£5M Grant Fuels Breakthrough Diarrhoea Research

The Ineos Oxford Institute has been awarded a £5 million Wellcome Discovery Award to develop vaccines against pathogens that cause diarrhoea - the third most common cause of death for children under five years of age. The work will be led by Professor Sam Sheppard , Principal Investigator of IOI's digital microbiology programme.

Current meta-genomic epidemiology can be expensive, time consuming, and complex. As we set up our international hubs, we hope to train a new generation of scientists equipped with knowledge of genomic surveillance that will have impact beyond the lifetime of the grant.

Professor Sam Sheppard, Ineos Oxford Institute

Diarrhoeal disease is responsible for killing around 444,000 children every year , mainly in low- and middle-income countries (LMICs). Worryingly, antibiotics are becoming increasingly ineffective against the bacteria that cause diarrhoea as these evolve to resist the action of these medicines.

An international collaboration led by Professor Sheppard will tackle this challenge by creating a framework of meta-genomic epidemiology surveillance. This advanced approach is used to monitor and track the spread of infectious diseases by analysing the genetic material of all microorganisms present in a sample, including bacteria, viruses, fungi, and parasites. The aim is to apply the genetic data to develop a vaccine for livestock: one of the most effective ways to prevent the spread of antibiotic-resistant diseases.

This work will focus on Campylobacter, the most common bacterial cause of diarrhoea. These bacteria are prevalent in livestock such as poultry, cattle, pigs, and sheep and can be transmitted to humans via contaminated water and food. The research team will study the genetic make-up of Campylobacter populations recovered from hospital and farm sites, and use these data to develop a vaccine for animals that will interrupt the transmission chain and prevent the spread of Campylobacter to humans.

Pilot research has already taken place in The Gambia, Burkina Faso, Ghana and Peru. With the new funding, the team will further expand this work across Africa, where local partners will collect samples from infected humans and children, wild and domesticated animals, retail meat from supermarkets, and the natural environment (such as waterbodies).

Professor Sam Shepphard: a white man in a laboratory wearing a lab coat. On the bench in front of him are petri dishes filled with coloured and clear agar media. Professor Sam Shepphard.

Professor Sam Sheppard, Principal Investigator, Ineos Oxford Institute for antimicrobial research, said: 'Contemporary meta-genomic epidemiology techniques will help us understand cryptic disease networks and track how the disease is transmitted from animals to humans. Working in partnership with a network of 19 countries and nine African Co-investigators, the Wellcome Discovery Award will allow us to create a global genomic surveillance hub to track the spread of diarrhoeal diseases.'

The team will work with industrial partners who will support large-scale protein screening to investigate antibody responses in bacteria samples. The results from this screening will allow scientists to identify optimal vaccine targets and develop a state-of-the art glycoconjugate vaccine: a type of vaccine that combines a carbohydrate (sugar) molecule with a protein to enhance the immune response.

However, the work will go beyond developing the vaccine itself.

Professor Sheppard added: 'We need to ensure that the vaccine that we develop is stable, affordable and effective- that is the only way that there will be successful uptake, especially in low-and-middle income countries. Using the data collected in trials, we will monitor the effectiveness of the vaccine and quantify the impact of multiple factors to optimise vaccine delivery.'

'We also hope that the impact of our work will continue after a vaccine has been successfully developed. The genomic infrastructure and microbiology techniques set up in our partner countries as part of this project can be continued for further metagenomics work and vaccine development.'

The award from Wellcome will create opportunities for up to eight PhD students and Fellowships for African researchers over eight years.

This project is an excellent example of how strong, global collaboration, alongside developing innovative new tools and technology, are essential to discovery research, enhancing our understanding of disease, health and wellbeing.

Georgia Walton, Research Manager in Discovery Research at Wellcome

Georgia Walton, Research Manager in Discovery Research at Wellcome, said: 'We are excited to follow the research, which shows the potential to be highly impactful for public health by preventing the spread of this diarrhoeal diseases, with a clear vision on building capacity and training the next generation so that the data and tools can be applied to vaccine development more broadly.'

Besides the University of Oxford, the project involves researchers at Centre Suisse de Recherche Scientifique, Cote d'Ivoire; the Medical Research Council Unit, The Gambia; London School of Hygiene and Tropical Medicine, UK; and the Nigerian Institute of Medical Research African.

Further information about Professor Sheppard's work on digital microbiology can be found on the IOI website.

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