NCT02215226

GBS Sero-correlate of Protection

Establishing a Sero-correlate of Protection Against Invasive Group B Streptococcus Disease in Newborns and Young Infants Aged <=90 Days

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 35,274 (actual)
• Sponsor: University of Witwatersrand, South Africa · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

Compare anticapsular antibody levels against Group B Streptococcus at delivery in mothers and their infants who develop disease versus those who do not. Use this comparison to establish antibody levels associated with reductions in risk of GBS disease in infants aged less than 90 days.

Detailed description

Group B Streptococcus (GBS) is a leading cause of invasive disease during the neonatal period in developed and developing countries. The global incidence of disease is 0.53 per 1000 live births, though a substantially higher incidence has been reported from South Africa (3 per 1000 live births). Of the disease-causing serotypes, types Ia and III account for over 70% of invasive disease in young infants. The introduction of screening for maternal rectovaginal GBS colonization, with subsequent treatment of colonized women with intrapartum antibiotic prophylaxis (IAP) at delivery, has led to a \>80% reduction in the incidence of disease in some settings (Schrag, 2012). However, the residual burden of early-onset disease (EOD) in countries which have implemented universal screening and IAP remains similar to the incidence of late-onset disease (LOD), which has not declined over time. The resources necessary to implement a screening and IAP program has limited the establishment of this intervention in other developed and most developing countries. GBS capsular polysaccharide-protein conjugate vaccines (GBS-CV) aimed at the immunization of pregnant women, with protection of the newborn expected from trans-placental acquisition of the induced antibodies in utero have been developed. There are a number of challenges to undertaking a large efficacy trial of GBS-CV aimed at licensure of this vaccine. Consequently, licensure of GBS-CV may depend on establishing an immunologic/serologic correlate of protection against invasive disease in newborns, as has been successfully motivated for and adopted in the licensure pathway of meningococcal vaccines. Although previous studies have aimed to identify serotype-specific correlates of anticapsular antibody protection against invasive GBS disease during early-infancy; differences in study-design, age-range of invasive-cases, antibody assay methods and a lack of standardized reference serum between tests mean a robust sero-correlate of protection against GBS has yet to be identified. We propose to conduct a case control study nested within a prospective, longitudinal cohort of mothers and their infants \<=90 days of age, at one academic hospital center in South Africa. The limited intrapartum antibiotic exposure (10-12% deliveries), relatively high incidence of both EOD and LOD (2 per 1000 live births and 1 per 1000 live births respectively) and standardized laboratory surveillance (for case identification) offers an optimal setting in which to establish correlates of protection against the GBS serotypes that predominate in this setting (serotypes Ia and III for EOD and serotype III for LOD).

Conditions

• Invasive Group B Streptococcus Disease

Timeline

• Start date: 2014-07-01
• Primary completion: 2016-12-09
• Completion: 2016-12-31
• First posted: 2014-08-13
• Last updated: 2018-09-13

Locations

1 site across 1 country: South Africa