New research to investigate next generation ‘trans-amplifying’ mRNA vaccines

mRNA vaccines, Credit: Shutterstock
  • Promising technology to be tested in preclinical studies funded by CEPI
  • The innovation could enable up to 100 times less antigen-encoded mRNA per vaccine dose and for parts of the vaccine to be made ahead of an outbreak
  • Some lifesaving COVID-19 vaccines use mRNA, and the innovation could be key to more rapidly responding to future threats

07 March 2024, OSLO, Norway and BOSTON, MA – Scientists in the US are set to test a new vaccine approach that could overcome some of the challenges associated with the latest mRNA vaccine designs and more rapidly create pandemic-busting vaccines in as little as 100 days.

With up to US $1 million in funding from CEPI, researchers at Amplitude Therapeutics will perform preclinical studies that assess whether their trans-amplifying mRNA vaccine approach could provide a simplified alternative to the self-amplifying mRNA vaccine technique being used today.

Alongside conventional* mRNA vaccines—the technology behind multiple safe and effective COVID-19 vaccines that have helped to save millions of lives—self-amplifying mRNA designs have become more prominent in recent years, with the first-ever licensure of a self-amplifying mRNA COVID-19 vaccine in Japan in November 2023

Rather than the traditional vaccine approach of injecting an antigen (a substance that induces an immune response) directly into the recipient, mRNA platforms use the body’s own cell machinery to make the antigen. Self-amplifying mRNA vaccines are even more specialised as they contain genetic instructions that not only encode for the antigen but also replicase, an enzyme that serves as a built-in photocopier teaching the body how to make more mRNA. 

While this self-copying design offers important advantages over conventional mRNA vaccines, such as the potential to reduce the dose of mRNA needed while maintaining the effectiveness of the vaccine, there are limitations. For example, the additional genetic instructions required for the replicase make the vaccine sequence at least three times longer than standard mRNA vaccine sequences which can lead to difficulties during manufacturing and delivery. 

Trans-amplifying mRNA vaccines, which consist of two separate, shorter RNA fragments—one encoding the antigen and one encoding the replicase—may provide an important solution. By separating out the target antigen and replicase sequences, the vaccine could be more easily produced in vaccine manufacturing facilities. Compared to conventional mRNA vaccines, the design could also mean up to 100 times less antigen-encoded RNA is needed per dose and the replicase enzyme can be produced ahead of an outbreak as it does not need to be combined with the target antigen sequence.

Dr In-Kyu Yoon, Acting Executive Director of Vaccine R&D, CEPI, said: “Many exciting technologies are coming out of the COVID-19 pandemic, and we must investigate whether they fit the bill of developing vaccines against future viral threats within a 100-day timeline. We already know mRNA is fast and flexible, and now new techniques like trans-amplifying mRNA vaccine technologies may further enhance its offering by significantly extending antigen supply while also allowing for key components of the vaccine to be made ahead of time.”

Dr Cory Sago, CEO of Amplitude Therapeutics, said: “We are grateful for CEPI’s support as we work to advance trans-amplifying RNA vaccines for pandemic preparedness. Our data suggests that trans-amplifying RNA may have some distinct advantages over existing mRNA technologies, including improved expression and flexibility of manufacturing.”

This is the first partnership to be announced as part of CEPI’s call for vaccine R&D and manufacturing innovations which could be critical to helping the world better prepare for future epidemics and pandemics in support of the 100 Days Mission. The ambitious goal, embraced by the G7 and G20, seeks to develop vaccines, diagnostics and therapeutics against novel pathogens within 100 days of virus identification and give the world a chance of preventing the next pandemic. 

CEPI and Amplitude Therapeutics are committed to enabling equitable access to the outputs of their partnership, 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.



Notes to Editors

CEPI is supporting preclinical work to establish the Amplitude Therapeutics platform using Influenza as the model target pathogen.

Further details on CEPI’s Call for Innovations to Prepare for Future Epidemics and Pandemics Call for Proposals are available here. Applications are open for two Focus Areas: 1) advancing innovative rapid-response vaccine platforms that can transform the response to a future Disease X and 2) developing new vaccine candidates against CEPI priority pathogens with epidemic or pandemic potential and viral families.

Additional awardees supported by CEPI’s innovations call are expected to be announced in the coming months, following accelerated expert review of submitted proposals. 


About CEPI 

CEPI was launched in 2017 as an innovative partnership between public, private, philanthropic and civil organisations. Its mission is to accelerate the development of vaccines and other biologic countermeasures against epidemic and pandemic threats so they can be accessible to all people in need. CEPI has supported the development of more than 50 vaccine candidates or platform technologies against multiple known high-risk pathogens or a future Disease X. Central to CEPI’s pandemic-beating five-year plan for 2022-2026 is the ‘100 Days Mission’ to compress the time taken to develop safe, effective, globally accessible vaccines against new threats to just 100 days.


About Amplitude Therapeutics 

Amplitude Therapeutics, founded in 2022, is a biotechnology company developing a next-generation trans-amplifying RNA platform that has advantages over existing RNA technologies including increased in vivo expression and improved manufacturing. Amplitude is applying the trans-amplifying RNA platform to create differentiated vaccines and therapeutics across protein replacement, immunology and genetic medicines.