CpG motifs for optimization of DNA vaccines

The immunogenicity of DNA vaccines is due in part to the presence of stimulatory CpG motifs, which may actually be essential to their function. CpG motifs are unmethylated cytosine-guanine dinucleotides within a certain flanking base context and such sequences are commonly found in bacterial but not mammalian DNA. It appears that through evolutionary adaptation, the vertebrate immune system developed the ability to recognize these sequences as a "danger signal" and respond by rapid activation of the innate immune system. This innate activation synergizes with signals mediated through antigen receptors, and thus also augments antigen-specific responses. Other sequences, known as "neutralizing" motifs, which can counteract stimulatory CpG motifs, are also found in DNA vaccines. The immunogenicity of a DNA vaccine may depend on the balance between stimulatory and neutralizing motifs, and if so, their efficacy might be improved through the removal of neutralizing motifs and addition of species-specific stimulatory CpG motifs.