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PDBsum entry 4hpo
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Immune system/viral protein
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PDB id
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4hpo
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Contents |
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217 a.a.
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213 a.a.
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15 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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Vaccine induction of antibodies against a structurally heterogeneous site of immune pressure within HIV-1 envelope protein variable regions 1 and 2.
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Authors
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H.X.Liao,
M.Bonsignori,
S.M.Alam,
J.S.Mclellan,
G.D.Tomaras,
M.A.Moody,
D.M.Kozink,
K.K.Hwang,
X.Chen,
C.Y.Tsao,
P.Liu,
X.Lu,
R.J.Parks,
D.C.Montefiori,
G.Ferrari,
J.Pollara,
M.Rao,
K.K.Peachman,
S.Santra,
N.L.Letvin,
N.Karasavvas,
Z.Y.Yang,
K.Dai,
M.Pancera,
J.Gorman,
K.Wiehe,
N.I.Nicely,
S.Rerks-Ngarm,
S.Nitayaphan,
J.Kaewkungwal,
P.Pitisuttithum,
J.Tartaglia,
F.Sinangil,
J.H.Kim,
N.L.Michael,
T.B.Kepler,
P.D.Kwong,
J.R.Mascola,
G.J.Nabel,
A.Pinter,
S.Zolla-Pazner,
B.F.Haynes.
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Ref.
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Immunity, 2013,
38,
176-186.
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PubMed id
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Abstract
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The RV144 HIV-1 trial of the canary pox vector (ALVAC-HIV) plus the gp120
AIDSVAX B/E vaccine demonstrated an estimated efficacy of 31%, which correlated
directly with antibodies to HIV-1 envelope variable regions 1 and 2 (V1-V2).
Genetic analysis of trial viruses revealed increased vaccine efficacy against
viruses matching the vaccine strain at V2 residue 169. Here, we isolated four V2
monoclonal antibodies from RV144 vaccinees that recognize residue 169,
neutralize laboratory-adapted HIV-1, and mediate killing of field-isolate
HIV-1-infected CD4(+) T cells. Crystal structures of two of the V2 antibodies
demonstrated that residue 169 can exist within divergent helical and loop
conformations, which contrasted dramatically with the β strand conformation
previously observed with a broadly neutralizing antibody PG9. Thus, RV144
vaccine-induced immune pressure appears to target a region that may be both
sequence variable and structurally polymorphic. Variation may signal sites of
HIV-1 envelope vulnerability, providing vaccine designers with new options.
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