Fig. 5: Comparison of antibody characteristics between samples with (Enhanced cohort) or without (Non-Enhanced cohort) evidence of complement-enhanced neutralisation.

a Total SARS-CoV-2 spike IgG titres measured via electrochemiluminescence (ECL) using Meso Scale Discovery assays (p = 0.0029). Each dot represents the average ECL signal of each background-subtracted sample tested in duplicate (b) Median fluorescence intensity (MFI) of SARS-CoV-2 spike-specific IgG1-4 in all samples determined via flow cytometry. Each dot represents the average MFI of each background-subtracted sample tested in duplicate. c Pairwise comparison of MFI of IgG1-4 SARS-CoV-2 spike-specific titres (IgG1, p = 0.0321; IgG2, p = 0.0098; IgG3, p = <0.0001; IgG4, p = 0.3216). Each dot represents MFI values as described for (b) Dotted lines show the mean MFI of negative samples plus 3 standard deviations. d Pairwise comparison of antibody-dependent complement deposition (ADCD) between the Enhanced and Non-Enhanced cohorts, using MFI to measure C3c deposition (p = 0.0031). Each dot represents the average MFI from each sample tested in duplicate and interpolated from a standard curve assigned with arbitrary ‘Complement Activating Units’. For (a–d), statistical significance was determined using an unpaired, two-sided t-test and error bars show the mean value with standard deviation (SD), comparing the Enhanced (a, n = 14; b–d, n = 13) and Non-Enhanced cohorts (n = 17). e Two-tailed Pearson correlation with Benjamini Hochberg false discovery rate of 0.05 to compare relationships of antibody characteristics within the two cohorts. f Mean decrease in gini, representing the order of variable importance for determining node purity in the random forest model to classify outcome of complement-enhanced neutralisation. g Ridge regression coefficients in order of positive relationship with complement-enhanced neutralisation. Dots represent the mean coefficient for each antibody characteristic, with 95% confidence intervals (CIs). Features with CIs not overlapping 0 were considered to be important predictors. f and g used data containing total SARS-CoV-2 spike-specific IgG titres, IgG subclass titres, ADCD, and antibody epitope specificity to Coronavirus antigens to determine complement-enhanced neutralisation. Statistical analysis for (a–e) was determined using GraphPad Prism (Version 10). Modelling for (f and g) was performed in RStudio. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Receptor binding domain (RBD), spike protein (S), nucleocapsid (N), coronavirus (CoV). Source data are provided as a Source Data file.