Fig. 4: Association between IgG levels to conserved vaccine antigens and protection from culture-confirmed S. pyogenes events.

a, The proportion of visits (n = 4,677) with IgG levels above each threshold associated with a culture-confirmed S. pyogenes event within 45 days. IgG levels were measured from n = 1,987 visits and assumed to remain constant between measurements. b, Piecewise logistic regression analysis with mixed effects to explore the relationship between IgG level and event within 45 days (n = 4,677 visits with 1,987 antibody measurements). Transition points in the relationship between IgG levels and event risk were identified from a and refined using AIC analysis. Piecewise logistic regression with titers above and below the transition point was performed. The blue line shows the fitted regression model, capturing the association between titer levels above the breakpoint and the probability of a S. pyogenes event within 45 days; gray shading represents the 95% CIs for model predictions. OR for each log₁₀ IgG level change compared to the transition point, 95% CIs and P values from two-sided piecewise logistic regression models are displayed. No multiple testing correction was applied. The red vertical line indicates the transition point. Putative 50% protective thresholds were calculated using 10-fold cross-validation as the IgG level at which the predicted probability of an event with 45 days was 50% that of the predicted probability at the transition point. 50% thresholds are plotted with blue dashed lines along with 95% CIs (blue error bars) (*P < 0.05). c, Density plot showing the distribution of IgG measurements (n = 1,987) in relation to IgG level. The red line marks the transition identified in a. d, Forest plot to visualize the association between IgG level above the transition point for each conserved antigen (n = 4,677 visits with 1,987 antibody measurements) and any culture-confirmed event within 45 days. Points represent OR estimates from a mixed-effects logistic regression model adjusting for age, sex and household size. Horizontal bars represent 95% Wald CI. e, IgG level distribution by age in years at study baseline (n = 413), including the percentage of participants with IgG levels above (purple) the identified 50% protective threshold (red dashed line). ref, reference.