核酸免疫与核酸疫苗

核酸疫苗是最近几年从基因治疗研究领域发展起来的一种全新免疫防治剂。核酸疫苗是指将含有编码某种抗原蛋白基因序列的质粒载体作为疫苗 ,直接导入动物细胞内 ,通过宿主细胞的转录系统合成抗原蛋白 ,诱导宿主产生对该抗原蛋白的免疫应答 ,从而使被接种动物获得相应的免疫保护。免疫应答包括细胞激活、细胞因子分泌、细胞毒淋巴细胞 (CTL)产生以及特异性抗体形成等。因此 ,核酸疫苗又称基因疫苗或裸DNA疫苗。这种免疫称为核酸免疫、基因免疫、遗传免疫或DNA介导免疫等。核酸疫苗与传统疫苗相比有许多潜在的优势 ,从而被誉为第三次疫苗革…     

核酸疫苗的研究和应用

90年代中期 ,研制了一种新的免疫防治制剂 -核酸疫苗。所谓核酸疫苗是指将含有编码某种抗原蛋白基因序列的质粒载体作为疫苗 ,直接导入动物细胞内 ,通过宿主细胞的转录系统合成抗原蛋白 ,诱导宿主产生对该抗原蛋白的免疫应答 ,从而使被接种动物获得相应的免疫保护。免疫应答包括了细胞激活、细胞毒淋巴细胞 ( CTL)产生、细胞因子分泌以及特异性抗体形成等。核酸疫苗又称为基因疫苗或裸 DNA疫苗。这种免疫称为核酸免疫、基因免疫 ,DNA介导的免疫以及遗传免疫等。核酸疫苗与传统疫苗相比有许多潜在的优势 ,从而被誉为疫苗领域的第三次革命…     

提高DNA疫苗免疫效果研究进展

<正>DNA疫苗本质上是质粒,包括真核表达载体和整合到载体上的表达特定基因的序列。DNA疫苗通过特定的递送方式进入宿主细胞核,载体携带的特定抗原基因发生转录,m RNA随即至细胞浆,翻译成抗原蛋白。不同于传统的蛋白或多肽疫苗,DNA疫苗免疫宿主后,所表达的抗原(蛋白或多肽)能够在基质细胞(如肌肉细胞)和树突状细胞中表达,这些抗原经过处理,激活B淋巴细胞,诱导产生抗体,发挥体液免疫应答效应;抗原     

禽类病毒免疫逃避的机制

为了在宿主体内生存,病毒在进化过程中形成了一系列逃避机体免疫的能力,包括潜伏感染、抗原变异、干扰抗原加工和呈递、调节宿主细胞因子网络、调控细胞凋亡以及抑制补体抗体系统等.本文以禽病毒为例对病毒免疫逃避的机制进行了综述.     

猪内源性反转录病毒囊膜蛋白基因的克隆及其蛋白二级结构和B细胞表位预测

猪内源性反转录病毒（PERV）是与猪-人异种移植病原安全性密切相关的一类病毒。env基因编码病毒的囊膜蛋白,它与病毒的亚型分类、宿主感染范围、细胞的嗜性以及对宿主细胞的感染机制、诱导宿主产生中和抗体等密切相关。本研究利用RT-PCR的方法,从五指山小型猪外周血淋巴细胞中扩增PERV的囊膜蛋白基因并进行测序,随后用生物信息学相关软件和方法,对PERV-Env蛋白二级结构及B细胞表位进行预测。经综合分析评价,结果发现PERV-Env蛋白有18个可能的B细胞优势抗原表位区域,7个可能的糖基化位点。该分析预测结果不但有利于PERV疫苗的设计、单抗及诊断试剂研制,而且将有助于分析Env蛋白的功能及PERV对人源细胞的感染机制。     

T细胞、细胞因子在抗病毒免疫中的作用机制

抗病毒免疫的机制极其复杂,宿主的免疫系统需要经过抗原肽的加工提成、淋巴细胞活化、抗体和细胞因子的产生等一系列步骤才能最终清除病毒的感染。从蛋白酶体在病毒抗原加工中的作用、免疫支配效应的意义、CTL杀伤病毒感染细胞的机制、细胞因子的作用和免疫逃逸机制等方面阐述了抗病毒免疫机制,对于病毒的防治将是十分重要的。     

影响猪繁殖与呼吸综合征病毒感染与增殖的因素

猪繁殖与呼吸综合征病毒(PRRSV)感染宿主细胞以及在宿主细胞内进行复制的过程受到宿主细胞的细胞受体、胞内大分子及细胞因子影响。随着单克隆抗体制备技术、分子生物学技术与蛋白质研究技术的日趋成熟,使深入研究影响PRRSV感染与增殖的因素成为可能。目前在猪肺巨噬细胞(PAM)与Marc-145细胞中发现了多个PRRSV细胞受体,这与PRRSV感染宿主细胞所具有严格的细胞嗜性有关。同时胞内大分子物质可导致PRRSV在宿主细胞内产生增殖性感染。包括干扰素在内的细胞因子具有抑制PRRSV在宿主细胞内增殖的作用。研究影响PRRSV感染与增殖的因素,对于预防PRRSV感染与合理利用PRRSV具有重要意义。     

DNA疫苗在兽医学中的应用

DNA疫苗又称DNA免疫、核酸免疫和基因免疫等.它是指将编码抗原的基因以重组表达载体的形式经各种基因转移途径转入机体细胞,借用宿主细胞的表达加工机构合成抗原分子,以MHC-Ⅰ和/或MHC-Ⅱ类分子抗原处理和输送途径将抗原递呈给T淋巴细胞,从而激发体液免疫和细胞免疫.     

核酸疫苗的构成及主要特点

核酸疫苗 (ｎｕｃｌｅｉｃａｃｉｄｖａｃｃｉｎｅｓ)是将编码某种抗原蛋白的外源基因 (ＤＮＡ或ＲＮＡ)直接导入动物体细胞内 ,并通过宿主细胞的表达系统合成抗原蛋白 ,诱导宿主产生对该抗原蛋白的免疫应答 ,以达到预防和治疗疾病的目的。核酸疫苗又称为基因疫苗或ＤＮＡ疫苗 ,这种免疫称为核酸免疫、基因免疫、ＤＮＡ介导的免疫以及遗传免疫等。核酸疫苗是由基因治疗而发展起来的。 70年代末 ,Ｍ .Ａ .Ｉｓｒａｌ等〔1,2〕将纯化的多瘤病毒完整的ＤＮＡ直接注射小鼠使其感染 ,首次证明ＤＮＡ可被动物体细胞摄入并到达细胞核得以转录。 1 9…     

弓形虫感染引起小鼠体内CD_8~+T淋巴细胞免疫的研究

弓形虫感染可诱导宿主机体产生强烈的CD_8~+T淋巴细胞免疫应答,这对机体有效控制弓形虫感染具有重要作用。在感染过程中,CD_8~+T淋巴细胞可刺激机体产生IFNγ等细胞因子,并促进细胞溶解,能够有效阻止机体内潜伏性感染的活化过程。然而,部分易感小鼠体内CD_8~+T淋巴细胞会在感染期间发生功能障碍。文章就慢性感染中CD_8记忆应答的发展及其功能障碍机制展开论述。     

Antibody and IFN-gamma responses induced by a recombinant canarypox vaccine and challenge infection with equine influenza virus

In horses, equine influenza virus (EIV) is a leading cause of respiratory disease. Conventional inactivated vaccines induce a short-lived immune response. By comparison, natural infection confers a long-term immunity to re-infection. An aim of new equine influenza vaccines is to more closely mimic natural infection in order to achieve a better quality of immunity. A new live recombinant vaccine derived from the canarypox virus vector and expressing haemagglutinin genes of EIV (subtype H3N8) has been developed. Stimulation of the immune system was studied after immunisation with this canarypox-based vaccine and challenge infection by exposure to a nebulised aerosol of EIV. The humoral immune response was evaluated by measuring serum antibody levels using the single radial haemolysis (SRH) assay. The cellular immune response was assessed by the measurement of interferon gamma (IFN-gamma) synthesis in peripheral blood mononuclear cells (PBMC). Clinical signs of the disease (temperature, coughing, nasal discharge, dyspnoea, depression and anorexia) and virus excretion were monitored after challenge infection. Clinical signs and virus shedding were significantly reduced in vaccinates compared with unvaccinated controls. EIV-specific immunity was stimulated by vaccination with a recombinant vaccine as serological responses were detected after immunisation. This study also provided the first evidence for increased IFN-gamma protein synthesis in vaccinated ponies following challenge infection with EIV compared with control ponies.     

Equine immunity to viruses.

The identification of some of the adaptive immune responses to infection with equine viruses has been the first step toward rational immunoprophylactic design. Sufficient knowledge of infection-induced immunity and informed estimates of the requirements for long-term immunity for EIV have now been obtained. Thus, the future for inactivated EIV vaccines is promising now that new adjuvants have been applied to induce cellular immunity and safe methods have been designed to stimulate virus-neutralizing (VN) antibody at mucosal surfaces. Adenoviruses induce circulating VN antibody, the presence of which appears to correlate with protection from reinfection. Therefore, the potential of vaccines to induce VN antibody and protect from challenge is an important next step with this virus. With persistent viruses such as EHV-1, antibody-mediated protection from infection can be achieved only at the site of initial infection, that is, the nasopharynx and upper respiratory tract. Systemic dissemination is very rapid and consequently VN antibody is unlikely to play a major role in prevention of disease once the initial infection event has occurred. Cellular immune responses, particularly CTLs, play a dominant role in protection and recovery and are important in immune surveillance and determination of the outcome of reactivation of latent virus. Therefore, the key to future EHV-1 vaccine design is to focus on stimulation of CTL responses, and this requires the successful presentation of vaccine-derived antigenic peptides to MHC class I molecules that are recognized by specific receptors on CTL. There is some evidence that stimulation of EHV-1-specific CTL precursors may correlate with immunity to this virus. By analogy with gamma herpesviruses in humans, CTL precursor frequency may also function as an immune correlate for EHV-2. Although EAV infection induces strong immunity in females and geldings, persistent infection of the genital tract is an important route of dissemination from stallions. Although inactivated vaccines induce strong immunity (which depends upon VN activity of serum antibody) to first infection, the immunologic control of persistent infection is currently poorly understood; however, analogy with other persistent viruses suggests that CTLs are also likely to play an important role in the control of persistent EAV infections.     

Subversion and piracy: DNA viruses and immune evasion

During the co-evolution of viruses with their vertebrate hosts, the DNA viruses have acquired an impressive array of immunomodulatory genes to combat host immune responses and their hosts have developed a sophisticated immune system to contain virus infections. In order to replicate, the viruses have evolved mechanisms to inhibit key host anti-virus responses that include apoptosis, interferon production, chemokine production, inflammatory cytokine production, and the activity of cytotoxic T-cells, natural killer cells and antibody. In addition, some of the viruses encode cytokine or chemokine homologues that recruit or expand cell numbers for infection or that subvert the host cellular response from a protective response to a benign one. The specificity of the viral immunomodulatory molecules reflects the life cycle and the pathogenesis of the viruses. Herpesviruses achieve latency in host cells by inducing cell survival and protecting infected cells from immune recognition. This involves interference with cell signal transduction pathways. Many of the viral immunomodulatory proteins are homologues of host proteins that appear to have been pirated from the host and reassorted in the virus genomes. Some of these have unique functions and indicate novel or important aspects of both viral pathogenesis and host immunity to viruses. The specific example of orf virus infection of sheep is described.     

环核苷酸（cAMP／cGMP）与肉鸡内分泌及免疫功能的关系

以艾维茵肉鸡为实验对象，研究了血清环核苷酸与肉鸡内分汔及免疫功能的关系。结果表明，以性法氏囊病病毒（IBDV）强毒株攻击后，肉鸡垂体－肾上腺轴活动加强，并发生针对IBDV的特异性免疫反应，血清cAMP与cGMP含量均上升，但cAMP/cGMP比值保持稳定，提示垂体－肾上腺轴活动加强使cAMP上升与抗IBDV特异性免疫细胞内效应大分子的合成有关，而cAMP/cGMP比值的稳定则是保持一种高阈平衡，以维持内环境的稳态。由于IBDV强毒株破坏了机体免疫系统，未经IBDV疫苗免疫的肉鸡cAMP、抗IBDV抗体和IL－2的上升幅度均比经IBDV疫苗免疫的肉鸡小。     

Studies on the mechanism of vaccinal immunity to Marek''s disease

Current knowledge of the nature of the antigens and of the host immune responses in vaccinal immunity to Marek's disease is reviewed. It is suggested that a two-step mechanism of resistance operates. The first step involves humoral and cell-mediated responses directed against viral antigens; the second step occurs after challenge with Marek's disease virus and consists of cellmediated responses directed against tumour cells.     

Mechanisms of recovery from Herpesvirus infections -a review.

A variety of specific immunological mechanisms have been shown to be effective at neutralizing herpesviruses or destroying herpesvirus infected cells. These include both humoral and cell mediated immune responses or combinations thereof. Thus, it is genarlly accepted that humoral immunity is probably responsible for preventing reinfection whereas cellular immunity, mediated by T lymphocytes or by the interaction of antibody and Fc receptor bearing cells, is more important in recovery from infections. In addition to these specific responses to herpesvirus infection, a number of nonspecific cellular and humoral components have been shown to inhibit the progression of virus replication and therefore, have been implicated in assisting the host in the recovery process. The various interactions and counteractions between the various nonspecific and specific components of the immune response are discussed with respect to their role in recovery from both primary and recurrent disease as well as how they may eventually be manipulated so as to control herpesvirus recrudescent disease.     

A DNA vaccine coding for glycoprotein B of pseudorabies virus induces cell-mediated immunity in pigs and reduces virus excretion early after infection

Glycoproteins B (gB), gC and gD of pseudorabies virus (PRV) have been implicated as important antigens in protective immunity against PRV infection. As cell-mediated immunity plays a major role in this protective immunity, we determined the significance of these glycoproteins in the actual induction of cell-mediated immunity. We vaccinated pigs with plasmid DNA constructs coding for gB, gC or gD and challenged them with the virulent NIA-3 strain of pseudorabies virus. Vaccination with plasmid DNA coding for gB induced the strongest cell-mediated immune responses including cytotoxic T cell responses, whereas plasmid DNA coding for gD induced the strongest virus neutralising antibody responses. Interestingly, vaccination with gB-DNA reduced virus excretion early after challenge infection while vaccination with gC-DNA or gD-DNA did not.This is the first study to demonstrate that DNA vaccination induces cytotoxic T cell responses in pigs and that cell-mediated immunity induced by vaccination with gB-DNA is important for the reduction of virus excretion early after challenge infection.     

羊口疮病毒与宿主互作研究进展

羊口疮是一种人兽共患传染病，主要由羊口疮病毒（Orf virus，OrfV）感染所致，目前尚无特效药物可治疗。囊膜蛋白是OrfV的主要抗原性蛋白，其机理主要是为病毒侵入宿主细胞创造一系列条件，同时降低宿主免疫力，增强了病毒的毒力。当病毒侵入宿主体内后，宿主会产生抗病毒免疫应答来清除病毒粒子，包括特异性体液免疫和非特异性细胞免疫应答，但主要以非特异性的细胞免疫应答为主。宿主对病毒会产生抗病毒免疫应答，同时病毒也会对宿主的免疫应答形成一种免疫逃避机制，通过该机制来躲避宿主免疫细胞对病毒粒子的捕获和清除，为病毒粒子在宿主体内的增殖、成熟及增强病毒毒力创造了各种条件。作者归纳总结了近年来羊口疮病毒与宿主互作的研究，阐述了OrfV囊膜蛋白的生物学功能、宿主的抗病毒免疫应答、病毒在宿主体内的免疫逃避机制和OrfV的其他一些毒力因子的致病作用，以期为羊口疮病毒的致病机制及疫苗防制研究提供参考。     

新城疫病毒样颗粒研究进展

新城疫(Newcastle disease,ND)是由新城疫病毒(Newcastle disease virus,NDV)引起的一种急性、高度接触性禽类烈性传染病,以呼吸道、消化道及神经系统症状为主要特征,在易感家禽中死亡率高达100%,给中国及世界养禽业和贸易往来带来了严重的经济损失。病毒样颗粒(virus-like particles,VLPs)是由病毒蛋白在感染过程中体外表达或自发组装而形成的不含病毒基因组、不能复制、不具有感染能力的病毒样蛋白颗粒。VLPs适宜的大小及独特的表面结构可被天然免疫细胞和分子有效识别,诱导良好的先天性免疫应答和适应性免疫应答,且VLPs不含病毒的感染性核酸,安全性较高,近年来成为疫苗领域中的研究热点。树突状细胞(dendritic cells,DCs)作为专职抗原递呈细胞,在连接天然免疫与适应性免疫之间具有独特功能,是目前抗原递呈能力最强的专职免疫细胞。成熟DCs (mature DCs,mDCs)迁移至次级淋巴组织能刺激初始型T细胞活化和增殖,被认为是特异性免疫应答的始动者,体外培养的不成熟DCs (immature DCs,imDCs) 也可辅助增强抗原递呈能力。NDV-VLPs主要是以NDV-M蛋白为骨架,来装配HN、F和NP蛋白,可表现出与活的NDV颗粒相似的外观和免疫原性。可见通过NDV-VLPs制成的疫苗同样具备安全、稳定、可刺激体液和细胞免疫应答、作为载体表达其他抗原及可设计成区分自然感染与免疫接种等诸多优点。文章主要就NDV-VLPs的相关内容展开探讨,以期为后续研究提供参考。     

Immune response to foot-and-mouth disease virus in an experimental murine model. II. Basis of persistent antibody reaction

A murine model was used to study the mechanisms involved in the prolonged immune response to live and inactivated foot-and-mouth disease virus (FMDV). The antibody response elicited by the infection persisted throughout the entire life of the animal, while immunization with inactivated virus induced a transient response. The administration of inactivated virus in a water-in-oil emulsion increased antibody titres to values as high as those obtained by infection. There was a high correlation between neutralizing antibody titre and transfer of immunity with primed cells, and the protection afforded against challenge with infectious virus. It appears that the mechanism involved in the induction of prolonged immune memory in infected animals is not due to viral persistence. Nude mice infected with FMDV also evidenced a prolonged immune response, showing marked differences in antibody levels but equal effectiveness against challenge when nu/nu and nu/+ animals were compared. Furthermore, athymic and euthymic littermates were efficient in conferring protection when cells were transferred to irradiated animals. It is concluded that there is an effective, T-cell-independent, prolonged immune memory against FMDV in this murine model, and that the difference in the immune responses to live and inactivated virus is due mainly to differential antigenic processing rather than to a difference in the degree of sensitization of effector cells.