菌影作为新型疫苗递送载体的研究进展

尽管基于重组蛋白或DNA的新型疫苗的开发以指数级上升,但是其免疫原性常弱于传统疫苗,缺少有效的递送系统是其应用的主要限制因素,因此迫切需要开发新型改良的递送系统和佐剂.菌影(bacterial ghost,BG)系统正是这类载体系统,它能将结合的抗原靶向APC,并具有佐剂活性.BG是一种无生命的革兰阴性菌包膜,无胞质内容物,但保留了细胞形态和天然表面抗原结构.由于BG具有颗粒特性并包含许多已知的免疫刺激成分,因此BG能增强抗其传递的靶抗原的免疫应答.作为一种新型的疫苗递送载体,菌影将被用于人用和兽用疫苗的生产.     

菌影在蛋白亚单位疫苗和DNA疫苗递送中的应用

菌影（bacterialghost,BG）是由噬菌体ФX174E基因表达蛋白介导革兰阴性菌裂解所形成的空胞,无胞质内容物,但保留了天然的胞壁结构。由于BG具有颗粒特性并含有天然表面抗原组分,因此易于被抗原呈递细胞识别并激发体液和细胞免疫应答。BG可负载外源蛋白和DNA,并可通过各种免疫途径进行接种。因此,BG是一种有潜力的疫苗递送系统。     

脂质体作为生物大分子载体的研究进展

对脂质体作为生物大分子载体，即作为基因物质，生物药物的载体，新型疫苗佐剂和载体，以及生物药物脂质体的给药途径进行了讨论。     

沙门菌载体疫苗研究进展

近年来沙门菌作为外源抗原的送递系统的研究取得很大进展,沙门菌已成为理想的外源抗原载体.此文概述了研发沙门菌载体疫苗所采用的抗原载运平台、Red重组酶系统以及其他新技术.     

酵母微囊作为口服药物递送载体的研究进展

酵母微囊是一种表面粗糙多孔、核心中空的天然药物递送载体,具有良好的安全性和高靶向性、高稳定性,在口服药物递送系统中具有极佳的应用前景。酵母细胞经过酸碱和有机溶剂处理、洗涤后可获得疏松多孔的酵母微囊,后者可借助静电相互作用、被动扩散、疏水作用等方式包载药物。酵母微囊表面主要由β-葡聚糖组成,可在胃肠环境中保持稳定,可被免疫细胞表面相关受体识别,从而激活免疫反应,并可在被摄取后随淋巴细胞的运动将所载药物运送至病变部位。酵母微囊安全性高,非常适合递送疫苗、抗炎药物及抗肿瘤药物,其不仅可实现上述药物的口服递送,而且能增强药物效果,提高药物的靶向性。今后可开展更多全身转运机制的相关研究或开发更加高效的联合给药系统,以充分发挥酵母微囊的临床价值。     

外泌体作为药物递送载体的研究进展

外泌体(exosomes)是一种由细胞分泌的纳米尺度(40~100 nm)的囊泡,在细胞间物质运输和信号交流中发挥重要作用。外泌体在大小和功能上与合成的纳米颗粒类似,但作为天然内源性转运载体,具有毒性低、无免疫原性、渗透性好等优势,故可能成为更有应用前景的药物递送载体。本文主要介绍了外泌体的基本性质和获得方法、载药方法及其作为纳米载体在小分子和生物大分子药物递送和靶向研究中的应用进展情况,并分析探讨了外泌体在载药和靶向递送方面的不足。     

应用于mRNA疫苗的非病毒载体递送系统研究进展

核酸疫苗相较传统疫苗,能诱导更加全面、持久的免疫应答反应,且易于快速生产。其中,mRNA疫苗抗原设计精确,耐受性良好,免疫应答强烈,表达机制比DNA疫苗更为安全和简单,具有十分广泛的应用前景。然而,mRNA疫苗稳定性较差,且难以穿过细胞膜,设计能够保护mRNA疫苗并将其运送到靶细胞发挥作用的递送系统至关重要。综述目前应用于mRNA疫苗体内递送的脂质、聚合物、肽类及其他非病毒载体和（或）递送系统的特点及研究现状,并对其研究前景进行展望。     

外泌体作为药物递送载体的研究进展

外泌体是一种由细胞主动分泌的纳米级脂质双层囊泡,其腔内或脂质双分子层中包裹着蛋白质、脂质和核酸等多种生物成分。外泌体具有低免疫原性、高物理化学稳定性、高组织穿透能力,以及先天的运输能力,因此有望成为一类新型的药物递送载体。目前,外泌体作为药物递送载体的研究已取得了可喜的进展,有关外泌体分离以及提高其药物负载和递送效率的新方法不断涌现。然而,仍有许多困难制约了外泌体的临床应用。综述了外泌体作为药物递送载体的研究进展,对外泌体大规模生产和纯化中的技术难点进行了分析,并总结了外泌体用于药物递送的法规问题。     

Bacterial ghosts as antigen delivery vehicles

The bacterial ghost system is a novel vaccine delivery system unusual in that it combines excellent natural intrinsic adjuvant properties with versatile carrier functions for foreign antigens. The efficient tropism of bacterial ghosts (BG) for antigen presenting cells promotes the generation of both cellular and humoral responses to heterologous antigens and carrier envelope structures. The simplicity of both BG production and packaging of (multiple) target antigens makes them particularly suitable for use as combination vaccines. Further advantages of BG vaccines include a long shelf-life without the need of cold-chain storage due to their freeze-dried status, they are safe as they do not involve host DNA or live organisms, they exhibit improved potency with regard to target antigens compared to conventional approaches, they are versatile with regards to DNA or protein antigen choice and size, and as a delivery system they offer high bioavailability.     

细菌多重耐药外排泵抑制剂研究进展

细菌耐药性，尤其是多重耐药性（multi-drug resistance，MDR）已经成为非常严重的医疗问题，而多种类型细菌外排泵（efflux pumps）的存在是细菌多重耐药的重要机制，因此寻找有应用前景的外排泵抑制剂（efflux pump inhibitors，EPI）是十分必要且迫切的。目前已经发现外排泵抑制剂的作用机制分为：（1）干扰外排泵组装；（2）阻断外排泵能量来源；（3）阻碍底物通过外排通道；（4）机制未知。本文按照作用机制对已经发现的细菌多重耐药外排泵抑制剂的特点进行分述。     

Cholesterol-bile salt vesicles as potential delivery vehicles for drug and vaccine delivery

The aim of this study was to further investigate the interactions between cholesterol (CH) and mixed bile salts (BS) (sodium cholate and sodium deoxycholate) and their suitability for drug and vaccine delivery. Insulin was used as a model protein to assess the ability of CH:BS vesicles to entrap a therapeutically relevant macromolecule. The association of protein (FITC-insulin) with the CH:BS structure was confirmed with fluorescence microscopy, and the overall morphology of the vesicles was examined with atomic force microscopy (AFM). Results demonstrate that the nature of the vesicles formed between CH and BS is dependent not only on the concentration of BS but also on the increasing CH concentration leading to CH crystal formation.     

Advances in oral vaccine delivery options

Vaccines have been one of the most far-reaching and important public health initiatives of the 20th century. Yet as we move into the 21st century, millions of people still die from vaccine-preventable diseases such as measles and tetanus, and complex diseases, such as malaria and HIV, for which we have no vaccines. New vaccines that can be administered orally, are stable at ambient temperature, and can be produced cheaply, have the potential to transform health policy and practice in both developed and developing countries. Although oral delivery is the preferred route of administration, it is inefficient for the delivery of ‘naked’ antigens. Delivery of a vaccine via the oral route in a sufficient dose to induce a protective immune response depends on overcoming the loss of antigen integrity that occurs during intestinal passage. Several strategies have been employed to prevent this loss of antigen(icity) and improve the delivery of vaccinogens by the oral route. These include live vectors, transgenic plants, and particulate formulations such as microparticles, liposomes, and virus-like particles. Although many of these systems have progressed to clinical trials, the most promising results are seen where strategies are combined. Prime-boost schedules and combined technologies are likely to be a critical component of future oral vaccination schedules. Further technological breakthroughs may also be required before strong protective immune responses can be consistently induced in humans. Nonetheless, the potential of future oral vaccination strategies is readily apparent.     

新型肺炎链球菌疫苗研究进展

肺炎链球菌是肺炎、脑膜炎、败血症、中耳炎和鼻窦炎的主要致病菌.目前针对肺炎链球菌疾病的预防主要是以多糖为基础的23价多糖疫苗和7价多糖蛋白结合疫苗,但因其有血清型的限制,应用有很大的局限性.因此以肺炎链球菌表面毒力因子或蛋白为基础的、无血清型限制的肺炎链球菌蛋白疫苗将成为新型肺炎链球菌疫苗发展的方向,此文综述了肺炎链球菌蛋白疫苗的研究进展.     

Advances in vaccine delivery: transcutaneous immunisation

Needle-free delivery of vaccines has become a global priority. Transcutaneous immunisation (TCI), topical application of vaccine antigens to the skin, can elicit systemic antibody and T-cell responses, suggesting that this new technique may provide a means for vaccination without needles. TCI requires the use of an adjuvant such as cholera toxin added to a vaccine antigen, such as diphtheria toxoid, to induce antibodies to diphtheria toxoid. The adjuvant and antigen are thought to target Langerhans cells, potent antigen-presenting cells found in the superficial layers of the skin. TCI appears to be a highly practical technique for delivery of vaccines that provides unique access to the immune system.     

细菌硝酸盐还原中的关键酶影响细菌耐药性的研究进展

硝酸盐的还原是细菌氮代谢中最重要的生化反应之一.随着对细菌耐药机制的不断探索,氮代谢过程尤其是某些代谢酶对细菌耐药性的影响得以揭示.作为硝酸盐还原过程中的关键代谢酶,硝酸还原酶(nitrate reductase,NR)与亚硝酸还原酶(nitrite reductase,NiR)不仅催化着细菌体内硝酸盐的一系列还原反应,还从多方面影响了细菌的耐药性.本文综述了NR/NiR与细菌耐药性之间关系的最新研究进展,以期为新药物靶标的发现及提出新治疗措施提供依据.     

Cationic liposomes as in vivo delivery vehicles

Optimization of cationic liposomal complexes for in vivo applications is complex involving many diverse components. These components include nucleic acid purification, plasmid design, formulation of the delivery vehicle, administration route and schedule, dosing, detection of gene expression, and others. This review will primarily focus on optimization of the delivery vehicle formulation. These formulation issues include morphology of the complexes, lipids used, flexibility versus rigidity, colloidal suspension, overall charge, serum stability, half-life in circulation, biodistribution, delivery to and dissemination throughout target tissues. Optimizing all components of the delivery system will allow broad use of liposomal complexes to treat or cure human diseases or disorders.