Association Of Group B Streptococcus (Gbs) Serum Serotype-Specific Anticapsular Immunoglobulin G Concentration And Risk Reduction For Invasive Gbs Disease In South African Infants: An Observational Birth-Cohort, Matched Case-Control Study

Background: Licensure of a group B Streptococcus (GBS) polysaccharide-protein conjugate vaccine for protecting infants against invasive GBS disease (IGbsD) will likely need to be based on demonstrating vaccine safety in pregnant women, and benchmarking immunogenicity against a serological threshold associated with risk reduction of IGbsD. We investigated the association between naturally derived GBS serotype Ia and III IgG and risk reduction of IGbsD in infants <= 90 days of age.Methods: In a matched case-control study, IGbsD cases were identified from a cohort of 38 233 mother-newborn dyads. Mothers colonized vaginally with serotype Ia or III at birth and their healthy infants were eligible as matched controls. GBS serotype-specific anticapsular immunoglobulin G (IgG) was measured on maternal and cord blood/infant sera by multiplex Luminex assay, and the IgG threshold associated with 90% risk reduction of IGbsD was derived by estimating absolute disease risk.Results: In infants born at >= 34 weeks' gestational age, cord-blood IgG geometric mean concentrations (GMCs) were lower in cases than controls for serotypes Ia (0.05 vs 0.50 mu g/mL; P=.004) and III (0.20 vs 0.38 mu g/mL; P=.078). Cord-blood IgG concentrations >= 1.04 and >= 1.53 mu g/mL were associated with 90% risk reduction of serotype Ia and III IGbsD, respectively. The maternal sera IgG threshold associated with 90% risk reduction was >= 2.31 mu g/mL and >= 3.41 mu g/mL for serotypes Ia and III, respectively.Conclusions: The threshold associated with a reduced risk for serotype Ia and III IGbsD identified on infant sera supports the case for licensure of a GBS polysaccharide-protein conjugate vaccine based on an immunogenicity evaluation benchmarked against the defined thresholds.