mRNA technology revolutionised our traditional approach to vaccine technology in the wake of COVID-19. But what next for the platform?

The UK stands at the cusp of a new era in medical innovation and can be a global leader in this rapidly developing area Professor Paul Kellam Professor of Virus Genomics

More than 75 of the UK’s leading scientists, clinicians and industry experts gathered at an Imperial Business Partners’ event in September to discuss the latest advances in mRNA technology and the UK’s role in progressing this technology as a global leader in the life sciences.

The event, Future directions: mRNA technology in the UK, examined the current landscape of mRNA technologies, the role of artificial intelligence in vaccine creation and clinical applications of mRNA technology. It brought together immunologists and vaccine experts, pharmacologists and biochemists, computer scientists, clinicians, regulatory specialists, industrial scientists, manufacturers and start-up entrepreneurs, delivered through Imperial Business Partners. 

Opening the event, Paul Kellam, Professor of Virus Genomics at Imperial College London, said: “The UK stands at the cusp of a new era in medical innovation and can be a global leader in this rapidly developing area.”

“When you have a new technology such as mRNA that operates in an area as fundamental as how cells translate their DNA genomes into proteins, then rapid advances can be made in many disciplines,” Professor Kellam said. “The UK can lead the world in applying this technology. In West London’s new MedTech corridor, we have an environment for innovation. Across the UK, we have a health system open to innovation. We also have a large, diverse population, the scientific expertise, and the pharmaceutical and manufacturing base.”

Advances in mRNA technology: the current landscape

The relationship between high expression levels in cell cultures and the effectiveness of a vaccine in the body is not clear. This is an open challenge Tobias von der Haar Professor of Systems Biology, University of Kent

The event was organised across three sessions, the first of which explored the current landscape of mRNA technologies with three speakers: Tobias von der Haar, Professor of Systems Biology at the University of Kent, Robin Shattock, Professor of Mucosal Infection and Immunity at Imperial and Dr James Thaventhiran, Principal Investigator, MRC Toxicology Unit, University of Cambridge. Key points from the discussion included:

• On mRNA vaccine applications, the discussion explored different vaccine platforms as well as the potential of new technologies such as self-amplifying RNA (saRNA) for longer expression, while recognising that this is still in the early stages of clinical development. It also highlighted the importance of developing a better understanding of the impact of body weight and obesity on vaccine efficacy and durability.
• On vaccine formulation, it was pointed out that there are numerous formulation strategies, but few predictive models for responses in humans and there is uncertainty about the best delivery strategy.
• The panel agreed that RNA technology was a significant opportunity for realising personalised medicine, with targeted therapies based on genetic profiles. However, there is a need for scalable manufacturing processes. One option suggested was decentralised manufacturing, with small-scale local manufacturing sites to meet specific patient needs. This brings with it challenges around consistency and quality control.
• The panel advocated for empowering regulatory bodies to respond swiftly and fostering new partnerships between academia and industry to drive innovation and address manufacturing challenges.

“Most people start RNA development with cell culture experiments and look for high expressions of the target protein. But the relationship between high expression levels in cell cultures and the effectiveness of a vaccine in the body is not clear. This is an open challenge.” Tobias von der Haar, Professor in Systems Biology at the University of Kent

“At the moment, no mRNA vaccine can compete with an attenuated vaccine or a viral vector, which can give decades long protection from disease, whereas saRNA, with its longer expression, may prove to be more durable.” Robin Shattock, Professor of Mucosal Infection and Immunity at Imperial

Artificial intelligence: a new paradigm in mRNA vaccine development

The second session explored the potential of artificial intelligence (AI) in mRNA vaccine development, with four industry and academic experts: Aldo Faisal, Professor of AI & Neuroscience at Imperial, Joshua Blight, CEO at Baseimmune, Simon Daniel of Imperial's Future Vaccine Manufacturing Hub and Wade Davis, VP of Computational Science and Head of Digital for Research for Moderna.

AI is a toolkit. It may be a jump in learning, but it’s still a tool. Joshua Blight CEO, Baseimmune

Applying AI has potential to optimise drug trials and to transform vaccine development, said Professor Faisal, opening the discussion: “These systems can think in bigger scope and more efficiently than us”.

Key points from the wider discussion included:

• Large, structured datasets are essential to harness the potential of AI for vaccine development, making it possible to generate meaningful insights and streamline the research process.
• In this context, it is important to integrate models based on human scientific knowledge with AI to guide data-driven models and achieve interpretable results.
• There was agreement that AI required researchers to rethink how we formulate scientific questions, how we search for answers and verify hypotheses. 
• Opening the discussion to the floor, one attendee said it was important to synchronise languages between computational science and vaccinology to enable interdisciplinary understanding.

 “AI is a toolkit. It may be a jump in learning, but it’s still a tool. If used properly, we can use it to explore the space we don’t understand through deep computational learning,” Joshua Blight, CEO at Baseimmune

Clinical applications of mRNA technologies

The final session explored clinical applications of mRNA technologies. Sander Fortanier, Clinical Programme Director at CSL Seqirus, outlined challenges around mRNA technologies for flu. This includes developing a better understanding of the causes of reactogenicity, the physical markers such as chills and headaches which show an inflammatory response to a vaccine. He also highlighted the sensitive balance between inducing an immune response and the durable expression of proteins, and establishing the optimum dosing interval. 

The next speaker, Dr Katrina Pollock, Associate Professor in Vaccinology at the University of Oxford, and Honorary Clinical Senior Lecturer at Imperial, discussed her work on the LEGACY Network, an international collaborative programme to advance understanding of how ancestry affects our immune response to vaccines. The aim is to try to map cell-level responses to commonly used vaccines as part of the ongoing Human Cell Atlas, an international research initiative that aims to create a map of all human cells. As part of this research, Dr Pollock has worked closely with people to understand what they want from mRNA technology.

Future hopes for clinical applications of mRNA

If we can engineer mRNA to enhance T follicular helper cells in the lymph nodes, we could potentially create more effective vaccines. Dr Katrina Pollock MRC Clinician Scientist in Vaccinology at the Oxford Vaccine Group

In a final panel, the speakers discussed their hopes for future clinical applications of mRNA technology. Key points from the discussion included:

• mRNA technology has potential in applications to control diseases of ageing, such as cancer and vaccines specifically for older people and those who are immunosuppressed.
• However, scientists need to better understand the ageing immune system, carrying out comparative studies with older and younger people to understand the mechanism of action in target tissues.
• While mRNA technology has potential in this area, there are challenges around cost-effectiveness. How do you manufacture individualised vaccines at scale? One answer could be developing an RNA platform that can be used for different cancers or diseases, while still being tailored to an individual’s genetic profile.  
• Developing quality control and regulatory frameworks for new vaccine technologies, especially for cancer and rare diseases, is another crucial challenge.
• From a commercial point of view, industry is especially interested in exploring mRNA applications for cancer, rare diseases and chronic diseases. There is a need for larger clinical trials to advance this area.

“If we can engineer mRNA to enhance T follicular helper cells in the lymph nodes, we could potentially create more effective vaccines. This is an exciting possibility for mRNA technology, but it's a complex challenge that requires collaboration across different scientific disciplines." Dr Katrina Pollock, Associate Professor in Vaccinology at the University of Oxford and Honorary Clinical Senior Lecturer at Imperial

The future of healthcare innovation lies in continued collaboration across industries, academia and regulatory bodies, said Professor Kellam, closing the event: “To realise the potential of mRNA in clinical applications we must work together to address the challenges of developing scalable manufacturing, regulatory frameworks and new treatments.

"We encourage scientists, healthcare professionals and industry leaders to forge new multidisciplinary partnerships, driving this vital research forward to benefit patients and public health.”