Use of CpG DNA for Enhancing Specific Immune Responses

Abstract

Bacterial DNA, in contrast to vertebrate DNA, has the capacity to act as a potent immune stimulator (Tokunaga et al. 1984; Messina et al. 1991; Yamamoto et al. 1992b). This is now known to be due to unmethylated CpG dinucleotides that are immunostimulatory when present within the context of certain flanking bases (CpG-S motifs) (Krieg et al. 1995). CpG dinucleotides are present at the expected frequency of 1/16 bases in bacterial DNA but are under-represented (1/50–1/60 bases) in vertebrate DNA, where they are almost always methylated (Bird et al. 1987). CpG-S motifs are virtually absent from vertebrate DNA, and the rapid immune activation in response to CpG DNA appears to be an evolutionary adaptation whereby CpG-S motifs act as a “danger” signal that the vertebrate innate immune defense mechanisms can recognize and respond to (Krieg et al. 1996).