Preparing for Maternal GBS Vaccine Trials in Africa

Recruiting

• Conditions: Group B Streptococcus; Invasive Bacterial Diseases (IBD); Maternal Immunization

• Registration Number: NCT06833957
• Lead Sponsor: Barcelona Institute for Global Health

Brief Summary

Infections are one of the key causes of newborn deaths. Among them, Group B Streptococcus (GBS) is the leading cause of sepsis and bacterial meningitis in the first 90 days of life.

Fortunately, GBS vaccines for pregnant women, a powerful tool for fighting infections, are currently in development. Once vaccine trials are completed, these vaccines can stop preventable newborn deaths.

The PReparing for Optimal Phase III/IV maTErnal Group B StreptococCal vaccine Trials in Africa (PROTECT) project, funded by the European \& Developing Countries Clinical Trials Partnership (EDCTP) and European Commission, is supporting medical sites in Kenya, Malawi, Mozambique, and Uganda to establish uniform pregnancy and infant health data collection processes. It is also establishing surveillance of GBS in newborns to determine incidence rates and measure the burden of disease. With better reporting systems, medical sites can participate in vaccine trials and monitor vaccine safety. At the same time, the consortium is working to understand the drivers of vaccine hesitancy and to develop culturally appropriate communication tools to facilitate engagement with vaccines.

The end goal is to set up a network of sites that can monitor vaccine safety for current and future vaccines.

Detailed Description

Two vaccines designed for pregnant women, to protect their unborn infant, are entering late phase development and will prevent infections from GBS and respiratory syncytial virus, respectively. For these vaccines to be approved, the vaccine must work effectively without causing any unwanted responses. To implement these vaccines in countries with low resources, healthcare systems must be strengthened by improving vaccine safety monitoring and surveillance of infection, and advancing vaccine delivery, vaccine confidence, and patient participation.

The PROTECT study, funded by the EU Commission EDCTP, is three-fold:

1. Establishment of pregnancy exposure registries:

The rapid rollout of electronic health records (EHR) in some East African countries offers an opportunity to use routine data to strengthen reporting of rates of adverse pregnancy, neonatal and infant outcomes, and any adverse events following immunisation; this will be imperative in informing and preparing for future large scale vaccination rollout campaigns. The approach will develop pregnancy registries embedded within national reporting systems to establish this data, including baseline rates of pregnancy and infancy outcomes for Tetanus and COVID19 vaccines currently in use. These reporting systems will allow monitoring of potential safety signals once new vaccines are introduced.

2. Developing sentinel site GBS microbiological surveillance:

The investigators will conduct a prospective observational GBS surveillance study among infants less than 90 days old who are admitted with laboratory confirmed GBS. The investigators will develop and strengthen invasive bacterial disease (IBD) surveillance, with a focus on GBS in Kenya, Malawi, Mozambique and Uganda. Each of the proposed lead sites has access to microbiological capacity that will be leveraged to monitor microbiologically confirmed neonatal sepsis burden. In doing so, the investigators will improve the nations' ability to participate in late phase clinical trials and post-licensure effectiveness studies.

3. Vaccine Confidence:

The aim of this study is evaluating the knowledge and practices of pregnant women and other key stakeholders around vaccination and factors influencing vaccine confidence during pregnancy. The investigators will also create tools and communication strategies to improve willingness of pregnant women to participate in vaccine trials and consequently increase confidence in vaccines and vaccine trials during pregnancy in Mozambique, Uganda, Malawi and Kenya.

The investigators will work closely with the World Health Organization (WHO), African Medicines Agency and Country Stakeholders. This programme of work culminates in a network of maternal vaccine trial sites that can rapidly evaluate vaccines in pregnancy from late-stage trials through to introduction on a national level.

Study Timeline

• Status Verified: 2025-01
• Study First Submitted: 2025-02-13
• Study First Submitted QC: 2025-02-13
• Study First Posted: 2025-02-19
• Study Start: 2025-03-01
• Last Update Submitted: 2025-04-29
• Last Update Posted: 2025-05-02
• Primary Completion: 2027-02-28
• Study Completion: 2027-02-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 18100

Inclusion Criteria

• WP2 Pregnancy Exposure Registries inclusion criteria:

All women and their infants attending for antenatal and/or delivery and postpartum services at the study sites in Uganda, Malawi, Mozambique, and Kenya.

WP3 GBS Surveillance inclusion criteria:

• Infants aged less than 90 days old with laboratory-confirmed GBS infection admitted at participating health facilities in Uganda, Malawi, Mozambique, and Kenya.
• Infants whose parents or guardians provided written informed consent for their participation.
• Residents in the catchment area of participating health facilities.

WP4 Vaccine Confidence inclusion criteria:

• In Uganda, Kenya and Mozambique, pregnant women at any gestation period aged 18 years and above (reproductive age).
• In Malawi, pregnant women aged 16 years are eligible to be included in the study because they are considered emancipated minors.
• Pregnant women who consent to the study and give written consent.
• Stakeholders who include pregnant women, health workers, women leaders, community leaders, national stakeholders, cultural and religious leaders who are willing to take part and can give written informed consent.

Exclusion Criteria

WP4 Vaccine Confidence exclusion criteria:

• Pregnant women who are visiting/non-resident in the research area.
• Those who may be unwell and unable to consent to take part in the study.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Pregnancy exposure registries outcome 1.1	01.03.2026 - 28.02.2027	To establish pregnancy episode registries at sentinel site locations, at least 1 - 3 sites per country.
Pregnancy exposure registries outcome 1.2	01.03.2026 - 28.02.2027	To generate longitudinal cohort data on pregnancies, deliveries and infant outcomes for maternal vaccine safety assessment, specifically rates of obstetric and neonatal outcomes as defined by the GAIA project.
Pregnancy exposure registries outcomes 1.3	01.03.2026 - 28.02.2027	To generate comparable essential data across Kenya, Malawi, Mozambique and Uganda on adverse pregnancy, neonatal and infant outcomes using consensus definitions for maternal vaccine safety assessment.
Sentinel site GBS disease surveillance outcome 2.1	01.01.2025 - 01.09.2025	To develop and strengthen capacities for GBS disease surveillance in infants less than 90 days old at sentinel sites in four African countries, using microbiological and molecular detection methods.
Sentinel site GBS disease surveillance outcome 2.2	01.03.2026 - 28.02.2027	To determine the incidence rates of early and late onset iGBS disease among infants less than 90 days old admitted across established sentinel sites.
Vaccine confidence outcome 3.1	01.03.2025 - 28.02.2027	To enhance understanding of the importance of vaccination in pregnancy.
Vaccine confidence outcome 3.2	01.03.2025 - 28.02.2027	To understand willingness to participate in maternal vaccine trials in the four countries.
Vaccine confidence outcome 3.3	01.11.2025 - 20.08.2026	To co-develop an educational/communication toolkit with key stakeholders to enhance understanding of the importance of maternal vaccines in pregnancy in the four countries.

Secondary Outcome Measures

Name	Time	Method
Sentinel site GBS disease surveillance outcome 2.3	01.09.2025 - 28.02.2027	To assess the antimicrobial resistance patterns of GBS isolates among infants less than 90 days old.
Sentinel site GBS disease surveillance outcome 2.4	01.09.2025 - 28.02.2027	To determine the genomic profile of iGBS strains.

Trial Locations

Locations (9)

Ndirande Health Centre; 🇲🇼 Blantyre, Malawi

Mariakani Sub-County Hospital; 🇰🇪 Mariakani, Coast, Kenya

Rabai Sub County Hospital; 🇰🇪 Rabai, Kilifi, Kenya

Queen Elizabeth Central Hospital; 🇲🇼 Blantyre, Blantyre District, Malawi

Manhiça District Hospital; 🇲🇿 Manhiça, Mozambique

Lirangwe Health Centre; 🇲🇼 Blantyre, Blantyre District, Malawi

Hospital Geral De Mavalane; 🇲🇿 Maputo, Mozambique

Jose Macamo General hospital; 🇲🇿 Maputo, Mozambique

Kawempe National Referral Hospital; 🇺🇬 Kampala, Uganda