Notably, double-stranded DNA can potently activate innate immune signaling; prior studies have documented that DNA vaccine immunogenicity is associated with the STING/TBK1/IFN-αβ axis, as DNA vaccines can engage DNA sensors (e.g., cGAS/STING, AIM2, IFI16, DExD/H-box helicase family members, RNA polymerase III, DAI, DNA-PK, and MRE-11) [49,50,51,52] to indirectly activate the MAPK pathway—a signaling cascade intricately linked to infection, immunity, and inflammation through cellular signal transduction and immune response modulation [53]. This evidence concerns the gene IFI16 and infection.