Until recently, V2 was virtually overlooked as a target for vaccine development, but its potential importance as a vaccine target has recently emerged as a result of data from the RV144 HIV-1 vaccine efficacy trial showing that high levels of Abs specific for the V1/V2 region were correlated with a statistically significant reduction in the rate of HIV infection. Studies of various human V2 monoclonal Abs (mAbs) demonstrate that both polyclonal and monoclonal V2-specific Abs can be highly cross-reactive, display neutralizing activity, capture virus particles, mediate ADCC, and block gp120/4 7 interaction. Recent data show that the V1/V2 region harbors at least 3 distinct epitope regions as defined by the reactivity of various mAbs. (1) PG9, a mAb specific for a conformational epitope which includes portions of V1, V2, and V3, reacts with two glycans and amino acids in the B and C-strands of the 4-stranded -sheet domain assumed by V1/V2 when presented on a scaffold protein and bound to this mAb. (2) mAbs CH58 and CH59 react with linear V2 peptides. The epitopes recognized by these mAbs, which were derived from the cells of an RV144 vaccinee, consist of amino acids that map to the aforementioned C-strand in V2. (3) Seven additional mAbs (e.g., 697D) were developed from subjects with chronic HIV-1 infection; the epitopes recognized by these mAbs are highly conformation-dependent and target a discontinuous region in V2 which is located in a region between -strands C and D. The epitopes recognized by these latter mAbs map to a surface area clearly different from those recognized by CH58, CH59 and PG9. The current data thus indicate that there are at least three distinct types of V2 epitopes.
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