Invasive Group B Streptococcus disease in young infants: understanding host and pathogen immunity ito inform maternal GBS vaccination development

Infections during the first month of life are the leading cause of death in Africa and Group B Streptococcus (GBS) is emerging as a major culprit. GBS is a bacterium living in the back passage and vagina of women. GBS can cause lethal infection in pregnant women, stillbirths and premature births. It can be passed from mother to baby at birth or in breastmilk. Once passed on, GBS either remains harmless or causes severe pneumonia, sepsis and meningitis in new born babies. One way a mother protects her baby is by passing antibody against GBS through the placenta and in breastmilk after birth. However, we do not yet know how much antibody needs to be passed in this way to protect babies from disease. It is also unclear what changes GBS undergoes to become a potentially fatal bacteria.

At present, babies in the Africa are still dying or being born too early and too small because of infections like GBS. Our research group is dedicated to finding out why GBS passes from mother to child, what the "protective" antibody levels need to be passed through the placenta to stop babies from getting sick in the first place and how to prevent GBS disease through new treatments such as maternal vaccination. We use a variety of different ways to find out the answers - through doing fieldwork (where mother and their babies are followed up over three months from birth to see what effect GBS has on their health) or by developing laboratory tests to see how antibody works to protect against GBS.

We will use these answers to change how we look after pregnant women and monitor their babies for signs of infection. We do this so that we can improve the health of women and their babies. We bring together a number of different ways of working with the single aim of preventing GBS infections in babies (and their mothers). Our planned work includes the following:
1. Following mothers and babies in Uganda and collecting blood samples to work out how much antibody a mother needs to pass to her infant to protect against GBS infection;
2. Collecting bacteria and blood samples from babies who get GBS disease (via public health agencies we work with already) in the UK, Netherlands and France to compare if the type of bacteria found in different populations affects the amount of antibody needed to protect babies against GBS disease.
3. Helping hospitals in Uganda to investigate infections in babies by strengthening diagnostic laboratory capacity and working with clinicians to investigate and treat infections early.
4. Engaging with women in the African sites to understand whether a vaccine given to pregnant women to prevent GBS-as is currently being developed- is likely to be taken up sufficiently to be effective.

Over 3 million infants and 300,000 women died in the period between birth and during the first month postpartum each year. It is estimated that 40% of these deaths are due to infectious diseases and most of these deaths occur in countries in sub-Saharan Africa such as Uganda. It is therefore unsurprising that infection during the peripartum and postnatal period is a critical area of development highlighted in the United Nations Sustainable Development Goal 3. The success of the maternal tetanus vaccination programmes has seen deaths from neonatal tetanus decline by 80% over the last 20 years and highlights the potential benefits to mother and infant of vaccination against key infectious diseases during pregnancy.
Group B Streptococcus (GBS) is the leading cause of invasive infant disease during the first three months of life in many countries and is emerging as a leading cause of stillbirth and maternal infection. Maternal vaccines against the major disease-causing serotypes of GBS are under development, yet major gaps in knowledge of serotype prevalence and disease in countries with the highest mortality and morbidity from infant infections prevent a comprehensive assessment of potential vaccine efficacy in populations such as Uganda.
It is widely accepted that efficacy trials of a potential GBS vaccine will be difficult outside of high burden settings such as South Africa and there is much interest in alternative pathways to licensure such as serocorrelates of protection.
This research programme aims to plug these gaps by providing epidemiological data from a high HIV-burden setting of serotype-specific GBS antibody to predict serocorrelates of protection against invasive disease in HIV-infected and uninfected Ugandan cohorts and compare these to European cohorts using standardised assays developed by the consortium that Dr Le Doare currently leads.
The outcomes of this research will be of direct interest to industrial partners, Pfizer, GSK, Minervax, Biovac and PATH, all of whom are developing GBS vaccines for high and low resource settings. All data will be made available as soon as possible in a freely available and widely accessible format as per UKRI policies to enable data analysis across platforms and to compare results from different studies. In this way, it is anticipated that the impact may be achieved through intellectual property protection (e.g. patenting) and subsequent commercialisation through licensing out the novel assay to an external commercial partner, thereby making the assay available to the market to benefit society and economy. I am in close contact with SGUL JRES Enterprise and Innovation which will provide expert knowledge, support and additional resources to achieve this impact. It is anticipated that the first data will be available within the first 4 years of this fellowship.
The close collaboration with WHO and NIHR through my membership on advisory panels will ensure that national and international policy-makers are kept fully informed of the serocorrelates work as it progresses. We anticipate annual stakeholder meetings to present our findings. Additionally, the data generated from Uganda will be of direct benefit to the Ugandan government in deciding whether a GBS vaccine can be adopted onto the extended programme on immunisation country schedule. The results of this work will also be available to Global Alliance for Vaccines Initiative to inform vaccine cost-effectiveness analyses as vaccine development progresses.
Most importantly, though, the results of this programme of research will directly benefit pregnant women and their infants in Uganda, by providing the most comprehensive information on infection in pregnancy and infancy to date. The platform that this research will create will initially be used for GBS vaccine trials but can be extended to other vaccine-preventable disease because of the comprehensive data that will be generated.