The Plasmid-launched live-attenuated vaccines (PLLAV), sometimes referred to as the infective DNA (iDNA) vaccine, combine genetic immunisation properties with the potential of a live replicative virus. Due to its origin as bacterial plasmid DNA, however, the effective distribution of PLLAV could result in unfavourable local proinflammatory and antiviral reactions, such as cGAS-STING-mediated cytosolic sensing. The study examined a panel of small molecules known to interfere with antiviral signalling in order to improve the YF17D replication and hence efficacy of PLLAV-YF17D transfection, using various complementary cell-based systems and with the yung fever vaccine (YF17D) and the respective PLLAV-YF17D.
They identified two powerful TANK-boundary inhibitors 1, BX795 and CYT387. In tissue cultivation, as confirmed by type I interferon dependent manner, (i) marked changes in signatures of gene expression, (ii) a full YF17D replication rescue, and (iii) a dramatically higher virus yield, BX795 can revert the blood that transfection of plasmid by YF17D infection in the form of interferon-like type I were found. TBK1 inhibitors could thus be seen as an adjuvant to new PLLAV vaccines that could improve the administration of PLLAV in vivo.