Vaccines and global health

Vaccines have made a major contribution to global health in recent decades but they could do much more. In November 2011, a Royal Society discussion meeting, 'New vaccines for global health', was held in London to discuss the past contribution of vaccines to global health and to consider what more could be expected in the future. Papers presented at the meeting reviewed recent successes in the deployment of vaccines against major infections of childhood and the challenges faced in developing vaccines against some of the world's remaining major infectious diseases such as human immunodeficiency virus (HIV), malaria and tuberculosis. The important contribution that development of more effective veterinary vaccines could make to global health was also addressed. Some of the social and financial challenges to the development and deployment of new vaccines were reviewed. The latter issues were also discussed at a subsequent satellite meeting, 'Accelerating vaccine development', held at the Kavli Royal Society International Centre. Delegates at this meeting considered challenges to the more rapid development and deployment of both human and veterinary vaccines and how these might be addressed. Papers based on presentations at the discussion meeting and a summary of the main conclusions of the satellite meeting are included in this issue of Philosophical Transactions of the Royal Society B.     

Veterinary and human vaccine evaluation methods

Despite the universal importance of vaccines, approaches to human and veterinary vaccine evaluation differ markedly. For human vaccines, vaccine efficacy is the proportion of vaccinated individuals protected by the vaccine against a defined outcome under ideal conditions, whereas for veterinary vaccines the term is used for a range of measures of vaccine protection. The evaluation of vaccine effectiveness, vaccine protection assessed under routine programme conditions, is largely limited to human vaccines. Challenge studies under controlled conditions and sero-conversion studies are widely used when evaluating veterinary vaccines, whereas human vaccines are generally evaluated in terms of protection against natural challenge assessed in trials or post-marketing observational studies. Although challenge studies provide a standardized platform on which to compare different vaccines, they do not capture the variation that occurs under field conditions. Field studies of vaccine effectiveness are needed to assess the performance of a vaccination programme. However, if vaccination is performed without central co-ordination, as is often the case for veterinary vaccines, evaluation will be limited. This paper reviews approaches to veterinary vaccine evaluation in comparison to evaluation methods used for human vaccines. Foot-and-mouth disease has been used to illustrate the veterinary approach. Recommendations are made for standardization of terminology and for rigorous evaluation of veterinary vaccines.     

Plasmid-DNA lipid and polymeric nanovaccines: a new strategic in vaccines development

Vaccination is the most effective and least expensive technique used for human diseases prevention and eradication. The need for more vaccine doses and the rapid establishment of facilities for the development of new vaccines are stimulating significate changes in the vaccine industry, which is gradually moving towards cell culture production. One approach is the third generation of vaccines, which are based on the use of plasmid DNA (pDNA) containing transgenes that encode an antigen capable of mimicking intracellular pathogenic infection and triggering both humoral and cellular immune responses. Plasmid DNA vaccination has distinct advantages over other vaccine technologies in terms of safety, ease of fabrication and stability. The effectiveness of pDNA vaccines against viruses, bacteria, parasites and cancer cells has been demonstrated in preclinical and clinical assays. Furthermore, currently there are a few veterinary pDNA vaccines in the market. The application of a simple formulation of naked pDNA as a vaccine is attractive, but a low transfection efficiency is often obtained. The use of nanoparticles to increase transfection efficiency is an approach that has been tested clinically. This review provides a summary of vaccine production, advances and major challenges associated with pDNA lipid and polymeric nanovaccines applications.     

植物口服疫苗的研究进展

植物口服疫苗是通过转基因植物生产,通过口服的方式预防疾病的生物制品.作为一种新型疫苗,其研究开始于三十几年前.由于植物口服疫苗可以最大程度地降低传统疫苗的潜在风险,在疫苗生产中具有优势,因此拥有良好的商业生产前景.植物疫苗价格低廉,生产过程安全,可产生与注射疫苗相似效价效果,无论是在控制养殖业抗生素滥用的情况下作为替代...     

人3型副流感病毒疫苗的研究进展

人3型副流感病毒是一种主要感染人类肺部上皮细胞的副黏病毒,可引起肺炎和支气管炎,在婴幼儿和免疫力低下的成人中有较高的发病率。经过多年的研究,对人3型副流感病毒疫苗的研究取得了重要的进展,但还没有有效的抗病毒药物和批准的疫苗上市。目前研究主要集中在减毒活疫苗及亚单位疫苗等,对人3型副流感病毒当前疫苗的研究情况做简要的综述。     

Development of lipid-core-peptide (LCP) based vaccines for the prevention of group A streptococcal (GAS) infection

Traditional vaccines consisting of whole attenuated micro-organisms, or microbial components administered with adjuvant, have been demonstrated as one of the most cost-effective and successful public health interventions. Their use in large scale immunisation programs has lead to the eradication of smallpox, reduced morbidity and mortality from many once common diseases, and reduced strain on health services. However, problems associated with these vaccines including risk of infection, adverse effects, and the requirement for refrigerated transport and storage have led to the investigation of alternative vaccine technologies. Peptide vaccines, consisting of either whole proteins or individual peptide epitopes, have attracted much interest, as they may be synthesised to high purity and induce highly specific immune responses. However, problems including difficulties stimulating long lasting immunity, and population MHC diversity necessitating multiepitopic vaccines and/or HLA tissue typing of patients complicate their development. Furthermore, toxic adjuvants are necessary to render them immunogenic, and as such non-toxic human-compatible adjuvants need to be developed. Lipidation has been demonstrated as a human compatible adjuvant for peptide vaccines. The lipid-core-peptide (LCP) system, incorporating lipid adjuvant, carrier, and peptide epitopes, exhibits promise as a lipid-based peptide vaccine adjuvant. The studies reviewed herein investigate the use of the LCP system for developing vaccines to protect against group A streptococcal (GAS) infection. The studies demonstrate that LCP-based GAS vaccines are capable of inducing high-titres of antigen specific IgG antibodies. Furthermore, mice immunised with an LCP-based GAS vaccine were protected against challenge with 8830 strain GAS.     

活菌疫苗载体的研究与应用

目前在疫苗研究中,要求新型疫苗不仅能够激发高效持久的免疫应答,而且应易于接种、生产费用低。减毒或无毒的活微生物作为疫苗载体能够激起持久的系统和黏膜免疫反应,批量制备成本较低,且具有良好的安全性,近年来已成为疫苗研究领域的热点。本文综述了几种活菌疫苗载体,包括沙门氏菌、卡介苗、耶尔森菌等的研究状况及其在疫苗载体方面的应用。     

mRNA疫苗在疾病预防与治疗中的研究进展与展望

基于信使RNA(messenger RNA, mRNA)的核酸疫苗是近年来兴起的一种mRNA技术。mRNA疫苗比传统疫苗有许多优点,能够实现快速、经济、高效的生产。单个mRNA疫苗可以编码多种抗原,增强对特定病原体的免疫反应,提高疾病的治疗效率,以单一配方针对多种病原微生物或疾病。mRNA疫苗相关技术在新型冠状病毒肺炎疫情防控中被视作一种革命性的疫苗技术,以创纪录的速度完成研发并成功应用。由于mRNA自身稳定性差,新型递送系统的开发与应用至关重要。随着mRNA相关药理学的深入研究,mRNA疫苗的临床应用进入了一个崭新的阶段。近年来。mRNA疫苗在传染性疾病预防、肿瘤治疗等方面获得充分发展并取得了一定的研究成果,对其进行概述并进行一定程度的展望。     

联合疫苗应用现状及评价*

联合疫苗含有两种或多种免疫原（活的、灭活的病原体或者提纯的抗原）,用于预防多种疾病或由同一病原体的不同亚型或血清型引起的疾病,可以避免常规免疫多次注射的问题。然而和单价疫苗相比,联合疫苗研发的复杂性大大增加,将多种免疫原混合到一起进行免疫时不同免疫原间可能因为物理、化学和免疫学机制而干扰其他免疫原的免疫反应,此外佐剂和防腐剂等非活性成分也可能对联合后的活性成分产生影响,这就对联合疫苗的评价提出了特别的要求。本文对联合疫苗的研究应用现状、临床评价和发展前景等方面做一综述。     

Vaccines against malaria

There is no licenced vaccine against any human parasitic disease and Plasmodium falciparum malaria, a major cause of infectious mortality, presents a great challenge to vaccine developers. This has led to the assessment of a wide variety of approaches to malaria vaccine design and development, assisted by the availability of a safe challenge model for small-scale efficacy testing of vaccine candidates. Malaria vaccine development has been at the forefront of assessing many new vaccine technologies including novel adjuvants, vectored prime-boost regimes and the concept of community vaccination to block malaria transmission. Most current vaccine candidates target a single stage of the parasite's life cycle and vaccines against the early pre-erythrocytic stages have shown most success. A protein in adjuvant vaccine, working through antibodies against sporozoites, and viral vector vaccines targeting the intracellular liver-stage parasite with cellular immunity show partial efficacy in humans, and the anti-sporozoite vaccine is currently in phase III trials. However, a more effective malaria vaccine suitable for widespread cost-effective deployment is likely to require a multi-component vaccine targeting more than one life cycle stage. The most attractive near-term approach to develop such a product is to combine existing partially effective pre-erythrocytic vaccine candidates.     

A New Vaccine for Tuberculosis: The Challenges of Development and Deployment

Tuberculosis (TB) is one of the world’s leading causes of death due to infection and efforts to control TB would be substantially aided by the availability of an improved TB vaccine. There are currently nine new TB vaccines in clinical development, and the first efficacy trials are due to commence in 2009. There are many complex ethical issues which arise at all stages of TB vaccine development, from the need to conduct trials in developing countries to informed consent and the process of ethical review. While it is important that these issues are discussed, it may also be timely to consider the challenges which may arise if a vaccine in clinical development proves to be highly effective. We examine a number of scenarios where decisions on the deployment of a new TB vaccine may impact on the rights and liberty of the individual. Competing Interest Statement  Helen McShane is an inventor on a composition of matter patent and a shareholder in a Joint Venture, Oxford-Emergent Tuberculosis Consortium, formed to develop MVA85A. The views expressed in this article are those of the author(s) and do not necessarily represent those of the Oxford-Emergent Tuberculosis Consortium Ltd     

新型兽用疫苗的研究进展

新型兽用疫苗是免疫学和病毒学的研究热点,主要包括亚单位疫苗、基因工程缺失苗、重组病毒活载体疫苗和基因疫苗。上前已经被广泛的应用于研究和疫病的防治上。最近的疫苗发展方向集中于在基因疫苗上。高效、安全、稳定、成本低是疫苗开发的重点。本文介绍了新型疫苗的现状,以及今后发展的趋势和策略。     

Extraneous agent detection in vaccines--a review of technical aspects

The quality and safety of commercial vaccines have a profound importance. Contrary to all precautions and efforts the use of biological material in vaccine development and production may lead to potential contamination of the vaccines with known and unknown extraneous agents (EAs). In veterinary field official lists of EAs have been compiled as legal framework to describe the potential agents, which must be tested during manufacture of vaccines. Nevertheless, detection of known and unknown contaminants in vaccines is a common duty for manufacturers and authorities of both veterinary and human field sharing similar needs of special technical approaches. State-of-art molecular methods such as randomly primed PCR combined with massive parallel sequencing (MPS) or microarrays may open new perspectives in extraneous agent testing. The robustness and efficacy of this technical approach in vaccine control was clearly demonstrated on a human vaccine example when porcine circovirus type 1 (PCV1) contamination was revealed in Rotarix, a human rotavirus vaccine. The consequences and implications are reviewed hereby from a veterinary regulatory point of view.     

Research Advances on Transgenic Plant Vaccines

In recent years, with the development of genetics molecular biology and plant biotechnology, the vaccination (e.g. genetic engineering subunit vaccine, living vector vaccine, nucleic acid vaccine) programs are taking on a prosperous evolvement. In particular, the technology of the use of transgenic plants to produce human or animal therapeutic vaccines receives increasing attention. Expressing vaccine candidates in vegetables and fruits open up a new avenue for producing oral/edible vaccines. Transgenic plant vaccine disquisitions exhibit a tempting latent exploiting foreground. There are a lot of advantages for transgenic plant vaccines, such as low cost, easiness of storage, and convenient immune-inoculation. Some productions converged in edible tissues, so they can be consumed directly without isolation and purification. Up to now, many transgenic plant vaccine productions have been investigated and developed. In this review, recent advances on plant-derived recombinant protein expression systems, infectious targets, and delivery systems are presented. Some issues of high concern such as biosafety and public health are also discussed. Special attention is given to the prospects and limitations on transgenic plant vaccines.     

A vaccine against Asian schistosomiasis: the story unfolds

The development of an effective vaccine against the Asian schistosome is at a critical stage. Despite the fact that progress has been relatively slow, the successful use in animals of attenuated vaccines combined with recent encouraging results using defined native and recombinantly derived Schistosoma japonicum antigens, suggests that development of a safe and effective vaccine is feasible. This review examines current progress aimed at achieving this objective, and a summary is provided of recent results obtained with the most encouraging vaccine antigens. When available for wide-scale use, it is envisaged that the vaccine would be applied in the first instance, at least in China, in the veterinary context (to impact on human transmission) and then, perhaps, if required, clinically (to prevent or reduce disease). The search for the final product is likely to be demanding, and funding issues pertaining to Good Manufacturing Practice-scale-up of the vaccine for the required extensive veterinary coverage, and to support any future human trials, will need to be resolved. As such, we may still have to wait some time before the ultimate vaccine, possibly comprising a cocktail of several molecules, is available. Even then, the vaccine would probably be used optimally as one component of an integrated programme of schistosomiasis control that would include effective and well-tested approaches, such as health education and targeted chemotherapy.     

转基因植物疫苗的研究进展

近些年,随着遗传技术和植物基因工程的发展进步,疫苗（亚单位疫苗、活载体疫苗和核酸疫苗等）的研究迅速发展起来。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的关注,在转基因植物（蔬菜、水果、农作物）的可食用部位表达抗原生产人或动物治疗用重组蛋白和疫苗的技术为可食性疫苗的研制开辟了新途径,展现了诱人的开发前景。植物来源的疫苗具有很多优势,如生产成本低、易于保存、免疫接种方便、甚至不需提取纯化等处理而直接食用。目前已有很多转基因植物疫苗产品投入开发和生产。文章综述了近几年转基因植物疫苗在表达系统、生产、生物安全／管理、公众健康等方面的研究进展,对转基因植物疫苗存在的问题进行了分析,并对其研究前景提出了展望。     

全球冠状病毒疫苗专利分析

冠状病毒是一类可感染人类和动物的RNA病毒,可引起严重急性呼吸综合征(SARS)和中东呼吸综合征(MERS)等严重疾病。新型冠状病毒是以前从未在人体中发现的冠状病毒新毒株,其人际传播迅速,引起了各国政府的高度重视并积极寻求疫苗防控对策。基于冠状病毒疫苗领域全景专利,在综合对比分析该领域的全部专利的发展趋势、主要国家和主要机构的专利产出的同时,重点揭示了其中的人用相关疫苗的发展与分布情况以及重点分析了人用疫苗产品的研发现状,以期为我国冠状病毒疫苗领域的科研工作者和管理决策者提供参考数据。     

Cytokines as potential vaccine adjuvants

There is a compelling clinical need for adjuvants suitable for human use to enhance the efficacy of vaccines in the prevention of life-threatening infection. Candidate populations for such vaccine-adjuvant strategies include normal individuals at the two extremes of life, as well as the ever increasing population of immunocompromised individuals. In addition, adjuvants that would increase the efficiency of vaccination with such vaccines as those directed against hepatitis B andStreptococcus pneumoniae would have an even greater general use. Cytokines, as natural peptides intimately involved in the normal immune response, have great appeal as potential adjuvants. An increasing body of work utilizing recombinant versions of interleukin-1, -2, -3, -6, -12, gamma-interferon, tumor necrosis factor, and granulocyte-monocyte-colony stimulating factor has shown that cytokines do have vaccine adjuvant activity. However, in order to optimize adjuvant effect and minimize systemic toxicity, strategies in which the cytokine is fused to the antigen, or the cytokine is presented within liposomes or microspheres appear to be necessary to make this a practical approach suitable for human use. There is much promise in this approach, but there is much work to be accomplished in order to optimize the pharmacokinetics of cytokine administration as well as its side effect profile.Abbreviations IL interleukin - TNF tumor necrosis factor - NK natural killer - pIL-1 interleukin-1 peptide - LPS lipopolysaccharide - r recombinant - HSV-2 herpes simplex virus 2 - gamma     

Adjuvants in tuberculosis vaccine development

Tuberculosis remains a major public health problem around the world. Because the Mycobacterium bovis Bacilli–Calmette–Guerin (BCG) vaccine fails to protect adults from pulmonary tuberculosis, there is an urgent need for improved vaccine formulations. Unlike BCG, recombinant vaccines purified from bacterial expression vectors, as well as naked DNA, require an additional adjuvant. Recent improvements in our understanding of disease immunopathology, together with advances in biochemical and molecular techniques, have permitted the successful development of promising tuberculosis vaccine delivery and adjuvant combinations for human use. Here, we summarize the current state of adjuvant development and its impact on tuberculosis vaccine progress.     

Mitigating the looming vaccine crisis: production and delivery of plasmid-based vaccines

The exponentially growing human population and the emergence of new diseases are clear indications that the world can no longer depend solely on conventional vaccine technologies and production schemes. The race to find a new vaccine technology is crucial to help speed up and complement the World Health Organization (WHO) disease elimination program. The ultimate goal is to uncover fast and efficient production schemes in the event of a pandemic, and also to effectively fight deadly diseases such as malaria, bird flu, hepatitis, and human immunodeficiency virus (HIV). Plasmid DNA vaccines, if properly formulated, offer specific priming of the immune system and similar or even better prophylactic effects than conventional vaccines. This article discusses many of the critical issues that need to be considered when developing fast, effective, and reliable plasmid DNA vaccine manufacturing processes. Different modes of plasmid production via bacterial fermentation are compared. Plasmid purification by chromatography is specifically discussed as it is the most commercially viable bioprocess engineering technique for continuous purification of supercoiled plasmid DNA. Current techniques and progress covering the area of plasmid DNA vaccine design, formulation, and delivery are also put forward.