CEPI announced in March 2024 that it is providing up to $1 million funding to researchers at Amplitude Therapeutics in the US to support preclinical studies to assess the potential benefits of their trans-amplifying mRNA vaccine approach. This partnership comes under CEPI’s call for innovations to support the 100 Days Mission for pandemic preparedness.
A new approach
While “conventional” mRNA vaccines found fame during the COVID-19 pandemic as safe and effective ways to save lives, self-amplifying mRNA designs are also becoming “more prominent”. Self-amplifying mRNA vaccines are “more specialised”, containing genetic instructions for the antigen and replicase, an enzyme that “serves as a built-in photocopier” to teach the body to replicate mRNA. This design present “important advantages” over “conventional mRNA vaccines”, such as the possible reduction of a dose. However, there are limitations. As the additional genetic instructions make the vaccine sequence “at least three times longer” than standard mRNA vaccine sequences, manufacturing and delivery challenges can arise.
Trans-amplifying mRNA vaccines comprise two separate, shorter RNA fragments: one encodes the antigen, and one encodes the replicase. This separation could facilitate easier production and mean up to 100 times less antigen-encoded RNA required per dose. Furthermore, the replicase enzyme can be produced before an outbreak.
From one pandemic to another
Dr In-Kyu Yoon, Acting Executive Director of Vaccine R&D at CEPI identifies “many exciting technologies” coming out of the COVID-19 pandemic.
“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 is “grateful” for CEPI’s support as the team works to “advance trans-amplifying RNA vaccines for pandemic preparedness”.
“Our data suggest that trans-amplifying RNA may have some distinct advantages over existing mRNA technologies, including improved expression and flexibility of manufacturing.”
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