Studies on linear epitopes of Semliki Forest virus in protection studies against lethal challenge virus infection.

Purified reduced and non-reduced glycoproteins E1 and E2 of Semliki Forest Virus (SFV) were used to investigate the protection potency to prevent clinical disease after lethal virus challenge. In parallel synthetic oligopeptides deduced from conserved regions of the nucleotide sequences coding for the glycoproteins E1 and E2 were included. It could be demonstrated that both reduced and non-reduced glycoprotein preparations induced protection against lethal virus challenge, whereas the oligopeptides did not. The role of linear epitopes in immunity and their potential use as synthetic vaccines against Alphaviruses are critically discussed.     

寄生虫虫苗的研究概况

目前，寄生虫虫苗可以分为５类，即弱毒活苗，排泌物抗原苗，基因工程苗，化学合成苗及基因苗。本文对此５类虫苗的研究现状、制备方法及种类与应用前景作了概述。     

口蹄疫新型疫苗研究进展

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。     

Prospects for molecular vaccines in veterinary parasitology

Despite the profound developments in recombinant DNA technology there is only one marketed recombinant vaccine (for human viral hepatitis B). The development of others proceeds with great difficulty. Molecular vaccines against veterinary parasites are at the utmost pole of complexity in the spectrum of potential vaccines since these parasites are complex eukaryotic organisms, often dwelling at mucosal surfaces where anamnestic responses are problematic, where the immunogenicity of the parasite components is poorly understood and where the effector mechanisms of immunity are unresolved. Cloning a "protective" gene is only the first step, and perhaps the easiest, in a long process which will be necessary to develop vaccines against parasites. Additional steps will involve comprehensive analyses of the immunological responses to ensure that vaccine antigens contain the correct epitopes to induce appropriate immune effector mechanisms for parasite elimination and immunological memory and that these responses are not genetically restricted. The great expectations for recombinant vaccinia-based vaccines must be modified substantially in the light of recent evidence indicating immunological and other constraints on this approach. The use of anti-idiotype vaccines is an underexplored opportunity for practical parasite vaccines since they have several potentially important advantages. The need to include T cell antigenic peptides in peptide vaccines to extend the range of genetic responsiveness and to induce anamnestic responses is now clear. New algorithms for the prediction of such sites exist and these can be tested experimentally with synthetic peptides. There are no major technical obstacles to the development of vaccines for parasites which cannot be overcome. However substantial long term basic research is needed over a range of disciplines to achieve this worthwhile objective.     

免疫佐剂的研究进展

随着DNA重组疫苗、合成肽疫苗等新型疫苗的不断涌现,免疫佐剂研究越来越受到人们的关注.本文综述了近年来免疫佐剂研究概况,着重介绍了目前常用及研究较多的佐剂的特点,并就免疫佐剂现状及研究发展趋势提出自己的见解,为开发研制高效、低毒、结构新颖的免疫佐剂提供参考.     

新型猪瘟疫苗的研究进展

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。     

鱼类疫苗研究进展

经过试验探索、生产应用 ,鱼类疫苗的研究已进入用新技术和新方法研制高效疫苗的时期。疫苗的种类逐渐增多 ,除传统的死疫苗、活疫苗、化学疫苗以外 ,新型疫苗得到快速发展。主要包括 DNA疫苗、合成肽疫苗。一些疫苗已经成为工业化生产的商品用疫苗 ,如弧菌病疫苗、红嘴病疫苗、疖病疫苗、传染性造血器官坏死病疫苗。鱼类的免疫应答和疫苗的免疫接种方法等都会影响鱼类疫苗的应用。尽管鱼类疫苗面临着一些困难 ,但是它有广阔的发展前景     

免疫佐剂作用机理的研究进展

随着DNA重组疫苗、合成肽疫苗等新型疫苗不断涌现,免疫佐剂研究越来越受到人们的关注.尽管佐剂活性物质的研究报道很多,但由于佐剂加强免疫反应是一个非常复杂的过程,关于各种佐剂的作用机制至今尚未完全了解.本文对近年来免疫佐剂作用机理研究进展作-综述,为促进免疫佐剂作用机理的深入研究及免疫佐剂的合理应用提供参考,并初步探讨其作用机理研究的重要性及意义.     

口蹄疫合成肽疫苗研究进展

口蹄疫(FMD)是一种严重威胁世界畜牧业发展和国际进出口贸易的重大传染病。尽管FMD传统疫苗在免疫效力上具有一定优势,但其自身仍存在诸多弊端及隐患。随着分子生物学技术的飞速发展,及其在兽医领域不断取得的创新性应用,FMD合成肽疫苗作为新型基因工程疫苗的一种,以其具有更为广谱的特异性、更加安全稳定、经济实用等特点,现已成为FMD研究领域的主要热点及方向。论文从抗原位点的选择、空间构象的研究、疫苗载体的探索以及免疫佐剂的优化等多方面对FMD合成肽疫苗的发展过程及其研究进展进行了深入探讨,旨在为FMD合成肽疫苗的进一步发展以及其他病原微生物合成肽疫苗的深入研究提供借鉴。     

Current status of foot-and-mouth disease vaccines including the use of genetic engineering

SUMMARY Foot-and-mouth disease virus (FMDV) vaccines are used to protect animals against infection by the 7 FMDV serotypes composed of greater than 60 FMDV subtypes. Because of problems of both live attenuated and inactivated FMDV vaccines and also because of the very large market for an effective safe vaccine, research into other types of vaccines has been undertaken. One of the 4 virus structural proteins, VP1, is believed to be the main protein that stimulates virus neutralising antibodies and studies have concentrated on its potential as a subunit vaccine. Genetic engineering has been used to clone the VF1 gene of FMDV and VP1 synthesised from the cloned gene has been used in experimental vaccine studies. The studies in small numbers of cattle and pigs demonstrated that 2 vaccinations with genetically engineered VP1 could confer protection against FMDV challenge. However, there are a number of areas that need further research before such a genetically engineered vaccine could be used commercially. The use of chemically synthesised antigenic fragments of VP1 has recently been reported, and these synthetic fragments appear to be potentially better at producing immunity to FMDV than the whole genetically engineered VP1 protein, perhaps because of conformational problems in the presentation of whole VP1. Other possible future directions in the research and in the development of safe, effective FMDV vaccines are discussed. In conclusion, although very significant progress has been made in cloning FMDV-VP1 genes, we are still far from a genetically engineered VP1-FMDV subunit vaccine. In the meantime, properly inactivated and safety-tested FMDV vaccines will continue to be used and to be of benefit to the livestock industry in countries where foot-and-mouth is endemic or in combating introductions of the disease.     

Commercialization of plant-based vaccines from research and development to manufacturing

The benefits of using plant-based oral vaccines are discussed. Transgenic maize expressing an antigen of transmissible gastroenteritis virus (TGEV) is reported as a model to demonstrate efficacy. Young pigs that were fed the TGEV corn orally were protected against challenge with virulent TGEV. Additional parameters important in providing a reliable and consistent supply of plant-based vaccines are discussed. Finally, vaccines developed in maize are evaluated for their potential to contaminate either the food supply or the environment.     

Computed tomography measurements of thoracic structures in 26 clinically normal goats

There is increasing evidence that activation of innate immunity, in animals and man, by live vaccines, sub-unit vaccines or synthetic or non-synthetic stimulants can induce a profound and rapidly induced resistance to pathogens, including infectious agents that are unrelated to the stimulating antigen or agent. We review the evidence for this phenomenon and present the proposition that this approach might be used to stimulate immunity during the life of the animal when susceptibility to infection is high and when normal vaccination procedures may be inappropriate.     

猪口蹄疫O型合成肽疫苗抗体水平检测

为了解猪口蹄疫O型合成肽疫苗的免疫效果,选用了两个厂家生产的猪口蹄疫O型合成肽疫苗,对80头试验仔猪进行了免疫注射,并在6、7、8、9、11、13、20周龄采血,通过ELISA检测抗体水平的变化。结果显示,猪口蹄疫O型合成肽疫苗能快速诱导产生高水平的抗体;疫苗的免疫副作用小;使用VP1ELISA和LPB-ELISA检测猪口蹄疫O型合成肽疫苗免疫抗体试验相关性较好。     

DNA vaccination against influenza viruses: a review with emphasis on equine and swine influenza

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.     

Maturation of functional antibody affinity in animals immunised with synthetic foot-and-mouth disease virus.

A good correlation exists between specific neutralising antibody titre and protection against challenge with foot-and-mouth disease virus (FMDV) in infected or virus-vaccinated cattle, but not in the case of animals immunised with synthetic FMDV peptides. Therefore, mechanisms other than simple neutralisation are likely to be important in vivo. Antibody affinity may influence the protective capacity of sera from immunised animals and experiments were carried out to measure the functional affinity for synthetic FMDV peptide of sera from guinea pigs and cattle given various synthetic vaccines. In guinea pigs given a single dose of synthetic vaccine, antibody affinity increased with time after immunisation. In cattle, however, administration of a second dose of peptide 21 days after the first markedly retarded the process of affinity maturation. For guinea pig sera of equivalent neutralising activity, those of higher functional affinity had higher protective indices than those of lower functional affinity. Knowledge of the importance of antibody affinity in protection against FMD is important for an improved understanding of the mechanisms of protection and for the design of novel vaccines.     

Prospects for a novel vaccine against tuberculosis

The development of a new and improved vaccine against tuberculosis has in the last 10 years been accelerated tremendously from the completed Mycobacterium tuberculosis genome and the progress in molecular biology. This has resulted in the identification of a large number of antigens with potential in tuberculosis vaccines. The next phase of this work has now started--putting the most relevant molecules back together as fusion molecules and cocktails. This requires carefully monitoring of aspects as immunodominance, recognition in different populations as well as the influence of different adjuvants and delivery systems. The most advanced of these vaccines such as the fusion between ESAT6 and Ag85B have been evaluated in a range of animal models including non-human primates and are now entering into clinical trials. For these vaccines to be successfully implemented in future vaccination programmes it is necessary to understand the immunological background for the failure of BCG and optimize the vaccines for their ability to boost the immuno-response primed by BCG.     

猪口蹄疫○型合成肽疫苗诱导的免疫抗体的监测

设3组猪群,首免和二免分别注射生理盐水1 mL、猪口蹄疫0型合成肽疫苗1 mL(说明书推荐免疫剂量)及猪口蹄疫0型合成肽疫苗3 mL(说明书推荐免疫剂量3倍量),二免28天后检测猪群的口蹄疫抗体,结果显示3组猪群的抗体合格率分别为33%、78%和100%,疫苗诱导的抗体水平达到农业部规定的动物强制免疫标准。     

New technology for improved vaccine safety and efficacy.

Nearly all of the 2000 vaccines presently licensed by the US Department of Agriculture for veterinary use in the United States are conventional vaccines containing either killed or modified live whole bacteria or viruses. Recent advances in molecular biology, immunology, microbiology, and genetics and in understanding microbial pathogenesis have led to the development of a wide variety of new approaches for developing safer and more effective vaccines. This article briefly describes these new technologies and their potential advantages and disadvantages as compared with conventional killed and modified live vaccines.     

猪口蹄疫、猪瘟、猪蓝耳病疫苗最佳免疫方法研究

为探索生猪重大疫病的科学免疫方法,确定最佳免疫程序,笔者设计并开展了口蹄疫（FMD）合成肽苗（或灭活苗）、猪瘟（HC）脾淋苗、高致病性蓝耳病弱毒疫苗（或灭活苗）的不同组合注射、单独注射、不同疫苗类型注射的试验研究.结果表明：3种疫苗不同组合注射或单独注射,以及使用不同类型疫苗注射,其免疫副反应均无明显差异;平均免疫抗体效价及群体合格率各组间存有差异;采用猪口蹄疫、猪瘟、猪蓝耳病3种疫苗同时分点注射,以及仔猪首免口蹄疫、猪蓝耳苗,再免疫口蹄疫、猪瘟苗的免疫效果最佳.     

CpG-Induced Stimulation of Cytokine Expression by Peripheral Blood Mononuclear Cells of Foals and Their Dams

A relative immunodeficiency of young foals is considered to account for the increased susceptibility of foals to infectious diseases, including pneumonia caused by Rhodococcus equi. In this report, peripheral blood mononuclear cells (PBMCs) from healthy foals at 14 and 56 days of age, or from their dams, were incubated with three stimulatory and one nonstimulatory (control) synthetic cytosine-phosphate-guanosine oligodeoxynucleotides (CpG-ODNs), and mRNA expression of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin (IL) -6, IL-8, IL12-p35, and IL-12p40 were determined. Results indicated that synthetic CpG-ODNs can induce strong, rapid cytokine responses in healthy foals and adult horses. B-class CpG-ODNs 2135 and 2142 induced greater messenger RNA (mRNA) expression of IFN-γ, IL-6, and IL-12p40 than the C-class CpG-ODN 2395 in foal PBMCs. In foals, B-class CpG-ODNs induced IFN-γ, IL-6, and IL-12P40 mRNA expression that was similar to or higher in magnitude than that observed in adult horses. These observations indicate that CpG-ODNs might be useful as immunomodulators or as potential adjuvants for vaccines to aid in preventing R. equi pneumonia and other bacterial diseases of foals.