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PDBsum entry 5idl
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Viral protein
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PDB id
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5idl
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References listed in PDB file
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Key reference
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Title
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Hiv-1 broadly neutralizing antibody precursor b cells revealed by germline-Targeting immunogen.
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Authors
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J.G.Jardine,
D.W.Kulp,
C.Havenar-Daughton,
A.Sarkar,
B.Briney,
D.Sok,
F.Sesterhenn,
J.Ereño-Orbea,
O.Kalyuzhniy,
I.Deresa,
X.Hu,
S.Spencer,
M.Jones,
E.Georgeson,
Y.Adachi,
M.Kubitz,
A.C.Decamp,
J.P.Julien,
I.A.Wilson,
D.R.Burton,
S.Crotty,
W.R.Schief.
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Ref.
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Science, 2016,
351,
1458-1463.
[DOI no: ]
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PubMed id
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Abstract
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Induction of broadly neutralizing antibodies (bnAbs) is a major HIV vaccine
goal. Germline-targeting immunogens aim to initiate bnAb induction by activating
bnAb germline precursor B cells. Critical unmet challenges are to determine
whether bnAb precursor naïve B cells bind germline-targeting immunogens and
occur at sufficient frequency in humans for reliable vaccine responses. Using
deep mutational scanning and multitarget optimization, we developed a
germline-targeting immunogen (eOD-GT8) for diverse VRC01-class bnAbs. We then
used the immunogen to isolate VRC01-class precursor naïve B cells from
HIV-uninfected donors. Frequencies of true VRC01-class precursors, their
structures, and their eOD-GT8 affinities support this immunogen as a candidate
human vaccine prime. These methods could be applied to germline targeting for
other classes of HIV bnAbs and for Abs to other pathogens.
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