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新型佐剂CpG ODN的研究进展 被引量:10

Research progress of the novel adjuvant CpG ODN
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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.
出处 《中国新药杂志》 CAS CSCD 北大核心 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)
关键词 CPG ODN 疫苗 新型佐剂 免疫刺激 安全性 CpG ODN vaccine novel adjuvant immunostimulatory action safety
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参考文献94

  • 1DEATON AM, BIRD A. CpG islands and the regulation of tran- scription [ J ]. Genes Dev, 2011, 25 (10) : 1010 - 1022.
  • 2ANDREWS CD, HUH MS, PATTON K, et al. Encapsulating immunostimulatory CpG oligonucleotides in listeriolysin O-lipo- somes promotes a Thl-type response and CTL activity [ J ]. Mol Pharm, 2012, 9(5) :1118 - 1125.
  • 3YAMAMOTO T, YAMAMOTO S, KATAOKA T, et al. Lipofec- tion of synthetic oligodeoxyribonucleotide having a palindromic se- quence of AACGTT to murine splenocytes enhances interferon production and natural killer activity [ J]. Microbiol lmmunol, 1994, 38(10) : 831 -836.
  • 4BARTON GM, KAGAN JC, MEDZHITOV R. Intracellular local- ization of Toll-like receptor 9 prevents recognition of self DNA bat facilitates access to viral DNA[ J]. Nat Immunol, 2006, 7 (1) : 49 -56.
  • 5KRIEG AM. CpG motifs in bacterial DNA and their immune effects[ J]. Annu Rev Immunol, 2002, 20:709 - 760.
  • 6KLINMAN DM, CONOVER J, COBAN C, Repeated administra- tion of synthetic oligodeoxynucleotides expressing CpG motifs pro- vides long term protection against bacterial infection [ J ]. Infect lmmun, 1999, 67(11) : 5658 -5663.
  • 7KRIEG AM. Therapeutic potential of Toll-like receptor 9 activa- tion[J]. Nat Rev Drug Discov, 2006, 5(6) : 471 -484.
  • 8VOLLMER J, KRIEG AM. Immunotherapeutic applications of CpG oligodeoxynueleotide TLR9 agonists [ J ]. Adv Drug Deliv Rev, 2009, 61(3) : 195 -204.
  • 9DONHAUSER N,HELM M, PRITSCHET K, et al. Differential effects of P class versus other CpG oligodeoxynucleotide classes on the impaired innate immunity of plasmacytoid dendritic cells in HIV type 1 infection[J]. AIDS Res Retroviruses, 2010, 26(2) : 161 - 171.
  • 10TAFAGHODI M, JAAFARI MR, SAJADI TABASSI SA. Nasal immunization studies using liposomes loaded with tetanus toxoid and CpG-ODN[JI. Eur J Pharm Biopharm, 2006, 64(2): 138 - 145.

二级参考文献24

  • 1胡向农,魏强.CpG ODN诱导浆细胞样树突状细胞免疫调节的作用机制[J].现代免疫学,2005,25(4):337-340. 被引量:3
  • 2罗清琼,陈万涛,胡水清,陈福祥.口腔鳞状细胞癌细胞TLR3表达及其配体poly(I:C)的诱导凋亡作用[J].上海交通大学学报(医学版),2011,31(1):5-8. 被引量:5
  • 3王磊,覃少华,愈吉杰,荣俊,江善祥.聚肌胞对小鼠的急性毒性和蓄积毒性[J].中国组织工程研究与临床康复,2007,11(15):2826-2828. 被引量:7
  • 4Barton GM, Medzhitov R. Toll like receptor signaling path ways[J]. Science, 2003,300:1524 -1525.
  • 5Gelman AE, LaRosa DF, Zhang J, et al. The adaptor mole cule MyD88 activates PI 3kinase signaling in CD4 ^+ T cells and enables CpG oligodeoxynucleotide mediated costimulation [J]. hnmunity, 2006,25:783 -793.
  • 6KriegAM, WuT, WeeratnaR, etal. Sequence motifs inad enoviral DNA block immune activation by stimulatory CpG motifs[J]. ProcNatlAcadSciUSA, 1998,95:12631- 12636.
  • 7Liu CW, Lou YY, Lizee G, et al. Plasmacytoid dendritic cells induce NK cell-dependent, tumor antigen-specific T cell cross-priming and tumor regression in mice[J]. J Clin Invest, 2008,118:1165 -1175.
  • 8Haltmann G, Krieg AM. Mechanism and function of a newly identified CpG DNA motifin human primary B cells[J].J Iramunol, 2000,164:944 -953.
  • 9Brown GD. Dectin 1 : a signalling non-TLR pattern recognition receptor[J]. Nat Rev, 2006,6:33 -43.
  • 10Tross D, Klinman DM. Effect of CpG oligonucleotides on vaccine induced B cell memory[J]. J Immunol, 2008,181: 5785 -5790.

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