A multicentre, international case-control study to develop a biobank of sera from 150 cases of serotype III GBS disease and associated clinical information from seven countries (Malawi, Uganda, UK, the Netherlands, Italy and France), with 3:1 (450) serotype matched healthy controls.
Group B Streptococcus (GBS) causes severe infections in young infants across the world. In 2015 it was estimated that there were at least 319,000 infants under three months of age with GBS disease worldwide, resulting in 90,000 deaths and at least 10,000 children with long term disabilities. Around 20% of all pregnant women carry GBS in their vagina and bowel, and babies are exposed to GBS bacteria around the time of birth. The options for prevention are currently limited to offering antibiotics during labour. A vaccine that could be given to pregnant women has the greatest potential to benefit mothers and babies worldwide. There are vaccines currently being tested in clinical trials, including in pregnant women. Given the complexity, size and costs associated with a phase III trial, it is generally agreed that indirect evidence (correlates) of protection (CoP), based on immunologic data from vaccine and seroepidemiological studies, opsonophagocytic assays and supported by animal models, could be pivotal for vaccine licensure, with effectiveness subsequently confirmed in post-licensure evaluations. This study aims to develop a biobank of sera from 150 cases of serotype III GBS disease and associated clinical information from seven countries (Malawi, Uganda, UK, the Netherlands, Italy and France) with 3:1 (450) serotype matched healthy controls. GBS cases will be identified through active surveillance of GBS disease in infants, as part of ongoing epidemiological studies in Uganda, the UK, Italy, France, the Netherlands and Malawi. Upon identification of cases, consent will be requested to obtain a serum sample (1-2 mL of blood collected from infant), the GBS isolate and to collect brief clinical and demographic details. Each site will aim to collect around 50 cases of invasive GBS disease cases (with all samples) over the course of 2 years. Each site will also recruit approximately 1000 women to have a rectovaginal swab at 35-37 weeks gestation and cord and maternal blood samples at delivery. These women and their infants will be followed up to 90 days of age and considered appropriate controls if the infants are exposed to the same serotype/strain of GBS at delivery as the case - but do not develop GBS the first 90 days of life. We will select 3 controls for every case. The biorepository will be established at the St George's University of London for all samples from the European Union and Malawi and the MRC/UVRI \& LSHTM Uganda Research Unit for Ugandan samples.
Study Type
Assistance Publique Hopitaux de Paris (AP-HP)
Paris, France
RECRUITINGAzienda Ospedaliero-Universitaria di Modena (AOU)
Modena, Italy
RECRUITINGQueen Elizabeth Central Hospital College of Medicine, P.O. Box 30096 Chichiri,
Blantyre, Malawi
To establish a biobank of at least 150 GBS serotype III cases including both the isolate and associated maternal and infant serum.
Biobank at St George's, University of London
Time frame: Over the course of 2 years
To determine the quantity of antibody associated with protection against GBS disease
Geometric mean and median antibody titres will be calculated for cases and controls and comparisons made as appropriate
Time frame: Over the course of 2 years
To determine the functional antibody associated with protection against GBS disease.
Samples will be tested using opsonophagocytosis killing assay for both anti-capsular and anti-protein antibodies.
Time frame: Over the course of 2 years
To demonstrate the relationship between antibody quantity and function in protection against GBS disease
To directly compare total antibody concentration titers (measured by multiplex LUMINEX) with opsonophagocytosis from functional antibodies at the time of birth and at the time of disease.
Time frame: Over the course of 2 years
To refine estimates for serocorrelates of protection against GBS disease.
To provide initial data on the relationship between antibody and invasive GBS disease risk by estimating the odds ratio of invasive GBS disease for antibody concentrations above various thresholds for STIII
Time frame: Over the course of 2 years
To provide training to participating African laboratories to assure the quality of sample collection and data curation.
A South-South partnership between Makerere University John Hopkins Research Collaboration (MUJHU),and Malawi-Liverpool-Wellcome Trust Clinical Research Programme (MLW) to optimise the capacity for conducting clinical trials for maternal immunisation in Sub-Saharan Africa
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
OBSERVATIONAL
Enrollment
600
Academisch Medisch Centrum,Universiteit van Amsterdam
Amsterdam, Netherlands
RECRUITINGMUJHU - Makerere University Johns Hopkins University Research Collaboration/MUJHU Care Ltd
Kampala, Uganda
RECRUITINGSt George's, University of London
London, United Kingdom
RECRUITINGTime frame: Over the course of 2 years