The first wave of broadly neutralizing antibodies targets residues in the V2 region.

<p><b>A</b>) Longitudinal neutralization of ConC V2 mutants. ConC wild-type (wt) is shown in red. V2 mutants F159A, N160A, R166A, K168A, K169E, K171A, and I181A that abrogated wave 1 neutralization are shown in purple. The D167N mutation that enhanced wave 1 neutralization is shown in orange, while the L165A mutation that resulted in universal neutralization sensitivity is shown in grey. The timing of wave 1 (red), wave 2 (green), and wave 3 (brown) neutralization is summarized above as horizontal lines, while the peak titers at each wave are indicated with dotted lines. ID₅₀ titers (y-axis) are shown versus weeks p.i. (x-axis). <b>B</b>) The dependence of CAP257 wave 1 neutralizing antibodies (at 67 weeks p.i.) on V2 residues in ConC, compared to monoclonal antibodies PGT145, CH01-04, and PG9/16. Complete abrogation of neutralization is colored red, 2–10 fold reductions in IC₅₀ are colored yellow, and >10 fold reductions in IC₅₀ are colored orange.