Manufacturing saRNA success

RNA vaccine technology has recently come of age, with RNA vaccine products from Pfizer and Moderna, showing the highest efficacy values against COVID-19 in multiple countries. However, both vaccines are the most expensive to come to market and have limited access in low- and middle-income countries. The success of these imported vaccines serves to highlight the lack of RNA vaccine development and manufacturing expertise within the UK. Imperial College has been at the international forefront in the development of a low dose RNA vaccine platform based on novel self-amplifying RNA technology (saRNA). This is delivered by an RNA sequence that both encodes a vaccine target such as the spike protein of the COVID-19 virus and replicase proteins capable of making multiple copies of the RNA sequence following injection into the muscle. This provides significant advantages allowing vaccine doses that are 30-100 times lower than that for conventional RNA vaccines, reducing cost, providing increased safety, and making it easier to generate combined vaccines. While the Imperial team were the first in the world to take this new technology into clinical trials, it is recognised that significant improvements could be made to this unique platform through optimising the manufacturing process. Of note, this first saRNA vaccine had to be manufactured outside of the UK as the required expertise for production were not available in country. We have advanced vaccines through preclinical development against several diseases of epidemic potential identified by the UK Vaccine Network including those against Ebola, Marburg, Rift Valley Fever, Lassa Fever and Plague. These are poised for clinical evaluation. Through this project we will determine the optimal production process to ensure maximal potency, bringing them to a state of readiness for manufacturing to the standards required for clinical assessment. We will apply innovative technology to the design, production, purification, and quality control for our existing vaccines targeted against pathogens with epidemic potential. To achieve our goal, we will work with the Centre for Process Innovation (CPI) delivering a clinical grade process by the end of the project. This project builds on existing UK investment in this emerging technology that will generate matchless knowhow and expertise in manufacturing of saRNA vaccines. The proposed work will help to realise the full potential of a unique vaccine platform providing the UK with national pandemic resilience while advancing vaccine candidates that could be deployed against outbreak pathogens in low- and middle-income countries.