Online tools to support literature-based discovery in the life sciences

In biomedical research, the amount of experimental data and published scientific information is overwhelming and ever increasing, which may inhibit rather than stimulate scientific progress. Not only are text-mining and information extraction tools needed to render the biomedical literature accessible but the results of these tools can also assist researchers in the formulation and evaluation of novel hypotheses. This requires an additional set of technological approaches that are defined here as literature-based discovery (LBD) tools. Recently, several LBD tools have been developed for this purpose and a few well-motivated, specific and directly testable hypotheses have been published, some of which have even been validated experimentally. This paper presents an overview of recent LBD research and discusses methodology, results and online tools that are available to the scientific community.     

Progress and obstacles in the development of an AIDS vaccine

Recent experimental observations suggest approaches to immunization that might finally result in at least a partially effective vaccine against infection with HIV-1. In particular, advances in our understanding of the contribution of vaccine-elicited cellular immunity to protecting memory CD4(+) T cells from virus-mediated destruction provide rational strategies for the development of this vaccine. This is therefore an ideal time to review our current understanding of HIV-1 and its control by the immune system, as well as the remaining problems that must be solved to facilitate the development of an effective vaccine against AIDS.     

Analyzing time series gene expression data

MOTIVATION: Time series expression experiments are an increasingly popular method for studying a wide range of biological systems. However, when analyzing these experiments researchers face many new computational challenges. Algorithms that are specifically designed for time series experiments are required so that we can take advantage of their unique features (such as the ability to infer causality from the temporal response pattern) and address the unique problems they raise (e.g. handling the different non-uniform sampling rates). RESULTS: We present a comprehensive review of the current research in time series expression data analysis. We divide the computational challenges into four analysis levels: experimental design, data analysis, pattern recognition and networks. For each of these levels, we discuss computational and biological problems at that level and point out some of the methods that have been proposed to deal with these issues. Many open problems in all these levels are discussed. This review is intended to serve as both, a point of reference for experimental biologists looking for practical solutions for analyzing their data, and a starting point for computer scientists interested in working on the computational problems related to time series expression analysis.     

Subunit protein vaccines: theoretical and practical considerations for HIV-1

With the spread of AIDS still rampant in many parts of the world, there is a global urgency to develop a vaccine against HIV-1. Without a doubt, developing an effective vaccine against the virus has been a monumental scientific challenge. Although advances in molecular biology and biotechnology over the years have enabled us to generate "designer antigens," our ability to transform them into successful vaccine candidates has been limiting. This review will be divided into three sections: First, the theoretical benefits and limitations of subunit protein vaccine strategy will be presented. Secondly, recent progress in our understanding of immune responses against AIDS vaccine candidates that incorporate recombinant proteins or peptides will be reviewed, mainly those that are designed to elicit humoral immune responses. Finally, some of the factors that must be considered in designing and evaluating future vaccine candidates will be discussed.     

反义技术及其在胚胎异常发育机制研究中的应用

综述了反义研究中的几个关键问题,提出严格的ODNs设计,有效的ODNs转运和设计合理的对照等是获得良好实验结果的关键;介绍该技术在各种体外胚胎试验中的应用。     

增强乙型肝炎疫苗免疫效果的研究进展

乙肝疫苗对于控制乙型肝炎病毒感染十分重要.近年人们仍在根据免疫学理论和生物工程技术进展不断研发更加科学有效的新型乙肝疫苗.就新型乙肝疫苗设计的免疫机制和提高免疫效果的关键因素作出综述.     

埃博拉病毒疫苗研究进展

埃博拉病毒是一种可引起人和非人灵长类动物出血热传染病的最为致命的烈性病毒,致死率可达90%。2014年在西非爆发的埃博拉疫情引起了全世界的关注。疫苗接种是预防和控制传染病最为常规和有效的方法,尽管目前还没有正式获得批准上市的埃博拉病毒疫苗,但是已有多个尚处于研究阶段的疫苗在非人灵长类动物上取得了很好的保护效果,并有几个已进入临床Ⅰ期试验阶段,有望尽快用于本次埃博拉疫情的防控。本文对目前处于研究阶段的多个类型的埃博拉病毒疫苗进行了综述,为相关研究人员提供参考。     

Promises and pitfalls of Pseudomonas aeruginosa lipopolysaccharide as a vaccine antigen

Antibodies directed to the Pseudomonas aeruginosa lipopolysaccharide (LPS) O-antigens have clearly shown to mediate the most effective immunity to infection caused by LPS-smooth strains. Such strains are major causes of disease in immunocompromised hosts such as burn or cancer patients, individuals in intensive care units, and those who utilize extended-wear contact lenses. Yet producing an effective vaccine composed of non-toxic, immunogenic polysaccharides has been challenging. The chemical diversity among the different O-antigens representative of the 20 major serotypes, plus additional diversity among some O-antigens representing variant subtype antigens, translates into a large degree of serologic variability that increases the complexity of O-antigen specific vaccines. Further complications come from the poor immunogenicity of the major protective epitope expressed by some O-antigens, and a large degree of diversity in animal responses that preclude predicting the optimal vaccine formulation from such studies. Nonetheless human trials over the years of vaccines eliciting O-antigen immunity have been encouraging, though no vaccine has yet been fully evaluated and found to be clinically efficacious. Newer vaccine approaches such as using polysaccharide-protein conjugates and passive therapy with monoclonal or polyclonal immune sera offer some additional means to try and produce an effective immunotherapeutic reagent for this problematic pathogen.     

Strategies for successful designing of immunocontraceptive vaccines and recent updates in vaccine development against sexually transmitted infections - A review

BackgroundThe world population is continuously growing. It has been estimated that half of the world’s population is from the Asian continent, mainly from China and India. Overpopulation may lead to many societal problems as well as to changes in the habitat. Birth control measures are thus needed to control this growth. However, for the last 50–60 years, there have not been any improvements in the field of contraception. Nevertheless, the immunocontraceptive vaccine is an emerging field, and it might be the only replacement for the existing mode of contraception for the next millennium. Sexually transmitted infections (STIs) are frequent, and their transmission rate increases yearly. As antibiotics are the prevailing treatment for this kind of infections, resistance in humans has increased; therefore, having effective antibiotic treatments for STIs is now a concern. Vaccines against STIs are now needed. It is thought that the improvements in the fields of proteomics, immunomics, metabolomics, and other omics will help in the successful development of vaccines.ObjectiveTo collect and review the literature about recent advancements in immunocontraception and vaccines against sexually transmitted diseases/infections.MethodsReliable scientific databases, such as PubMed Central, PubMed, Scopus, Science Direct, and Goggle Scholar, were consulted. Publications bearing important information on targeted antigens/immunogens for contraceptive vaccine design and advancements in vaccine development for STIs were gathered and tabulated, and details were analyzed as per the theme of each study.ResultsImportant antigens that have a specific role in fertility have been studied extensively for their contraceptive nature. Additionally, the advancements in the screening for the best antigens, according to their antigenic nature and how they elicit immune responses for an extended period were also studied. Herd immunity for STIs and advancements in the development of vaccines for syphilis, gonorrhea, and herpes simplex virus were also studied and tabulated in this review. An extensive knowledge on STIs vaccines was gained.ConclusionThis extensive review is aimed to provide insights for active researchers in vaccinology, immunology, and reproductive biology. Advancements in the development of vaccines for different STIs can be gathered as a wholesome report.     

Vaccine instability in the cold chain: Mechanisms,analysis and formulation strategies

Instability of vaccines often emerges as a key challenge during clinical development (lab to clinic) as well as commercial distribution (factory to patient). To yield stable, efficacious vaccine dosage forms for human use, successful formulation strategies must address a combination of interrelated topics including stabilization of antigens, selection of appropriate adjuvants, and development of stability-indicating analytical methods. This review covers key concepts in understanding the causes and mechanisms of vaccine instability including (1) the complex and delicate nature of antigen structures (e.g., viruses, proteins, carbohydrates, protein-carbohydrate conjugates, etc.), (2) use of adjuvants to further enhance immune responses, (3) development of physicochemical and biological assays to assess vaccine integrity and potency, and (4) stabilization strategies to protect vaccine antigens and adjuvants (and their interactions) during storage. Despite these challenges, vaccines can usually be sufficiently stabilized for use as medicines through a combination of formulation approaches combined with maintenance of an efficient cold chain (manufacturing, distribution, storage and administration). Several illustrative case studies are described regarding mechanisms of vaccine instability along with formulation approaches for stabilization within the vaccine cold chain. These include live, attenuated (measles, polio) and inactivated (influenza, polio) viral vaccines as well as recombinant protein (hepatitis B) vaccines.     

Formulation and evaluation of baits for oral rabies vaccination of raccoons (Procyon lotor)

Captive raccoons were offered a variety of vaccine containers and bait components in a series of three-choice tests. Paraffin wax ampules were the most readily accepted vaccine container. Preferred bait components included corn and shellfish oils, deep fried corn meal batter, and egg, apple and buttermilk flavorings. These results, together with factors including ease of bait formulation, cost, and suitability for field use, were used to develop an experimental delivery system for an oral rabies vaccine. The developed system was composed of a polyurethane sleeve (1.5 x 5.5 cm) dipped in a commercial food batter mix together with corn meal, milk and egg. The sleeve was deep fried in corn oil and a 2.0 ml ampule containing a recombinant rabies vaccine was then inserted into the sleeve bait. These baits were presented to 10 captive raccoons. Nine of the 10 animals developed high levels of rabies virus neutralizing antibodies. Field tests are needed to determine if the delivery system developed also is effective for wild raccoons.     

Comparison of different delivery systems of DNA vaccination for the induction of protection against tuberculosis in mice and guinea pigs

The great challenges for researchers working in the field of vaccinology are optimizing DNA vaccines for use in humans or large animals and creating effective single-dose vaccines using appropriated controlled delivery systems. Plasmid DNA encoding the heat-shock protein 65 (hsp65) (DNAhsp65) has been shown to induce protective and therapeutic immune responses in a murine model of tuberculosis (TB). Despite the success of naked DNAhsp65-based vaccine to protect mice against TB, it requires multiple doses of high amounts of DNA for effective immunization. In order to optimize this DNA vaccine and simplify the vaccination schedule, we coencapsulated DNAhsp65 and the adjuvant trehalose dimycolate (TDM) into biodegradable poly (DL-lactide-co-glycolide) (PLGA) microspheres for a single dose administration. Moreover, a single-shot prime-boost vaccine formulation based on a mixture of two different PLGA microspheres, presenting faster and slower release of, respectively, DNAhsp65 and the recombinant hsp65 protein was also developed. These formulations were tested in mice as well as in guinea pigs by comparison with the efficacy and toxicity induced by the naked DNA preparation or BCG. The single-shot prime-boost formulation clearly presented good efficacy and diminished lung pathology in both mice and guinea pigs.     

The development and use of vaccine adjuvants

Interest in vaccine adjuvants is intense and growing, because many of the new subunit vaccine candidates lack sufficient immunogenicity to be clinically useful. In this review, I have emphasized modern vaccine adjuvants injected parenterally, or administered orally, intranasally, or transcutaneously with licensed or experimental vaccines in humans. Every adjuvant has a complex and often multi-factorial immunological mechanism, usually poorly understood in vivo. Many determinants of adjuvanticity exist, and each adjuvanted vaccine is unique. Adjuvant safety is critical and can enhance, retard, or stop development of an adjuvanted vaccine. The choice of an adjuvant often depends upon expensive experimental trial and error, upon cost, and upon commercial availability. Extensive regulatory and administrative support is required to conduct clinical trials of adjuvanted vaccines. Finally, comparative adjuvant trials where one antigen is formulated with different adjuvants and administered by a common protocol to animals and humans can accelerate vaccine development.     

轮状病毒疫苗研究现状

轮状病毒自上世纪70年代初发现至今,仍是婴幼儿病毒性腹泻最主要的病原体。每年约60万婴幼儿因轮状病毒感染导致严重脱水死亡。轮状病毒疫苗从上世纪90年代初开始研制,至今已有三种疫苗用于预防轮状病毒感染。这三种疫苗均为减毒活疫苗:其中包括单一血清型Rotarix、罗特威和重组5价疫苗RotaTeq。它们已在全球多国使用,有些国家已将其纳入免疫规划。疫苗的使用使人群轮状病毒感染下降,特别是死亡率明显减少。但也出现了一些问题,因此除了减毒活疫苗,也有一些实验室研究其他形式的疫苗,例如重组疫苗、灭活疫苗等。本文主要介绍轮状病毒疫苗的研究现状,为我国轮状病毒疫苗的研究、使用和推广提供一定理论依据。     

Plurality of opinion, scientific discourse and pseudoscience: an in depth analysis of the Séralini et al. study claiming that Roundup™ Ready corn or the herbicide Roundup™ cause cancer in rats

A recent paper published in the journal Food and Chemical Toxicology presents the results of a long-term toxicity study related to a widely-used commercial herbicide (Roundup?) and a Roundup-tolerant genetically modified variety of maize, concluding that both the herbicide and the maize varieties are toxic. Here we discuss the many errors and inaccuracies in the published article resulting in highly misleading conclusions, whose publication in the scientific literature and in the wider media has caused damage to the credibility of science and researchers in the field. We and many others have criticized the study, and in particular the manner in which the experiments were planned, implemented, analyzed, interpreted and communicated. The study appeared to sweep aside all known benchmarks of scientific good practice and, more importantly, to ignore the minimal standards of scientific and ethical conduct in particular concerning the humane treatment of experimental animals.     

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.     

Ethical considerations in fish research

Fishes are used in a wide range of scientific studies, from conservation research with potential benefits to the species used to biomedical research with potential human benefits. Fish research can take place in both laboratories and field environments and methods used represent a continuum from non-invasive observations, handling, through to experimental manipulation. While some countries have legislation or guidance regarding the use of fish in research, many do not and there exists a diversity of scientific opinions on the sentience of fish and how we determine welfare. Nevertheless, there is a growing pressure on the scientific community to take more responsibility for the animals they work with through maximising the benefits of their research to humans or animals while minimising welfare or survival costs to their study animals. In this review, we focus primarily on the refinement of common methods used in fish research based on emerging knowledge with the aim of improving the welfare of fish used in scientific studies. We consider the use of anaesthetics and analgesics and how we mark individuals for identification purposes. We highlight the main ethical concerns facing researchers in both laboratory and field environments and identify areas that need urgent future research. We hope that this review will help inform those who wish to refine their ethical practices and stimulate thought among fish researchers for further avenues of refinement. Improved ethics and welfare of fishes will inevitably lead to increased scientific rigour and is in the best interests of both fishes and scientists.     

简述疫苗安全性管理

疫苗接种是保护公众健康最有效的措施之一,疫苗可有效降低传染病的发病率和死亡率。与疫苗的有效性评估不同,疫苗的安全性不能直接测定,只能通过有限的疫苗不良事件的相关情况来推断。对疫苗安全性监测的科学理论,全球关注的个案研究,以及注册前有关疫苗的临床试验安全性的相关事宜进行了简介。     

Determining Vaccination Frequency in Farmed Rainbow Trout Using Vibrio anguillarum O1 Specific Serum Antibody Measurements

Background

Despite vaccination with a commercial vaccine with a documented protective effect against Vibrio anguillarum O1 disease outbreaks caused by this bacterium have been registered among rainbow trout at Danish fish farms. The present study examined specific serum antibody levels as a valid marker for assessing vaccination status in a fish population. For this purpose a highly sensitive enzyme-linked immunosorbent assay (ELISA) was developed and used to evaluate sera from farmed rainbow trout vaccinated against V. anguillarum O1.

Study Design

Immune sera from rainbow trout immunised with an experimental vaccine based on inactivated V. anguillarum O1 bacterin in Freund’s incomplete adjuvant were used for ELISA optimisation. Subsequently, sera from farmed rainbow trout vaccinated with a commercial vaccine against V. anguillarum were analysed with the ELISA. The measured serum antibody levels were compared with the vaccine status of the fish (vaccinated/unvaccinated) as evaluated through visual examination.

Results

Repeated immunisation with the experimental vaccine lead to increasing levels of specific serum antibodies in the vaccinated rainbow trout. The farmed rainbow trout responded with high antibody levels to a single injection with the commercial vaccine. However, the diversity in responses was more pronounced in the farmed fish. Primary visual examinations for vaccine status in rainbow trout from the commercial farm revealed a large pool of unvaccinated specimens (vaccination failure rate = 20%) among the otherwise vaccinated fish. Through serum analyses using the ELISA in a blinded set-up it was possible to separate samples collected from the farmed rainbow trout into vaccinated and unvaccinated fish.

Conclusions

Much attention has been devoted to development of new and more effective vaccines. Here we present a case from a Danish rainbow trout farm indicating that attention should also be directed to the vaccination procedure in order to secure high vaccination frequencies necessary for optimal protection with a reported effective vaccine.