钩体基因疫苗对豚鼠延髓原癌基因表达的影响

我们的研究已表明，赖型０１７株钩体外膜疏水蛋白ＯｍｐＬ３９是稳定的免疫原，在此我们分别用ＯｍｐＬ３９与钩体死菌苗和生理盐水对照免疫豚鼠，研究ＯｍｐＬ３９的免疫保护作用和免疫机理，对ＯｍｐＬ３９的抗原特异性刺激引起中枢原癌基因（Ｃｆｏｓ基因）表达进行了观察。结果表明，ＯｍｐＬ３９在豚鼠体内能产生高效价的阳性抗体，免疫保护率为１００％。在ＯｍｐＬ３９对中枢Ｃｆｏｓ基因表达的影响中，我们观察到ＯｍｐＬ３９免疫的豚鼠较空白和死菌苗组Ｃｆｏｓ表达明显少于死菌苗组和空白对照组（ｐ＜００５）。提示ＯｍｐＬ３９能特异性地抑制Ｃｆｏｓ基因的表达，减轻强毒钩体对动物体内的病理损伤，有较死菌苗强的免疫保护作用。     

Enhancement of long-lasting immunoprotective effect against Androctonus australis hector envenomation using safe antigens: Comparative role of MF59 and Alum adjuvants

Envenomation is a public health problem in many regions of the world. The only available treatment is the serotherapy that has limited efficiency due to the delay of its administration. The goal of this study is to provide a new and more efficient alternative to this treatment. A comparative study of the effects of two adjuvants in their ability to enhance the efficiency of the detoxified and safe antigens to produce a long lasting immunoprotection is undertaken using Aluminum Hydroxide adjuvant (Alum) or the water-in-oil MF59 adjuvant mixed with Androctonus australis hector (Aah) detoxified venom, and compare their effects on the immune system.Immunization schedule was performed with two groups of rabbits, which were injected with attenuated venom and Alum or MF59 adjuvant preparations, once a month during three months. Blood samples were collected each week for cell count, evaluation of myeloperoxidase (MPO) and eosinoperoxydase (EPO) activities and antibody titer. After four months from the last immunization, rabbits were challenged with increased doses of native Aah venom.Results showed that MF59 effect was immediate in the first 24 h post-immunization by activating the recruitment of lymphocytes, monocytes and neutrophils, while Alum adjuvant effect seems to be delayed, and appeared in the second week after immunization. An important cell infiltration was observed with Alum preparation, due to its specific local depot effect. However, immunized animals with MF59 preparation challenged with the native venom showed a protective effect against its toxicity until 6 LD50 compared to those immunized with Alum preparation which are only protected at 4 LD50.One week after challenge, only immunized animals with Alum preparation present an increase in cell infiltration, MPO and EPO activities. These results are correlated with the ability of MF59 adjuvant to induce a potent immunoprotective effect against Aah venom compared to Alum adjuvant.     

New and safe formulation for scorpion immunotherapy: Comparative study between saponin and FCA adjuvants associated to attenuated venom

Envenoming by scorpion is a major health problem in Maghreb regions as well as in several regions of the world. Immunotherapy is the only effective treatment for scorpion stings. The immune sera are obtained from hyper-immunized animals with a formulation of venom associated to Freund’s Complete Adjuvant (FCA). This formulation seems to protect against several alterations in immunized animals leading to worsening of their health due to added toxicity of native venom and FCA adjuvant. This study aims to provide a more efficient and non-toxic alternative to this formulation. Two formulations of saponin or FCA associated to irradiated venom of Androctonus australis hector (Aah) were used to compare their safety and their efficiency to better enhance the antibody titers against toxic antigens.Both of these formulations were used in immunization schedule of three months. Blood samples were collected every week, cell count, myeloperoxydase (MPO) and eosinophil peroxidase (EPO) activities and specific antibody titers were evaluated. Four months after the last immunization, rabbits were challenged with increased doses of native Aah venom.Results showed that immunization with saponin formulation induced lower inflammatory cell activation as well as reduced MPO and EPO activities compared to that using FCA. The formulation of irradiated venom with saponin seems also to be more efficient in the activation of lymphocytes resulting in higher titers of specific IgG. The immunoprotective effect evaluation showed that the formulation using saponin seems to protected animals until 3 LD50 of native venom compared to that using FCA which protected only until 2 LD50. These results indicate that saponin formulation with irradiated antigen could be more efficient and safe immunizing preparation for the production of sera against scorpion envenomation.     

日本血吸虫重组线粒体相关蛋白免疫学活性鉴定

分子筛进一步纯化并复性的融合蛋白均能刺激家兔产生特异性抗体 ,粗提包涵体蛋白免疫家兔 ,血清抗体滴度为 1∶2 5 6 0 0 ,复性蛋白及经分子筛纯化的蛋白免疫的家兔血清抗体滴度均为 1∶5 12 0 0 ,Westernblot结果显示 ,粗提包涵体蛋白、复性蛋白及经过分子筛进一步纯化并复性的蛋白均能被重感染兔血清和rSj338/2 6GST特异性免疫兔血清所识别。攻击实验中 ,粗提包涵体蛋白和经分子筛纯化的蛋白分别可诱导小鼠产生 2 7.8% (P <0 .0 1)和 30 .4 % (P <0 .0 1)的减虫率 ,4 0 .4 % (P <0 .0 1)和 4 3.5 % (P <0 .0 1)肝总减卵率。粗提包涵体蛋白中rSj338和经分子筛纯化的蛋白中rSj338分别可诱导小鼠产生 13.9% (P <0 .0 5 )和 2 0 .0 % (P <0 .0 5 )的减虫率 ,30 .0 % (P <0 .0 1)和 4 1.7% (P <0 .0 1)肝总减卵率。结论　获得的日本血吸虫线粒体相关的重组融合蛋白(rSj338/2 6GST)具有良好的免疫学活性 ,重组融合蛋白 (rSj338/2 6GST)及rSj338均可诱导宿主抗血吸虫感染的部分保护力。     

细粒棘球蚴延伸因子-1重组蛋白对小鼠的免疫保护性研究

目的:探讨细粒棘球蚴(Eg)延伸因子(Eg.EF-1)重组蛋白对小鼠的免疫保护性及其作为候选疫苗的潜在价值。方法:ICR小鼠随机分为免疫组和佐剂对照组,每隔2周皮下免疫1次,在第3次免疫后2周,用Eg原头节进行攻击感染,感染后20周剖杀小鼠,检获Eg包囊,计算免疫保护力,并用酶联免疫吸附法测定血清中免疫球蛋白(Ig)G及其亚型和IgE水平。结果:与佐剂对照组比较,免疫组小鼠的免疫保护力为85.6%,血清IgG、IgG1、IgG2a水平显著性升高(P<0.05),IgG2b水平轻微降低(P>0.05),IgG3和IgE水平无明显变化。结论:rEg.EF-1重组蛋白能诱导小鼠产生一定的免疫保护力,是潜在的疫苗候选抗原分子。     

问号状钩端螺旋体外膜蛋白Loa22的克隆、表达及对豚鼠的免疫保护作用研究

目的构建问号状钩体强毒赖型56601株外膜蛋白Loa22的重组质粒,表达Loa22蛋白,研究该蛋白对豚鼠的保护作用。方法以问号状赖型钩体56601株基因组为模板扩增目的基因,将Loa22基因克隆至原核表达载体PQE-31,构建PQE31-Loa22重组体,将其转入大肠杆菌M15中诱导表达目的蛋白。于0、2、4周将蛋白及对照PBS分别经豚鼠腹股沟、腋下免疫豚鼠。每次剂量为蛋白50μg/只,末次免疫后2周,用培养3d的56601株钩体从腹腔攻击各免疫组豚鼠(1ml/只)。连续观察15d,观察各免疫组豚鼠发病情况,并取各免疫组豚鼠的肺、肝、肾做病理切片。分析蛋白Loa22对豚鼠的免疫保护作用。结果成功扩增出Loa22基因,构建原核重组质粒PQE31-Loa22。重组质粒能在大肠杆菌M15中高效表达Loa22蛋白。用Loa22蛋白主动免疫的豚鼠用56601株钩体攻击,结果显示无发病现象,而免疫对照组的豚鼠中出现了食欲不振、活动减少等现象,病理切片有明显改变。结论成功构建了Loa22重组原核表达质粒,表达纯化的蛋白可以使豚鼠抵抗同型钩体的攻击,免疫保护作用为82%。     

本刑2007年文献来源指标、文献被引指标、期刊高被引指数和引证报告中被引频次最高的前5篇文章

随着计划免疫工作的深入开展,水痘已被列为北京市重点管理的疾病.为了解水痘疫苗的保护情况,以便进一步为制定北京市小学水痘疫情防控措施提供科学依据,现将北京市朝阳区某小学水痘突发疫情调查报告分析如下.     

Immunoregulatory activity of CpG oligonucleotides in humans and nonhuman primates

Oligodeoxynucleotides (ODN) containing CpG motifs mimic the ability of microbial DNA to activate the innate immune system. The resultant response limits the early spread of infectious organisms while promoting the development of adaptive immunity. CpG ODN show promise as vaccine adjuvants and in the treatment of asthma, allergy, infection, and cancer. Due to evolutionary divergence in CpG recognition between species, CpG ODN that are most active in rodents are poorly immunostimulatory in primates. Thus, evidence that CpG ODN have therapeutic activity in mice must be confirmed in primates. Two distinct types of CpG ODN were identified that stimulate primate PBMC. D-type ODN trigger plasmacytoid DC to secrete IFNalpha, monocytes to mature into functionally active DC, and NK cells to secrete IFNgamma. K-type ODN stimulate B cells and monocytes to proliferate and secrete IgM, IL-10, and/or IL-6. In vivo studies in nonhuman primates indicate that proinflammatory or humoral immune responses can be selectively facilitated by judicious use of these distinct types of ODN.     

日本血吸虫（中国大陆株）线粒体相关蛋白对小鼠免疫保护性的初步研究

目的 研究日本血吸虫（中国大陆株）线粒体相关蛋白（rSj338/26GST)对小鼠的免疫保护性，预测其作为血吸虫疫苗候选分子的潜能。方法 将编码日本血吸虫线粒体相关蛋白的cDNA经PCR扩增后亚克隆人载体质粒pGEX-6p-1进行表达，并用表达的重组抗原的融合蛋白免疫BABL／c小鼠。结果 与对照组相比，rSj338/26GST重组蛋白免疫小鼠获得了32．3％的减虫率及46．5％肝总减卵率；与Sj26GST免疫组相比，rSj338抗原可能使小鼠获得22．5％的减虫率及30．0％的肝总 减卵率。结论 证明重组的日本血吸虫线粒体相关蛋白(rSj338/26GST及rSj338)可诱导宿主抗血吸虫感染的部分保护力，可望成为新的疫苗候选分子。