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Researchers at the University of Sheffield are leading a major £4.7 million international research programme to unlock the mysteries of Group A Streptococcus (Strep A).
Researchers at the University of Sheffield are leading a major international research programme to unlock the mysteries of Group A Streptococcus (Strep A) – a common bacterium that causes everything from sore throats and skin infections to life-threatening disease – with the aim of accelerating the development of effective vaccines.
The seven-year programme has been awarded £4.7 million through a prestigious Wellcome Discovery Award and brings together researchers from the University of Sheffield, the Medical Research Council (MRC) Unit The Gambia, the University of Auckland, the Walter and Eliza Hall Institute in Melbourne and Institut Pasteur in Paris.
Strep A is responsible for an estimated 500,000 deaths worldwide each year, primarily through rheumatic heart disease – a serious condition that can develop when the body's immune response to infection mistakenly attacks the heart. The disease disproportionately affects children and young people living in low and middle income countries. Despite this, there are no available Strep A vaccines.
Although several Strep A vaccines are currently in development, scientists still do not know exactly what a protective immune response looks like or why repeated exposure to the bacteria during childhood often fails to provide lasting immunity. By answering these fundamental questions, this research aims to provide the evidence needed to design more effective vaccines and determine the best time to vaccinate children in the communities most at risk.
Professor Thushan de Silva, Professor of Infectious Diseases and Lead Investigator of the grant, University of Sheffield, said: “Despite repeated exposure to Strep A from infancy, many children in the countries most affected by the disease do not develop lasting protection against the bacteria. We also do not understand whether these exposures that happen very early in life are important in increasing the risk of developing rheumatic heart disease in later childhood and adolescence. This programme will help us understand our immune responses to early Strep A exposure and provide evidence to guide both the development of Strep A vaccines and future vaccine policy”
The research will focus on three key questions:
Which antibody responses genuinely protect children from Strep A infection?
Why doesn't repeated exposure during early childhood lead to strong natural immunity?
Does the immune process that eventually causes rheumatic heart disease begin in infancy, and if so, what patterns of infection trigger it?
To answer these questions, researchers will combine advanced immunology, mathematical modelling and long-term clinical studies across several Gambian cohorts.
The programme includes a new birth cohort study in The Gambia, where children will be followed closely during their first two years of life. Researchers will also use an innovative proteome-wide antibody screening technology developed by collaborators at the University of Auckland to examine immune responses in unprecedented detail.
As part of the study, a carefully designed clinical trial will use a short course of the antibiotic azithromycin as a research tool to alter the timing of children's first exposure to Strep A. Comparing children exposed earlier and later in life will help researchers understand how early infections shape immunity and future disease risk.
The team will also link these findings with data from a multi-country study (The Gambia, Uganda and Malawi) screening more than 22,000 children for early signs of rheumatic heart disease.
The research team has already identified antibodies against three vaccine candidate proteins that appear to protect against Strep A throat infections, although not skin infections – an important finding for countries where skin infections are the more common route of exposure.
The new programme aims to identify additional protective immune targets, understand why natural immunity develops so poorly in early life, and discover early biomarkers that could identify children at greatest risk of developing rheumatic heart disease.
The findings are expected to directly inform the design of future Strep A vaccines and help determine the best age to vaccinate children in high-burden settings.
Alongside its scientific aims, the programme has a strong focus on strengthening research capacity in The Gambia. The project will support the training of African postdoctoral researchers in advanced serology and data science, helping to ensure future Strep A research is increasingly led by scientists working in the regions most affected by the disease.
Dr Eunice Kiamba, co-applicant on the award and an early career researcher (ECR) based at the MRC Unit The Gambia, said: “A major challenge facing health research in Africa is the limited investment in the development and retention of early career researchers, resulting in gaps in scientific leadership, specialised expertise and the capacity to lead locally relevant research programmes. As an ECR based in The Gambia, I am particularly excited by the programme’s commitment to sustainable capacity building in Africa, through training and mentorship in key Strep A research disciplines, including advanced serology, cellular immunology, and data science. “
The programme represents a significant step towards developing vaccines that could save lives and prevent long term complications of Step A infection worldwide.
The NIHR funds, enables and delivers world-leading health and social care research that improves people's health and wellbeing and promotes economic growth.
NIHR Biomedical Research Centres (BRCs) are collaborations between NHS organisations and universities. They bring together academics and clinicians to translate scientific discoveries into potential new treatments, diagnostics and technologies.
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