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PDBsum entry 4zpv
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Viral protein/immune system
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PDB id
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4zpv
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Contents |
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213 a.a.
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212 a.a.
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207 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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Evaluation of candidate vaccine approaches for mers-Cov.
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Authors
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L.Wang,
W.Shi,
M.G.Joyce,
K.Modjarrad,
Y.Zhang,
K.Leung,
C.R.Lees,
T.Zhou,
H.M.Yassine,
M.Kanekiyo,
Z.Y.Yang,
X.Chen,
M.M.Becker,
M.Freeman,
L.Vogel,
J.C.Johnson,
G.Olinger,
J.P.Todd,
U.Bagci,
J.Solomon,
D.J.Mollura,
L.Hensley,
P.Jahrling,
M.R.Denison,
S.S.Rao,
K.Subbarao,
P.D.Kwong,
J.R.Mascola,
W.P.Kong,
B.S.Graham.
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Ref.
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Nat Commun, 2015,
6,
7712.
[DOI no: ]
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PubMed id
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Abstract
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The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a
cause of severe respiratory disease highlights the need for effective approaches
to CoV vaccine development. Efforts focused solely on the receptor-binding
domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing
antibody (NAb) responses. Here we show that immunogens based on full-length S
DNA and S1 subunit protein elicit robust serum-neutralizing activity against
several MERS-CoV strains in mice and non-human primates. Serological analysis
and isolation of murine monoclonal antibodies revealed that immunization elicits
NAbs to RBD and, non-RBD portions of S1 and S2 subunit. Multiple neutralization
mechanisms were demonstrated by solving the atomic structure of a NAb-RBD
complex, through sequencing of neutralization escape viruses and by constructing
MERS-CoV S variants for serological assays. Immunization of rhesus macaques
confers protection against MERS-CoV-induced radiographic pneumonia, as assessed
using computerized tomography, supporting this strategy as a promising approach
for MERS-CoV vaccine development.
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