提高沙门菌传递外源抗原的能力

美国纽约州立大学(SUNY)和内布拉斯加大学的研究者提高了沙门菌作为抗原释放载体的效力.科学家利用沙门菌的生物组成,能用这个载体系统诱发细胞毒性T淋巴细胞(CTL)应答.     

细菌载体技术研究进展(下)

对预防人类疾病的新型和改良疫苗的需求始终没有减少.在传染病领域对传统疫苗需求持续增长的同时,在非传统领域(如肿瘤治疗、生物武器和食品安全)对新疗法的需求也在不断增长.由于这些变化,人们对应用和开发表达外源抗原的减毒活菌苗产生了新的兴趣.研究最深入的细菌载体疫苗是沙门菌减毒株.志贺菌、单核细胞增多性李斯特杆菌、牛分枝杆菌-卡介苗(BCG)和霍乱孤菌减毒株在抗原传递和免疫呈递方面提供了独特的选择,有希望成为有用的细菌载体.     

细菌载体技术研究进展(上)

对预防人类疾病的新型和改良疫苗的需求始终没有减少.在传染病领域对传统疫苗需求持续增长的同时,在非传统领域(如肿瘤治疗、生物武器和食品安全)对新疗法的需求也在不断增长.由于这些变化,人们对应用和开发表达外源抗原的减毒活菌苗产生了新的兴趣.研究最深入的细菌载体疫苗是沙门菌减毒株.志贺菌、单核细胞增多性李斯特杆菌、牛分枝杆菌-卡介苗(BCG)和霍乱弧菌减毒株在抗原传递和免疫呈递方面提供了独特的选择,有希望成为有用的细菌载体.       

phoP/phoQ激活的启动子应用于以减毒沙门菌为载体的疫苗系统

phoP/phoQ为沙门菌的双成分调节子,phoQ可感受巨噬细胞中一些因子的改变,显示组氨酸激酶活性,使phoP氨基端特定的残基磷酸化,磷酸化后的phoP结合于特定的启动子,诱导或抑制一系列基因的表达.受phoP/phoQ激活的pagC基因的启动子ppagC能有效地驱动外源基因在鼠伤寒杆菌中的表达,激发宿主抗该外源蛋白的抗体.使用ppagC可克服在减毒沙门菌中因外源基因的组成性表达而带来的低表达和表达质粒不稳定的问题.因此,ppagC在以减毒沙门菌为载体的疫苗研制中具有很好的应用前景.     

在无毒力鼠伤寒杆菌及伤寒杆菌中合成的HBcAg-前S蛋白用作口服疫苗

无毒力沙门菌作为口服菌苗载体表达外源基因的研究引起人们的兴趣.活菌苗株要求不带有抗生素抗性标记.为此,作者将as-dAI基因缺失引入沙门菌△cya△crp减毒菌苗株,以asd基因产物二氨基庚二酸(DAP)作为选择标记.同时构建具有asd基因的互补性质粒,成为无抗生素抗性标记.且能稳定表达外源基因的平衡致死系统.     

菌苗载体和卡介苗

生物技术的最近进展给疫苗（尤其是重组疫苗）的开发提供了新方法。菌苗载体优于病毒载体的地方是前者能够表达大量不同的抗原。尽管目前尚没有重组菌苗载体投入应用，卡介苗（ＢＣＧ）、沙门菌和大肠杆菌作为菌苗载体正在研制之中，本文综述了用于表达外源抗原的质粒系统和突变株（着重于与ＢＣＧ有关的质粒系统和突变株）的建立，还介绍了抗原表达系统方面的进展，以及重组ＢＣＧ菌株诱导的对细菌抗原和人类免疫缺陷症病毒（ＨＩＶ     

菌苗载体和卡介苗

生物技术的最近进展给疫苗（尤其是重组疫苗）的开发提供了新方法。菌苗载体优于病毒载体的地方是前者能够表达大量不同的抗原。尽管目前尚没有重组菌苗载体投入应用,卡介苗（BCG）、沙门菌和大肠杆菌作为菌苗载体正在研制之中,本文综述了用于表达外源抗原的质粒系统和突变株（着重于与BCG有关的质粒系统和突变株）的建立,还介绍了抗原表达系统方面的进展,以及重组BCG菌株诱导的对细菌抗原和人类免疫缺陷症病毒（HIV）抗原的免疫应答,并提出能稳定维持重组DNA（rDNA）的改良的重组BCG载体的选择。     

细菌载体技术研究进展（下）

对预防人类疾病的新型和改良疫苗的需求始终没有减少。在传染病领域对传统疫苗需求持续增长的同时，在非传统领域(如肿瘤治疗、生物武器和食品安全)对新疗法的需求也在不断增长。由于这些变化，人们对应用和开发表达外源抗原的减毒活菌苗产生了新的兴趣。研究最深入的细菌载体疫苗是沙门菌减毒株。志贺菌、单核细胞增多性李斯特杆菌、牛分枝杆菌-卡介苗(BCG)和霍乱孤菌减毒株在抗原传递和免疫呈递方面提供了独特的选择，有希望成为有用的细菌载体。     

细菌载体技术研究进展（上）

对预防人类疾病的新型和改良疫苗的需求始终没有减少。在传染病领域对传统疫苗需求持续增长的同时，在非传统领域(如肿瘤治疗、生物武器和食品安全)对新疗法的需求也在不断增长。由于这些变化，人们对应用和开发表达外源抗原的减毒活菌苗产生了新的兴趣。研究最深入的细菌载体疫苗是沙门菌减毒株。志贺菌、单核细胞增多性李斯特杆菌、牛分枝杆菌-卡介苗(BCG)和霍乱弧菌减毒株在抗原传递和免疫呈递方面提供了独特的选择，有希望成为有用的细菌载体。     

phoP／phoQ激活的启动子应用于以减毒沙门菌为载体的疫苗系统

phoP/phoQ为沙门菌的双成分调节子,phoQ可感受巨噬细胞中一些因子的改变,显示组氨酸激酶活性,使phoP氨基端特定的残基磷酸化,磷酸化后的phoP结合于特定的启动子,诱导或抑制一系列基因的表达。爱phoP/phoQ激活的pagC基因的启动子ppagC能有效地驱动外源基因在鼠伤寒杆菌中的表达,激发宿主抗该外源蛋白的抗体。使用ppagC可克服在减毒沙门菌中因外源基因的组成性表达而带来的低表达和表达质粒不稳定的问题。因此,ppagC在以减毒沙门菌为载体的疫苗研制中具有很好的应用前景。     

The use of live attenuated bacteria as a delivery system for heterologous antigens

Live attenuated mutants of several pathogenic bacteria have been exploited as potential vaccine vectors for heterologous antigen delivery by the mucosal route. Such live vectors offer the advantage of potential delivery in a single oral, intranasal or inhalational dose, stimulating both systemic and mucosal immune responses. Over the years, a range of strategies have been developed to allow controlled and stable delivery of antigens and improved immunogenicity where required. Most of these approaches have been evaluated in Salmonella vaccine vectors and, as a result, several live attenuated recombinant Salmonella vaccines are now in human clinical trials. In this review, these strategies and their use in the development of a delivery system for the Yersinia pestis V antigen are described.     

Attenuated salmonella and Shigella as carriers for DNA vaccines

The discovery that genes can be functionally transferred from bacteria to mammalian cells has suggested the possible use of bacterial vectors as gene delivery vehicles for vaccines. Attenuated invasive human intestinal bacteria, such as Salmonella and Shigella, have been used as plasmid DNA vaccine carriers and their potency has been evaluated in several animal models. This delivery system allows the administration of DNA vaccines together with associated bacterial immunostimulators directly to professional antigen presenting cells via human mucosal surfaces. Various strategies have been taken to improve the use of this delivery system to achieve robust immune responses at both mucosal and systemic sites of the immunized animals.     

破壁灵芝孢子粉致突变性的初步研究

目的研究破壁灵芝孢子粉致突变的可能性,探讨其是否具有遗传毒性。方法通过微核试验、精子畸形试验和Ames试验,观察不同剂量的破壁灵芝孢子粉对小鼠骨髓细胞微核形成、精子畸形的产生和鼠伤寒沙门氏菌的回复突变情况的影响。结果2.5-10.0g/kg.BW破壁灵芝孢子粉处理的各剂量组小鼠的骨髓细胞微核形成率和精子畸形率都未出现明显增加,与相应的对照组相比无显著性差异;在加和不加代谢活化系统条件下,8-5000μg/皿破壁灵芝孢子粉处理的各剂量组的鼠伤寒沙门氏菌回复突变率均未出现明显升高,与相应的对照组相比无显著性差异。结论在本研究条件下未发现破壁灵芝孢子粉具有直接或间接的致突变作用,也未发现其具有遗传毒性。     

Bacterial carriers and virus-like-particles as antigen delivery devices: role of dendritic cells in antigen presentation

Replicating attenuated strains of intracellular bacteria like Salmonella typhimurium, Listeria monocytogenes or Mycobacterium bovis Bacille Calmette Guérin (BCG), and non-replicating virus-like-particles (VLP) consisting, for instance, of the VP1-surface component of polyoma virus offer great potential as heterologous carriers delivering foreign protein antigens for immune recognition. Moreover, attenuated S. typhimurium and L. monocytogenes strains hold also great promise as delivery vehicles for DNA vaccines. Polyoma virus-specific VLP consisting of VP1-pentamers are also of interest as carrier devices for eukaryotic expression plasmids. At first sight these different replicating and non-replicating types of vehicles have little in common, but from an immunological point of view viable bacteria and non-viable VLP are both well suited for evoking protective immune responses via several routes of vaccine administration. As these antigen carriers generate humoral and cell-mediated immunity, the heterologous antigens are not only targeted to appropriate pathways of major histocompatibility (MHC) class I and class II antigen processing and presentation, but also generate an adequate cytokine milieu for promoting antigen-specific responses. The most prominent advantage of these carrier devices is presented by their capacity to directly target antigenic proteins or DNA vaccines to immature dendritic cells (DC) along their maturation pathway. Mature DC are the key antigen presenting cell population which efficiently mediates antigen transport to organised lymphoid tissues for the initiation of T cell responses. In general, uptake of these diverse antigen delivery systems by antigen presenting cells (APC) finally lead to efficacious immune responses in the control of pathogenic microorganisms and tumours.     

Research progress of tonic Chinese medicine on the immune system

The immune system as an important defense system of the body,bear the resistance to foreign pathogens invasion,removal of foreign heterogeneity,and protect the body′s safety.Modern research shows that tonic Chinese medicine,including single herband compound formula,has the function of improving immune organ index,enhancing immune cellfunction and affecting the immune molecule production and secretion.This article will review the effects of traditional Chinese medicine on immune organs,immune cells and immune molecules,and provide reference for the clinical research of traditional Chinese medicine.     

Ex-vivo uses and applications of cytokines for adoptive immunotherapy in cancer

Harnessing the power of the immune system to eliminate infection and cancer is a long-standing goal in clinical immunology. The development of a robust immune response to foreign antigen relies, in part, on communication between cellular components of the immune system. The proteins involved in governing the magnitude and longevity of an immune response are collectively called cytokines. Cytokines act directly on immune cells to induce proliferation, differentiation and tolerance, and signaling errors can lead to autoimmune disease or immune deficiency. Identification of the molecules involved in these signaling processes has allowed investigators to manipulate immune cells for therapeutic effect, both in vivo and ex vivo. While in vivo immune modulation using cytokines has produced some exciting results, the toxicity involved with systemic administration has limited their broad use in the clinic. Therefore, research has been focused on the ex vivo manipulation of immune cells for adoptive transfer to treat cancer and infection. This review will focus on the ex vivo manipulation of immune cells with particular emphasis on stimulating cytotoxic T cell responses. Adoptive transfer of ex vivo generated cell types may then be used to treat malignant and viral disease.     

The effects of chlorpromazine on the outer cell wall of Salmonella typhimurium in ensuring resistance to the drug

Chlorpromazine (CPZ), a compound employed for the management of psychosis, has a wide ranging antibacterial activity. The growth of Salmonella typhimurium100 mg/l), was initially inhibited during the first 8-16 h of exposure to concentrations of CPZ below the MIC. During this period of transient susceptibility, the distribution of ribosomes was markedly altered in a concentration dependent manner; the rough cell wall was transformed into a smooth form. The protein composition of the outer cell wall of 55 kDa was markedly decreased, whilst there was an increased number of high molecular weight proteins. After 16 h of exposure to sub-MIC levels of CPZ, the inhibitory effect of the drug was no longer apparent whereas the effects noted on the cell wall were retained. These Salmonella were, as the control, agglutinated by O antigen specific antibody. Whereas agglutination of the control Salmonella was blocked by the presence of CPZ at concentrations that induced the cell-wall effects, agglutination of CPZ exposed-Salmonella for periods in excess of 16 h was not blocked by any concentration of CPZ. These results suggested that eventual resistance to CPZ was dependent upon changes induced by CPZ at the cell wall level. The results also suggested that the CPZ binds to the 55 kDa protein and that such binding interfered with the recognition of the O antigen by antibody.     

疫苗黏膜输送系统的研究进展

疫苗经黏膜接种是一种简单有效的非侵入性给药方式,可同时诱导系统和黏膜免疫应答,且患者顺应性好,成为近年来疫苗接种的研究热点.以合适的药物输送系统为载体可减少抗原的降解和失活,提高免疫原性,减少接种次数.本文综述了纳米乳、胶束、脂质体、纳米粒、免疫刺激复合物和病毒样粒子等疫苗黏膜输送系统相关技术的研究进展.     

前列腺癌主动靶向药物传递系统的研究进展

目的 介绍前列腺癌主动靶向药物传递系统的研究进展。方法 查阅近年来国内外相关文献,对前列腺癌作用靶点为基础的主动靶向药物传递系统进行总结和归纳。结果 以前列腺特异性抗原和前列腺特异性膜抗原等作为靶点,应用抗体、适体或者多肽靶向修饰的脂质体、胶束、纳米粒、前体药物传递系统,可以将药物有效传递到前列腺癌靶组织、靶细胞,提高抗肿瘤药物作用效果。结论 主动靶向前列腺癌的药物传递系统具有广阔的研究和应用前景。     

Mechanisms of MHC class I-restricted antigen presentation

The vertebrate immune system monitors whether an organism is invaded by pathogens. Therefore, each cell has to prove itself as healthy. This is achieved by presenting fragments of intracellular protein degradation products on the surface, i.e., each cell displays peptides on specialised proteins known as major histocompatibility complex (MHC) class I proteins. A displayed peptide has to pass certain constraints before its presentation: It has to be excised out of a protein, translocated into the endoplasmic reticulum (ER) and fit into the binding groove of a MHC molecule. In theory, alteration of the cellular protein profile by mutation or infection should force pathogen-specific T-cells to take action via recognition of foreign peptide bound to MHC class I molecules on the cell surface. Unfortunately, pathogens and tumours have evolved many ways to affect antigen presentation and to escape from immune response. Understanding the exact mechanisms of antigen presentation, i.e., protein cleavage and peptide binding by MHC molecules, would allow their manipulation by drugs and lead to the re-establishment of the correct antigen presentation pathway. This review will summarise current knowledge of the mechanisms of antigen presentation and discuss putative targets for therapeutic treatment as well as for vaccination strategies.