Associations between antibody Fc features and broad HIV-1 neutralization activity.

<p>(A) Spearman correlation analysis between the antibody features analyzed in this study at 6 months post-seroconversion (SC) and geometric mean (geomean) half-maximal infective dilution (ID<sub>50</sub>) pseudovirus neutralization titers at 3 years post-SC (n = 166). Antibody fea...

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Main Author: Marloes Grobben (12465894) (author)
Other Authors: Margreet Bakker (255262) (author), Angela I. Schriek (12548386) (author), Liesbeth J.J. Levels (20417064) (author), Jeffrey C. Umotoy (1734142) (author), Khadija Tejjani (12557846) (author), Mariëlle J. van Breemen (5090225) (author), Ryan N. Lin (20417067) (author), Steven W. de Taeye (8801435) (author), Gabriel Ozorowski (711509) (author), Neeltje A. Kootstra (8157396) (author), Andrew B. Ward (7832180) (author), Stephen J. Kent (90625) (author), P. Mark Hogarth (5644580) (author), Bruce D. Wines (5644577) (author), Rogier W. Sanders (8078546) (author), Amy W. Chung (7487030) (author), Marit J. van Gils (9323428) (author)
Published: 2024
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Summary:<p>(A) Spearman correlation analysis between the antibody features analyzed in this study at 6 months post-seroconversion (SC) and geometric mean (geomean) half-maximal infective dilution (ID<sub>50</sub>) pseudovirus neutralization titers at 3 years post-SC (n = 166). Antibody features shown in this panel are for responses specific for gp120 and SOSIP proteins of subtype B strain 92BR020. Correlations with antibody Fc features at 3 years post-SC are shown in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1012739#ppat.1012739.s010" target="_blank">S9 Fig</a>. The color indicates the rho Spearman correlation coefficient and significant results are indicated by asterisks. The results were corrected for multiple comparisons using the Bonferroni-Holm method. (B) Spearman correlation analysis between the antibody features analyzed in this study at 6 months post-SC and geomean ID<sub>50</sub> pseudovirus neutralization titers at 3 years post-SC (n = 166). Antibody features shown in this figure are for responses specific for gp120 and SOSIP proteins of subtype B strain JRCSF, V1/V2, V3 and gp41 epitope constructs were also based on the JRCSF sequence. Constructs comprising the CD4 binding site (CD4bs), the membrane-proximal external region (MPER) and a covalently linked fusion of gp120 and CD4 (gp120-CD4) were previously described (see <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1012739#sec010" target="_blank">methods</a>). The color indicates the rho Spearman correlation coefficient and significant results are indicated by asterisks. The results were corrected for multiple comparisons using the Bonferroni-Holm method. (C) Partial least squares regression analysis geomean ID<sub>50</sub> pseudovirus neutralization titer as independent variable. Eleven Fc features were included in the model as selected by elastic net feature selection with alpha 0.5 and 16-fold cross-validation. The model comprised two latent variables (LVs), had a R<sup>2</sup> of calibration of 0.389, root mean square error of calibration of 0.267 and root mean square error of cross-validation of 0.336. (D) Loading and variable importance in projection (VIP) scores of all 11 included features, with variables with a VIP score higher than 1 shown in light blue (also indicated by the grey vertical line) and the remaining variables shown in dark blue. * = P<0.05, ** = P<0.01, *** = P<0.001, **** = P<0.0001.</p>