微生物所在热休克蛋白gp96抗乙肝病毒方面取得系列进展

周崇毅

　　热休克蛋白gp96(又称GRP94)是位于细胞内质网膜上的热休克蛋白90家族中的一员，在天然免疫和获得性免疫中发挥着重要作用。gp96能作为分子伴侣结合细胞中的肿瘤抗原、病毒抗原或胞内细菌抗原，并将结合的抗原表位呈递给抗原递呈细胞的“专用运输车”MHC  I类和II类分子，从而启动特异性T细胞CD8+和CD4+T细胞免疫应答。另一方面，gp96分子本身作为免疫活性分子通过与Toll样受体（TLR）作用，促进CD8+和CD4+  T细胞细胞增殖和分泌细胞因子，并促进抗原呈递细胞成熟并增强其功能。



　　中科院微生物研究所的病原微生物研究团队自1997年开展gp96免疫学功能的研究，探索gp96在乙肝感染中介导的T细胞免疫，取得了多项重要进展。2011年在前期研究中发现调节性T细胞（Treg）对gp96免疫活性起负调控作用，课题组进一步查明清除Treg可显著提高gp96的T细胞免疫活性和抗肿瘤活性，为提高gp96疫苗的免疫活性以及目前gp96作为肿瘤自体疫苗在临床中治疗肿瘤提供理论指导；通过乙肝病毒（HBV）转基因鼠模型，发现gp96介导的T细胞免疫应答可有效抑制和清除乙肝病毒，gp96佐剂疫苗能有效激活HBV特异性T  细胞，并降低转基因鼠Treg的数量。小鼠免疫5-8周后血清中的HBV  S抗原降低50%以上，病毒DNA拷贝数下降1000倍，肝脏细胞中病毒清除95%以上，表明gp96治疗性疫苗免疫能有效打破免疫耐受、激活T细胞清除病毒，这为研发gp96乙肝治疗性疫苗提供依据；同时，首次应用汉逊酵母表达出有免疫活性的重组gp96蛋白，为研究gp96的生物学功能和疫苗佐剂开发奠定了基础。

论文链接：http://www.ncbi.nlm.nih.gov/pubmed/21167226



(6.合.彩).足球.篮球...各类投注开户下注

第一投注.现金网:招代理年薪10万以上:6668.cc

周崇毅

又一新发现，不知是真是假，提供给各位专家参考!

qdmhyneg

还有有关的其它消息吗？比如其它数据，临床之类的。

ypf10001

求真假！

富贵数字

看见这个 真像对那些砖家 草泥马 这三字

富贵数字

除了发现 发现就不能来点实际的

tonychant

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
王彦中; 王赛锋; 张小俊; 李杨; 赵世宇; 孟颂东;
【作者英文名】 Yanzhong Wang1; 2; Saifeng Wang1; Xiaojun Zhang1; Yang Li1; Shiyu Zhao3; and Songdong Meng1 1 CAS Key Laboratory of Pathogenic Microbiology and Immunology; Institute of Microbiology; Chinese Academy of Sciences; Beijing 100101; China 2 Graduate University of Chinese Academy of Sciences; Beijing 100049; China 3 Beijing Tiantan Biological Products Co.; Ltd.; Beijing 100024; China;
【作者单位】 中国科学院微生物研究所中国科学院病原微生物与免疫学重点实验室; 中国科学院研究生院; 北京天坛生物制品股份有限公司;
【文献出处】 生物工程学报, Chinese Journal of Biotechnology, 编辑部邮箱 2011年 05期  
期刊荣誉：中文核心期刊要目总览  ASPT来源刊  CJFD收录刊
【关键词】 乙肝治疗性疫苗; HSP70; gp96; 佐剂;
【英文关键词】 HBV therapeutic vaccine; HSP70; gp96; adjuvant;
【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。
【英文摘要】 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]-th...
【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~~

tonychant

该研究发表在国内期刊，可信度极低

StephenW

研究是真实的，并在动物模型看起来有前途的。必须等待，看看如果它在人类有效.
[我个人的意见].

Vaccine journal homepage: www.elsevier.com/locate/vaccine
Heat shock protein gp96 enhances humoral and Tcell responses, decreases Treg
frequency and potentiates the anti-HBV activity in BALB/c and transgenic mice.

Saifeng Wang a,1, Lipeng Qiu a,1, Guangze Liu b, Yang Li a, Xiaojun Zhang a, Wensong Jin a, George F. Gao a, Xianping Kong b, Songdong Meng a,∗
a CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences(CAS), Beijing,China
b Transgenic Engineering Research Laboratory,Infectious Disease Center,458th Hospital,Guangzhou,China
a r t i c l e info
Article history:
Received 26 April 2010
Received in revised form 7December 2010
Accepted 5 May2011
Available online xxx
Keywords:
Hepatitis Bvirus
gp96
HBcAg
HBsAg
Treg
HBV transgenic mice
Anti-HBV
a b s t r a c t
More than 350 million people worldwide are chronically infected with hepatitis B virus(HBV). Broad
repertoire and strong magnitude of HBV-specific T cell responses are thought to play key roles for virus control and clearance. Previous studies together with ours showed that heatshock protein gp96 as adjuvant induces antigen specific Tcell responses, yet little is known for its anti-viral properties.Here,we investigated the role of gp96 mediated cellular and humoral immunity in antiviral effects in HBV trans-genic mice. Immunization with HBV surface (HBsAg) and core(HBcAg) antigens combined formulation along with gp96 induced robust antiviral T-cell and antibody immunity against HBsAg andHBcAg. Compared with non-immunized control, immunization with gp96 adjuvant vaccine led to decrease of serum HBs level and HBc expression in hepatocyte by 45% and 90% at maximum, respectively, and decreased serum HBV-DNA level to below or close to the detection limit 4 weeks after the last immunization, suggesting the therapeutic effect. A significant enhancement in cellular responses towards HBcAg and increased infiltration of CD8+Tcells in liver of transgenic were observed under treatment with gp96
compared with no treatment (P < 0.05or0.01). Treatment with gp96 was capable of reducing Tregs by overall 30–40%.The superior immune responses induced with the aid of gp96 correlated with improved antiviral effect by vaccination with HBsAg and HBcAg. We conclude that gp96 may contribute to enhanced antiviral immunity in transgenic mice at least partly by Treg down-regulation. HBcAg may act as potent
adjuvant for Th1 response. Our study reveals the novel property of gp96 in immune modulation and its potential use for breaking immuno tolerance in immunotherapy of chronic HBV infection.
© 2011 Elsevier Ltd. All rights reserved.

hchu

当初，我们曾经视乙克为大救星，就是因为它清除了小鼠身上的病毒。