人用疫苗佐剂研究的新趋向

随着免疫机制的进一步阐明及生物学技术的进步 ,疫苗的研究已逐渐从以往盲目筛选及混合物形式 ,向靶向和表位抗原分子设计及人工合成方向发展 ,疫苗作用的特异性与安全性均有提高。但由于绝大多数新型疫苗的免疫原性较差 ,因此对佐剂的研究提出了新的挑战 ,要求从过去单一追求诱导抗体的传统佐剂研究逐渐转向致力于细胞免疫的新型佐剂研究。新型佐剂的研究不仅对于预防性疫苗的应用具有重要意义 ,而且将有力地推动新一代粘膜疫苗、治疗性疫苗和联合疫苗的研制。人用疫苗佐剂的安全性与有效性是不可或缺的两个方面 ,目前最常见的人用疫苗佐剂…     

新型疫苗佐剂的研究进展

与传统的灭活或活体疫苗相比,由基因工程重组抗原或化学合成多肽组成的现代疫苗往往存在免疫原性弱等问题,需要新型的免疫佐剂来增强其作用。尽管传统的铝盐佐剂是目前唯一全球公认的人用佐剂,但存在激发细胞免疫应答能力差等不足,因此,需要研发更为安全有效的人用新型佐剂,尤其是安全无毒、能够刺激较强细胞免疫应答的佐剂,以及适合粘膜疫苗、DNA疫苗和癌症疫苗的免疫佐剂。分析阐述了新型佐剂研究状况和佐剂发展方向,并进一步对新型佐剂的临床前和临床试验研究以及已批准上市的新型疫苗佐剂进行了综述。     

免疫佐剂分类及作用机制

通过现代生物技术制成的DNA疫苗、重组疫苗和亚单位疫苗等新型疫苗,虽然安全性较传统疫苗有所提高,但其免疫原性不及传统疫苗,需要通过佐剂增强疫苗的免疫效力。随着对佐剂研究的不断深入,铝佐剂、油乳佐剂、微生物类佐剂、蜂胶佐剂、左旋咪唑佐剂、脂质体佐剂、中药佐剂及小肽类佐剂等相继问世,其作用机制也随研究的不断深入逐渐清晰。通过动物免疫实验结果发现,小肽类免疫佐剂不仅可以增强特异性免疫反应,具备免疫增强剂的功效,而且获取简单,便于运输保存,安全性高,可能是未来佐剂研究的一个主要方向。     

新型疫苗佐剂的研究进展

近年来,核酸疫苗、基因工程疫苗、合成肽疫苗等新型疫苗的研究取得快速的发展,但这些疫苗与传统的灭活或活体疫苗相比,往往存在免疫原性差等问题,因此需要佐剂来增强其作用.佐剂已被证明是疫苗中的关键成分,佐剂种类众多,尚无统一的分类方法,目前应用最多的佐剂是铝佐剂和弗氏佐剂,但随着新型疫苗的开发,新型佐剂的开发必不可少.根据目...     

人用疫苗佐剂的安全性

从铝佐剂诞生至今,佐剂发挥着免疫调节、抗原递送的作用。新型人用疫苗佐剂陆续批准上市,以弥补疫苗免疫原性较弱的缺点。然而,人体免疫系统、病原体、佐剂之间的作用机制尚未完全清楚,佐剂诱导的自身免疫/炎性综合征(autoimmune/inflammatory syndrome induced by adjuvants,ASIA)及相关不良反应,限制了人用疫苗佐剂的大量使用,这些均引起了人们对佐剂安全性的高度关注。现就7种已上市人用疫苗佐剂(铝佐剂、MF59、AS03、ISA51、病毒体佐剂、AS01及AS04)的作用机理、应用情况及其安全性问题作一阐述,为新型人用疫苗佐剂合理、可靠的分析与评价提供思路。     

疫苗佐剂的研究进展

铝佐剂是目前应用最广泛的疫苗佐剂,随着新型疫苗不断得到开发,传统的铝佐剂已不能满足新型疫苗对佐剂的需求,这带动了研究者对疫苗佐剂研究的深入,不断有新的佐剂被发现,本文对佐剂的分类及研究进展作一综述。     

汉坦病毒疫苗研制进展

本文从脑组织灭活疫苗、培养细胞单双价灭活疫苗、基因重组疫苗、DNA疫苗、减毒活疫苗、佐剂、灭活方法、免疫策略等方面概述了汉坦病毒疫苗研制近况.     

不同佐剂肾综合征出血热纯化疫苗体液免疫效果的研究

在肾综合征出血热(HFRS)纯化疫苗原液中分别加入Al(OH)3、IL-2、GM-CSF、CFA等佐剂的一种或两种,以不加佐剂的纯化疫苗原液作为对照,分别免疫BALB/c小鼠,定期进行眼眶采血,用ELISA法检测血清中抗HFRS病毒的抗体水平。用不同佐剂的HFRS纯化疫苗免疫BALB/c小鼠后,其抗体产生的时间和滴度均不同。佐剂组与对照组相比抗体产生早且(或)滴度高,IL-2佐剂组在免后第3天就可以检测到抗体;联合使用两种佐剂组与单独使用一种佐剂组相比,抗体产生早、滴度高。结果表明,上述各种佐剂对HFRS纯化疫苗诱导BALB/c小鼠产生的免疫应答均有一定的增强作用;IL-2对早期免疫应答、早期抗体的产生有显著意义;联合应用两种佐剂疫苗的免疫效果优于只加其中一种佐剂的疫苗。     

幽门螺杆菌的治疗性疫苗

幽门螺杆菌感染的传统治疗方案面临着耐药性和依从性差的问题,而其治疗性疫苗有着广阔的应用前景.该文综述近年来幽门螺杆菌治疗性疫苗的研究进展,分别阐述幽门螺杆菌的感染免疫机制、主要抗原、佐剂、已有的治疗性疫苗等方面.     

疫苗研制技术的现状与展望

感染性病原是引起人类发病和死亡的主要原因之一。研制预防性疫苗和治疗性疫苗仍然是解决感染性疾病最有效和最有前景的方法,本文就疫苗研制领域的近来研究现状,包括疫苗研制技术的发展阶段,载体疫苗,粘膜免疫,新型佐剂和治疗性疫苗进行了综述,并对理想的新一代疫苗进行了简要的展望。     

Recent advances in veterinary vaccine adjuvants

Next generation veterinary vaccines are going to mainly comprise of either subunit or inactivated bacteria/viruses. These vaccines would require optimal adjuvants and delivery systems to accord long-term protection from infectious diseases in animals. There is an urgent need for the development of new and improved veterinary and human vaccine adjuvants. Adjuvants can be broadly divided into two classes, based on their principal mechanisms of action: vaccine delivery systems and 'immunostimulatory adjuvants'. Vaccine delivery systems are generally particulate e.g. emulsions, microparticles, ISCOMS and liposomes, and mainly function to target associated antigens into antigen presenting cells (APC). In contrast, immunostimulatory adjuvants are predominantly derived from pathogens and often represent pathogen associated molecular patterns, e.g. LPS, MPL and CpG DNA, which activate cells of the innate immune system. Recent progress in innate immunity is beginning to yield insight into the initiation of immune responses and the ways in which immunostimulatory adjuvants might enhance this process in animals and humans alike.     

粘膜免疫佐剂研究进展

粘膜免疫佐剂在新型疫苗的设计中具有重要作用。常用的粘膜免疫佐剂主要包括细菌性物质、细胞因子以及抗原递送系统。本文综述了这些佐剂的研究进展,以期为新型疫苗研究提供参考。     

细菌芽胞—— 一种新型的疫苗载体

杆菌属的芽胞作为益生菌已经应用于人和动物的食品生产和细菌疗法.目前,芽胞作为一种新型的疫苗载体,开始用于破伤风、炭疽等疫苗的研究.与目前的第二代疫苗相比,细菌芽胞热稳定性好,遗传操作方便,是一种理想的疫苗载体.本文就其作为疫苗载体的相关研究进行综述.     

Recent developments in adjuvants for vaccines against infectious diseases

New generation vaccines, particularly those based on recombinant proteins and DNA, are likely to be less reactogenic than traditional vaccines, but are also less immunogenic. Therefore, there is an urgent need for the development of new and improved vaccine adjuvants. Adjuvants can be broadly separated into two classes, based on their principal mechanisms of action; vaccine delivery systems and 'immunostimulatory adjuvants'. Vaccine delivery systems are generally particulate e.g. emulsions, microparticles, iscoms and liposomes, and mainly function to target associated antigens into antigen presenting cells (APC). In contrast, immunostimulatory adjuvants are predominantly derived from pathogens and often represent pathogen associated molecular patterns (PAMP) e.g. LPS, MPL, CpG DNA, which activate cells of the innate immune system. Once activated, cells of innate immunity drive and focus the acquired immune response. In some studies, delivery systems and immunostimulatory agents have been combined to prepare adjuvant delivery systems, which are designed for more effective delivery of the immunostimulatory adjuvant into APC. Recent progress in innate immunity is beginning to yield insight into the initiation of immune responses and the ways in which immunostimulatory adjuvants may enhance this process. However, a rational approach to the development of new and more effective vaccine adjuvants will require much further work to better define the mechanisms of action of existing adjuvants. The discovery of more potent adjuvants may allow the development of vaccines against infectious agents such as HIV which do not naturally elicit protective immunity. New adjuvants may also allow vaccines to be delivered mucosally.     

Approaches To New Vaccines

ABSTRACT:?

The explosive technological advances in the fields of immunology and molecular biology in the last 5 years had an enormous impact on the identification of candidate vaccines against diseases, which until a few years ago seemed uncontrollable. Increased knowledge of the immune system has helped to define the mechanisms that underlie successful immunization and is now being exploited to develop improved versions of existing vaccines and new vaccines against emerging pathogens, tumors, or autoimmune diseases. An understanding of the mechanisms of action of novel adjuvants and the development of new vector and delivery systems will have a major impact on vaccine strategies. The use of DNA encoding antigens from pathogenic viruses, bacteria, and parasites as vaccines is a new approach that is receiving considerable attention. This and other innovative approaches, including vaccine production in plants, are appraised in this review. The successful eradication of smallpox and the imminent eradication of poliomyelitis by worldwide immunization campaigns provide positive examples of how the vaccine-mediated approach can lead to disease elimination; with the advent of new vaccines and improved delivery systems, there is no scientific reason why these successes cannot be repeated.     

Mucosal adjuvants and delivery systems for protein-, DNA- and RNA-based vaccines

Almost all vaccinations today are delivered through parenteral routes. Mucosal vaccination offers several benefits over parenteral routes of vaccination, including ease of administration, the possibility of self-administration, elimination of the chance of injection with infected needles, and induction of mucosal as well as systemic immunity. However, mucosal vaccines have to overcome several formidable barriers in the form of significant dilution and dispersion; competition with a myriad of various live replicating bacteria, viruses, inert food and dust particles; enzymatic degradation; and low pH before reaching the target immune cells. It has long been known that vaccination through mucosal membranes requires potent adjuvants to enhance immunogenicity, as well as delivery systems to decrease the rate of dilution and degradation and to target the vaccine to the site of immune function. This review is a summary of current approaches to mucosal vaccination, and it primarily focuses on adjuvants as immunopotentiators and vaccine delivery systems for mucosal vaccines based on protein, DNA or RNA. In this context, we define adjuvants as protein or oligonucleotides with immunopotentiating properties co-administered with pathogen-derived antigens, and vaccine delivery systems as chemical formulations that are more inert and have less immunomodulatory effects than adjuvants, and that protect and deliver the vaccine through the site of administration. Although vaccines can be quite diverse in their composition, including inactivated virus, virus-like particles and inactivated bacteria (which are inert), protein-like vaccines, and non-replicating viral vectors such as poxvirus and adenovirus (which can serve as DNA delivery systems), this review will focus primarily on recombinant protein antigens, plasmid DNA, and alphavirus-based replicon RNA vaccines and delivery systems. This review is not an exhaustive list of all available protein, DNA and RNA vaccines, with related adjuvants and delivery systems, but rather is an attempt to highlight many of the currently available approaches in immunopotentiation of mucosal vaccines.     

提高黏膜免疫的方法及研究进展

黏膜是很多病原体入侵机体的重要入口,黏膜疫苗能诱导产生黏膜保护性免疫应答和系统性免疫应答,阻止病原微生物黏附、入侵和繁殖。但多数候选黏膜疫苗的安全性、稳定性、免疫效力及保护作用还无法达到理想的效果,佐剂或载体的使用改善了黏膜疫苗存在的不足,使黏膜疫苗有了广阔的发展前景。文章综述了提高黏膜免疫的方法及研究进展。     

Alternative routes of mucosal immunization in large animals

Mucosal immunization regimes that employ the oral route of delivery are often compromised by antigen degradation in the stomach. Moreover, tolerance or immunological unresponsiveness to orally delivered vaccine antigens is also a major problem associated with this route of immunization. Immunization by alternative routes including intrarectal (i.r.) and intranasal (i.n.) is becoming increasingly recognized in large animals for generating protective antibody responses at mucosal surfaces. These approaches are particularly useful in ruminant species which have four stomachs that can potentially interfere with antigen presentation to mucosal inductive sites of the gut. Modifications to enhance existing mucosal immunization regimes have also been explored through the use of alternative antigen delivery systems and mucosal adjuvants. The combination of alternative immunization routes and the use of appropriate antigen delivery systems appear to be a rational approach for providing protective immunity at mucosal surfaces. There has been a considerable amount of research conducted on evaluating the efficacy of emerging antigen delivery systems and novel adjuvants for improved immunity to mucosal immunization but very little of this work has been specific to the mucosal compartment of large animals. The aim of this review is therefore to assess the feasibility and practicality of using large animals (particularly sheep, cattle and pigs) for inducing and detecting specific immune responses to alternative mucosal routes of immunization.     

广谱流感疫苗的研究进展

广谱流感疫苗是指能够诱导针对流感病毒的广谱中和抗体或广谱的细胞免疫反应,从而保护动物或人类免受多数流感病毒毒株感染的疫苗。流感病毒广谱中和抗体的发现及机制研究为广谱流感疫苗的研发提供了新的思路。同时,流感病毒细胞免疫方面的研究进展、佐剂以及免疫策略等的研究进展都极大促进了广谱流感疫苗的研发。本文从以上几个方面介绍广谱流感疫苗的研究进展,并对未来的应用进行评价及展望。     

Beyond empiricism: informing vaccine development through innate immunity research

Although a great public heath success, vaccines provide suboptimal protection in some patient populations and are not available to protect against many infectious diseases. Insights from innate immunity research have led to a better understanding of how existing vaccines work and have informed vaccine development. New adjuvants and delivery systems are being designed based upon their capacity to stimulate innate immune sensors and target antigens to dendritic cells, the cells responsible for initiating adaptive immune responses. Incorporating these adjuvants and delivery systems in vaccines can beneficially alter the quantitative and qualitative nature of the adaptive immune response, resulting in enhanced protection.