As already discussed, the backbone of bacterial DNA includes cytosine-phosphate-guanine (CpG) unmethylated regions as sequence motifs that stimulate innate immunity, creating an inflammatory milieu for triggering the adaptive immune response [74] . The role of CpG motifs as adjuvants of immune response to DNA vaccines is well documented in mice [75] . Preclinical studies showed that the addition of CpG motifs in the plasmid can result in the induction of proinflammatory cytokines, for example, IL-12 or IFN-I [75] . CpGs are recognized by TLR9, a receptor found on APCs, helping cytotoxic T-lymphocyte (CTL) differentiation and priming. The coadministration of genes encoding ligands for Toll-like receptors (TLRs) or their signaling molecules has been shown to improve the immunogenicity of DNA vaccines [66, 76] .