Monoclonal antibody technology in the development of vaccines for livestock parasites

Vaccination against animal parasites offers an alternative to chemotherapy for the control of losses due to morbidity and mortality. However, only a few vaccines are currently available, and these are based on controlled infections with living parasites. Further advancement in the development of defined vaccines against parasite infections has been hindered by incomplete knowledge of the immunological relationship between the host and the parasite. The advent of monoclonal antibody technology has provided a powerful new tool for the identification and isolation of parasite antigens. Exploitation of this technique in veterinary parasitology has greatly facilitated progress toward the development of vaccines against several animal parasites.     

Developments and hurdles in generating vaccines for controlling helminth parasites of grazing ruminants

As a direct consequence of rising drug resistance among common nematodes of grazing animals, efforts toward state-of-the-art vaccine development have clearly intensified in recent years, fuelled primarily by the advent of newer technologies in gene discovery, by advancements in antigen identification, characterisation and production. In this regard, it is appropriate to review progress that has been made in generating helminth vaccines and in particular, vaccines against common nematodes of production animals for consumption. In like manner, it is prudent to evaluate barriers that have hindered progress in the past and continue to present obstacles that must be solved when utilizing and depending on host immunity to attenuate parasitic infections.     

细菌类动物疫苗安全检验方法概述

安全检验是判定疫苗安全性的重要检验项目,涉及实验动物的筛选、不同免疫方法的选取以及免疫后的观察等方面。从免疫方法、实验动物两方面对细菌类动物疫苗安全检验方法进行综述,以期为动物疫苗安全检验提供参考。     

Biotechnology: hail to man and animal

There are two basic remarks that must be made about this series of articles on the theme 'Modern biotechnology: a blessing or concern?'. Firstly, it is difficult to define what 'biotechnology' is due to the diversity of techniques employed. Secondly, it is striking how biotechnological techniques may be employed for such a wide variety of goals. In this article, the ethics of using biotechnology within veterinary science and research will be discussed. Aside from its usefulness to humankind, an animal has its own value as a living creature; a fact that we should always take into account. Ethical issues such as the health, welfare and integrity of animals are discussed here in relation to developments in biotechnology. These ethical arguments reveal that biotechnology does not always have a positive impact on animals. This does not necessarily mean that biotechnology should be rejected out of hand, but that it is essential that the purpose for which the animals are being used be adequately justified. In this regard, the veterinarian may play a unique role as the guardian of both animal and human health. The veterinary profession, in all its diversity, is a participant in the development and (future) practical application of biotechnological techniques. Changes in the broader society and within the veterinary profession may continue to play a role in the societal discourse on biotechnology and its practical application, it must actively consider the ethical aspects and consequences of these scientific developments.     

The contribution of molecular biology to the development of vaccines against nematode and trematode parasites of domestic ruminants.

Rapid developments in molecular biology have had an enormous impact on the prospects for the development of vaccines to control the major nematode and trematode infestations of livestock. Vaccine candidates are purified using conventional protein chemistry techniques but the limitations imposed by the scarcity of parasite material provide an insurmountable barrier for commercial vaccine production by this means. The ability to purify mRNA from different parasite life-cycle stages and to prepare cDNA expression libraries from it has proven central to the identification of immunogenic parasite proteins. Potentially, protective parasite antigens can now be produced in recombinant form in a variety of vectors and this represents a key breakthrough on the road to commercial vaccine production. The contribution of molecular biology to this process is discussed using several examples, particularly in vaccine development against the pathogenic abomasal nematode of sheep and goats, Haemonchus contortus, and the liver fluke of sheep and cattle, Fasciola hepatica. The difficulties of producing recombinant proteins in the correct form, with appropriate post-translational modification and conformation, are discussed as well as emerging means of antigen delivery including DNA vaccination. The opportunities offered by genome and expressed sequence tag analyses programmes for antigen targeting are discussed in association with developing microarray and proteomics technologies which offer the prospect of large scale, rapid antigen screening and identification.     

Importation of parasites by tourism and animal trading

International transport of animals is associated with an enhanced risk of import of a number of parasite species that are not endemic in Germany. Pets accompany tourists on journeys all over the world, but in particular to southern Europe, and dogs are increasingly imported from (sub-)tropical countries for reasons of animal welfare. Veterinary practitioners are thus confronted with parasites that are unusual in their patients. The specific transmission routes determine whether an imported parasite is able to become endemic. Although parasites eradicated in Germany such as Trypanosoma equiperdum and Tritrichomonas foetus may be principally imported they are unlikely to re-establish due to the current epidemiological conditions. Imported animals that harbour parasites which may occur naturally but are currently rare in Germany are a potential source of increased infection risk. Certain areas in Germany have probably become endemic for Babesia canis and the respective vector tick Dermacentor reticulatus has been found. Whether other vector borne parasitic diseases such as leishmaniosis or heartworm disease have the potential to spread into Germany is still a matter of debate.     

Progress in the development of tuberculosis vaccines for cattle and wildlife

Vaccination against bovine tuberculosis is likely to become an important disease control strategy in developing countries, which cannot afford a test and slaughter control programme, or in countries which have a wildlife reservoir of Mycobacterium bovis infection. In the past decade, considerable progress has been made in the development and evaluation of tuberculosis vaccines for cattle and for a range of wildlife maintenance hosts including possums, badgers, deer and African buffaloes. Experimental challenge systems have been established for the different target species and the resulting disease process has mimicked that seen in the field. In cattle, neonatal vaccination with BCG appeared to be more effective than vaccination of 6-month-old calves and in most situations no other vaccine has been shown to be better than BCG. However, prime-boost strategies involving combinations of BCG with a protein or DNA vaccine, to improve on BCG vaccination alone, have produced very encouraging results. Differential diagnostic tests have been developed using mycobacterial antigens that are only present in virulent M. bovis to differentiate between BCG-vaccinated and M. bovis-infected cattle. BCG vaccine has been shown to reduce the spread of tuberculous lesions in a range of wildlife species and a prototype oral bait delivery system has been developed. Prospects for the development of improved vaccines against bovine tuberculosis are promising and vaccination approaches could become very valuable in the control and eradication of bovine tuberculosis.     

Strains of cattle parasites in the Netherlands with different propensities for inhibited development

A field study was undertaken of the possible differences in propensity for inhibited development in strains of cattle nematodes from two different locations in The Netherlands. In one location (Lelystad) the strains were thought to lack the ability for inhibited development as a result of environmental stimuli on the infective larvae, while in the other location (Utrecht) this ability was presumed to be present. The Lelystad strains were kept at the original location and were also transferred to a pasture in Utrecht, while the Utrecht strains remained in Utrecht. At both locations all permanent grazing calves showed high proportions of inhibited early fourth stage larvae of Ostertagia ostertagi, the proportion of the Utrecht strain being higher than the local and the transferred Lelystad strain. For Cooperia oncophora and Nematodirus helvetianus no clear differences between locations were observed in the permanently grazed calves. No inhibition occurred in tracer calves turned out in August in either location, but differences were seen among tracer calves turned out in October. The Lelystad strains, kept in Lelystad or transferred to Utrecht, showed no inhibition, while in the tracer calves grazed on pastures contaminated by the Utrecht strains a marked inhibition of O. ostertagi and N. helvetianus was observed. The Lelystad strains appear to lack the ability, possessed by the Utrecht strains, to inhibit their development in autumn in response to environmental stimuli.     

The epidemiology and control of swine parasites. Immunity and vaccines

This article discusses the status of two experimental swine helminthic vaccines and how further knowledge of parasite biochemistry and swine immunology and the application of techniques of modern biotechnology may affect their future development.     

Plant-made vaccines: biotechnology and immunology in animal health

The use of plants as production systems for vaccine antigens has been actively investigated over the last 15 years. The original research focused on the value of this expression system for oral delivery based on the hypothesis that plant-expressed antigens would be more stable within the digestive tract and would allow for the use of the oral route of administration to stimulate a mucosal immune response. However, while first conceived for utility via the oral route, plant-made antigens have also been studied as classical immunogens delivered via a needle to model animal systems. Antigens have been expressed in a number of whole plant and cell culture systems. Several alternative expression platforms have been developed to increase expression of antigens or to elicit preferred immunological responses. The biotechnological advances in plant expression and the immunological testing of these antigens will be reviewed in this paper focusing primarily on diseases of livestock and companion animals.     

Duration of immunity induced by companion animal vaccines

Concerns about possible adverse effects from annual vaccination have prompted the reanalysis of vaccine protocols for cats and dogs. In the last decade, several veterinary advisory groups have published protocols that recommend extended revaccination intervals for certain 'core' vaccines. In addition, practicing veterinarians have been asked to consider vaccination as an individualized medical procedure, based on an analysis of risks and benefits for each vaccine in an individual animal. The calls for extended revaccination intervals prompted considerable debate in USA and internationally. Areas of concern include the amount of evidence to support prolonged immunity from various vaccines, the risk of poor responses in individual animals and the possible effects on population immunity. This review examines how the duration of immunity (DOI) to a vaccine is established in animals and humans. It reviews factors that can affect the DOI in an individual animal, including the types of immune defenses stimulated by the pathogen, and the vaccine, host factors such as age and the level of exposure to the pathogen. In addition, it examines DOI studies that were published for canine and feline core vaccines.     

常规动物用活疫苗冻干保护剂的改良初探

目前国内动物用活疫苗仍然以5%蔗糖脱脂奶作为冻干保护剂,其冻干外型稳定,易溶性良好,成本低廉,但其耐热性能差,对病毒的保护作用较差。本试验以鸡新城疫Lasota冻干活疫苗为例,分别以不同浓度的海藻糖取代蔗糖,进行冻干保护性试验,结果表明海藻糖在2%以上时,对病毒的保护效果明显优于5%蔗糖脱脂奶组,证明其具有很好的应用前景。     

Progress in the replacement of animal experiments in the quality control of clostridial vaccines

Animal experiments still play a central role in the quality control of vaccines. Generally, performance of these experiments is provided by law and laid down in the European Pharmacopoeia. Classical vaccines, the efficacy of which is calculated in International Units, require a very high number of experimental animals for quality control testing. The testing mainly consists of infection and intoxication experiments causing extreme suffering of the animals involved. This classical product group includes clostridial vaccines which are used to a great extent in veterinary medicine in particular. Within the last years, considerable efforts have been made to reduce the number of animal experiments in this field, lower the number of animals, and decrease the suffering of the animals during testing. Several research projects for the development and validation of alternative methods have been initiated. Furthermore, the 3R Concept (Replacement, Reduction and Refinement) is increasingly taken into consideration when developing or revising legal provisions. This led to various improvements regarding animal welfare in the quality control of clostridial vaccines.     

Virus-like particles: The new frontier of vaccines for animal viral infections

Vaccination continues to be the main approach to protect animals from infectious diseases. Until recently, all licensed vaccines were developed using conventional technologies. Subunit vaccines are, however, gaining attention from researchers in the field of veterinary vaccinology, and among these, virus-like particles (VLPs) represent one of the most appealing approaches. VLPs are robust protein cages in the nanometer range that mimic the overall structure of the native virions but lack the viral genome. They are often antigenically indistinguishable from the virus from which they were derived and present important advantages in terms of safety. VLPs can stimulate strong humoral and cellular immune responses and have been shown to exhibit self-adjuvanting abilities. In addition to their suitability as a vaccine for the homologous virus from which they are derived, VLPs can also be used as vectors for the multimeric presentation of foreign antigens. VLPs have therefore shown dramatic effectiveness as candidate vaccines. Here, we review the current status of VLPs as a vaccine technology in the veterinary field, and discuss the potential advantages and challenges of this technology.