Hull York researcher joins team awarded £5.79m to transform immune responses to viral infections

Dr Ioannis Kourtzelis, Senior Lecturer in Immunology at Hull York Medical School, University of York is part of a project team that has been awarded £5.79 million funding from the Advanced Research and Invention Agency (ARIA) as part of the Sustained Viral Resilience Programme.  

The epiPRIME project (Epigenetically Programmed Resilience through Innate Memory Engineering) is led by Dr Chiara Herzog at the Cambridge Stem Cell Institute and involves a team that spans six institutions – bringing together expertise in epigenetics, chemistry, molecular biology, immunology, and human ex vivo lung models. 

ARIA, a UK-based research and development funding agency, also announced awards for ten other teams as part of the Sustained Viral Resilience funding, backed by a total of £57 million. ARIA’s programmes seek to catalyse scientific progress and create new communities and industries along the way, aimed at unlocking technological capabilities that seem intractable today but could prove critical for the UK in the long-term.  

The central target of the Sustained Viral Resilience programme is the demonstration of durable and safe prophylaxis against at least three separate families of respiratory viruses with a single course of administration. The teams, called ‘R&D Creators’, will work on individual projects across three technical areas, which span early proof-of-concept work exploring innovative approaches for broad-spectrum viral prophylaxis (Explorers, technical area [TA]1), the tools and platforms needed to accelerate this work (Accelerators, TA2), and the research needed to carry candidates towards clinical and commercial reality (Translators, TA3), but also collaborate to develop solutions to today’s most pressing viral issues. 

Viral infections remain among the most pressing public health and economic challenges worldwide. The COVID-19 pandemic is estimated to have claimed more than 15 million lives and cost the global economy over £10 trillion, while seasonal flu continues to infect a billion people and hospitalise millions every year. Both can also leave lasting health consequences, including heightened risk of autoimmune, neurological and cardiovascular disease. 

epiPRIME aims to tackle this challenge by developing broad prophylactic strategies that boost host resilience rather than targeted approaches to specific viruses and strains. While vaccines have been a major success story of medicine of the 20th century, they fail to keep pace with challenges today’s viruses. This is because vaccines are developed to target the ‘adaptive’ part of the immune system, which aims to prevent specific pathogens. epiPRIME will instead study the ‘innate’ part of the immune system, which rapidly clears viruses and can prevent or curb infections. The team hopes to achieve this by tapping into the body’s ability to create epigenetic ‘memories’ – modifications on top of DNA that switch genes on or off – and will aim to precisely install new memories, essentially upgrading the software of our immune cells so they can recognise and respond to threats they’ve never encountered before.  

There is already precedent for this type of broad ‘innate’ vaccine capability. The BCG vaccine, which is used for tuberculosis prevention, has also been found to protect recipients from a range of respiratory viruses as a positive side effect. However, this vaccine has varying levels of efficacy across individuals, and researchers have less control over its level of protection or mechanisms by which it is achieved. With the epiPRIME project, the researchers hope to build on this knowledge to eventually create precisely engineered, sustained innate immunoprophylactics (SIIPs) for broad viral coverage. 

Dr Ioannis Kourtzelis says: 

‘We are excited to provide key expertise in the regulation of trained immunity in vivo. Our contribution is essential for the in-situ identification of the innate immune and non-immune regulatory networks that orchestrate SIIP efficacy including durability, specificity and safety. Our £603,000 award will allow us to lead critical research activities in York, foster cross-partner collaboration and maximize the translational impact of epiPRIME.’ 

Other members of the epiPRIME team from across the UK: Professor Jordana Bell (King’s College London), Dr Gabrielle Ficz (Queen Mary University of London), Dr Pratik Gurnani (University College London), and Dr Aaron Scott (University of Birmingham).  

Brian Wang, ARIA Programme Director, says: 

‘We're excited to be funding the epiPRIME team, which is bringing together epigeneticists, computational biologists, respiratory immunologists, and delivery chemists across six institutions to identify and programme virally resilient cell states with CRISPR-based epigenetic editing. Epigenetic editing is a relatively new approach in drug discovery and has been enabled by advances in synthetic biology over just the past few years. We look forward to seeing how applying this cutting-edge technology could help us create a new paradigm in antiviral protection, and we believe epiPRIME's interdisciplinary team is especially well-placed to test this ambitious idea.’  

In the future, epiPRIME hope that their solution to broad disease prevention in humans will have the potential to expand beyond viral infections to cancer or ageing-related illnesses.