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

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posted on 31.10.2013 by Constantinos Kurt Wibmer, Jinal N. Bhiman, Elin S. Gray, Nancy Tumba, Salim S. Abdool Karim, Carolyn Williamson, Lynn Morris, Penny L. Moore

A) 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) 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.