Fig. 7: Predictive gene signatures for neutralizing antibody response and clinical outcome in macaques.

a, b Top 50 most predictive genes (quantified by digital transcriptomics at day 30) for neutralizing antibody levels at day 56 (before challenge) form a densely linked network centered around B cell activation (a). Color codes show significantly enriched pathways and protein networks identified by STRING analysis (b). c Kinetics of B Cell Activating Factor (BAFF, also known as BLyS, encoded by TNFSF13B), and its receptor (B Cell Maturation Antigen, BCMA, encoded by TNFRSF17) after vaccination. Transcript quantification was performed by digital transcriptomics. Multiple comparisons were analyzed using a mixed-effects model with Restricted Maximum Likelihood (REML) estimation; all tests were two-sided. d, e Univariate linear regression and ranking (attribute selection by machine learning) of top 20 most predictive genes for NAbs at day 56 after vaccination (n = 6, d) and for peak viral load in plasma at day 60 (n = 10, e). Individual data points represent independent animals. The solid line indicates the mean of the simple linear regression; the shaded area representing the 95% confidence interval. The goodness of fit (R) and corresponding p-values are shown in each panel. f Heatmap of Spearman’s correlations and hierarchical clustering (Euclidean distance metric and complete linkage agglomeration method) of selected parameters, including immune pathway scores, transcript levels, viral load, and frequency of cytokine-producing T cells. The bar on the right indicates the scale of the correlation values.