幽门螺杆菌基因工程疫苗探讨

幽门螺杆菌（HP）感染是慢性B型胃炎、胃和十二指肠消化性溃疡的主要病因,也是胃肠癌、胃黏膜淋巴组织淋巴癌的关键病因,因此其预防和治疗显得尤为重要。本文就我国幽门螺杆菌疫苗的研究探讨如下。     

纳米给药系统在幽门螺杆菌靶向治疗中的研究进展

幽门螺杆菌是一种定植于胃黏液层和胃黏膜表面的常见致病菌,全球感染率已超过50%。幽门螺杆菌感染与消化性溃疡、慢性胃炎、胃癌等多种消化系统疾病的发生发展有着密切的联系,临床以抗生素为主的联合疗法为常见。随着抗生素的酸不稳定及细菌耐药性的不断升高,幽门螺杆菌的根除率不断下降,为药物递送提出了新的挑战。纳米给药系统在提高药物生物利用度、达到靶向、缓控释递药等方面具有独特优势,为幽门螺杆菌感染治疗带来了机遇。本文分析了H. pylori的结构特征与其定植、耐药性的产生之间的联系,并针对H. pylori特征结构,归纳总结了纳米给药系统在幽门螺杆菌靶向治疗中的研究进展,以期为幽门螺杆菌的治疗研究和制剂开发提供参考。     

胃肠疾病，“三分治七分养”

自从澳大利亚医生发现幽门螺杆菌后,医学界乃至普通民众都认为幽门螺杆菌是胃、食管、十二指肠疾病的主要原因,事实并非如此。最具说服力的一点是,我国人口的幽门螺杆菌感染率在60%以上,而胃、食管、十二指肠疾病的患病率仅在10%左右。这就表明绝大多数幽门螺杆菌感染者是不发病的。再者那些感染幽门螺杆菌并发生胃、食管、十二指肠疾病的患者,在抗幽门螺杆菌治疗失败的情况下,通过止酸剂、胃黏膜保护剂等药物治疗,改变饮食、起居习惯,也可得到缓解和痊愈。     

幽门螺杆菌疫苗研究新进展

幽门螺杆菌感染全世界一半以上人口,已被世界卫生组织列为Ⅰ类致癌原.目前治疗方法以药物治疗为主,但存在病人的依从性、对抗生素的耐药性、费用高、感染复发等缺陷.而制备幽门螺杆菌疫苗将克服上述问题,达到预防和治疗的目的.至今人们对幽门螺杆菌疫苗的研究已在抗原和佐剂的选择、免疫途径、疫苗免疫机制等方面进行了深入的探讨.本文就近几年来幽门螺杆菌疫苗研制的发展方向加以综述.     

幽门螺杆菌疫苗研究新进展

幽门螺杆菌感染全世界一半以上人口，已被世界卫生组织列为Ⅰ类致癌原。目前治疗方法以药物治疗为主，但存在病人的依从性、对抗生素的耐药性、费用高、感染复发等缺陷。而制备幽门螺杆菌疫苗将克服上述问题，达到预防和治疗的目的。至今人们对幽门螺杆菌疫苗的研究已在抗原和佐剂的选择、免疫途径、疫苗免疫机制等方面进行了深入的探讨。本文就近几年来幽门螺杆菌疫苗研制的发展方向加以综述。     

中药抗幽门螺杆菌概述

幽门螺杆菌是引起胃炎、胃和十二指肠溃疡乃至胃癌的主要致病菌。近年来,随着大量广谱抗生素的广泛应用。使得耐药的幽门螺杆菌菌株呈不断上升趋势。开发高效和高选择性的抗幽门螺杆菌药物已经成为全球关注的课题。本文对近五年来文献报道的抗幽门螺杆菌中药进行简要归纳,分为单味中药和复方中药制剂两方面抗幽门螺杆菌。为研究和开发幽门螺杆菌感染性疾病的治疗新药提供参考。     

幽门螺杆菌疫苗研究进展

幽门螺杆菌感染在全世界广泛存在,能引起多种胃部疾病,包括胃癌.尽管抗生素治疗有效,但是人们一致认为幽门螺杆菌疫苗可能是控制幽门螺杆菌感染的最佳方法.有效的幽门螺杆菌疫苗策略可显著增进全世界人群的健康.此文就幽门螺杆菌疫苗的保护性抗原、佐剂、动物模型、免疫机制的研究进展进行综述.     

~(13)C-尿素呼气试验筛查幽门螺杆菌感染的临床分析

<正>幽门螺杆菌系胃黏膜内微需氧螺杆菌属,是慢性胃炎、消化道溃疡、胃癌、胃淋巴瘤的主要致病因素之一,全球自然人群中幽门螺杆菌感染达50%[1],及时诊断有效根治幽门螺杆菌感染,成为当今医学界关注的焦点。我中心于2010年3月至2012年3月对1 200名体检人群采用13C-尿素呼气试验(UBT)检测幽门螺杆菌感染,诊断阳性率高,现     

幽门螺杆菌感染与胃肠系统疾病

幽门螺杆菌感染(Helicobacter infections)是指幽门螺杆菌(Helicobacter Pylori,HP)在胃及十二指肠球部的感染。研究资料证明此菌与慢性胃炎特别是慢性活动性胃炎及胃和十二指肠溃疡有密切关系。认为幽门螺杆菌先引起急性胃炎,尔后转成慢性胃炎,而消化性溃疡是在慢性胃炎基础上,因某种因素引起的。近年来国内外大量研究表明HP与胃癌及胃非霍奇金恶性淋巴病的发生有密切关系,并有报道HP可能也参与了冠心病的形     

抗幽门螺杆菌药物研究进展

幽门螺杆菌（Helicobacter pylori,HP）感染是胃炎、胃溃疡和胃癌等疾病的主要致病因素之一.近年来,其诱发的胃部疾病发病率呈现上升趋势,抗幽门螺杆菌药物研发已成为热点.本文对抗HP临床现有药物和活性化合物研究现状进行综述.     

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.     

mRNA疫苗技术概述及新型冠状病毒肺炎mRNA疫苗的研究进展

mRNA疫苗技术的发展受到分子本身不稳定、自身免疫原性高以及体内递送效率低等因素的限制，经过30多年的研究，近年来随着其稳定性、高效传递系统方面的技术日趋成熟，肿瘤和传染病mRNA疫苗研究进展明显。与传统疫苗技术相比，该技术可诱导机体产生体液免疫和细胞免疫，疫苗生产工艺简单、研发周期短、成本低，便于标准化生产，适用于大流行疾病和传染病暴发流行期间的疫苗开发和生产，是一种应用前景广阔的疫苗。在当前新型冠状病毒肺炎全球大流行的背景下，本文从mRNA疫苗的特征、疫苗递送系统入手，结合新型冠状病毒肺炎mRNA疫苗的研究现状进行了分析和阐述，以期为后续的mRNA疫苗研究开发提供参考依据。     

基于脂质载体的mRNA疫苗递送系统研究进展

转录信使RNA（mRNA）具有安全有效的蛋白质表达谱,在遗传病新疗法、表达功能性蛋白和抗体、疫苗或基因编辑的开发上具有良好的应用前景。随着病原生物学与免疫学的发展,mRNA疫苗凭借其高效性与稳定性而愈发被重视。目前,有效的体内递送手段是mRNA疫苗所面临的较大挑战,脂质载体的mRNA疫苗递送系统具有靶向性强、包封率高、细胞亲和性好的特点,部分脂质载体能够使mRNA疫苗在体内以非侵入性的方式进行靶向递送。从mRNA疫苗递送的主要难点、脂质载体在mRNA疫苗递送中的研究现状以及针对新型冠状病毒（SARS-CoV-2）的mRNA脂质载体疫苗开发进展,共3个方面总结了目前基于脂质载体的mRNA疫苗递送系统研究进展,并对未来的基因疫苗递送系统研究方向进行展望。     

轮状病毒疫苗的研究现状及进展

轮状病毒是全球范围内引起婴幼儿腹泻的主要病原体,接种轮状病毒疫苗为目前最经济、有效的预防手段,很大程度上缓解了轮状病毒导致的疾病负担,但目前上市疫苗均为减毒活疫苗,存在毒力回复以及肠道不良反应等风险。因此,优化的传统活疫苗、灭活疫苗以及病毒样颗粒等亚单位疫苗成为潜在的候选疫苗,以提高轮状病毒疫苗的安全性和有效性。此文总结了市面上主要轮状病毒疫苗的应用现状以及进入临床试验新疫苗的研究情况,为后续的疫苗开发奠定基础。     

Recent developments in leishmaniasis vaccine delivery systems

Background: The observation that recovery from infection with Leishmania confers immunity to reinfection suggests that control of leishmaniasis by vaccination may be possible. New generation vaccines, particularly those based on recombinant proteins and DNA, are found to be less immunogenic. Objective: There is an urgent need for the development of new and improved vaccine adjuvants. Methods: Based on their principal mechanisms of action, adjuvants can be broadly separated into two classes: immunostimulatory adjuvants and vaccine delivery systems. Vaccine delivery systems can carry both antigen and adjuvant for effective delivery to the antigen-presenting cells (APCs). In this article, we review the adjuvants, the delivery systems and their combinations used in the search of an effective vaccine against leishmaniasis. Conclusion: Based on current knowledge, cationic liposomes appear to have better prospects as effective delivery systems for developing a vaccine for leishmaniasis.     

Strategies for DNA vaccine delivery

Strategies for gene delivery comprise a diverse range of live and synthetic approaches; DNA delivery for the purposes of immunisation in turn comprises a large part of this research. This review mainly discusses synthetic systems for application in the delivery of plasmid DNA vaccines, outlining polylactide-co-glycolide, liposome, chitosan and complex combination delivery systems. Areas of promise for DNA vaccine candidates include immune modulation of allergic responses and veterinarian application. The potential for realistic consideration of DNA vaccines as an alternative to existing approaches is dependent on the development of efficient DNA vaccine vectors and improved systems for DNA vaccine delivery. DNA vaccine technology may yet prove to be an important asset in an environment where there is a critical need for therapeutic and prophylactic strategies to combat a wide range of disease states.     

A review of multiple approaches towards an improved hepatitis B vaccine

Background: Hepatitis B is a DNA virus that can cause liver inflammation, cirrhosis, and cancer in chronically infected and symptomatic carriers. Antiviral treatments are usually limited in their effectiveness in treating the disease states. Vaccination against hepatitis B in pediatric and adolescent populations has proven to be a generally effective means for preventing diseases that could be potentially caused by this virus. Some 5 – 10% of the vaccinees do not develop protective immunity against the virus. Therefore, a significant amount of effort has been made in many research laboratories across the world to increase the potency of the vaccine by various innovative means, e.g., increasing the immunogenicity of the antigen or through introduction of novel adjuvants that elicit strong humoral and cell-mediated immune responses. Objectives/methods: The objective of this review is to highlight publications of significant developments that have been made over the past decade and efforts that are continuing towards producing an improved vaccine. A number of patents that protect novel hepatitis B vaccine formulations, including those claiming novel hepatitis B core antigen formulations and combinations of a vaccine with small molecule therapeutics, are discussed. Conclusion: There have been promising developments in the area of new adjuvants and delivery systems. The practical need for reducing the total number of childhood vaccinations has driven development of, and patent filings on, multivalent and combination vaccine formulations in which the hepatitis B vaccine is included as one component. Efforts and some advances have also been made in the critical area of therapeutic application of the vaccine. The existence of a large population of already infected patients and the inadequacy of most of the current antiviral drugs against hepatitis B diseases have also inspired efforts to produce a vaccine that would be efficacious in clearing an exiting infection.     

Delivery of Chlamydia vaccines

The plethora of ocular, genital and respiratory diseases of Chlamydia, including nongonococcal urethritis, cervicitis pelvic inflammatory disease, ectopic pregnancy, tubal factor infertility, conjunctivitis, blinding trachoma and interstitial pneumonia, and chronic diseases that may include atherosclerosis, multiple sclerosis, adult onset asthma and Alzheimer’s disease, still pose a considerable public health challenge to many nations. Although antibiotics are effective against Chlamydia when effectively diagnosed, asymptomatic infections are rampart, making clinical presentation of complications often the first evidence of an infection. Consequently, the current medical opinion is that an effective prophylactic vaccine would constitute the best approach to protect the human population from the most severe consequences of these infections. Clinical and experimental studies have demonstration that Chlamydia immunity in animals and humans is mediated by T cells and a complementary antibody response, and the completion of the genome sequencing of several isolates of Chlamydia is broadening our knowledge of the immunogenic antigens with potential vaccine value. Thus, major advances have been made in defining the essential elements of a potentially effective subunit vaccine design and parameters for evaluation. However, the challenge to develop effective delivery systems and human compatible adjuvants that would boost the immune response to achieve long-lasting protective immunity remains an elusive objective in chlamydial vaccine research. In response to evolving molecular and cellular technologies and novel vaccinology approaches, considerable progress is being made in the construction of novel delivery systems, such as DNA and plasmid expression systems, viral vectors, living and nonliving bacterial delivery systems, the use of chemical adjuvants, lipoprotein constructs and the codelivery of vaccines and specific immuno-modulatory biological agonists targeting receptors for chemokines, Toll-like receptors, and costimulatory molecules. The application of these novel delivery strategies to Chlamydia vaccine design could culminate in timely achievement of an efficacious vaccine.     

Delivery of a peptide via poly(d,l-lactic-co-glycolic) acid nanoparticles enhances its dendritic cell–stimulatory capacity

Nanoparticles (NPs) are attractive carriers for vaccines. We have previously shown that a short peptide (Hp91) activates dendritic cells (DCs), which are critical for initiation of immune responses. In an effort to develop Hp91 as a vaccine adjuvant with NP carriers, we evaluated its activity when encapsulated in or conjugated to the surface of poly(d,l-lactic-co-glycolic) acid (PLGA) NPs. We found that Hp91, when encapsulated in or conjugated to the surface of PLGA-NPs, not only activates both human and mouse DCs, but is in fact more potent than free Hp91. Hp91 packaged within NPs was about fivefold more potent than the free peptide, and Hp91 conjugated to the surface of NPs was ～20-fold more potent than free Hp91. Because of their capacity to activate DCs, such NP-Hp91 systems are promising as delivery vehicles for subunit vaccines against infectious disease or cancer.From the Clinical EditorIn this paper, nanoparticle-based dendritic cell activating vaccines are described and discussed. The authors report that the presented PLGA NP based vaccine constructs increase the potency of the studied vaccine by up to 20-fold, making them promising as delivery vehicles for subunit vaccines against infectious diseases or cancer.     

Advantageous Features of Plant-based Systems for the Development of HIV Vaccines

Plants have recently become an attractive option for the production of recombinant proteins. Plant-based systems can be used to produce many classes of foreign proteins including candidate vaccine antigens. The selected antigen can be purified from plant material prior to delivery by the preferred route, or alternatively delivered orally in edible plant material that has been processed to give a homogeneous and stable product. Several plant species have been used to express a wide range of vaccine candidates with tobacco, potato and corn being particularly favored. Corn seed is especially well suited to various food processing technologies that generate dry homogeneous material suitable for extended storage and refrigeration-free transport and distribution. Many antigens have been expressed in corn and assessed for efficacy in trials with generally positive results. Candidate HIV vaccines are particularly good targets for plant-based oral delivery since there is a great need for an easily distributed affordable vaccine that could be administered without injection and induce strong mucosal immune responses. As a first step in evaluating plant expression technology with a relevant antigen that might easily be tested in an animal system, we expressed the SIV major surface glycoprotein gp130 (analogous to HIV gp120) in corn seed. Expression levels were achieved that are compatible with conducting oral delivery trials in animals.