Fig. 6. The V3-crown IgG1 response in HIV-1 infection recognizes distinct V3-crown conformations and is linked with the development of neutralization breadth.

Relative plasma IgG1 binding activity (distributed uniformly in [0,1]) to linear V3 and structurally constrained BG505 V3-crown mimetics (V3-IY, V3-IF, V3-RF, V3-RY) from 4281 chronic HIV-1 infected individuals enrolled in the Swiss 4.5 K Screen^{13, 47} were obtained and assessed in the context of neutralization activity data of the cohort (defined as a cross, broad and elite neutralization, or no neutralization) available from⁴⁷. Source data are provided as Supplementary Data 10. a Unweighted average linkage hierarchical clustering based on the Spearman correlation of relative V3-crown peptide IgG1 binding activities across the cohort indicates reactivity clusters dependent on V3-crown peptide conformation. b A two-dimensional representation (t-SNE map) of all 4,281 plasma samples based on relative IgG1 binding activities to the five V3 peptides. Red color denotes high binding activity and blue color denotes low binding activity to the V3 peptide indicated on the top of each panel. c Comparison of relative V3 binding activity in plasma from patients with (n = 909) and without (n = 2250) heterologous virus-neutralizing activity by multivariable linear regression analysis. Grey bars indicate the mean difference in relative binding activity for individual peptides (two-tailed p-values from t-test are provided; they are not adjusted for multiple testing). Black error bars indicate the 95% confidence intervals. These data belong to a comprehensive analysis of host, virus, and disease parameters, shown in Supplementary Fig. 14c and Supplementary Data 11, where only the n = 3159 patients with complete information on all parameters were included. d The top 105 neutralizing plasmas of the cohort were stratified by bnAb epitope specificity (using neutralization fingerprinting⁴⁷) and their mean relative V3 binding activities were compared.