Related Experiment Video
Updated: Nov 25, 2025
A Murine Model of Group B Streptococcus Vaginal Colonization
Published on: November 16, 2016
Association of Group B Streptococcus (GBS) Serum Serotype-Specific Anticapsular Immunoglobulin G Concentration and
Shabir A Madhi1,2, Alane Izu1,2, Gaurav Kwatra1,2
1South African Medical Research Council Vaccines and Infectious Diseases Analytical Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Insights
This study determined antibody levels in infants to establish thresholds for a Group B Streptococcus (GBS) vaccine. Achieving these GBS serotype Ia and III IgG thresholds in infants could protect against invasive GBS disease.
Area of Science:
- Immunology
- Vaccinology
- Neonatal Health
Background:
- Group B Streptococcus (GBS) causes invasive GBS disease (IGbsD) in infants.
- Licensure of a GBS vaccine requires demonstrating safety in pregnant women and establishing immunogenicity thresholds linked to disease risk reduction.
- This study investigated the association between GBS serotype Ia and III IgG levels and IGbsD risk reduction in infants.
Purpose of the Study:
- To identify serological thresholds for GBS serotypes Ia and III IgG in infants that correlate with a 90% reduction in invasive GBS disease (IGbsD) risk.
- To inform the licensure requirements for a GBS polysaccharide-protein conjugate vaccine by establishing immunogenicity benchmarks.
Main Methods:
- A matched case-control study involving 38,233 mother-newborn dyads.
- Measurement of GBS serotype-specific anticapsular immunoglobulin G (IgG) in maternal and infant sera using a multiplex Luminex assay.
- Derivation of IgG thresholds associated with 90% IGbsD risk reduction by estimating absolute disease risk.
Main Results:
- Lower GBS serotype Ia and III IgG geometric mean concentrations (GMCs) were observed in infants with IGbsD compared to controls.
- Infant cord-blood IgG concentrations of ≥1.04 µg/mL for serotype Ia and ≥1.53 µg/mL for serotype III were associated with a 90% risk reduction.
- Maternal serum IgG thresholds for 90% risk reduction were ≥2.31 µg/mL for Ia and ≥3.41 µg/mL for III.
Conclusions:
- The identified infant IgG thresholds for GBS serotypes Ia and III support the use of immunogenicity evaluation for GBS vaccine licensure.
- Benchmarking vaccine immunogenicity against these defined thresholds can facilitate the approval process for a GBS polysaccharide-protein conjugate vaccine.
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 µg/mL; P = .004) and III (0.20 vs 0.38 µg/mL; P = .078). Cord-blood IgG concentrations ≥1.04 and ≥1.53 µg/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 µg/mL and ≥3.41 µg/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.
Clinical Trials Registration:
NCT02215226.
Related Concept Videos
01:22Development of Immunocompetence
The initial cells that migrate from the fetal thymus settle within the skin and epithelial tissues lining the mouth, digestive tract, and in females, the uterus and vagina. These cells, including skin-based dendritic cells, serve as antigen-presenting cells, playing a key role in T cell activation.
Subsequent T...
01:26Factors Affecting the Risk of Infection
The integrity and count of the white blood cells help the body resist pathogens and fight infection. When impaired, it reduces the body's resistance to pathogens. The acidic pH levels of the gastrointestinal, genitourinary tracts, and skin...
01:15Transcytosis of IgG
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...