Professor Jordana Bell and Dr Paul Lavender from King's College London are part of a project team that has been awarded £5.79 million in 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.
£227,000 of the funding will support work at King's, where Professor Bell will lead a package of work focused on identifying 'epigenetic signals' - ways our body controls what genes are turned on and off without making changes to the DNA - that protect the body from viral infections. This will combine large-scale data with computational approaches, utilising TwinsUK cohort data generated within a Wellcome LEAP Dynamic Resilience award and integrating Dr Lavender's research in respiratory epigenetics.
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,' or preventive medicines, 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.
Addressing a global public health and economic challenge
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 the challenges of 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.
We look forward to working together with ARIA and the research teams to tackle this important challenge, by integrating research activities at King's College London. Our contributions focus on prioritising regions of the genome that have potential to form an epigenetic blueprint of innate immune resilience, and that other epiPrime research team members can explore in functional experiments towards developing sustained innate immunoprophylactics.
Professor Jordana Bell, Professor in Epigenomics at King's College London
Other members of the epiPRIME team from across the UK include Dr Gabrielle Ficz (Queen Mary University of London), Dr Pratik Gurnani (University College London), Dr Aaron Scott (University of Birmingham) and Dr Ioannis Kourtzelis (University of York).
We're excited to be funding the epiPRIME team, which is bringing together 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.
Brian Wang, ARIA Programme Director
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.
