CpG Oligodeoxynucleotides as Adjuvants for Clinical Use

CpG oligodeoxynucleotides (ODNs) bind to and activate Toll-like receptor 9 (TLR9), initiating an innate immune response that supports the subsequent development of adaptive immunity. Preclinical studies demonstrate that TLR9 agonists improve antigen presentation and the induction of vaccine-specific cellular and humoral responses. More than 100 clinical trials utilizing CpG ODNs have been conducted that evaluated their utility in preventing or treating allergy, infectious diseases, and cancer. This chapter reviews the results of those clinical trials. In broad terms, the data indicate that CpG ODNs are safe when used as vaccine adjuvants. They improve humoral and cellular immune responses, accelerate the induction of protective antibodies, and support the generation of higher and more persistent antibody titers when added to protein-based vaccines. CpG ODNs show great promise for inclusion in prophylactic vaccines designed to prevent infection. However, the magnitude of the immunity they induce appears insufficient to control the spread of established cancers.