Next generation vaccine tech offers post-COVID opportunities – global experts

The Imperial-led Future Vaccine Manufacturing Research (FVMR) Hub co-hosted an event with the Vax-Hub on what we have learnt from COVID-19.

The event, entitled ‘Vaccine manufacturing during a global pandemic: what have we learnt from COVID-19?’ explored the role of academia in vaccine manufacturing research and innovation, the UK's position in global health research and international development, and the lessons learnt from the COVID-19 pandemic to shape future research in this area. 

Speakers included Professor Robin Shattock, Chair in Mucosal Infection and Immunity and Director of the FVMR Hub at Imperial, Professor Sarah Gilbert, Professor of Vaccinology at the Jenner Institute and Co-Director of the Vax-Hub, University of Oxford, and Steve Bagshaw, of the Vaccines Taskforce Programme, Department for Business, Energy and Industrial Strategy. 

Imperial’s FVMR Hub and the Vax-Hub, led jointly by UCL and the University of Oxford, are funded by the DHSC and began in December 2017. The FVMR Hub has focused on supporting innovative platform technologies that are promising for vaccine manufacturing.  

The Hubs focus on supporting vaccine technologies for Official Development Assistance (ODA) demographics – in most basic terms this means those living in developing countries (also known as lower- and middle-income countries, or LMICs). In light of the UK government's decision to reduce the funds available for ODA, the Hubs face challenges in obtaining follow-on funding if they are to maintain focus on ODA targets. 

The event highlighted the importance of vaccine manufacturing research, and how well-funded academic projects can directly help to support vaccine manufacturing, and thus rapid responses to pandemics.   

Professor Robin Shattock outlined Imperial's work on self-amplifying RNA-based vaccines (saRNA): “Self-amplifying RNA allows you to use lower doses. This allows you to manufacture far more doses, the safety profile is better and it allows us to think about combination vaccines. We see this as technology of the future for multi-component vaccines in the RNA space.” 

However, Professor Shattock went on to emphasise that the UK must invest to keep up with RNA vaccine revolution and build capacity to develop the vaccine much faster. “In other countries, RNA vaccines had very strategic investments from governments. There are significant lessons the UK can learn from that investment in innovation and manufacturing in the RNA space.” 

There are significant lessons the UK can learn from other countries' investment in innovation and manufacturing in the RNA space.  Professor Robin Shattock Imperial College London

Professor Sarah Gilbert, the lead researcher on the University of Oxford's vaccine team and Co-Director of the Vax-Hub, presented the background to and processes behind the success of the Oxford/AstraZeneca vaccine, noting the importance of the vaccine hubs.

“It was very good foresight to have these hubs both working on different technologies but providing very useful outputs,” said Professor Gilbert, praising the flexible funding that allowed the Vax-Hub to move quickly during the COVID-19 pandemic.  

Earlier in June 2021, the UK government outlined its intention to work towards the ambition of a 100 Days Mission, which follows crucial discussions at UK-hosted G7 Health Ministers’ and life sciences meetings in Oxford. The collaboration aims to protect against future pandemic threats and slash time to develop and deploy new diagnostics, therapeutics and vaccines to 100 days.  

The final part of the event convened discussions around how we can better prepare for the next pandemic and future innovations in vaccine manufacturing. The discussion ranged from working through the barriers to facilitate and help local manufacturing to be developed across the globe, to the slow and silent pandemic of antimicrobial resistance. 

Professor Gilbert concluded by noting the importance of the way that the hubs have worked together to bring together networks, expertise and different types of organisations, and how valuable this activity has been - and could continue to be - in adding to our resilience for the future. 

In Professor Shattock's closing remarks, he noted how the funding of the hubs was very well timed and came out of ODA funding, but was limited to three years. He said long term investment is essential to the development of technologies and to build capacity in the UK and in other countries.

Innovation in vaccine manufacturing 

The FVMR Hub set out to rethink the way we approach vaccine design and manufacture. Whilst current vaccination programmes have been very successful, our capacity to respond rapidly to emerging disease threats has been limited. Prior to COVID-19, the timeline from emerging threat to licenced vaccine was typically around 10 years. Even when successful vaccines have been developed, the cost of making and distributing the vaccines is often unaffordable for LMICs. The Hub has focused on two main strategies to tackle these problems: improving existing vaccine manufacture and distribution, and overhauling the entire process in favour of newer, more efficient technologies. A key philosophy of the Hub has been to work alongside LMIC partners to ensure that research remains focused on providing affordable solutions that work for all.

Professor Nilay Shah, Head of the Department of Chemical Engineering, has been using modelling to redesign and optimise a new flexible modular system for rapid development and deployment of vaccines. Tackling a global pandemic requires the design and production of billions of doses of vaccines within months, with several hurdles along the way including safety testing, regulatory approval and acquiring manufacturing facilities. Professor Shah's team works on modelling this entire process ahead of time so that quality vaccines can be produced as efficiently as possible during a pandemic.

A highly promising strategy which Professor Shah has endorsed is the use of RNA vaccine technology. RNA vaccines have been one of the major success stories of the COVID-19 pandemic, with two messenger RNA (mRNA) vaccines now in use. The speed of development here is hugely impressive, since RNA vaccines were a relatively new technology that had never been licenced for use in humans prior to 2020. One of the reasons RNA platforms are so promising is that they can be designed and manufactured much quicker and more easily than traditional vaccine technologies.

Traditional vaccines train your immune system to combat disease by exposing to an antigen – this is usually in the form of a dead pathogen, or parts of a pathogen. With mRNA vaccines, a different approach is taken: these vaccines deliver instructions which your body uses to make the antigen itself.

However, mRNA is still very expensive to make. Professor Robin Shattock and his team are working on a solution to this problem by developing the next generation of RNA vaccine, known as self-amplifying RNA (saRNA). This is very similar to mRNA, but in addition to the instructions for making the antigen, the vaccine also contains instructions to make more copies of itself. This self-amplifying effect means you can give a much smaller dose of the vaccine than mRNA while maintaining efficacy, significantly reducing cost and manufacturing requirements.

Professor Jason Hallett is working on making both new and existing vaccine technologies more accessible by stabilising vaccines so that they can be stored without the need for refrigeration. Most vaccines (including RNA vaccines) need to be kept cold to prevent spoilage, leading to costly distribution infrastructure known as the “cold chain” – literally the chain of refrigeration facilities required to get the vaccine from A to B. Professor Hallett's team are working on strategies to eliminate the need for the cold chain entirely. This will drastically aid vaccine distribution, especially within LMICs where setting up cold chain infrastructure can be prohibitively expensive. In the meantime, improving stability so that vaccines can be stored in the fridge rather than deep-freezing at -80 °C can still have major cost and logistical benefits.