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IgG1 and Fcγ-receptor binding profiles at peak immunogenicity track with polyfunctionality and durability.

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posted on 2021-11-29, 18:52 authored by Stephanie Fischinger, Deniz Cizmeci, Davy Deng, Shannon P. Grant, Nicole Frahm, Julie McElrath, Jonathan Fuchs, Pierre-Alexandre Bart, Giuseppe Pantaleo, Michael Keefer, William O. Hahn, Nadine Rouphael, Gavin Churchyard, Zoe Moodie, Yeycy Donastorg, Hendrik Streeck, Galit Alter

A: A Partial Least Squares Regression analysis (PLSR) shows the regression of all antibody profile features (72 features) on polyfunctionality for all the trials at peak immunogenicity. Trials are indicated by different shapes. The degree of polyfunctionality is depicted by the blue shade. B: The Loadings plot shows variables associated with polyfunctionality, loadings were scaled, and the color indicates the VIP score, VIP scores >0.7 are shown. C: The network shows the features associated with the selected variables from the Loadings plot which are drawn as rectangles, whereas co-correlated features are depicted as circles. Colors indicate the type of measurement as indicated in the legend. A Spearman correlation was performed, and only features with r>0.7 and p<0.01 after Benjamini-Hochberg correction were included. D: The PLSR plot shows the regression of all antibody features (72 features) at peak immunogenicity and ADCP levels at the durability time point (12 months). The shape depicts the trial. The shade of blue indicates the ADCP phagoscore, which was z-scored across all trial responses. E: The Loadings plot shows the only 2 critical features at peak immunogenicity associated with ADCP levels at the durability time point, colors indicate the Z-score and loadings were scaled. F: The network shows the co-correlates of peak immunogenicity predictors of ADCP durability. Squares depict the PLSR selected features and circles depict the co-correlates, while the color indicates the type of measurement. A Spearman correlation was performed to select the co-correlates, only features with r>0.7 and p<0.01 were included.

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