乙型肝炎病毒核心DNA疫苗研究进展

第一代乙型肝炎疫苗是从乙型肝炎表面抗原(HBsAg)无症状携带者血清中分离HBsAg颗粒,经灭活后制成的乙型肝炎血源疫苗;第二代乙型肝炎疫苗即为HBSAg基因重组疫苗,该疫苗可诱导体液免疫应答产生中和抗体,但不能诱导细胞免疫应答,     

肝炎病毒基因疫苗研究现状

疫苗按其在传染病防治中的作用,可分为预防性疫苗(prophylactic vaccine)和治疗性疫苗(thera peutic vaccine)。预防性疫苗根据接种对象是否已接触病原体可分为暴露前预防(pre-exposure prophylaxis)和暴露后预防(postexposure prophylaxis)。治疗性疫苗主要用于治疗微生物慢性感染者。后者过去称为主动免疫疗法,现称为疫苗疗法(vaccine therapy),传统的疫苗是应     

DNA疫苗

在所有基因疗法中，不论是把病人先天缺失的基因导入体内以纠正病人的缺陷，或把侵入体内的病毒用“相反”的基因（反意ＤＮＡ）消除，或者用能干扰病毒复制的变异株基因片断导入以抑制病毒复制（优势负性变异株法，ｄｏｍｉｎａｎｔｎｅｇａｔｉｖｅｍｕｔａｎｔｓ）等都...     

DNA疫苗诱导小鼠特异性细胞免疫及抗乙型肝炎病毒皮下移植瘤的研究

目的观察乙型肝炎病毒(HBV)DNA疫苗(pCR3 1-S)诱导Balb/c小鼠(H-2d)的特异性细胞免疫应答及其对稳定表达HBsAg的小鼠肥大细胞瘤P815细胞(P815 HBV-S)(H-2d)成瘤性的影响.方法肌肉注射DNA疫苗,背部皮下接种P815-HBV S细胞,观察成瘤情况,4h 51Cr释放法检测小鼠脾细胞细胞毒T细胞(CTL)杀伤活性.结果DNA疫苗可以降低成瘤率,抑制肿瘤生长,延长小鼠平均存活期,提高小鼠存活率.CTL细胞杀伤活性明显增加(P＜0.001).结论DNA疫苗可以诱导细胞免疫应答,对体内HBV感染可能具有预防及治疗作用.     

乙型肝炎病毒复制调控元件对HBV DNA疫苗诱导的免疫应答

目的研究乙型肝炎病毒（HBV）复制调控元件增强子Ⅰ（ENHⅠ）及前S2（Pre-S2）抗原基因对HBV DNA疫苗诱导的免疫应答的影响。方法采用常规聚合酶链反应（PCR）从HBV adr亚型全基因DNA序列中分别扩增HBsAg、PreS2-HBsAg、HBsAg-ENHI和PreS2-HBsAg-ENHⅠ基因片段，重组到VR1012载体中，构建4种HBV DNA疫苗，转染HepG2细胞并免疫Balb／C小鼠。通过细胞免疫化学、酶联免疫分析（ELISA）、酶联免疫斑点试验（ELISPOT）等方法检测其在HepG2细胞内的表达及小鼠的体液及细胞免疫应答。结果转染的HepG2细胞表达相应的目的蛋白．ENHⅠ及Pre-S2抗原基因均可增强HBV DNA疫苗转染HepG2细胞表达HBsAg；免疫接种小鼠后第2周产生抗-HBs及HBsAg特异性细胞毒T淋巴细胞（CTL），Pre—S2抗原基因可增强HBV DNA疫苗免疫Balb／C小鼠诱导的抗-HBs及HBsAg特异性CTL的产生，ENHⅠ基因对免疫应答无影响。结论ENHI及Pre—s2抗原基因均可增强HBVDNA疫苗转染HepG2细胞表达HBsAg．Pre-S2抗原基因可增强HBVDNA疫苗免疫Balb／C小鼠引起的免疫应答。     

DNA芯片技术检测乙型肝炎病毒及丁型肝炎病毒的初步研究

现分别针对乙型肝炎病毒（HBV），丁型肝炎病毒（HDV）基因保守区域设计多对聚合酶链反应（PCR）引物，打印制备成芯片，并用限制性显示（RD）技术标记样品，探索此方法制备基因芯片的可行性。     

疟疾的DNA疫苗

疟疾是世界上最严重的寄生虫病之一 ,全球每年发病人数达 3～ 5亿 ,其中 10 0～ 2 0 0万人死于此病。疟疾的感染和发病主要发生在发展中国家 ,特别是儿童 ,同时也给进入疫区的商人、游客和军队的部署构成严重的威协。随着疟原虫对抗疟药物的耐药性以及按蚊对杀虫剂耐药性的增加 ,近年 ,疟疾的发病率和死亡率又有增加的趋势。因此迫切需要研究有效的疟疾疫苗。从射线减毒原虫疫苗 ,到后来发展起来的亚单位疫苗 ,虽然取得了一些进展 ,但至今仍没有可推广应用的疟疾疫苗 [1 ] 。 DNA疫苗的出现给研制有效的疟疾疫苗带来了新的希望。DNA疫苗…     

丙型肝炎病毒包膜基因对核心基因DNA疫苗免疫应答强度的影响

目的 研究丙型肝炎病毒(HCV)包膜基因E1E2对核心基因C DNA疫苗诱生的免疫应答作用。方法 将包含HCV C或CE1E2基因片段插入真核表达载体pcDNA3中,构建重组质粒pHCV-C或pHCV-CE1E2,分别免疫Balb/c小鼠,每间隔2wk加强免疫1次,同时剪尾取血。ELISA法检测免疫小鼠血清中HCV C特异性抗体的水平。以pHCV-C转染并表达HCcAg的BLAB/c小鼠骨髓瘤Sp4/0细胞为靶细胞,采用~(51)Cr释放试验检测特异性CTL的杀伤作用。结果 两个实验组20只小鼠均产生抗HCV C特异性抗体,当效/靶细胞比例为100:1时,CTL的杀伤率均明显高于对照组(p<0.01);而pHCV-CE1E2与pHCV-C组之间,无论是抗HCV C抗体的滴度还是CTL的杀伤率均无显著性差异(p>0.05)。结论 E1E2基因的加入,并没有增加HCV C基因DNA疫苗诱导的抗HCcAg特异性抗体的滴度和CTL的杀伤作用。     

关于丙型肝炎病毒疫苗的前景

问：抗HCV疫苗的前景如何？ 答：在过去的20年中，关于抗病毒性肝炎疫苗的发展已有了很大的进步。尤其是安全和有效的抗HBV疫苗已使用大约20年了，并且在大多数国家中从婴儿开始接种已成为一种常规。同样安全和有效的抗甲肝疫苗也很有作用，尽管该疫苗不推荐全部婴儿接种但可广泛使用在具有甲肝病毒感染风险的旅行者和其他个体中。     

乙型及丙型肝炎病毒受体的研究

0引言关于病毒受体的研究开展较早,已知的EB病毒受体?人免疫缺陷病毒(HIV)受体与共受体均为该方向的研究范围.在嗜肝病毒受体的研究领域中,也已取得了一定成绩,但却无最终定论.乙型和丙型肝炎呈全球分布,目前全世界有1.7亿人感染丙型肝炎病毒(HCV),3.5亿人感染乙型肝炎病毒(HBV),其中相当一部分感染者发展为慢性肝炎,少数还发展成肝硬化甚至肝癌,对人类健康造成极大危害,至今缺乏有效的控制.病毒粘着?并进一步侵入肝细胞是感染启动的关键一步,这两种病毒的细胞作用受体一直是研究者们关注的重点,本文简要介绍近年来在这方面的研究进展.…     

寄生虫病DNA疫苗研究进展

寄生虫病防治策略之一是研制安全有效的疫苗,DNA疫苗是近10多年发展起来的新型疫苗。近年来寄生虫病DNA疫苗研究取得了很大进展。本文就DNA疫苗的免疫机理、构建与优化、佐剂、递送途径,以及疟疾、血吸虫病、囊尾蚴病、弓形虫病等重要寄生虫病DNA疫苗的研究进展作一综述。     

Progress in the development of vaccines for hepatitis C virus infection

The hepatitis C virus(HCV), first described in 1989, is now a leading cause of liver cirrhosis and hepatocellular carcinoma. With more than 170 million people infected globally, this virus is a major public health issue. The current standard therapy is based on interferon in combination with ribavirin. This costly therapy often fails to completely clear the infection and is associated with adverse side effects. Recent anti-HCV therapies are interferon-free direct-acting antiviral(DAA) regimens for HCV, including simeprevir, sofosbuvir, and ledipasvir, which have effects on non-structural proteins. DAA regimens have several advantages, such as specifically targeting HCV viral replication, accompanied by very high sustained virological response rates and lower side effects like flu-like syndrome. These facts plus the fact that most HCV cases progress to chronic infection suggest the potential need for an efficient HCV vaccine. Different innovative methods, including methods based on peptide, recombinant protein, DNA, vector-based, and virus-like particles, have been introduced for the development of HCV vaccines. An extensive number of studies have been published on these vaccines, and some vaccines were even tested in clinical trials. In the current review, progress in the development of preventive and therapeutic vaccines against the HCV is reviewed in the context of peptide vaccines, recombinant protein vaccines, HCV-like particle, DNA vaccines and viral vectors expressing HCV genes.     

血吸虫病DNA疫苗联合免疫研究进展

血吸虫病是严重危害人类健康的人兽共患寄生虫病，疫苗是预防控制血吸虫病的重要手段。为提高血吸虫病疫苗的免疫效果，国内外通过不同抗原基因的连接、不同疫苗抗原的组合或从噬菌体肽库中筛选到若干个不同抗原表位的混合等途径，来实现复合疫苗或多种单一疫苗的联合免疫，并取得较好的成果。     

Progress in the development of preventive and therapeutic vaccines for hepatitis C virus

Hepatitis C virus (HCV) is a blood borne disease estimated to chronically infect 3% of the worlds' population causing significant morbidity and mortality. Current medical therapy is curative in approximately 50% of patients. While recent treatment advances of genotype 1 infection using directly acting antiviral agents (DAAs) are encouraging, there is still a need to develop vaccine strategies capable of preventing infection. Moreover, vaccines may also be used in future in combination with DAAs enabling interferon-free treatment regimens. Viral and host specific factors contribute to viral evasion and present important impediments to vaccine development. Both, innate and adaptive immune responses are of major importance for the control of HCV infection. However, HCV has evolved ways of evading the host's immune response in order to establish persistent infection. For example, HCV inhibits intracellular interferon signalling pathways, impairs the activation of dendritic cells, CD8(+) and CD4(+) T cell responses, induces a state of T-cell exhaustion and selects escape variants with mutations CD8(+) T cell epitopes. An effective vaccine will need to produce strong and broadly cross-reactive CD4(+), CD8(+) T cell and neutralising antibody (NAb) responses to be successful in preventing or clearing HCV. Vaccines in clinical trials now include recombinant proteins, synthetic peptides, virosome based vaccines, tarmogens, modified vaccinia Ankara based vaccines, and DNA based vaccines. Several preclinical vaccine strategies are also under development and include recombinant adenoviral vaccines, virus like particles, and synthetic peptide vaccines. This paper will review the vaccines strategies employed, their success to date and future directions of vaccine design.     

DNA vaccines

BACKGROUND AND OBJECTIVES: Humoral and cellular immune responses to protein antigens can be efficiently primed by nucleic acid or DNA vaccination. In DNA-based vaccination, immunogenic proteins are expressed with correct posttranslational modification, conformation or oligomerization; this ensures the integrity of epitopes that stimulate neutralizing antibody (B cell) responses. DNA (or RNA) immunization is exceptionally potent in stimulating T cell responses because antigenic peptides are efficiently generated in (endogenous or exogenous) processing pathways (without interference by viral proteins) from intracellular or extracellular protein antigens expressed after transient in vivo transfection. Both features are difficult to achieve with recombinant subunit vaccines produced in eukaryotic or prokaryotic expression systems. The current state of vector designs, strategies for delivery of DNA vaccines, priming humoral and cellular immune responses by DNA vaccines, experimental strategies facilitated by DNA vaccines, unique advantages of DNA vaccination, experience of DNA vaccination in preclinical animal models and clinical trials, and potential risks of DNA vaccination are discussed. Excellent reviews on DNA-based vaccination have been published recently [1-3].     

Safety of hepatitis B vaccines

Although concerns about vaccine safety have increased, true adverse reactions associated with hepatitis B vaccines are few, apart from minor symptoms at the site of injection and occasionally systemic reactions. There is no evidence of an association with hepatitis B vaccination and Sudden Infant Death Syndrome, Multiple Sclerosis and the Chronic Fatigue Syndrome. Hepatitis B vaccines are safe and essential for the prevention of this important and common infection.     

慢性乙型肝炎治疗性疫苗的研究进展

治疗性疫苗能激发和诱导机体对某些抗原,如肿瘤抗原、病毒抗原的特异性免疫应答,为肿瘤、慢性感染性疾病、自身免疫性疾病的治疗提供了新方法。据美国国家卫生研究院(NIH)临床试验数据库统计,目前已有347种治疗性疫苗进入了临床试验阶段,其中乙肝治疗性疫苗是近年来研发的热点,兹就其研究作一概述。     

The GB hepatitis viruses

Summary. The genomes of three new flavi-like viruses, GBV-A, GBV-B and GBV-C have been identified. Nucleic acid molecules corresponding to the genomes of GBV-A and GBV-B were isolated from tamarins with hepatitis which had been infected with the GB agent. RNA sequences corresponding to GBV-C have been shown to be present in sera from humans with non-A-E hepatitis. Sequence comparisons show that these three viruses are more closely related to each other and to hepatitis C virus (HCV) than to any other known viruses. Together with HCV they appear to form a discrete cluster of related viruses within the larger genus of flaviviridae. The pathological significance of these viruses and their association with hepatitis is currently emerging.