CpG-Containing Oligonucleotides Mediated Immune Cell Stimulation
Internalized CpG-containing ISOs are mainly recognized by TLR9, which activates a complex signaling cascade resulting in the nuclear translocation of transcription factors including AP1, IRF7, and nuclear factor κB (NF-κB). Transcriptional activation of pro-inflammatory genes regulates the maturation of pDCs, the activation and proliferation of B cells, as well as the production of type I interferons and Th1-type cytokines. CpG-mediated immune cell activation, as well as the subsequent secretion of cytokines, stimulates the immune response to the co-administered antigen (not shown), and it produces a more rapid and longer lasting antibody response when compared to alternative vaccine adjuvants. In addition to vaccine adjuvants, single-stranded CpG-containing ISOs are currently also being tested in cancer patients and to modulate the immune response in inflammatory diseases (Table 1).