Serotypic heterogeneity in the response to pneumococcal vaccine

Abstract The assessment of pneumococcal vaccine response currently relies on a single IgG concentration threshold, identical for all serotypes, as recommended by the WHO and AAAAI. However, the recommended thresholds do not take the wide inter-serotype variability into account. The purpose of this study was to determine if the antibody threshold linked to a functional immune response varies according to serotype. We performed a retrospective analysis on 729 samples from adults at risk of invasive pneumococcal disease (IPD), sent between 2018 and 2024 to assess vaccine response. Specific IgG concentrations for seven vaccine serotypes were measured by ELISA and compared to opsonophagocytic assay (OPA) results, a functional test considered as the gold standard. For each serotype, we determined the most predictive IgG concentration (PIC) for a positive OPA result using ROC curves, Youden’s index, and bootstrap analysis with 1,000 resamples. The resulting PIC were then compared using non-parametric tests (Kruskal-Wallis test followed by Dunn’s post-hoc test with Holm’s correction). The PIC varied considerably among serotypes, ranging from 0.84 to 4.74 µg/mL. This variability was found to be statistically significant (p