The Coalition for Epidemic Preparedness Innovations (CEPI) is teaming up with leading scientists at the Houston Methodist Research Institute to further develop a promising type of disease-defense technology that could pave the way for new 'circular RNA’ vaccines that are more stable, durable and cost-effective.


With CEPI funding of up to $3.8 million, the Houston Methodist vaccinology team aims to advance its ‘circRNA’ platform, a high-impact innovation offering significant potential beyond mRNA vaccines in defending populations against future epidemic and pandemic disease threats. The project is focused on the design and preclinical evaluation of ‘circRNA’ vaccine candidates, initially against Chikungunya – a CEPI priority pathogen that is a member of the Togaviridae family - and aims to generate the data necessary to establish preclinical proof of concept for the vaccine platform.


RNA vaccine technology, which uses the body’s own machinery to make antigenic protein rather than injecting an antigen into the recipient, has made significant progress in recent years.  The most ground-breaking advance came with its validation for the first time during the COVID-19 pandemic, when it was used to develop new vaccines in less than a year that went on to save millions of lives and reduce the number of severe cases of COVID-19.


While mRNA vaccines are now expected to play a crucial role in preventing and controlling future outbreaks and pandemics, they have some limitations – including the potential to provoke local reactions or short-term fever in people who receive them. Relative to other types of vaccine, they are currently expensive to manufacture and require costly and complex cold-chain storage and transportation infrastructure.


As the name suggests, circular RNA vaccine technology uses a closed-loop RNA, which could enable vaccine candidates based on it to be more stable and durable than current linear-based mRNA candidates. The technology could also deliver improved efficacy in smaller doses. HMRI’s circRNA platform is still in the early-stages of development, but, if successful, it has the potential to be effective in single-dose regimens, to reduce the amount of RNA needed per dose and to lower the cost of RNA-based vaccines, which could altogether contribute to the accessibility of mRNA vaccines.


“Despite being once thought of as ‘molecular junk’, recent research has suggested that, with its stable looped structure, ‘circular RNA’, could be harnessed for RNA-based medicines, like vaccines” explains Dr In-Kyu-Yoon, Acting Executive Director of Vaccine R&D at CEPI. “If effective, these circRNA vaccines could progress this new scientific era of mRNA vaccinology even further, leveraging not only the speed at which the technology can be designed and tested in response to infectious disease outbreaks but also the potential to create more durable and accessible mRNA vaccines for greater global protection when faced with a deadly disease threat.”


CEPI’s investment in HMRI is the latest in its program to advance novel RNA vaccine platform technologies for emerging and select endemic infectious diseases. The program aims to evaluate whether the next-generation of RNA technologies could offer substantial advantages over existing mRNA platforms, for example improved immunogenicity, storage, stability, productivity, response time, and cost-of-goods. Improvements to rapid response mRNA technologies may contribute to the 100 Days Mission, a goal backed by leaders of the G7 and G20, to compress vaccine development timelines to 100 days.


“We are excited to be working with CEPI on the development of circular RNA vaccine technology to protect the world against emerging viral threats,” said H. Dirk Sostman, M.D. President and CEO of the Houston Methodist Academic Institute. “This effort is led by Dr. John Cooke, director of our Center for RNA Therapeutics, with a team of innovative scientists including Drs. Dan Kiss, Jimmy Gollihar, Kristopher Brannan and Francesca Taraballi, together with our colleagues at University of Texas Medical Branch. Houston Methodist is leading medicine by generating fundamental scientific insights that have transformational effects on human health.”


Enabling equitable access to vaccines


CEPI and HMRI are committed to enabling equitable access to the outputs of this CEPI-supported program, in line with CEPI’s Equitable Access Policy. This ultimately includes commitment to vaccines being available first to populations at risk when and where they are needed at an affordable price should a related vaccine be developed further using CEPI funding. Project results including data generated as part of this project will be published open access for the benefit of the global scientific community.