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热休克蛋白HSP70和gp96增强乙肝DNA疫苗的细胞和体液免疫应答 被引量:8

Enhancement of cellular and humoral immune responses of HBV DNA vaccine by HSP70 and gp96
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摘要 旨在以乙肝病毒(HBV)的主要结构蛋白-表面蛋白(HBsAg)和核心蛋白(HBcAg)作为抗原设计DNA疫苗,研究热休克蛋白HSP70和gp96作为新型免疫佐剂增强疫苗的细胞免疫和体液免疫水平。利用酶联免疫斑点实验、流式细胞内因子染色、3H-TdR实验、酶联免疫吸附实验技术分析,结果显示HSP70和gp96可使疫苗的细胞免疫水平提高1~6倍,提高体液免疫水平20%~60%。研究结果为设计以HSP70和gp96作为免疫佐剂的新型乙肝治疗性疫苗提供了依据。 While currently therapeutic vaccines for chronic hepatitis B virus(HBV) infection are actively being developed to complement standard antiviral treatments,their immune activity,especially T cell activity,remains to be further improved.Here,we investigated the role of heat shock proteins HSP70 and gp96 on cellular and humoral immunity,using the main structure antigens of hepatitis core(HBcAg) and surface(HBsAg) as the DNA vaccine.By ELISPOT(enzyme linked immunospot assay),IFN-γ intracellular staining,[3H]-thymidine incorporation and ELISA(enzyme linked immunosorbent assay) analyses,we showed that immunization with HBsAg/HBcAg DNA formulation along with HSP70 or gp96 induced significant increase of T-cell(about 1-6-fold) and antibody(about 20%-60%) immunity against HBsAg and HBcAg.These results may provide bases for designing HSP70-and gp96-based vaccines aimed at eliciting T-cell responses for therapeutic applications.
出处 《生物工程学报》 CAS CSCD 北大核心 2011年第5期790-798,共9页 Chinese Journal of Biotechnology
基金 中国科学院知识创新项目(Nos.KSCXZ-YW-R-1 KSCXZ-YW-R-183) "重大新药创制"科技重大专项项目(No.2009ZX09503-007) 国家高技术研究发展计划(863计划)(No.2006AA02A241)资助~~
关键词 乙肝治疗性疫苗 HSP70 GP96 佐剂 HBV therapeutic vaccine HSP70 gp96 adjuvant
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参考文献16

  • 1Michel ML, Tiollais P. Hepatitis B vaccines: protective efficacy and therapeutic potential. Pathol Biol, 2010, 58(4): 288-295.
  • 2Zoulim F, Locarnini S. Hepatitis B virus resistance to nucleos(t)ide analogues. Gastroenterology, 2009, 137(5): 1593 -1608.
  • 3Zheng YL, Zhao LS, Zhou TX, et al. Efficacy of consensus interferon in treatment of HbeAg-positive chronic hepatitis B: a multicentre, randomized controlled trial. Virol J, 2009, 6: 99.
  • 4李杨,王赛锋,王亚男,孟颂东.乙肝治疗性疫苗的研制与临床应用[J].生物技术通报,2010,26(4):33-37. 被引量:4
  • 5Shen ML, Wang SX, Ge GH, et al. Profiles of B and T cell immune responses elicited by different forms of the hepatitis B virus surface antigen. Vaccine, 2010, 28(45): 7288-7296.
  • 6Michel ML, Loirat D. DNA vaccines for prophylactic or therapeutic immunization against hepatitis B. Intervirology, 2001, 44(2/3): 78-87.
  • 7Michel ML, Davis HL, Schleef M, et al. DNA-mediated immunization to the hepatitis B surface antigen in mice: aspects of the humoral response mimic hepatitis B viral infection in humans. Proc Natl Acad Sci USA, 1995, 92(12): 5307-5311.
  • 8Udono H, Levey DL, Srivastava PK, et al. Cellular requirements for tumor-specific immunity elicited by heat shock proteins: tumor rejection antigen gp96 primes CD8+ T cells in vivo. Proc Natl Acad Sci USA, 1994, 91(8): 3077-3081.
  • 9Han LF, Wang W, Fang Y, et al. Soluble B and T lymphocyte attenuator possesses antitumor effects and facilitates heat shock protein 70 vaccine-triggered antitumor immunity against a murine TC-1 cervical cancer model in vivo. J Immunol, 2009, 183(12): 7842-7850.
  • 10Nicchitta CV. Re-evaluating the role of heat-shock protein-peptide interactions in tumor immunity. Nat Rev Immunol, 2003, 3(5): 427-432.

二级参考文献25

  • 1Zoulim F,Locarnini S.Hepatitis B virus resistance to nucleos(t)ide analogues.Gastroenterology,2009,137(5):1593-608.
  • 2Zheng YL,Zhao LS,Wu TX,et al.Efficacy of consensus interferon in treatment of HbeAg-positive chronic hepatitis B:a multicentre,randomized controlled trial.Virol J,2009,6:99.
  • 3Liang X,Bi S,Yang W,et al.Evaluation of the impact of hepatitis B vaccination among children born during 1992-2005 in China.J Infect Dis,2009,200(1):39-47.
  • 4Webster G,Bertoletti A.Quantity and quality of virus-specific CD8 cell response:relevance to the design of a therapeutic vaccine for chronic HBV infection.Mol Immunol,2001,38(6):467-73.
  • 5Webster GJ,Reignat S,Brown D,et al.Longitudinal analysis of CD8^+ T cells specific for structural and nonstructural hepatitis B virus proteins in patients with chronic hepatitis B:implications for immunotherapy.J Virol,2004,78(11):5707-19.
  • 6Westover KM,Hughes AL.Evolution of cytotoxic T-lymphocyte epitopes in hepatitis B virus.Infect Genet Evol,2007,7(2):254-62.
  • 7Tan AT,Loggi E,Boni C,et al.Host ethnicity and virus genotype shape the hepatitis B virus-specific T-cell repertoire.J Virol,2008,82(22):10986-97.
  • 8Tsai SL,Sheen IS,Chien RN,et al.Activation of Th1 immunity is a common immune mechanism for the successful treatment of hepatitis B and C:tetramer assay and therapeutic implications.J Biomed Sci,2003,10(1):120-35.
  • 9Desmond CP,Bartholomeusz A,Gaudieri S,et al.A systematic review of T-cell epitopes in hepatitis B virus:identification,genotypic variation and relevance to antiviral therapeutics.Antivir Ther,2008,13(2):161-75.
  • 10Xu D,Fu J,Jin L,et al.Circulating and liver resident CD4^+ CD25^+ regulatory T cells actively influence the antiviral immune response and disease progression in patients with hepatitis B.J Immunol,2006,177(1):739-47.

共引文献3

同被引文献126

  • 1沈肖方,李建远,王海燕,王学波,靳绍华,刘芙君,刘运祥.IL-2 preS DNA疫苗免疫正常小鼠和HBV转基因鼠的免疫应答研究[J].中华微生物学和免疫学杂志,2004,24(11):914-918. 被引量:3
  • 2刘惠萍,杨富强,饶桂容,莫国玉,陈光明.治疗性HBV DNA疫苗诱导健康Balb/c小鼠细胞免疫应答的实验研究[J].免疫学杂志,2006,22(6):612-614. 被引量:6
  • 3章金刚,倪道明.生物制品的现状与展望[J].中国输血杂志,2006,19(5):349-351. 被引量:8
  • 4Linderoth NA,Popowicz A,Sastry S.Identification of the peptide-binding site in the heat shock chaperone/tumor rejection antigen gp96(Grp94).J Biol Chem,2000,275(8):5472-5477.
  • 5Kropp LE,Garg M,Binder RJ.Ovalbumin-derived precursor peptides are transferred sequentially from gp96and calreticulin to MHC class I in the endoplasmic reticulum.J Immunol,2010,184(10):5619-5627.
  • 6Robert J,Ramanayake T,Maniero GD,et al.Phylogenetic conservation of glycoprotein96 ability to interact with CD91and facilitate antigen cross-presentation.J Immunol,2008,180(5):3176-3182.
  • 7Randow F,Seed B.Endoplasmic reticulum chaperone gp96is required for innate immunity but not cell viability.Nat Cell Biol,2001,3(10):891-896.
  • 8SenGupta D,Norris PJ,Suscovich TJ,et al.Heat shock protein-mediated cross-presentation of exogenous HIV antigen on HLA class I and class II.J Immunol,2004,173(3):1987-1993.
  • 9Qin-Long Gu,Xue Huang,Wen-Hong Ren,Lei Shen,Bing-Ya Liu,Si-Yi Chen.Targeting hepatitis B virus antigens to dendritic cells by heat shock protein to improve DNA vaccine potency[J].World Journal of Gastroenterology,2007,13(44):5911-5917. 被引量:7
  • 10Kaul G,Thippeswamy H. Role of heat shock proteins in diseases and their therapeutic potential[J].Indian Journal of Microbiology,2011,(02):124-131.

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