A US case-control study to estimate infant group B streptococcal disease serological thresholds of risk-reduction

Maternal vaccines to prevent infant Group B Streptococcus (GBS) disease have progressed through phase II development and may be licensed based on immunologic endpoints, which have yet to be approved by regulatory authorities. Here we present a multistate case control study to characterize the relationship between serotype-specific anti-capsular polysaccharide (CPS) immunoglobulin G concentrations near birth and infant GBS disease risk reduction. Antibody concentration distributions are significantly lower for cases (n = 643) than controls (n = 2801) and serologic thresholds varied by serotype and age at onset, with 80% serotype-specific protective thresholds ranging from 0.52 to 2.49 mcg/mL for early-onset disease (EOD; <7 days old) and 0.02 to 0.14 mcg/mL for late-onset disease (LOD; 7-89 days old). Our study provides the most robust data to date that protection thresholds vary by serotype and are notably lower for LOD than EOD, thereby informing potential serological endpoints for phase III trials evaluating CPS-based maternal GBS vaccine candidates.