Here, the scientists demonstrate that mRNA lipoplexes induce a potent type I IFN response upon subcutaneous, intradermal and intranodal injection. Regardless of the route of immunization applied, these type I IFNs interfered with the generation of potent cytolytic T cell responses. Most importantly, blocking type I IFN signalling at the site of immunization through the use of an IFNAR blocking antibody greatly enhanced the prophylactic and therapeutic anti-tumour efficacy of mRNA lipoplexes in the highly aggressive B16 melanoma model. As type I IFN induction appears to be inherent to the mRNA itself rather than to unique properties of the mRNA lipoplex formulation, preventing type I IFN induction and/or IFNAR signalling at the site of immunization might constitute a widely applicable strategy to improve the potency of mRNA vaccination
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Here, the scientists demonstrate that mRNA lipoplexes induce a potent type I IFN response upon subcutaneous, intradermal and intranodal injection. Regardless of the route of immunization applied, these type I IFNs interfered with the generation of potent cytolytic T cell responses. Most importantly, blocking type I IFN signalling at the site of immunization through the use of an IFNAR blocking antibody greatly enhanced the prophylactic and therapeutic anti-tumour efficacy of mRNA lipoplexes in the highly aggressive B16 melanoma model. As type I IFN induction appears to be inherent to the mRNA itself rather than to unique properties of the mRNA lipoplex formulation, preventing type I IFN induction and/or IFNAR signalling at the site of immunization might constitute a widely applicable strategy to improve the potency of mRNA vaccination