反向疫苗学:恶性疟疫苗研制新策略

基因组技术和生物信息学的发展催生了反向疫苗学,它是从全基因组水平筛选保护性免疫抗原的新方法.疟疾主要由4种人体疟原虫引起.恶性疟原虫14条染色体上的全基因组序列测定目前已经完成,因此,利用反向疫苗技术研制恶性疟候选疫苗将是有效的新策略.     

血吸虫反向疫苗学理论与技术的研究现状与展望

【提要】 近年发展起来的反向疫苗学,以“序列-结构-功能”思想为依据,以免疫信息学、计算机预测设计以及高通量的各种组学（包括基因组学、 转录本组学、 蛋白质组学等）综合集成技术为核心,可能为血吸虫疫苗候选分子的发现提供一条新途径。本文简要介绍了反向疫苗学常用的理论预测和实验方法;概述了应用反向疫苗学理论与技术筛选和鉴定血吸虫候选疫苗分子（保护性抗原或表位）的进展情况;最后,讨论了通过模拟辐照致弱血吸虫疫苗或人群获得性免疫的效应机制等来发展血吸虫反向疫苗学的可能的研究方向。     

血吸虫疫苗候选分子的研究进展

近年来,对血吸虫病疫苗进行了广泛的研究,并取得一些进展,已鉴定、克隆和表达了近百种血吸虫病疫苗候选分子。虽然这些疫苗候选分子都没有获得如照射减毒活尾蚴疫苗那样好的免疫效果,但已有一些被WHO认为是最有希望的疫苗候选分子,它们在各种动物试验中均能诱生一定的免疫保护力。本文将血吸虫疫苗候选分子方面研究作一综述性介绍。     

狂犬病毒HEP-dG株的拯救

目的筛选免疫原性高、致病性低的狂犬病疫苗候选株。方法应用反向遗传技术,在狂犬病毒弱毒株HEP-Flury株全基因组3'-N-P-M-G-L-5'的假基因区域(G与L之间),插入一个G基因,构建携带双G基因的全长感染性克隆,其与辅助质粒共转染BHK-21细胞,盲传十代,用荧光抗体和RT-PCR鉴定病毒。结果成功获得携带双G基因的狂犬病毒HEP-dG株,该病毒在BHK-21细胞中稳定生长,其病毒滴度达到1010FFU/mL。结论HEP-dG株会为研制高效的狂犬病病毒基因工程口服疫苗提供了良好的疫苗候选株。     

血吸虫疫苗研究面临的问题

本文综述了世界卫生组织热带病研究与培训规划署(WHO/TDR)提出的6种血吸虫候选疫苗分子的概况和不足;着重讨论了当前血吸虫疫苗研究面临的问题。建议在研究工作中寻找新的候选分子并开辟新的途径。     

反向遗传学技术对呼吸道病毒研究的促进作用

反向遗传学技术,即病毒的全长感染性cDNA克隆技术,它解决了对RNA病毒基因组难以操作这一多年难题。由于多数呼吸道病毒属于RNA病毒,因此反向遗传学技术在深入研究呼吸道病毒基因组结构功能、研制筛选候选疫苗株等方面显示出非常好的应用前景。本文就呼吸道病毒反向遗传学技术的建立及应用进展进行了综述。     

血吸虫疫苗研究面临的问题

本综述了世界卫生组织热带病研究与培训规划署（ＷＨＯ／ＴＤＲ）提出的６种血吸虫候选疫苗分子的概况和不足;着重讨论了当前血吸虫疫苗研究面临的问题。建议在研究工作中寻找新的候选分子并开辟新的途径。     

呼唤血防明天──日本血吸虫疫苗研究专项课题3年评估报告

本文综述了国内日本血吸虫疫苗研究在总理预备金项目支持下开展3年来的技术进展，根据课题下14项专题的总结或中期汇报内容，具体就候选抗原分子筛选、新保护性抗原探索、合成从抗原、核酸疫苗、新型佐剂、人群再感染保护力发展规律的探讨及其它一些有关的外延性研究进行了扼要的记录和评述．文章还就项目评估会议对日本血吸虫疫苗研制的前景、今后策略和实施路线以及建议等的讨论意见于以阐述，提供报告．     

呼吸血防明天：——日本血吸虫疫苗研究专题课题3年评估报告

本文综述了国内日本血吸虫疫苗研究在总理预备金项目支持下开展了３年来的技术进展，根据课题下１４项专题的总结或中期汇报内容，具体就候选抗原分子筛选、新保护性抗原探索、合成肽抗原、核酸疫苗、新型佐剂、人群再感染保护力发展规律的探讨及其它一些有关的外延性研究进行了扼要的记录和评述。文章还就项目评估译日本血吸虫疫苗研制的前景、今后策略和实施路线以及建议等的讨论意见予以阐述，提供报告。     

乙肝表面抗原载体多价重组核酸疫苗研究进展

研究表明,乙肝病毒的包膜蛋白HBsAg不仅可以作为疫苗的理想候选分子,还可作为基因工程疫苗的理想载体,用来成功构建多种重组核酸疫苗。本文概述了以乙肝表面抗原为载体,重组或联合其他病毒、寄生虫、细胞因子等其他基因制作多价核酸疫苗的研究进展。     

Vaccine discovery and translation of new vaccine technology

An unprecedented increase in new vaccine development has occurred over the past three decades. This activity has resulted in vaccines that protect against an increased range of vaccine-preventable diseases, vaccines that reduce the number of required injections, and vaccines with improved safety and purity. New methods of discovery, such as reverse vaccinology, structural biology, and systems biology, promise new vaccines for different diseases and efficient development pathways for these vaccines. We expect development of vaccines not only for infectious diseases in children but also for healthy adults, pregnant women, and elderly people, and for new indications such as autoimmune disease and cancer. We have witnessed a concomitant development of new technology for assessment of vaccine safety to rapidly identify potential safety issues. Success of these new approaches will depend on effective implementation of vaccination programmes, creative thinking on the part of manufacturers and regulators as to how best to ensure that safe and effective vaccines are available in a timely manner, and improvement of public awareness about the benefits and risks of new vaccines in a way that encourages confidence in vaccines.     

Immunization update and hot topics in clinical immunology: how does this relate to my practice?

The prevention of infectious diseases by the use of vaccines represents one of medicine's greatest triumphs during the 20th century. This era has witnessed the global eradication of smallpox as a result of Jennerian cowpox vaccination, the elimination of paralytic poliomyelitis from the western hemisphere, and within 5-10 years the anticipated eradication of poliomyelitis worldwide as a result of the poliovirus vaccines. Next slated for worldwide eradication is measles, the great killer of infants and children, which each year extracts a global mortality of one million victims. Throughout the 20th century the percutaneous (i.e., subcutaneous or intramuscular) route has almost exclusively been the preferred way to administer vaccines. However, as a result of several important scientific discoveries made during the 20th century, including new tissue-culturing techniques, the development of recombinant DNA technology, and genetic sequencing, a whole new generation of tailor-made modern vaccines has become available, including DNA vaccines and transgenic plant vaccines. Moreover, it became apparent that alternative routes of administration of vaccines, such as by aerosol immunization might be more appropriate and more effective than immunization via the parenteral route. The overall success in vaccine development, however, has not been without cost. For every new vaccine that has been developed, an adverse effect has been seen. Thus, although modern vaccines are extremely safe and effective, they are neither completely safe nor completely effective. The goal of vaccine development, therefore, is to achieve the highest degree of protection and the lowest rate of adverse effects. This paper describes some of the recent advances in vaccine development and will focus on some hot topics relating to the recent development and use of respiratory aerosolized vaccines.     

布鲁氏菌病新型疫苗研究进展北大核心CSCD

布鲁氏菌病(简称布病)是一种严重危害人类及动物健康的人兽共患传染性疾病,接种疫苗是控制布病流行的有效手段之一,而目前还没有获得许可的疫苗来预防人类布病,兽用疫苗存在毒力恢复及不能区分疫苗接种与野菌株感染的不足。随着基因工程、分子克隆等技术的日益发展,重组蛋白疫苗、DNA疫苗、纳米颗粒疫苗、载体疫苗等新型疫苗相关研究逐渐成为布病疫苗领域的研究热点。本文就近十年出现的新型布病疫苗研究进展情况作一综述,以期为开发更为有效、安全的布鲁氏菌病新型疫苗提供新的思路。     

HIV vaccines

In summary, the development of HIV vaccines has progressed from simple first-generation env subunit vaccines to second-generation vaccines containing multiple subunits. Vaccines with epitopes for CMI and Ab responses have broadened the immune response and the potential efficacy of these vaccines. It is hoped that newer technologies including the development of adjuvants, new types of vaccines, such as naked DNA, and new delivery systems, such as liposomes, will evoke stronger immune responses with longer duration. Improved schedules for dosing and combinations of HIV vaccines may result in longer lasting immune responses. A phase III trial is anticipated to begin within the next 2 years. After a temporary lull, the outlook for HIV vaccine development is being met once again with strong enthusiasm and encouragement for the future.     

Adjuvants for malaria vaccines

There is a renewed enthusiasm about subunit vaccines for malaria coincident with the formation of new alliances and partnerships raising international public awareness, attracting increased resources and the re-focusing of research programs on adjuvant development for infectious disease vaccines. It is generally accepted that subunit vaccines for malaria will require adjuvants to induce protective immune responses, and availability of suitable adjuvants has in the past been a barrier to the development of malaria vaccines. Several novel adjuvants are now in licensed products or in late stage clinical development, while several others are in the earlier development pipeline. Successful vaccine development requires knowing which adjuvants to use and knowing how to formulate adjuvants and antigens to achieve stable, safe, and immunogenic vaccines. For the majority of vaccine researchers this information is not readily available, nor is access to well-characterized adjuvants. In this minireview, we outline the current state of adjuvant research and development as it pertains to effective malaria vaccines.     

Financing of vaccines

This article discusses the need to increase the financial assistance for vaccine development. A health situation was cited to present the intolerable impact of the shortfall in funding for vaccines. This situation, on the other hand, has awakened the world community to respond by forming organizations and projects that will help eliminate this kind of problem in the future. However, this renewed interest in vaccine development would be impossible if there is no adequate funding and political commitment. Furthermore, the research and development to conduct and achieve highly effective vaccines will require a hundred to a hundred million US dollars in annual combined public and private research expenditures. To help solve this problem, one suggested solution is the development of a global fund to support production and distribution of new vaccines. Aside from that, other alternatives being looked into are the mechanisms used in other sectors that generated successful funding. This leads to the idea of creating a new treaty, which will provide the flexibility to gain support from new constituencies, to strengthen institutions, and to create adequately strong budgetary commitments.     

Alternative routes of immunization for prevention of infectious diseases: a new paradigm for the 21st century.

The prevention of infectious diseases by the use of vaccines represents one of medicine's greatest triumphs during the 20th century. This era has witnessed the global eradication of smallpox as a result of Jennerian cowpox vaccination, the elimination of paralytic poliomyelitis from the western hemisphere, and within 5-10 years the anticipated eradication of poliomyelitis worldwide as a result of the poliovirus vaccines. Next slated for worldwide eradication is measles, the great killer of infants and children, which each year extracts a global mortality of one million victims. Throughout the 20th century the percutaneous (i.e., subcutaneous or intramuscular) route has almost exclusively been the preferred way to administer vaccines. However, as a result of several important scientific discoveries made during the 20th century, including new tissue-culturing techniques, the development of recombinant DNA technology, and genetic sequencing, a whole new generation of tailor-made modern vaccines has become available, including DNA vaccines and transgenic plant vaccines. Moreover, it became apparent that alternative routes of administration of vaccines, such as by aerosol immunization and transcutaneous skin patches, might be more appropriate and more effective than immunization via the parenteral route. This paper describes some of the recent advances relating to alternative methods of immunization and will focus primarily on the development and use of respiratory aerosolized vaccines.     

包虫病基因重组疫苗的研究

分子生物学技术的快速发展,使基因工程疫苗的研究更加深入。与此种新型疫苗相比传统疫苗已体现出预防效果不够理想,不容易保存,技术难度大,成本高等诸多缺陷。因此,对基因工程疫苗的开拓研究已成为当前疫苗领域的一个热点。本文简要概述了近年来包虫病基因工程疫苗研究现状及其发展前景。     

人用狂犬病疫苗和被动免疫制剂研发进展

狂犬病(Rabies)是由狂犬病毒(Rabies virus)引起的一种人兽共患病。人一旦发病致死率几乎100%。目前预防狂犬病的人用疫苗为狂犬病毒灭活疫苗。随着基因工程技术的进步,新一代以狂犬病毒G蛋白(Glycoprotein)为免疫原的疫苗在开发中,包括不同表达系统的G蛋白亚单位疫苗,G蛋白DNA疫苗,G蛋白病毒载体疫苗等。同时本文还探讨了未来可能取代狂犬病免疫球蛋白的被动免疫制剂(单克隆抗体)的研发进展。     

Tuberculosis vaccine development

If the end of the 20th century saw the flowering of genomics, the beginning of the 21st century is witnessing an equally rapid blossoming of proteomics. These twin technologies have had a dramatic influence on the study of tuberculosis (TB), and nowhere more so than in the development of new TB vaccines. Only a few years ago, it was generally accepted that clinical trials of new TB vaccines would not take place for at least a decade. However, the first trials are now scheduled to start within months. Much TB vaccine research has thus shifted from developing new vaccines, to selecting the best vaccines for human use from the increasing number of effective new candidates becoming available. This selection is being eased by the improved animal models that have been developed over the past few years and by our increasing understanding of immunity to TB.