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机构地区:[1]中国食品药品检定研究院国家药物安全评价监测中心药物非临床安全评价研究北京市重点实验室,北京100176 [2]中国食品药品检定研究院,北京100050
出 处:《中国新药杂志》2014年第2期161-170,共10页Chinese Journal of New Drugs
基 金:国家“重大新药创制”科技重大专项(2012ZX09302001,2012ZX09505001-004)
摘 要:目的:对CpG ODN对免疫系统的作用、作为疫苗佐剂的有效性和安全性研究进展进行综述,为CpG ODN作为新型佐剂的研究和应用提供参考。方法:通过查阅近年来与CpG ODN免疫刺激活性、疫苗佐剂作用和安全性研究相关的国内外文献,进行归纳总结。结果:CpG ODN具有强免疫刺激作用,能促进DC、B细胞、NK、巨噬细胞等的增殖或活化,具有促进Th1型免疫应答的特点,CpG ODN的免疫刺激作用与激活TLR9有关。CpG ODN,尤其是B型CpG ODN,可作为佐剂增强针对感染性疾病的预防性疫苗和针对感染性疾病或肿瘤的治疗性疫苗的免疫效应。现有资料显示CpG ODN在一定的剂量范围内具有较好的安全性,在引起注射部位反应和过敏反应等方面,CpG ODN的安全性优于传统佐剂,但较高剂量下会引起一些其他方面的毒性作用。对CpG ODN结构及其传递系统的研究和改进是提高其临床应用有效性和安全性的重要手段。结论:CpG ODN具有强大的促进免疫应答的作用,是具有潜在应用前景的一种新型疫苗佐剂,目前CpG ODN的安全性尚未被完全阐明,有待于进行进一步的研究。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.
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