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

Abstract

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 (ClinicalTrials.gov NCT02215226), 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 anti-capsular 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 derived by estimating absolute disease risk. Results In infants born ≥34 weeks gestational age, cord-blood IgG geometric mean concentrations (GMC) were lower in cases than controls for serotype-Ia (0.05 vs. 0.50µg/ml; p=0.004) and III (0.20 vs. 0.38µg/ml; p=0.078). Cord-blood IgG concentration ≥1.04 and ≥1.53µg/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 and ≥3.41µg/ml for serotype-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 immunogenicity evaluation benchmarked against the defined thresholds.

Active Intrapartum SARS-CoV-2 Infection and Pregnancy Outcomes

“…Maternal and cord blood samples were collected as previously described. 12 Placentas were placed in 10% buffered formalin and referred to the designated laboratory. Nasopharyngeal swabs were collected within 72 hours of birth from infants of mothers with confirmed SARS-CoV-2 infection.…”

Advances towards licensure of a maternal vaccine for the prevention of invasive group B streptococcus disease in infants: a discussion of different approaches

“… 62 A subsequent study from this group evaluated protective thresholds through the first 90 days of life in maternal sera and infant sera for which both cord blood samples as well as sera taken at the time of infection were included. 67 This study estimated that serum titers of ≥0.93 µg/mL and ≥1.08 µg/mL of serotypes Ia- and III-specific IgG, respectively, were associated with >90% risk reduction against invasive GBS disease with the cognate serotype strains when analyzed with the combination cord and time-of-infection serum titers. Furthermore, in agreement with the prior finding, the protective thresholds estimated from maternal sera exceeded those obtained from sera reflective of titers in the infant.…”

Early-onset group B streptococcal disease in African countries and maternal vaccination strategies

“…This same threshold reduced the risk of disease by 80% for serotypes Ia and III from eight European countries ( 66 ). In South Africa, however, a higher threshold of protection was proposed (≥2.3 μg/mL and ≥ 3.4 μg/mL for serotypes Ia and III was associated with a 90% risk reduction in disease) ( 63 ). Importantly, benchmarking a correlate of protection to infant antibody levels, and supplementing that with maternal levels and transplcental tranfer ratios may be necessary because of the unpredictability of transplacental transfer.…”

“…Importantly, benchmarking a correlate of protection to infant antibody levels, and supplementing that with maternal levels and transplcental tranfer ratios may be necessary because of the unpredictability of transplacental transfer. An infant antibody level between 1 and 3 μg/mL protected 90% of infants from invasive GBS disease caused by serotype Ia and III in South Africa ( 63 , 67 ). Determination of single protective threshold for all GBS serotypes would be ideal.…”