免疫佐剂及其作用机制

免疫佐剂在疫苗免疫中起着巨大的作用，传统疫苗和新型疫苗在研究和实践中暴露的问题推动了免疫佐剂的研究，使生物科学家开始对佐剂的研究越来越关注，新型佐剂和新型疫苗正成为当今科技攻关的重点项目。本文总述了矿物质佐剂、油佐剂等传统佐剂和分子佐剂等新型佐剂的优缺点及其作用机制的研究进展，以期增加对免疫佐剂及其作用机制的认识．     

壳聚糖的理化性及其作为免疫佐剂的研究进展

免疫佐剂是一种免疫调节剂,可增强抗原的免疫原性、提高免疫效果。为增强疫苗的免疫原性在病毒性疫苗、DNA疫苗、多肽疫苗的研制中常加入免疫佐剂。目前批准可用于人体的免疫佐剂是铝佐剂,因只能引起体液免疫,不能有效诱导细胞免疫,因此寻找新的免疫佐剂已成为疫苗研制迫切需要解决的问题。研究表明,壳聚糖具有免疫佐剂效应,具有良好的组织相容性,可生物降解,安全无毒,因此壳聚糖将成为一种很有应用价值的免疫佐剂。本文就壳聚糖的理化性及其免疫佐剂研究做一综述。     

不同免疫佐剂对大肠杆菌疫苗免疫效果的影响

将大肠杆菌经培养后制成疫苗,分别加入矿物油佐剂、氢氧化铝佐剂和不加任何免疫佐剂,按一定免疫程序分别注射实验兔,取兔血清进行凝集试验测其抗体效价。结果表明：加矿物油佐剂苗的抗体效价最高（1：256）,不加佐剂苗的抗体效价次之（1：128）,加入氢氧化铝佐剂苗的抗体效价最低（1：64）。     

抗体生产中佐剂的选择和应用

当某些物质与抗原一起注入机体内,能增强机体对抗原的特异性体液和细胞调节的免疫应答,这些物质称为免疫佐剂(Immuno adjuvant),简称佐剂。免疫佐剂能够非特异地提高机体对弱免疫原性的特异抗原的免疫应答或改变免疫反应类型。当佐剂与抗原物质混合注入机体后,可形成抗原储存库     

新闻·视点

863计划现代农业技术主题畜禽重大疫病新型疫苗的研制开发取得重大突破863计划现代农业技术主题畜禽重大疫病新型疫苗的研制开发取得重大突破,获得了一批基因工程疫苗、DNA疫苗、核酸疫苗和分子免疫佐剂等,引导了新一代基因工程疫苗的发展方向,为重大动物疫病的防制奠定了坚实的基础。研制了伪狂犬病基因缺失活疫苗,并获国家新兽药     

纳米铝佐剂诱导鸡提前产生抗AIVH9体液免疫应答

接种灭活油佐剂疫苗是目前国内防控禽流感主要的措施,为有效防控禽流感的流行发挥了重要的作用,但灭活苗首次接种后需要较长时间抗体才能达到有效保护水平.纳米颗粒具有独特的生物学特性,作为疫苗佐剂能引起机体强烈的免疫应答.本研究用纳米铝颗粒作为AIV H9的佐剂,结果显示,小鸡产生有效免疫保护抗体时间较常规油佐剂疫苗提前4天且无副反应,但抗体峰值和持续时间均低于油佐剂疫苗.氢氧化铝纳米颗粒作为佐剂可能对禽流感等重大传染病的紧急预防接种具有潜在的应用价值.     

DNA疫苗的佐剂研究综述

DNA疫苗是新发展起来的一种疫苗。它有许多传统疫苗所没有的特点，但是其免疫原性较弱限制了应用。本文探讨了传统与新型分子免疫佐剂在提高DNA疫苗的免疫效果方面发生的作用，其中主要从细胞因子、趋化因子、CpG序列三个方面来说明。     

鸡传染性鼻炎三价灭活疫苗油乳佐剂的筛选及免疫效果评价

为了对比筛选出鸡传染性鼻炎(IC)三价灭活疫苗的最适油乳佐剂,使用三种不同的油乳佐剂制备了3批鸡传染性鼻炎(A型+B型+C型)三价灭活疫苗,并对疫苗的物理性状、安全性及免疫效力进行检测.结果 显示,三种佐剂制备的疫苗均为稳定的油包水乳剂,而佐剂3组的黏度(29.3 Pa.s)显著低于其余两种佐剂组(184.2 Pa.s...     

蜂胶乙醇提取物及其作为佐剂对雏鸡血液T、B淋巴细胞比例的影响

研究蜂胶乙醇提取物 (EEP)及其作为佐剂制备的减蛋综合症 (EDS 76 )疫苗对雏鸡血液中T、B淋巴细胞比例的影响 .结果表明 ,EEP及其作为佐剂制备的EDS 76疫苗皆可使雏鸡血液中的T淋巴细胞比例增加极显著 (P <0 .0 1) .     

甘油-3-磷酸对甲肝疫苗诱导的体液免疫影响*

目的 研究甘油-3-磷酸对甲肝疫苗诱导的小鼠体液免疫应答的影响。方法 选取49只雌性ICR小鼠,分7组,每组7只,这7组小鼠分别为阴性对照、单纯抗原组、铝佐剂组和4组甘油-3-磷酸组,分别在免疫之后的第4、8、12、16、20周用酶联免疫法(ELISA)测定小鼠血清中的特异性的anti-HAV IgG水平。结果 在小鼠免疫之后的第4、8、12、16、20周单纯抗原组、铝佐剂组和4组不同剂量甘油-3-磷酸组均能检测到特异性抗HAV抗体,并且趋势为先升高后降低,且在免疫后的第8周最高;第4周和第8周的甘油-3-磷酸实验组的结果均高于单纯抗原组,且差异均具有统计学意义(P<0.05),并且第4周甘油-3-磷酸组抗体水平均超过铝佐剂组,并具有统计学意义(P<0.05),其中甘油-3-磷酸2 mg为最佳剂量组,其抗体水平在免疫后的第4、8、12、16、20周均高于单纯抗原组,且在第8周抗体水平达到峰值,抗HAV IgG水平为lg(3.064±0.07851),铝佐剂的也是在第8周抗体水平达到峰值,抗HAV IgG水平为lg(3.150 ±0.1382)。结论 甘油-3-磷酸有免疫佐剂的作用,能够有效、迅速地增强HAV诱导的体液免疫应答,是一种潜在、安全有效的新型疫苗佐剂。     

Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants

Aluminium adjuvants, typically referred to as 'alum', are the most commonly used adjuvants in human and animal vaccines worldwide, yet the mechanism underlying the stimulation of the immune system by alum remains unknown. Toll-like receptors are critical in sensing infections and are therefore common targets of various adjuvants used in immunological studies. Although alum is known to induce the production of proinflammatory cytokines in vitro, it has been repeatedly demonstrated that alum does not require intact Toll-like receptor signalling to activate the immune system. Here we show that aluminium adjuvants activate an intracellular innate immune response system called the Nalp3 (also known as cryopyrin, CIAS1 or NLRP3) inflammasome. Production of the pro-inflammatory cytokines interleukin-1beta and interleukin-18 by macrophages in response to alum in vitro required intact inflammasome signalling. Furthermore, in vivo, mice deficient in Nalp3, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) or caspase-1 failed to mount a significant antibody response to an antigen administered with aluminium adjuvants, whereas the response to complete Freund's adjuvant remained intact. We identify the Nalp3 inflammasome as a crucial element in the adjuvant effect of aluminium adjuvants; in addition, we show that the innate inflammasome pathway can direct a humoral adaptive immune response. This is likely to affect how we design effective, but safe, adjuvants in the future.     

CD1-restricted T-cell responses and microbial infection

CD1, a conserved family of major histocompatibility (MHC)-like glycoproteins in mammals, specializes in capturing lipid rather than peptide antigen for presentation to T lymphocytes. The principles and mechanisms of this newly discovered immune strategy differ markedly from those governing classical MHC-peptide presentation. They might be exploited for the design of new lipid-based microbial vaccines and adjuvants.     

Chemical glycosylation in the synthesis of glycoconjugate antitumour vaccines

Therapeutic vaccines derived from carbohydrate antigen-adjuvant combinations are a promising approach for cancer immunotherapy. One of the critical limitations in this area is access to sufficient quantities of tumour-associated carbohydrate antigens and glycoconjugate adjuvants. At present, availability of the complex oligosaccharide constructs that are needed for the systematic design and evaluation of novel vaccine formulations relies on de novo chemical synthesis. The use of both state-of-the-art and emerging glycosylation technologies has led to significant advances in this field, allowing the clinical exploration of carbohydrate-based antigens in the treatment of cancer.     

1,25(OH)_2VD_3在过敏原特异性免疫治疗花粉过敏哮喘中的应用

以1,25(OH)₂VD₃为佐剂制备软叶针葵花粉变应原疫苗,以小鼠致敏哮喘模型为研究对象进行特异性免疫治疗.通过检测小鼠气道高反应性、血清中特异性抗体、细胞因子以及肺组织病理学切片等指标对治疗模型的构建进行评价,探讨1,25(OH)₂VD₃在过敏原特异性免疫治疗花粉过敏哮喘免疫机制中的作用.结果表明:以1,25(OH)₂VD₃为变应原疫苗能有效抑制花粉特异性IgE的产生和Th2细胞因子IL-4分泌,促进封闭性抗体IgG2a产生和Th1细胞因子IFN-γ的分泌,增加耐受性细胞因子IL-10生产,使Th2反应向Th1反应转变.1,25(OH)₂VD₃在花粉过敏性哮喘治疗中能大幅提高过敏原特异性免疫治疗的疗效.     

A 2020 vision for vaccines against HIV, tuberculosis and malaria

Acquired immune deficiency syndrome (AIDS), malaria and tuberculosis collectively cause more than five million deaths per year, but have nonetheless eluded conventional vaccine development; for this reason they represent one of the major global public health challenges as we enter the second decade of the twenty-first century. Recent trials have provided evidence that it is possible to develop vaccines that can prevent infection by human immunodeficiency virus (HIV) and malaria. Furthermore, advances in vaccinology, including novel adjuvants, prime-boost regimes and strategies for intracellular antigen presentation, have led to progress in developing a vaccine against tuberculosis. Here we discuss these advances and suggest that new tools such as systems biology and structure-based antigen design will lead to a deeper understanding of mechanisms of protection which, in turn, will lead to rational vaccine development. We also argue that new and innovative approaches to clinical trials will accelerate the availability of these vaccines.     

Foreign peptides displayed on the major coat protein of filamentous bacteriophage

The genome of filamentous bacteriophage can be engineered to display foreign peptides on the surface of the major coat protein. This display system offers an effective approach to researching the immunological recognition of protein. Studies show that this system has several advantages: 1) the specificity of the immune response; 2) the ability to recruit helper T cells; 3) needs no external adjuvants; 4) the structural mimicry of peptide epitopes. These suggest that this technology could be developed into a simple and inexpensive means to produce new biological reagents and vaccines. The development of this technology and the main property of filamentous bacteriophage are introduced in this paper. Some novel results about foreign peptides display using the main coat protein of filamentous bacteriophage are also summarized.     

Humoral and cell-mediated immune responses to live recombinant BCG-HIV vaccines

Several viral and bacterial live recombinant vaccine vehicles are being developed to produce a new generation of vaccines against a broad spectrum of infectious diseases. The human tuberculosis vaccine Mycobacterium bovis bacillus Calmette-Guerin (BCG) has features that make it a particularly attractive live recombinant vaccine vehicle. BCG and other mycobacteria are highly effective adjuvants, and the immune response to mycobacteria has been studied extensively. With nearly two billion immunizations, BCG has a long record of safe use in man. It is one of the few vaccines that can be given at birth, it engenders long-lived immune responses with only a single dose, and there is a worldwide distribution network with experience in BCG vaccination. Recently developed molecular genetic tools and methods for mycobacteria have provided the means to introduce foreign genes into BCG. Here we report that a variety of human immunodeficiency virus type 1 polypeptides can be expressed in BCG recombinants under the control of the mycobacterial hsp70 promoter and that the foreign polypeptides produced in BCG can induce antibody and T-cell responses. These results demonstrate that BCG can be used as a live recombinant vaccine vehicle to induce immune responses to pathogen proteins produced by the bacillus.     

Adjuvant-free IgG responses induced with antigen coupled to antibodies against class II MHC

The generation of strong serological responses to protein antigens in experimental animals usually requires the use of potent adjuvants, most of which cannot be used in human or veterinary vaccines because of deleterious side effects. Attempting to circumvent this problem, we have assessed an adjuvant-free antigen-delivery system based on the hypothesis that antigen coupled to monoclonal antibodies (mAbs) specific for class II major histocompatibility complex (MHC) determinants should be 'targeted' onto antigen-presenting cells, thus facilitating recognition by helper T cells. We found that the biotin-binding protein avidin could generate a serological response in mice, without adjuvant, when injected coupled to a biotinylated anti-class II MHC mAb. Equivalent amounts of avidin mixed with the non-biotinylated form of the same mAb failed to elicit a response. A targeting effect was demonstrated at low levels of injected conjugate because only mice bearing the appropriate class II antigens responded. Responses were also seen with a protein antigen other than avidin, offering a new, adjuvant-free approach to subunit vaccine construction.     

三种重组乙型肝炎疫苗异常毒性检查对动物影响的比较

摘要:目的 观察和比较三种重组乙型肝炎疫苗异常毒性检查对动物体质量增长情况和注射后状态的影响,探讨采用不同药用辅料生产的重组乙型肝炎疫苗检查对动物的影响。 方法 汇总 2016 年 3 月—2018 年 2 月,重组乙型肝疫苗(汉逊酵母 Hansenula ploymorpha) 、 重组乙型肝疫苗( 酿酒酵母 Saccharomyces cerevisiae) 和重组乙型肝炎疫苗( CHO 细胞)的异常毒性检查中的动物体质量和注射后状态情况,采用 IBM SPSS Statistics 23 分析软件进行统计分析。 结果 疫苗的异常毒性检查结果均符合规定。 注射疫苗后,动物均未见异常。 比较空白对照组 ICR 小鼠和三 种 乙 型 肝 炎 疫 苗 给 药 组 ICR 小 鼠 体 质 量 增 长 值, 差 异 没 有 统 计 学 意 义 ( P > 0. 05 ) , 重 组 乙 型 肝 疫 苗( S. cerevisiae)给 药 组 小 鼠 的 体 质 量 增 长 的 平 均 值 大 于 重 组 乙 型 肝 炎 疫 苗 ( CHO 细 胞) 和 重 组 乙 型 肝 疫 苗( H. ploymorpha)给药组小鼠的体质量增长值,差异有统计学意义( P< 0. 05) ;比较空白对照组 Hartley 豚鼠和三种乙型肝炎疫苗给药组 Hartley 豚鼠的体质量增长值,重组乙型肝炎疫苗( CHO 细胞) 组豚鼠与空白对照组豚鼠的差异,有统计学意义( P<0. 05) ,其他两组动物与空白对照组动物的差异无统计学意义( P> 0. 05) ,比较三种疫苗的给药组豚鼠的体质量增长值,差异没有统计学意义( P> 0. 05) 。 结论 本研究中的实验动物一般状态观察未见明显差别,均没有观察到文献记载的因铝佐剂导致的 ICR 小鼠腹膜刺激症状;三种重组乙型肝炎疫苗对 ICR 小鼠给药后 7 d 内的体质量增长值影响不同;对 Hartley 豚鼠给药后 7 d 内的体质量增长值未见明显影响。