转基因植物用作疫苗生产系统

表达具有工业或药用价值的外源蛋白的转基因植物是替代发酵生产系统的经济方法。在植物中暂时或稳定表达外源基因已产生了一些疫苗。最遑的研究表明，细菌性和病毒性病原体抗原的编码基因可在植物中表达，且表达的抗原仍保留天然免疫原性。     

疫苗和基因给药系统的研究进展

简述了当前疫苗和基因给药系统的研究进展，包括注射、口服、鼻腔和透皮等给药系统，并介绍了以转基因植物作为疫苗以及基因给药系统的病毒载体和非病毒载体系统。     

转基因植物作为新的疫苗来源

鉴于植物源疫苗价廉、安全,美国得克萨斯州的植物学家Arntzen等正在研制可食用的疫苗。首先要确定植物产生的蛋白质能在动物中诱导免疫应答。他们将HB-sAg编码基因导入烟草植物,结果转基因烟草不但能产生病毒蛋白,而且接种小鼠后能诱生识别HBsAg的抗体。 然后,他们对一种编码部分肠毒素蛋白的大肠杆菌基因进行研究,这种肠毒素在易感动物中诱发腹泻。他们把此基因引入土豆植物中,使土豆块茎制备肠毒素蛋白。生食这种土豆的小鼠产生了抗毒素抗体,包括能够分泌到消化系统的粘膜抗体。他们     

转基因植物用作疫苗生产系统

表达具有工业或药用价值的外源蛋白的转基因植物是替代发酵生产系统的经济方法。在植物中暂时或稳定表达外源基因已产生了一些疫苗。最近的研究表明,细菌性和病毒性病原体抗原的编码基因可在植物中表达,且表达的抗原仍保留天然免疫原性。表达细菌抗原的转基因土豆块茎作为食物摄入后,能激发体液和粘膜免疫应答。这些结果为植物用作疫苗生产载体提供了基础。     

转基因植物疫苗的研究进展

近年来,随着免疫学、遗传学和分子生物学的发展,疫苗研究得到了迅速发展,尤其是利用转基因植物技术生产植物疫苗的研究受到了广泛关注.通过在转基因植物的可食用部位表达抗原来生产人或动物疫苗的技术为可食性疫苗的研制开辟了新途径.目前已有很多转基因植物疫苗投入研究和开发.此文综述了近几年转基因植物疫苗的研究现状、作用机制及安全性评价等,并在对转基因植物疫苗存在的问题进行分析的基础上,对其研究前景提出了展望.     

狂犬病接触后处理的改进

1984年5月30日至6月1日在南斯拉夫杜布罗夫尼克市举行了一次狂犬病国际会议.会议讨论了人类狂犬病预防的现状、新近问世的疫苗、研究中的疫苗、用基因工程研制的疫苗以及狂犬病接触后处理法的改进等问题.     

利用双粒病毒组复制子系统在植物细胞中表达疫苗蛋白

植物源性疫苗可通过简单的方法纯化或者直接食用，因此经济而安全。这类疫苗可用转基因植物或植物病毒载体表达，但是通常较难制备能表达足够疫苗蛋白以激发免疫应答的转基因植物，此外高表达外源蛋白对植物宿主细胞有毒性。而植物病毒载体表达期短，且表达的多肽分子的大小有限。双粒病毒组表达系统具有表达水平高和表达蛋白分子不受限制的优点，已被用作基因放大系统。     

利用基因工程生产植物次生代谢产物

植物次生代谢产物对于控制和影响植物性状起着十分重要的作用。也为人类提供了所需的药物。染料，香料等众多的化合物，综述了植物次生代谢途径的研究，相关基因的克隆以及次生代谢的基因工程。     

利用双粒病毒组复制子系统在植物细胞中表达疫苗蛋白[英]

植物源性疫苗可通过简单的方法纯化或者直接食用,因此经济而安全。这类疫苗可用转基因植物或植物病毒载体表达,但是通常较难制备能表达足够疫苗蛋白以激发免疫应答的转基因植物,此外高表达外源蛋白对植物宿主细胞有毒性。而植物病毒载体表达期短,且表达的多肽分子的大小有限。双粒病毒组表达系统具有表达水平高和表达蛋白分子不受限制的优点,已被用作基因放大系统。美国Cornell大学Hefferon等设计了一个豆黄矮双粒病毒组(BeYDV)复制子载体,包含BeYDV复制所须的顺式作用元件,在植物烟草细胞株NT-1中研究了Rep基因的放大作用。首先在报…     

新型冠状病毒肺炎疫苗专利分析及研发策略研究

依据专利数据分析全球及我国目前在新型冠状病毒肺炎疫苗(简称新冠疫苗)领域的研究进展，对现有疫苗的主要类型和热点技术进行统计，为未来疫苗的研发提供合理建议。使用Innojoy专利搜索引擎和Baiten专利网进行专利数据检索，并利用技术预测概念模型进行技术预测。目前新冠疫苗的研究热点主要分布在利用抗原、抗体、肽类与基因工程相关技术的领域，我国对于新冠疫苗的研究多集中于重组蛋白/表位/多肽/亚单位疫苗与核酸疫苗，技术热点集中于抗原改进技术。全球及我国目前在新冠疫苗领域的研究已经取得了一些进展，且专利市场活跃，短期内新冠疫苗相关专利市场与技术格局有望趋于成熟。     

Intranasal immunization with inactivated influenza vaccine

The development of improved vaccines against epidemic and pandemic influenza virus infection remains a priority in vaccine research. Killed vaccines given by injection are both cost-effective and induce immunity; however, their limitations are well known. Live vaccines have been in development for many years, but difficulties and safety concerns have prohibited their licensing in Western countries. However, the newer technologies of vaccine development, including DNA vaccines and attenuated virus vaccines produced by reverse genetics, remain a hope for the future. With these problems in mind, emphasis has been given to the development of inactivated vaccines that are administered intranasally, either as repeated doses of saline vaccine or in conjunction with suitable carriers or adjuvants. This review describes these latter developments and concludes that this approach offers advantages and should be vigorously researched.     

我国疑似预防接种异常反应补偿制度的探讨

目的 对比世界卫生组织(WHO)25个成员国家因疫苗接种造成损害建立的补偿制度,研究2019版《中华人民共和国疫苗管理法》(简称"《疫苗法》")中的相关条款,为完善我国疑似预防接种异常反应(AEFI)补偿制度提供思路.方法 综合运用情报调研、文献定性分析方法,对比美国、新西兰、日本和欧洲等疫苗损害补偿制度的特点,研究分...     

Development of vaccines against bovine tuberculosis

Bovine tuberculosis caused by Mycobacterium bovis remains an economically important problem in Great Britain with potential zoonotic consequences, and the incidence is rising exponentially. In 1997 an independent scientific review recommended that the best option for disease control in Great Britain was the development of a cattle vaccine. Bovine tuberculosis remains a significant problem in countries of the developing world. Indeed, more than 94% of the world's population live in countries in which the control of bovine tuberculosis in buffalos or cattle is limited or absent. Effective vaccination strategies would have a major impact in countries that cannot afford expensive test and slaughter-based control strategies. Here, we present a review of progress toward that goal, and discuss how this progress has shaped our research strategy for the development of a vaccine.     

From pertussis to meningococcal disease and back

From pertussis to meningococcal disease and back represents nearly 30 years of research at Porton, first at the Centre for Applied Microbiology and Research and latterly as part of the Health Protection Agency. I joined the group lead by Andy Robinson developing an acellular pertussis vaccine and was part of an exciting period that encompassed basic antigen characterisation and pathogenesis studies with the development of an acellular vaccine containing fimbriae. Research then changed to focus on serogroup B meningococcal disease, studying the vaccine potential of iron-regulated proteins and then Neisseria lactamica. The resurgence of pertussis seen in some countries alerted me to the lack of understanding of protective immune responses to Bordetella pertussis infection and disease and this is now an active area of research.     

Rotavirus vaccine RIX4414 (Rotarix™): a pharmacoeconomic review of its use in the prevention of rotavirus gastroenteritis in developing countries

This article provides an overview of the clinical profile of rotavirus vaccine RIX4414 (Rotarix?) in the prevention of rotavirus gastroenteritis (RVGE) in developing countries, followed by a comprehensive review of pharmacoeconomic analyses with the vaccine in low- and middle-income countries. RVGE is associated with significant morbidity and mortality among children <5 years of age in developing countries. The protective efficacy of a two-dose oral series of rotavirus vaccine RIX4414 has been demonstrated in several well designed clinical trials conducted in developing countries, and the 'real-world' effectiveness of the vaccine has also been shown in naturalistic and case-control trials after the introduction of universal vaccination programmes with RIX4414 in Latin American countries. The WHO recommends universal rotavirus vaccination programmes for all countries. Numerous modelled cost-effectiveness analyses have been conducted with rotavirus vaccine RIX4414 across a wide range of low- and middle-income countries. Although data sources and assumptions varied across studies, results of the analyses consistently showed that the introduction of the vaccine as part of a national vaccination programme would be very (or highly) cost effective compared with no rotavirus vaccination programme, according to widely used cost-effectiveness thresholds for developing countries. Vaccine price was not known at the time the analyses were conducted and had to be estimated. In sensitivity analyses, rotavirus vaccine RIX4414 generally remained cost effective at the highest of a range of possible vaccine prices considered. Despite these favourable results, decisions regarding the implementation of universal vaccination programmes with RIX4414 may also be contingent on budgetary and other factors, underscoring the importance of subsidized vaccination programmes for poor countries through the GAVI Alliance (formerly the Global Alliance for Vaccines and Immunization).     

基于杆状病毒表达系统的流感病毒样颗粒疫苗研究进展

流感疫苗是目前应对流感最有效的措施,传统疫苗包括全病毒灭活疫苗、裂解疫苗和减毒活疫苗,近年来逐渐成为研发趋势的有重组亚单位疫苗、核酸疫苗、活病毒载体疫苗等。病毒样颗粒(virus-like particle,VLP)疫苗作为特殊形式的亚单位疫苗,具有生产迅速、安全性高、免疫原性较高等优势。VLP可以高效地诱发体液免疫与细胞免疫,且可经多种途径接种。目前已有多种表达系统用于制备VLP,其中应用最为广泛的是杆状病毒表达系统。此文综述了流感病毒VLP的类型、组装、抗原选择、免疫途径以及流感病毒VLP疫苗在杆状病毒表达系统中的研究进展。     

Vaccines - patenting dynamics of a powerful healthcare tool

Vaccines are considered to be some of the most powerful healthcare tools of this century. From an industrial perspective, in the past they have not provided particularly attractive targets for investment, but this situation changed dramatically in the late eighties and early nineties with governmental initiatives aimed at stabilising the vaccine liability situation together with advances in molecular biology and the emergence of biotechnology, opening-up new opportunities for solving the scientific problems associated with vaccine developments. This paper analyses how these developments are reflected in patenting activities worldwide. The comparison of vaccine patent applications with pharmaceutical patents as a whole indicates that vaccine research has been a very dynamic field during the last 15 years; total patent applications increased by a factor of 7.5 between 1980 and 1994. Genetic engineering approaches have established themselves as key tools for vaccine R&D, such techniques being applied in more than 50% of all vaccine patent applications during the nineties. International vaccine patent applications are mainly driven by the US and Europe, which together contributed 91% of all patents and 96% of the genetic engineering related vaccine patents in 1994. Within Europe, France, Germany, Great Britain and Italy are the most active countries. Key players in vaccine patenting are American governmental agencies, international pharmaceutical corporations, biotech firms, universities and non-university public research organisations. All-in-all, public research activities seem to play a crucial role in the creation of scientific and technological knowledge for the development of new vaccines.     

聚磷腈免疫佐剂的研究应用概况

聚磷腈免疫佐剂是一类以聚磷腈骨架为基础的新型免疫佐剂,在免疫刺激性能,药物运输性能方面具有其他佐剂无法比拟的优点。本文从聚磷腈免疫佐剂的结构特性、合成、分类、作用机理、降解性能及其微球制备等方面,阐述聚磷腈作为疫苗佐剂的优势和特点,并对聚磷腈免疫佐剂的的发展前景进行了展望。     

Combined hepatitis A and B vaccines: a review of their immunogenicity and tolerability

Three combined hepatitis A and B vaccine preparations are commercially available in various countries: a two-dose paediatric formulation (Ambirix) [administered at months 0 and 6-12]; and a three-dose adult (Twinrix Adult) or paediatric (Twinrix Paediatric) formulation (administered at months 0, 1 and 6). The adult vaccine provides consistent, marked immunogenicity which is at least similar to that of its constituent vaccines used together and with a tolerability profile that is possibly improved. An accelerated, day-0, -7 and -21 regimen has also shown immunogenicity similar to that of the monovalent vaccines given concurrently, and now has an emerging role in adults likely to travel to hepatitis A virus (HAV) and/or hepatitis B virus (HBV) endemic regions within 1 month. The adult vaccine appears effective and generally well tolerated when given concurrently with monovalent typhoid vaccine (Typherix). Immunogenicity of the two-dose paediatric vaccine is high and appears to be similar whether administered as a month-0, -6 or month-0, -12 schedule and when compared to that of the three-dose paediatric vaccine (months 0, 1, 6), both of which provide a similar degree of protection to the adult vaccine. Although both preparations also provide high end-of-schedule seroprotection against hepatitis B surface antigen, protection between the first and second doses of the two-dose regimen appears lower than with the three-dose schedule. Therefore, the three-dose paediatric vaccine is a practical option in individuals at risk of immediate exposure to HBV, while the two-dose regimen may have an important function in immunisation programmes in regions where such risk is low. Combined hepatitis A and B vaccines are generally well tolerated. The most frequently reported adverse events in clinical trials were injection-site pain and redness, and general fatigue and headache; most events were mild and transient. Pharmacoeconomic models suggest the combined vaccine is cost effective compared with no vaccine (in children/adolescents) or monovalent hepatitis B vaccine (in children/adolescents and prison inmates). CONCLUSION: The three commercially available combined hepatitis A and B adult and paediatric vaccines are highly immunogenic and generally well tolerated; the adult vaccine demonstrates immunogenicity at least as marked as that of monovalent hepatitis A and B vaccines. While further research is required to confirm potential advantages such as improved cost effectiveness, the combined vaccines have established a key role in the prevention of hepatitis A and B in defined risk groups, and have an expanding role in population-based vaccination programmes with younger age groups.     

Towards the development of a broadly protective group a streptococcal vaccine based on the Lipid-Core Peptide system

Preclinical studies carried out over the last seven years by our group have focused on the development of a group A streptococcal (GAS) vaccine based on the antiphagocytic bacterial surface M protein using the Lipid-Core Peptide (LCP) system. This synthetic peptide vaccine delivery system has several advantages over other delivery systems including its self-adjuvanting properties and the ability to incorporate multiple peptide epitopes into a single vaccine. This review describes various vaccine delivery strategies including the LCP system, highlighting its functional properties and applications in vaccine research using data obtained from various LCP-based GAS vaccine candidates evaluated in murine models.