Researchers in the lab of Prof. George Church at Harvard Medical School have developed a vaccine platform technology that can be applied to fields such as infectious diseases and oncology therapeutics. The team is looking to further demonstrate enhanced immunogenicity of mRNA vaccines through industrial collaboration.

The discovery was made to help overcome deficiencies with classical in vitro transcribed (IVT) mRNA. IVT-mRNA contain the code for protein production, and when delivered to target cells, are translated by cell machinery to produce antigen. The antigen, which could be cancer- or pathogen-specific, subsequently elicit an immune response from the host. While IVT-mRNA represents a novel vaccine class and provides advantages over traditional protein vaccines, such as ease of manufacture and favorable safety profile, one challenge is potentially insufficient immunity induced by IVT-mRNA alone.

Through study of the mechanisms of mRNA translation and innate immunity, the Church lab found that a critical aspect of generating a strong immune response to the vaccine was to activate the RIG-I virus surveillance mechanism of the cell. To accomplish this, the team developed an IVT-mRNA vaccine platform that combines the antigen-coding sequence in addition to a RIG-I activating adjuvant sequence within a single mRNA transcript. This strategy is a departure from classic strategies which involve co-administration of adjuvant with the IVT-mRNA transcript and allows precise spatial control of antigen and adjuvant, as well as “tunable” immuno-stimulation. Results demonstrate that this highly versatile strategy generates robust immune responses compared to unmodified IVT-mRNA for infectious disease and neo-antigen oncology vaccines.