RNA vaccines are the breakthrough vaccine technology from the COVID pandemic. However, RNA vaccination is still a young platform and the success of RNA vaccines has outstripped understanding of how they work. One specific area needing further research is how best to induce T cells with RNA vaccines as these may provide broader protection against pathogens. One of the underlying features of the successful RNA vaccines was the incorporation of N1-methylpseudouridine (m1Ψ) instead of uridine, reduces RNA sensing by the cellular innate immune system. This suggests that RNA vaccine induced inflammation itself inhibits response. However, we believe it is more nuanced than this. In this talk I will discuss data about the interplay of inflammation and the adaptive immune response to RNA vaccines. I will present data from two systems – modified mRNA vaccines and self-amplifying RNA (saRNA) vaccines. I will show the impact of modification on mRNA vaccines induced inflammation and the T and B cell responses. Modification of bases is not the only method to alter inflammation, formulation has a significant impact on the induced response. We have explored this in the context of saRNA vaccines. What both studies show is that the inflammatory response to RNA vaccines is more nuanced than predicted and that specific cytokines may be beneficial and others inhibitory. Understanding this interplay is critical in developing the next generation of RNA vaccines that have further improved efficacy and ideally reduced reactogenicity.