.Kwong.
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Ref.
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Science, 2013,
342,
592-598.
[DOI no: ]
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PubMed id
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Abstract
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Respiratory syncytial virus (RSV) is the leading cause of hospitalization for
children under 5 years of age. We sought to engineer a viral antigen that
provides greater protection than currently available vaccines and focused on
antigenic site Ø, a metastable site specific to the prefusion state of the RSV
fusion (F) glycoprotein, as this site is targeted by extremely potent
RSV-neutralizing antibodies. Structure-based design yielded stabilized versions
of RSV F that maintained antigenic site Ø when exposed to extremes of pH,
osmolality, and temperature. Six RSV F crystal structures provided atomic-level
data on how introduced cysteine residues and filled hydrophobic cavities
improved stability. Immunization with site Ø-stabilized variants of RSV F in
mice and macaques elicited levels of RSV-specific neutralizing activity many
times the protective threshold.
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