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1.
DNA vaccination represents one of the most recent novel approaches to vaccine development. Experimentally, DNA vaccines induce a broad range of long lasting immune responses including humoral and cell-mediated immunity against infectious diseases in humans and animals. Furthermore, DNA vaccines are potentially useful for the treatment of autoimmune diseases or cancer. However, most information on the efficacy of DNA vaccines has been generated in mice and studies in larger animals are limited. In this review, the potential application of DNA vaccines in livestock and pet animals are discussed. The principle of this new technology, its potency and future perspectives for use in veterinary medicine will be outlined.  相似文献   

2.
牛传染性鼻气管炎(infectious bovine rhinotracheitis,IBR)是由牛传染性鼻气管炎病毒(infectious bovine rhinotracheitis virus,IBRV)即牛疱疹病毒1型(BoHV-1)感染所引起的一种高度接触性传染病。该病给我国养牛业带来了巨大的经济损失。由于缺乏有效的治疗性药物,疫苗免疫仍然是防控该病的有效措施。当前,牛传染性鼻气管炎疫苗主要包括灭活疫苗、弱毒疫苗2种常规疫苗和亚单位疫苗、DNA疫苗、IBRV基因缺失疫苗、病毒活载体疫苗4种基因工程疫苗,各种疫苗各有优点。现对上述疫苗的最新研究进展进行综述,以期为IBRV疫苗的研究与开发提供参考。  相似文献   

3.
禽类DNA疫苗研究进展   总被引:2,自引:0,他引:2  
新型疫苗的研究对于禽类传染病的防制意义重大。传统疫苗是基于抗原刺激机体产生特异性抗体的原理,它们大多数激发机体的体液免疫,很难启动细胞免疫。脱氧核糖核酸(DNA)疫苗作为第3代疫苗,具备传统疫苗和其它基因工程苗不可比拟的优点,能够诱导全方位的免疫反应且使用更安全更方便,DNA疫苗是将外源基因与真核质粒重组后直接导入细胞内,使外源基因在宿主细胞内表达合成保护性抗原蛋白。这是模拟病毒自然感染提呈过程,既能产生细胞免疫,又能产生体液免疫。文章对DNA疫苗在禽类应用的可行性和应用研究新进展作了综述。  相似文献   

4.
In this report, we show that dimethylsulfoxide (DMSO) enhances liposome-mediated transfection of nucleic acid in chicken macrophage cells and that this could be exploited for the transcutaneous delivery of naked DNA through the intact skin of chickens. We found that DMSO enhanced transfection efficiencies of lipofectamine and polyethyleneimine in HD-11 chicken macrophage cells. Based on this principle, we showed that transcutaneous delivery of a DNA plasmid-dimethylsulfoxide mixture (1:1) to untreated skin of chickens results in a wide distribution of the plasmid in the body. Distribution studies were done using plasmids encoding enhanced green fluorescent protein (EGFP) reporter gene and a bivalent DNA vaccine coding for infectious bursal disease virus (IBDV) and Newcastle disease virus (NDV) immunogenic protein genes. This bivalent vaccine induced mucosal and systemic immune responses, as evidenced by IgA and IgM production in the tears and serum of vaccinated chickens. Mucosal immune responses in the tears after topical vaccination were significantly higher (P < 0.05) than after i.m. delivery of the same DNA vaccine and were characterized by the absence of an IgG response. The biodistribution of plasmid indicated that topical delivery with DMSO resulted in a wide distribution and persistence of the plasmid until 15 weeks post-primary vaccination. Both delivery methods resulted in insert-specific message being made in several body tissues, but after topical delivery the virus-specific mRNA could be detected in the bone marrow of one out of three chickens until 15 weeks post-primary vaccination. Furthermore, transcutaneous delivery of this DNA vaccine using DMSO conferred protection from challenge with virulent IBDV (86% survival) and NDV (86% survival). This novel transcutaneous method of delivery of a DNA vaccine shows promise as being an easy and effective way to deliver nucleic acids through intact skin for vaccination or therapeutic purposes.  相似文献   

5.
The epidermis of the skin is both a sensitive immune organ and a practical target site for vaccine administration. However, administration of vaccines into the epidermis is difficult to achieve using conventional vaccine delivery methods employing a needle and syringe. A needle-free vaccine delivery system has been developed that efficiently delivers powdered or particulate DNA and protein vaccines into the epidermal tissue. The delivery system can be used to directly transfect antigen presenting cells (APCs) by formulating DNA or protein vaccines onto gold particles (particle-mediated immunization). Antigen can be directly presented to the immune system by the transfected APCs. Antigen can also be expressed and secreted by transfected keratinocytes and picked up by resident APCs through the exogenous antigen presentation pathway. Alternatively, protein antigens can be formulated into a powder and delivered into the extracellular environment where they are picked up by APCs (epidermal powder immunization). Using any of these formulations, epidermal immunization offers the advantage of efficiently delivering vaccines into the APC-rich epidermis. Recent studies demonstrate that epidermal vaccine delivery induces humoral, cellular, and protective immune responses against infectious diseases in both laboratory animals and man.  相似文献   

6.
新型猪瘟疫苗的研究进展   总被引:1,自引:1,他引:0  
猪瘟是危害猪健康的重要传染病之一,具有急性、热性和高度接触性等特性,给世界养猪业造成了巨大的经济损失。目前,传统疫苗接种仍是预防猪瘟的主要手段,虽然传统疫苗(如C株)在防控猪瘟方面发挥着巨大的作用,但也存在一些缺陷,如无法区分野毒感染和疫苗免疫动物,猪瘟免疫失败时有发生等。因此,研制新型猪瘟疫苗具有重要意义。随着分子生物学技术与重组DNA技术的不断发展及基因工程疫苗研究的不断深入,亚单位疫苗、核酸疫苗、活载体重组疫苗、基因缺失疫苗、全长感染性cDNA标记疫苗和合成肽疫苗6种新型猪瘟疫苗被相继开发。与传统疫苗相比,新型疫苗拥有廉价、安全、高效、易于运输与保存、能区分野毒感染和疫苗免疫等优点。作者对6种新型猪瘟疫苗的研究进展作一综述,以期为猪瘟的防控提供参考。  相似文献   

7.
口蹄疫是由口蹄疫病毒感染引起的偶蹄动物共患的急性、热性、接触性传染病,接种疫苗是特异性预防口蹄疫的有效手段,口蹄疫疫苗主要有弱毒疫苗、灭活疫苗及新型疫苗。自20世纪80年代开始,基因工程亚单位疫苗、合成肽疫苗、病毒活载体疫苗、基因缺失疫苗、重组表位疫苗、核酸疫苗等新型疫苗研究日趋活跃,现对各类型疫苗的研究进展作一综述。  相似文献   

8.
Present and future of veterinary viral vaccinology: a review   总被引:7,自引:0,他引:7  
This review deals briefly with some key developments in veterinary vaccinology, lists the types of vaccines that are used for vaccinations commonly performed in food animals as well as in companion animals, and indicates that the practising veterinarian can select the best vaccine by comparing the results of efficacy studies. Diva (Differentiating Infected from Vaccinated Animals; also termed marker) vaccines and companion diagnostic tests have been developed that can be used for progammes aimed to control or eradicate virus infections. Vaccine-induced herd immunity, which can be measured relatively easily when diva vaccines are used, is a crucial issue in such programmes. Current vaccine research follows many routes towards novel vaccines, which can be divided into non-replicating ('killed') and replicating ('live') vaccines. Promising trends are the development of DNA vaccination, vector vaccines, and attenuation of DNA and RNA viruses by DNA technology. The lack of (in vitro) correlates of vaccine protection markedly hampers progress in vaccine research. Various characteristics of an 'ideal' vaccine are listed, such as multivalency and the induction of lifelong immunity after one non-invasive administration in animals with maternal immunity. Future research should be aimed at developing vaccines that approach the ideal as closely as possible and which are directed against diseases not yet controlled by vaccination and against newly emerging diseases.  相似文献   

9.
Numerous infectious diseases caused by bacteria or viruses persist in developed and developing countries due to ongoing transmission among wildlife reservoir species. Such diseases become the target of control and management programmes in cases where they represent a threat to public health (for example rabies, sylvatic plague, Lyme disease), or livestock production (for example bovine tuberculosis, brucellosis, pseudorabies), or where they threaten the survival of endangered animal populations. In the majority of cases, lethal control operations are neither economically feasible nor publicly supported as a practical means for disease management. Prophylactic vaccination has emerged over the last 15 years as an alternative control strategy for wildlife diseases, mainly driven by the success of widescale oral rabies vaccination programmes for meso-carnivores in North America and Northern Europe. Different methods have been trialled for the effective delivery of wildlife vaccines in the field, however oral vaccination remains the most widely used approach. Successful implementation of an oral wildlife vaccine is dependent on a combination of three components: an efficacious immunogen, a suitable delivery vehicle, and a species-specific bait. This review outlines the major wildlife disease problems for which oral vaccination is currently under consideration as a disease management tool, and also focuses on the technological challenges that face wildlife vaccine development. The major conclusion is that attenuated or recombinant live microbes represent the most widely-used vaccines that can be delivered by the oral route; this in turn places major emphasis on effective delivery systems (to maintain vaccine viability), and on selective baiting systems, as the keys to wildlife vaccine success. Oral vaccination is a valuable adjunct or alternative strategy to culling for the control of diseases which persist in wildlife reservoirs.  相似文献   

10.
Current approaches to vaccine preparation   总被引:2,自引:0,他引:2       下载免费PDF全文
Numerous conventional vaccines for animal use are currently available, and many of these vaccines have been instrumental in the control of infectious diseases of major economic importance. A vaccine has even been instrumental in global eradication of smallpox, an important human disease. However, many of the current vaccines are deficient in efficiency, potency, or safety. It has been recognized that the conventional methodologies are a limitation to further vaccine development. Introduction of monoclonal antibodies, recombinant DNA, and protein engineering techniques has facilitated a rather rapid increase in the knowledge of pathogenetic mechanisms, as well as of protective antigens at the molecular level. This knowledge provides the basis for development of a new generation of vaccines. As a rule, these vaccines contain purified immunogens, or even isolated epitopes, identified and prepared by molecular biological techniques. The efforts to find better delivery systems and better adjuvants accompany the research on vaccines.  相似文献   

11.
DNA vaccinations against fish viral diseases as IHNV at commercial level in Canada against VHSV at experimental level are both success stories. DNA vaccination strategies against many other viral diseases have, however, not yet yielded sufficient results in terms of protection. There is an obvious need to combat many other viral diseases within aquaculture where inactivated vaccines fail. There are many explanations to why DNA vaccine strategies against other viral diseases fail to induce protective immune responses in fish. These obstacles include: 1) too low immunogenicity of the transgene, 2) too low expression of the transgene that is supposed to induce protection, 3) suboptimal immune responses, and 4) too high degradation rate of the delivered plasmid DNA. There are also uncertainties with regard distribution and degradation of DNA vaccines that may have implications for safety and regulatory requirements that need to be clarified. By combining plasmid DNA with different kind of adjuvants one can increase the immunogenicity of the transgene antigen – and perhaps increase the vaccine efficacy. By using molecular adjuvants with or without in combination with targeting assemblies one may expect different responses compared with naked DNA. This includes targeting of DNA vaccines to antigen presenting cells as a central factor in improving their potencies and efficacies by means of encapsulating the DNA vaccine in certain carriers systems that may increase transgene and MHC expression. This review will focus on DNA vaccine delivery, by the use of biodegradable PLGA particles as vehicles for plasmid DNA mainly in fish.  相似文献   

12.
The debate over adverse reactions associated with companion animal vaccination has considerably exercised the veterinary profession internationally over the past decade. A range of suspected adverse reactions to vaccines is reported including the onset of inflammatory, allergic, autoimmune or neoplastic diseases. Lack of efficacy, interference with diagnostic testing and other occasional suspected product-related issues are also reported. Available data suggest that the overall prevalence of true adverse reactions is exceedingly low and that vaccination does not significantly contribute to ill-health in companion animals. There is increasing public interest in vaccination issues with transfer of focus from publicity over human vaccine side effects to those perceived to occur in animals. We must not lose sight of the fact that vaccination is a safe procedure that has impacted significantly on infectious disease control. Reduced population uptake of vaccination leads to re-emergence of disease in both humans and animals. Nevertheless, there have recently been a series of practical recommendations produced to ensure reduced 'vaccine load' on our companion animals and vaccine manufacturers are moving towards developing non-adjuvanted products with an extended duration of immunity. These measures will further reduce the very small current risk of any adverse consequences to vaccination in our pet population.  相似文献   

13.
A scientific review for the government of the United Kingdom has recommended that the development of a cattle vaccine against bovine tuberculosis holds the best prospects to control this disease in the national herd. As BCG vaccination of cattle results in variable degrees of protection, novel vaccine strategies that could replace or supplement BCG are required. In this study, the mycobacterial antigen HSP65 was used to determine whether priming cattle with a plasmid DNA vaccine and subsequently boosting with the recombinant protein in adjuvant (heterologous prime-boost approach) would result in improved and more homogenous immune responses over immunising with plasmid DNA or protein in adjuvant alone. The results demonstrated that strong, and compared to protein or DNA vaccination protocols alone, more homogenous, cellular immune responses were induced in cattle vaccinated with the prime-boost regimen. In addition, DNA prime-protein boost vaccination as well as protein vaccination resulted in stronger humoral immune responses with a balanced IgG profile compared to DNA vaccination alone. Importantly, none of the vaccination protocols sensitised cattle to the intradermal tuberculin test suggesting that TB subunit vaccines can be designed to allow the continued use of the tuberculin test to discriminate between vaccinated cattle and those infected with Mycobacterium bovis.  相似文献   

14.
The influenza virus vaccines that are commercially-available for humans, horses and pigs in the United States are inactivated, whole-virus or subunit vaccines. While these vaccines may decrease the incidence and severity of clinical disease, they do not consistently provide complete protection from virus infection. DNA vaccines are a novel alternative to conventional vaccination strategies, and offer many of the potential benefits of live virus vaccines without their risks. In particular, because immunogens are synthesized de novo within DNA transfected cells, antigen can be presented by MHC class I and II molecules, resulting in stimulation of both humoral and cellular immune responses. Influenza virus has been used extensively as a model pathogen in DNA vaccine studies in mice, chickens, ferrets, pigs, horses and non-human primates, and clinical trials of DNA-based influenza virus vaccines are underway in humans. Our studies have focused on gene gun delivery of DNA vaccines against equine and swine influenza viruses in mice, ponies and pigs, including studies employing co-administration of interleukin-6 DNA as an approach for modulating and adjuvanting influenza virus hemagglutinin-specific immune responses. The results indicate that gene gun administration of plasmids encoding hemagglutinin genes from influenza viruses is an effective method for priming and/or inducing virus-specific immune responses, and for providing partial to complete protection from challenge infection in mice, horses and pigs. In addition, studies of interleukin-6 DNA co-administration in mice clearly demonstrate the potential for this approach to enhance vaccine efficacy and protection.  相似文献   

15.
Vaccination is the best approach for controlling the spread of chlamydial infections, in animal and human populations. This review summarises the progress that has been made towards the development of effective vaccines over the last 50 years, and discusses current vaccine strategies. The ultimate goal of vaccine research is to develop efficacious vaccines that induce sterile, long-lasting, heterotypic protective immune responses. To date, the greatest success has been in developing whole organism based killed or live attenuated vaccines against the animal pathogens Chlamydophila abortus and Chlamydophila felis. However, similar approaches have proved unsuccessful in combating human chlamydial infections. More recently, emphasis has been placed on the development of subunit or multicomponent vaccines, as cheaper, safer and more stable alternatives. Central to this is a need to identify candidate vaccine antigens, which is being aided by the sequencing of representative genomes of all of the chlamydial species. In addition, it is necessary to identify suitable adjuvants and develop methods for antigen delivery that are capable of eliciting mucosal and systemic cellular and humoral immune responses. DNA vaccination in particular holds much promise, particularly in terms of safety and stability, although it has so far been less effective in humans and large animals than in mice. Thus, much research still needs to be done to improve the delivery of plasmid DNA, as well as the expression and presentation of antigens to ensure that effective immune responses are induced.  相似文献   

16.
A DNA vaccine against contagious agalactia was developed for the first time, encoding the P48 of Mycoplasma agalactiae. Specific immune responses elicited in BALB/c mice were evaluated. Both total IgG and IgG1 were detected in mice vaccinated with pVAX1/P48. Proliferation of mononuclear cells of the spleen, levels of gamma interferon, interleukin-12, and interleukin-2 mRNAs were enhanced in immunized animals. Results indicate that pVAX1/P48 vaccination induced both Th1 and Th2 immune responses. Nucleic acid immunization could be a new strategy against M. agalactiae infections and may be potentially used to develop vaccines for other Mycoplasma diseases.  相似文献   

17.
The immunologists' debt to the chicken   总被引:3,自引:0,他引:3  
The immune system of the chicken is an invaluable model for studying basic immunology and has made seminal contributions to fundamental immunological principles. Graft versus host responses and the key role of lymphocytes in adaptive immunity were first described in work with chicken embryos and chickens. 2. Most notably, the bursa of Fabricius provided the first substantive evidence that there are two major lineages of lymphocytes. Bursa-derived lymphocytes, or B cells, make antibodies while thymus-derived, or T cells, are involved in cell-mediated immune responses. 3. Gene conversion, the mechanism used by the chicken to produce its antibody repertoire, was first described in the chicken and requires the unique environment of the bursa. Subsequently it has been shown that some mammals also use gene conversion. 4. The chicken's Major Histocompatibility Complex (MHC), the first non-mammalian MHC to be sequenced, is minimal, compact and some 20-fold smaller than that of mammals. Uniquely, the chicken MHC is strongly associated with resistance to infectious diseases. 5. The first attenuated vaccine was developed by Louis Pasteur against a chicken pathogen, fowl cholera, and the first vaccine against a natural occurring cancer agent, Marek's disease virus, was developed for the chicken. 6. Vaccination of chick embryos on the 18th d of incubation, another breakthrough using chickens, provides protection early after hatching. In ovo vaccination now is widely practised by the poultry industry. 7. Evidence that widespread and intensive vaccination can lead to increased virulence with some pathogens, such as Marek's disease virus and infectious bursal disease virus, was first described with chicken populations. It warns of the need to develop mo resustainable vaccination strategies in future and provides useful lessons for other species, including in the human population. 8. Recombinant DNA technologies now provide the opportunity for the rational design of new vaccines. Such vaccines could contain the protective immunogenic elements from several pathogens and immunomodulatory molecules to direct and enhance immune responses so providing improved protection. The important thing will be to design vaccines that are sustainable and do not drive pathogens to ever-increasing virulence.  相似文献   

18.
Marek's disease is an economically important lymphoid neoplasm of chickens, caused by oncogenic strains of Marek's disease herpesvirus. The disease can be successfully controlled by vaccination with attenuated or non-pathogenic MDV strains. However, vaccine failures do occur as field strains continue to evolve towards pathotypes of greater virulence, and this evolution is likely to be driven by the vaccines themselves. Two general strategies can be considered to improve protection by vaccination. Firstly by the development of novel vaccines, and secondly by maximizing the potential of existing vaccines. This second goal requires investigation of optimal timing and vaccine delivery route, and optimal vaccination regimes for different breeds of chick. Accurate quantitation of Marek's disease vaccine virus in vaccinated chicks will contribute significantly to our understanding of vaccinal protection. We recently developed a real-time polymerase chain reaction (PCR) assay for quantitation of CVI988 vaccine virus in the feather tips, a rich source of viral DNA which can easily be sampled in a non-invasive manner. This PCR test is now used commercially to confirm the successful vaccination of chicks. We have also used the PCR to examine various aspects of vaccination in experimental chicks and commercial chicks with a view to determining how vaccine level in feathers correlates with protection against challenge, and for identifying optimal timing and vaccine delivery route, and optimal vaccination regimes for different breeds of chick. In this article we review some aspects of the current vaccinal control of Marek's disease, before highlighting some of the problems associated with current vaccines and vaccination strategies, and the challenges for the future. We go on to discuss the development and use of our real-time PCR feather test, its current applications and potential opportunities in Marek's disease vaccine research.  相似文献   

19.
DNA and recombinant virus vaccines against swine influenza virus (SIV) have been pursued with promising results, but induce poor immunogenicity. This study evaluated the effects of a vaccine regimen in mice including priming with three DNA vaccines expressing soluble HA (sHA), complete HA (tmHA), or sHA fused with three copies murine C3d (sHA-mC3d3) and boosting with recombinant pseudorabies virus expressing HA (rPRV-HA). Immune responses were monitored by ELISA, HI assays, and virus neutralization. Protective efficacy was evaluated by virus isolation from lungs, distribution in tissues, and pathology following challenge with H3N2 SIV. Priming with sHA-mC3d3 and boosting with rPRV-HA induced higher levels of HA-specific antibodies and yielded the most effective protection. This finding implied that priming with a DNA vaccine expressing C3d fused with antigen and boosting with a recombinant vector vaccine is an effective way to induce protective humoral immunity and prevent some infectious diseases.  相似文献   

20.
Several characteristics of BHV-1 have contributed to the successful development of both conventional and marker vaccines. BHV-1 is a stable virus, which grows to high titers in vitro, has a limited host range and causes acute viremic infections. Furthermore, the protective antigens, as well as the antigens that are suitable as marker, are present in the predominant virus isolates and induce significant and long-lasting immune responses, both in na?ve and in previously vaccinated animals. In many parts of the world including North-America control of BHV-1 is achieved by vaccination with conventional attenuated or inactivated vaccines. With parts of Europe being BHV-1 free, the ability to differentiate infected from vaccinated animals has become critical as a trading tool. Live and killed gE-deleted marker vaccines are now widely used in Europe, in combination with gE-based diagnostic tests to monitor cattle. However, several issues remain to be resolved. BHV-1 causes latency, which creates a need for stringent management practices in case eradication is to be achieved. Since intramuscular delivery with a syringe and needle leads to considerable tissue damage, needle-free delivery methods should be adopted for beef cattle. Furthermore, conventional inactivated and attenuated vaccines are less efficacious in neonates, so alternative vaccine types such as CpG adjuvanted protein vaccines or DNA vaccines are required for effective vaccination of this age group.  相似文献   

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