Fig. 5. dsRNA might be a central element in the immunogenicity of replicase-based genetic vaccines.
dsRNA is produced in cells infected with RNA-viruses, but is also expected to be an intermediate in the replicase-mediated duplication of mRNA after delivery of ‘self-replicating’ genetic vaccines. dsRNA is a potent inducer of interferon, which in turn induces the expression of PKR and 2-5A synthetase. These enzymes are activated by dsRNA and mediate at least some of the cellular effects associated with viral infection, including apoptotic cell death, aimed at preventing viral spread. The ‘danger signals’ resulting from the activation of these two enzymes could account for the increased immunogenicity of replicase-based genetic vaccines, providing an adjuvant-effect.