Objective:To review the effect of CpG ODN,a novel adjuvant of vaccine,on immune system and its efficacy and safety for providing references for the research and application of CpG ODN.Methods:The research progress was summarized by searching literature regarding the immunostimulatory action,efficacy and safety of CpG ODN as an adjuvant of vaccine recently published in China and abroad.Results:CpG ODN can promote the proliferation or activation of dentritic cells,B cells,natural killer cells and microphages,and has the potent immunostimulatory effect characterized by potentiating Th1-type immune response,which is related with the activation of the pathway involving TLR9.CpG ODNs,especially the B-class CpG ODNs,can improve the adjuvant activity of preventative and therapeutic vaccines targeting infectious diseases,and therapeutic vaccines targeting cancers.CpG ODN is relatively safe under certain dose levels.It is safer than traditional adjuvants in induction of injection site irritancy and allergic responses,but will cause other side effects at high dose levels.The improvement of CpG ODN structures and its delivery system is critical to increase the efficacy and safety of CpG ODN in clinical application.Conclusion:CpG ODN has the ability to trigger strong immune responses and is a promising candidate of novel vaccine adjuvants.The safety profile of CpG ODN has not been fully clarified and needs further study.