Unravelling the impact of RNA vaccine induced inflammation on adaptive immunity.

RNA vaccines are the breakthrough vaccine technology from the COVID pandemic. Building on the back of their success, there are many ongoing clinical trials testing RNA vaccines against a range of pathogens. One extremely promising next-generation RNA vaccine platform is self-amplifying RNA (saRNA), because it can induce an immune response for far lower doses.

However, RNA vaccination is still a young platform and the success of RNA vaccines has outstripped understanding of how they work. Better understanding is needed to optimise RNA vaccines for future use in the prevention of endemic pathogens such as influenza virus.

In the current project, building on 10-years of nucleic acid vaccine experience, I aim to define the role of inflammation in how RNA vaccines induce an immune response in order to further improve the platform. RNA vaccines are different to conventional protein vaccines in a number of ways: they need to be translated in situ, their main ingredient (RNA) is in itself directly inflammatory and they need formulation to get them into cells.

These differences affect the way in which immune responses are induced to RNA vaccines and the received view is that inflammation can dampen responses. However, my recently published data reveals an unanticipated, beneficial role for inflammation in the induction of an adaptive immune response to saRNA vaccines.

I have shown that rather than inhibiting RNA vaccines, inflammation is critical in the induction of an adaptive immune response. My hypothesis is that the kinetics of inflammation and expression need to be coordinated to ensure presentation of the expressed antigen and activation of adaptive cells.