Type I Interferons Modulate CD8+ T Cell Immunity to mRNA Vaccines

Abstract

mRNA vaccines have emerged as potent tools to elicit antitumor T cell immunity. They are characterized by a strong induction of type I interferons (IFNs), potent inflammatory cytokines affecting T cell differentiation and survival. Recent reports have attributed opposing roles for type I IFNs in modulating CD8+ T cell immunity to mRNA vaccines, from profoundly stimulatory to strongly inhibitory. The mechanisms behind this duality are unclear. Disentangling the factors governing the beneficial or detrimental impact of type I IFNs on CD8+ T cell responses is vital to the design of mRNA vaccines of increased potency. In light of recent advancements regarding the complex role of type I IFNs in regulating CD8+ T cell immunity to infectious diseases, we posit that the dual outcome of type I IFNs on CD8+ T cell responses to mRNA vaccination is determined by the timing and intensity of type I IFN induction relative to T cell receptor (TCR) activation.