日本血吸虫多价DNA疫苗pBK—Sj26（Sj32）—Sj23免疫效果的观察

为了观察血吸虫病多价DNA疫苗的保护力,将小鼠分成5组：空白对照组、空质粒对照组、单价抗原DNA疫苗pBK-CMV-Sj23组、多价抗原DNA疫苗pBK-CMV-Sj26-Sj23和pBK-CMV-Sj32-Sj32组。大量提取各组质粒DNA后,各组于0、3、5周在BALB／c小鼠股四头肌注射相应质粒DNA,9周用血吸虫尾蚴攻击感染,15周剖杀小鼠计算减虫率及减卵率。结果显示：与对照组比较,实验组小鼠减虫率及减卵率及极显著性差异（P＜0.01）;与单价pBK-CMV-Sj23组比较,多价DNA疫苗组的减虫率及减卵率有显著性差异,提示血吸虫多价DNA疫苗诱导小鼠对血吸虫的保护力优于单价DNA疫苗。     

日本血吸虫多价DNA疫苗pBK-Sj26(Sj32)-Sj23免疫效果的观察

为了观察血吸虫病多价DNA疫苗的保护力,将小鼠分成5组空白对照组、空质粒对照组、单价抗原DNA疫苗pBK-CMV-Sj23组、多价抗原DNA疫苗pBK-CMV-Sj26-Sj23和pBK-CMV-Sj32-Sj23组.大量提取各组质粒DNA后,各组于0、3、5周在BALB/c小鼠股四头肌注射相应质粒DNA,9周用血吸虫尾蚴攻击感染,15周剖杀小鼠计算减虫率及减卵率.结果显示与对照组比较,实验组小鼠减虫率及减卵率有极显著性差异(P<0.01);与单价pBK-CMV-Sj23组比较,多价DNA疫苗组的减虫率及减卵率有显著性差异.提示血吸虫多价DNA疫苗诱导小鼠对血吸虫的保护力优于单价DNA疫苗.     

弓形虫复合基因疫苗研究进展

弓形虫疫苗包括全虫疫苗、虫体特异组分疫苗、DNA 疫苗、基因工程疫苗,现阶段研究较多的是后两种,由原来的单一疫苗向复合疫苗发展,复合疫苗有多种联合方式：表面抗原联合、表面抗原与分泌抗原联合、其他类型抗原联合,疫苗免疫效力低下的缺点可采用有效免疫方式或使用佐剂提高效果。     

结核病DNA疫苗的研究进展

结核病是由结核分枝杆菌感染引起的世界性传染病。我国是世界上结核病发病率最高的22个国家之一,结核病患病人数仅次于印度,位居第二。卡介苗是目前唯一应用于结核的预防性疫苗,但对于成人肺结核的保护效力十分有限,再加上自身的不足以及外界因素的变化,研制新型的结核疫苗迫在眉睫。该文将对结核病传统和新型的单价DNA疫苗的研究进展进行综述。     

变形链球菌表面蛋白和葡糖基转移酶基因疫苗对唾液变形链球菌和牙菌斑的影响

目的　了解变形链球菌表面蛋白和葡糖基转移酶基因疫苗单独及联合免疫对定菌鼠唾液变链菌和牙面菌斑的影响。方法　 2 8d龄 Wistar大鼠 3 6只 ,随机分为 pc DNA3 - pac组、pc DNA3 - gtf B组、pc DNA3 - pac联合pc DNA 3 - gtf B组、变形链球菌灭活全菌组、pc DNA3空载体组和 PBS液组 ,进行三次双侧颌下腺腺周注射免疫 ,建立定菌鼠模型 ,作诱龋实验 3个月。唾液变链菌计数和菌斑计分。结果　唾液变链菌菌落计数和牙面菌斑计分在 pc D-NA3与 PBS组最高 ,其次为单基因疫苗免疫组 ,联合基因疫苗和灭活全菌细胞免疫组最低 ,各组间有显著性差异 ( P<0 .0 5 )。结论　 pc DNA3 - gtf B和 pc DNA3 - pac具有明显的免疫抑菌作用 ,联合基因疫苗免疫优于单基因疫苗     

DNA疫苗的结构与免疫应答的关系

DNA疫苗已被广泛用于抗病毒、 抗细菌、 抗寄生虫及抗肿瘤的研究。近几年研究表明, 虽然DNA疫苗具有广泛的优越性, 但免疫效果还不够理想、 均一。如何优化DNA疫苗的结构, 诱导机体产生理想的免疫应答, 成了目前最主要的课题。本文对近年DNA疫苗结构与功能的关系作一综述。一、 DNA疫苗的基本结构DNA疫苗是能在机体细胞内复制, 并表达出目的基因产物, 刺激机体产生保护性免疫的环状裸DNA。在结构上, 主要由载体DNA和目的基因DNA二部分组成。载体DNA可由细菌质粒DNA、 噬菌体DNA及病毒DNA或cDNA改造而成, 其结构上…     

日本血吸虫Rho GTPaseDNA及重组蛋白免疫保护效果研究

目的研究日本血吸虫中国大陆株Rho家族小分子G蛋白(Sj-Rho GTPase)DNA疫苗及重组蛋白疫苗免疫保护效果.方法将pcDNA3.1-SjRho GTPase DNA疫苗和pGEX-5X-3原核载体所表达的重组蛋白疫苗三次分别或联合免疫昆明鼠,3周后,每鼠感染40条尾蚴,42 d后剖杀小鼠,记数成虫和肝脏虫卵数. 结果与佐剂或空白质粒对照组相比,DNA疫苗、重组蛋白疫苗及联合免疫分别获得22.16%(P<0.01)、18.71%(P<0.05)和39.20%(P<0.001)的减虫率以及34.55%、20.07%和49.55%(P<0.001)的肝组织减卵率.结论 Sj-Rho GTPase DNA疫苗及重组蛋白疫苗均可诱导小鼠产生一定的免疫保护作用,且联合免疫方案保护效果好于单一疫苗.     

基因疫苗在肿瘤免疫治疗中的研究进展

肿瘤的治疗目前仍是世界性的难题,随着免疫学和分子生物学的发展,肿瘤疫苗的发展经历了肿瘤细胞疫苗、重组蛋白疫苗和基因疫苗三个阶段。肿瘤基因疫苗也称DNA疫苗,是目前研究的热点,主要包括与肿瘤相关抗原（TAAs）有关的全长、表位、独特型（Id）和融合DNA疫苗,能够自主复制的RNA疫苗,与树突细胞（DCs）相关的肿瘤基因疫苗等。近年来,肿瘤基因疫苗在动物基础研究和临床前研究,     

乙型肝炎DNA疫苗研究进展

DNA疫苗也有基因疫苗、核酸疫苗、DNA免疫、基因免疫等各种名称和相关概念.有人将DNA疫苗称为第三代疫苗.第一代疫苗以Jenner用牛痘预防天花为代表,人类从此开始摆脱许多疾病的困扰.第二代疫苗是运用基因重组技术,以特定的基因表达产生的抗原作为疫苗,重组乙型肝炎疫苗就是典型例子.DNA疫苗则是将编码目的抗原的基因与载体重组以后,经不同途径将基因直接转入机体细胞内,利用宿主细胞内的表达加工机构合成抗原,从而激发体液免疫和细胞免疫.近年来,DNA疫苗在打破HBV慢性感染的免疫耐受方面取得了一定的进展,对乙型肝炎及HBV无症状携带状态的临床治疗提供了值得探索的新途径.     

HIV疫苗实验研究的现状

目的研制免疫原性好、安全性高、有效的疫苗是控制HIV传播感染的重要手段之一。我国学者也开展了不同疫苗的研制工作，取得一定的效果。本文主要描述了HIV疫苗的两个种类，即预防性疫苗和治疗性疫苗，包括采用传统疫苗技术研制的减毒活疫苗和灭活疫苗以及采用现代生物技术研制的重组蛋白疫苗、DNA疫苗、病毒载体疫苗等，以期对疫苗研究开发提供思路和参考。     

Immunogenicities of Env glycoproteins from circulating HIV-1 isolates in China focusing on the strategy of ＂DNA prime plus protein boost＂

Background The adenovirus-based HIV-1 vaccine developed by Merck Company suffered from an unexpected failure in September 2007. This generated a big shift in the strategy of HIV vaccine development with renewed focus on the induction of neutralizing antibodies. A major challenge in developing an HIV-1 vaccine is to identify immunogens and adopt delivery methods that can elicit broadly neutralizing antibodies against primary isolates of different genetic subtypes. Methods Most circulating HIV-1 isolates in China are composed of clades Thai-B, CRF_BC and CRF01_AE. In order to construct DNA vaccines against these 3 HIV-1 subtypes, DNA vaccines carrying the gp120 regions from HIV-1 isolates of GX48（AE）, GX79（AE）, NX22（BC）, GS22（BC）, HN24（Thai-B） were constructed. Expression of gp120 from these DNA vaccines was detected by Western blotting in transiently transfected 293T cells. Pilot immunizations of New Zealand white rabbits were performed using the strategy of ＂DNA prime plus protein boost＂ and the neutralizing antibody response was detected in a Tzm-bl cell based assay against different HIV-1 strains. Results Response of gp120-specific antibody was relatively low after DNA primes （mean titer=10^4.72）; however, the titer of gp120-specific antibody went up with 2 protein boosts （mean titer=10^6.81）. Above all, neutralizing antibody （Nab） titers induced by this combined approach were much better than those elicited by DNA or protein used alone （P 〈0.01）. Neutralizing activities of immunized rabbit sera against several pseudoviruses and laboratorial strains were evaluated, most rabbit sera primed with monovalent vaccine were capable of neutralizing only 1 of 5 viruses, however, sera primed with the polyvalent DNA vaccines were able to neutralize at least 2 of 5 viruses. Conclusion Polyvalent DNA prime plus protein boost is an effective immunization strategy to broaden the neutralization breadth and further research should be performed on the basis of this pilot study.     

日本血吸虫复合DNA疫苗的组织表达及免疫保护效果研究

目的 :观察本课题组所构建日本血吸虫大陆株复合DNA疫苗VR10 12 SjGST和VR10 12 SjGST Sj32在小鼠肌肉组织中的表达 ,并进行免疫保护效果测定。方法 :用纯化质粒免疫昆明鼠 :4 8只小鼠分为 4组 ,两个对照组的小鼠分别于股四头肌注射生理盐水 10 0 μl或空质粒VR10 12 10 0 μg,两个实验组的小鼠则同法分别注射VR10 12 SjGST和VR10 12 SjGST Sj32各 10 0 μg。末次免疫后 ,每组解剖两只小鼠 ,以间接免疫荧光法观察SjGST、Sj32在肌肉组织中的表达。其余每只鼠经腹部感染 10条尾蚴 ,4 5d后剖杀计数各小鼠成虫数和肝卵数。结果 :小鼠肌肉组织表达出抗原特异性蛋白质抗原分子。与生理盐水组比较 ,两个实验组的减虫率分别为 33.9%和及 2 7.14 %(均为P <0 .0 5 ) ,减卵率分别为 6 1.86 %和 6 8.87% (均为P <0 .0 0 1)。与VR10 12 SjGST组相比 ,VR10 12 SjGST Sj32组的减卵率为 18.5 1% (P <0 .0 5 )。结论 :DNA疫苗VR10 12 SjGST和VR10 12 SjGST Sj32能在组织中正常表达 ,能诱导小鼠产生一定水平的抗日本血吸虫感染保护作用 ,复合疫苗的保护效果要大于单价疫苗     

全球乙型肝炎疫苗研发分析

世界上大多数国家都制定了乙型肝炎(乙肝)免疫计划,这为预防性乙肝疫苗的研发提供了导向.从第一代血源性疫苗到重组乙肝疫苗,再到合成肽疫苗和DNA疫苗,乙肝疫苗的研制技术不断进步,其应用范围也已从预防扩展到治疗.本文分析了各国乙肝免疫计划与乙肝疫苗研发的关系,总结了预防性和治疗性乙肝疫苗的研发思路,并提出乙肝疫苗进一步研发的方向.     

艾滋病疫苗的研究进展

HIV疫苗研制的困难在于HIV病毒的高度遗传变异.根据已发现的10种亚型HIV-1型病毒研制的能激发CTL的新疫苗,已证实在临床上有了实际的应用效果.目前的疫苗研制策略包括质粒DNA载体,活重组载体和联合疫苗等.本文着重介绍这几种艾滋病疫苗的研究现状和存在的问题.     

略述疫苗三次革命

自我们的祖先发明人痘、琴纳（Jenner）发明牛痘到今天,疫苗在防治许多疾病中的功绩已为世人所公认.1995年美国纽约科学院召开专门研讨脱氧核糖核酸（DNA,以下简称核酸）疫苗会议,称之为疫苗学的新纪元和疫苗的第三次革命.第一次疫苗革命是19世纪末以巴斯德（Pasteur）为代表的灭活疫苗和减毒活疫苗.第二次疫苗革命是20世纪80年代采用核酸重组技术和蛋白化学技术制备的亚单位疫苗.     

Guillain-Barré syndrome in recipients of A/New Jersey influenza vaccine

In late 1976, when 32% of the eligible population of Ohio received the A/New Jersey influenza (swine flu) vaccine, systematic contact of neurologists was used to evaluate the possible association of Guillain-Barré syndrome (GBS) with receipt of the vaccine. The overall rate of GBS was significantly higher among vaccine recipients (13.3/10(6)) than in nonrecipients (2.6/10(6)). Peak time of onset was two to three weeks after receiving the vaccine, and cases among vaccinees were less likely to have a history of antecedent infection than were cases in unvaccinated persons. Even when the effect of one highly associated vaccine lot was removed, an elevated risk of GBS remained in vaccinees regardless of manufacturer or vaccine type (bivalent or monovalent). Systematic surveillance is needed for rare serious reactions from all vaccines.     

A new subunit influenza vaccine; acceptability compared with standard vaccines and antigenicity in increasing dosage

Subunit influenza vaccines have the advantage of purity and a broad dosage range. Clinical studies were done with a new subunit vaccine produced by detergent fractionation with tri-(n-butyl) phosphate (TNBP). Acceptability by the recipients was compared in volunteers given 400 CCA units of A₂ and 300 of B Influenza vaccine as either Sharples, zonal centrifuged, ether subunit, or TNBP subunit bivalent vaccines. When given subcutaneously, subunit vaccine caused only slightly less pain and erythema induration than zonal or Sharples vaccine. Compared with the i.m. route, the same vaccine given subcutaneously produced twice the local pain and eight times the erythema induration. Fever was infrequent and low grade by either route. HI antibody rises were good in all groups. Increasing dosages of TNBP vaccine up to 6400 CCA units of A₂ and 4800 of B given i.m. as monovalent vaccine, produced no local and few febrile responses. An augmentation of the antibody titre occurred with the highest CCA unit dosages. Subunit vaccine given i.m. permitted administration of high CCA unit dosage beyond that accepted for standard vaccine without any increase in local reactions and with a measurable increase in antibody production and the induction of antibodies against related heterologous strains.     

Current trends in tuberculosis vaccine

Despite the global efforts made to control tuberculosis (TB) and the large number of available new anti-TB drugs, TB still affects one-third of the world population. The conventional vaccine bacille Calmette–Guérin (BCG) shows varying efficacy in different populations, and there are safety issues in immunocompromised patients. Hence, there is an urgent requirement for a new and better TB vaccine candidate than BCG. There are several alternate vaccines available for TB such as DNA, subunit, adjuvant, and live-attenuated vaccines. Use of auxotrophic vaccine is an emerging technology. Newer vaccine technologies include vaccine delivery methods such as adenovirus- and cytomegalovirus (CMV)-based vector delivery, chimeric monoclonal antibody, single-chain fragment variable, RNA-lipoplexes, and nanoparticle-based technology. Based on its application, TB vaccines are classified as conventional, prophylactic, booster, therapeutic, and reinfection preventive vaccines. Currently, there are 12 vaccine candidates in clinical trials. In this review, we have briefly discussed about each of these vaccines in different phases of clinical trials. These vaccines should be analyzed further for developing a safe and more efficacious vaccine for TB.     

肿瘤疫苗及其增强策略

肿瘤疫苗是利用肿瘤抗原激发机体自身的免疫保护机制达到防治肿瘤的目的,近来肿瘤疫苗已发展成为一种重要的肿瘤生物治疗手段本文根据肿瘤疫苗的常见种类,从细胞载体肿瘤疫苗、肿瘤多肽疫苗、肿瘤基因疫苗以及抗独特型抗体肿瘤疫苗等方面对肿瘤疫苗的设计原理、增强策略的研究进展作一综述。