UK rabies vaccine trial could also unlock protection against Disease X

The first participants have been vaccinated in a new UK trial of an investigational rabies vaccine that could be easier and cheaper to produce than existing vaccines,while also providing crucial insights into whether the vaccine’s underlying next-generation RNA technology can help rapidly respond to future pandemic threats. 

The first-in-human study, known as RAB-Vac, is led in collaboration between Imperial College London and Chelsea and Westminster Hospital NHS Foundation Trust and funded by the Coalition for Epidemic Preparedness Innovations (CEPI). 

Approximately 48 healthy adult participants will take part in the research department at Chelsea and Westminster Hospital in London to assess the safety of the vaccine candidate and the immune response generated following vaccination. 

People become ill with rabies after being bitten or scratched by infected animals, with stray dogs accounting for the majority of infections worldwide. If the illness reaches the brain, it results in neurological symptoms and, almost always, death. An estimated 60,000 people lose their lives to the disease each year, almost one person every nine minutes – with children particularly vulnerable - and the number of infections is increasing in parts of Asia and Africa. 

While rabies vaccines are licensed for use in people, current designs are difficult and expensive to manufacture which can limit getting supplies to where they are needed most. The investigational vaccine being tested in RAB-Vac could mean the vaccine is easier to make at a lower cost.

As the vaccine candidate uses an innovative fast and flexible RNA design, it could also unlock clues on the potential to repurpose the underlying platform to rapidly fend off infectious diseases with epidemic or pandemic potential, including a new or as-yet-identified ‘Disease X’. 

“We don’t know when the next Disease X is coming – nor what it may be - but we know it’s guaranteed,” explains Dr Kent Kester, Executive Director of Research and Development, CEPI. “We therefore need to leverage the world’s leading vaccine innovations, like the RNA technology Imperial College London is developing, to be ready to rapidly respond to whatever may come our way.”

mRNA technology became a pivotal part of the COVID-19 pandemic response, quickly producing safe and highly effective COVID-19 vaccines in record time. Its plug-and-play design means the technology can be quickly adapted to code for vaccines against other pathogens. As every day counts in response to an outbreak, this speed of development could be vital, supporting CEPI’s goal to create vaccines against new threats within 100 days and giving the world the chance to prevent a future pandemic.

Imperial’s vaccine candidate also holds potential in helping to respond to a future outbreak as it uses a self-amplifying mRNA approach. 

In addition to containing genetic instructions that safely code for immune-generating antigens, as is seen in conventional mRNA designs, the vaccine platform also contains the instructions for replicase, an enzyme that serves as a built-in photocopier temporarily teaching the body how to make more mRNA. This self-copying design could help to reduce the dose of RNA needed while maintaining the effectiveness of the vaccine which could help to extend supply of a vaccine to reach more people in an outbreak. 

“This marks a significant milestone in our partnership with CEPI and in the development of a next-generation self-amplifying RNA vaccine platform capable of delivering protection at lower doses than conventional mRNA vaccines” explains Professor Robin Shattock, Head of Mucosal Infection and Immunity within the Department of Medicine at Imperial College London and lead of the study.

“The clinical evaluation of our rabies vaccine is an important step in demonstrating the platform’s potential to support rapid, scalable vaccine responses to future pandemic threats.” 

CEPI has been supporting the development of Imperial College London’s self-amplifying RNA vaccine since 2018, providing up to £11.1 million into researching the technology. This included funding to a similar RNA platform evaluated during COVID-19 which demonstrated a favourable safety profile in more than 200 participants.

Both CEPI and Imperial College London are committed to ensuring any vaccines developed on the CEPI-supported technology are made affordable for low- and middle-income countries during an outbreak, if they are successful in testing. 

This study has received infrastructure support in part by the NIHR Imperial Biomedical Research Centre (BRC).

For more information on the trial and signing up to take part as a volunteer, visit the Imperial Medicine or Chelsea and Westminster Hospital Foundation NHS Trust websites.

Participants must meet certain eligibility criteria, including being aged 18-55 and availability for all follow-up visits.