Escape from V2 neutralizing antibodies drives the formation/exposure of broadly neutralizing antibody epitopes in the CD4bs.

<p><b>A</b>) Amino acid sequence alignment of the CAP257 B- and C- strands in the V1/V2 sub-domain of gp120, from twelve time points. The number of envelopes per unique V2 sequence is shown on the right. The timing of wave 1 (red), wave 2 (green), and wave 3 (brown) neutralization is summarized to the left with vertical lines. Potential N-linked glycans are shaded grey, and the presence (grey slices) or absence (red slices) of the N160 glycan within the population at each time point is shown with pie charts to the right. <b>B</b>) CAP257 develops a strain-specific V2 response prior to wave 1 broadly neutralizing antibodies. Neutralization of an autologous virus amplified from 174 weeks p.i. (CAP257 3 yr), is shown in grey. The V1/V2 region of this virus was back-mutated to the earliest known sequence (CAP257 3 yr(V1/V2s)) shown in black. Longitudinal neutralization of the N167D, N160D/S, and K169E mutants is shown in orange, purple, and pink respectively. The timing of wave 1 (red), wave 2 (green), and preceding strain-specific V2 (black) neutralization is summarized above with horizontal lines. ID₅₀ titers (y-axis) are shown versus weeks p.i. (x-axis). <b>C</b>) Wave 2 neutralization of Q842 (green) or RHPA (blue) wild-type (wt) viruses, and their N160K mutants (purple). The timing of wave 1 (red), wave 2 (green), and wave 3 (brown) neutralization is summarized above as in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003738#ppat-1003738-g001" target="_blank">Figure 1B</a>. ID₅₀ titers (y-axis) are shown versus weeks p.i. (x-axis).