Potent and Broad Neutralization of HIV-1 Subtype C by Plasma Antibodies Targeting a Quaternary Epitope Including Residues in the V2 Loop.
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Date
2010
Journal Title
Journal ISSN
Volume Title
Publisher
American Society for Microbiology.
Abstract
The targets of broadly cross-neutralizing (BCN) antibodies are of great interest in the HIV vaccine field. We
have identified a subtype C HIV-1-superinfected individual, CAP256, with high-level BCN activity, and characterized
the antibody specificity mediating breadth. CAP256 developed potent BCN activity peaking at 3 years
postinfection, neutralizing 32 (76%) of 42 heterologous viruses, with titers of antibodies against some viruses
exceeding 1:10,000. CAP256 showed a subtype bias, preferentially neutralizing subtype C and A viruses over
subtype B viruses. CAP256 BCN serum targeted a quaternary epitope which included the V1V2 region. Further
mapping identified residues F159, N160, L165, R166, D167, K169, and K171 (forming the FN/LRD-K-K motif)
in the V2 region as crucial to the CAP256 epitope. However, the fine specificity of the BCN response varied over
time and, while consistently dependent on R166 and K169, became gradually less dependent on D167 and
K171, possibly contributing to the incremental increase in breadth over 4 years. The presence of an intact
FN/LRD-K-K motif in heterologous viruses was associated with sensitivity, although the length of the adjacent
V1 loop modulated the degree of sensitivity, with a shorter V1 region significantly associated with higher titers.
Repair of the FN/LRD-K-K motif in resistant heterologous viruses conferred sensitivity, with titers sometimes
exceeding 1:10,000. Comparison of the CAP256 epitope with that of the PG9/PG16 monoclonal antibodies
suggested that these epitopes overlapped, adding to the mounting evidence that this may represent a common
neutralization target that should be further investigated as a potential vaccine candidate.
Description
Keywords
HIV infections--Virology., AIDS vaccines.
Citation
Moore P. L., et al. 2011. Potent and broad neutralization of HIV-1 subtype C by plasma antibodies targeting a quaternary epitope including residues in the V2 loop. J. Virol. 85, pp. 3128–3141.