Potent and Broad Neutralization of HIV-1 Subtype C by Plasma Antibodies Targeting a Quaternary Epitope Including Residues in the V2 Loop

摘要: The targets of broadly cross-neutralizing (BCN) antibodies are 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 antibody specificity mediating breadth. CAP256 developed potent activity peaking at 3 years postinfection, neutralizing 32 (76%) 42 heterologous viruses, titers against some viruses exceeding 1:10,000. showed bias, preferentially A over B viruses. serum targeted quaternary epitope which included V1V2 region. Further mapping residues F159, N160, L165, R166, D167, K169, K171 (forming FN/LRD-K-K motif) V2 region as crucial to epitope. However, fine response varied time and, while consistently dependent on R166 became gradually less D167 K171, possibly contributing incremental increase breadth 4 years. presence an intact motif was associated sensitivity, although length adjacent V1 loop modulated degree shorter significantly higher titers. Repair resistant conferred sometimes Comparison that PG9/PG16 monoclonal suggested these epitopes overlapped, adding mounting evidence this may represent common neutralization target should be further investigated potential candidate.