弓形虫SAG1,ROP1基因及其复合抗原基因的核酸免疫研究

目的 检测混合SAG1和ROP1编码基因真核表达质粒疫苗诱导小鼠的免疫应答,评价其抗弓形虫感染的保护性免疫效果.方法 将SAG1和编码基因片段克隆入pEGFP-N3表达载体,构建重组质粒;RT-PCR体外验证重组质粒在NH3T3细胞中的表达;通过检测抗体、抗体分型及细胞因子来评价体液免疫和细胞免疫;腹腔内注射毒性株弓形虫速殖子攻击免疫小鼠.结果 RT-PCR结果显示重组质粒能在哺乳动物细胞内表达;SAG1和ROP1混合重组质粒疫苗诱导小鼠产生很强的体液免疫和细胞免疫,对于毒性株弓形虫感染攻击具有保护作用.结论 不同候选抗原编码基因重组质粒能够诱导小鼠产生抗弓形虫感染保护性免疫,提示含有多种成分的混合DNA疫苗的研制可作为核酸免疫研究的策略之一.     

DNA疫苗在动物医学中的应用

DNA疫苗是继减毒疫苗、灭活疫苗、亚单位疫苗和重组多肽疫苗之后的又一新型疫苗,比其它疫苗高效、安全且易于大量生产。本文对DNA疫苗在牛、猪和鸡一些病毒病上的使用效果及其安全问题等方面的研究近况作一综述。     

国外科技期刊亮点

首次拍摄到HIV扩散过程近日美国加州大学戴维斯分校和西奈山医学院Wolfgang Hübner,Benjamin K.Chen等首次拍摄到HIV在人体内的扩散,发现HIV病毒以一种未知方式从感染细胞转移到健康细 胞。这是在HIV扩散过程方面所取得的重大突破，将有助于研发出可以对抗已导致2500万人死亡的HIV疫苗。     

分子生物学技术在SARS诊治中的应用价值

非典是由于SAPS病毒的感染而引起的,因而可针对其基因序列,利用分子生物学技术对其进行诊治,还可利用重组DNA技术和转基因动植物技术来改造SAPS病原体或有关收蛋白成分,研究出各种基因工程疫苗。     

程序性细胞死亡与艾滋病

1.引言 艾滋病(AIDS)是由人类免疫缺陷病毒(HIV)感染引起的一种以细胞免疫功能缺陷为特征的复杂综合征,其发生机制极为复杂,主要包括:(1)HIV感染细胞与未感染细胞融合为合胞体;(2)HIV对T_H细胞的选择性感染和破坏;(3)HIV引起免疫病     

小鼠结核分枝杆菌感染模型用于评价重组HBHA疫苗免疫效果的实验研究

目的通过复制小鼠结核病模型评价重组HBHA疫苗的免疫效果。方法将重组肝素结合血凝素(HBHA)疫苗接种BALB/c小鼠,观察其诱导的细胞免疫应答水平,并以MTB H37Rv毒株攻击免疫小鼠,研究重组疫苗诱导的保护力。结果重组HBHA免疫BALB/c小鼠后可诱发细胞毒作用,将体内MTB裂解。重组疫苗不仅能刺激CD4+T,CD8+T增殖、活化,还可诱导脾细胞分泌IFN-γ、IL-2等细胞因子。H37Rv毒株攻击后,被免疫小鼠的组织病理学症状减轻。结论本研究通过检测小鼠体内细胞免疫应答和肺脏组织病理学改变等指标,客观的反映了重组疫苗免疫小鼠结核模型的保护效果。     

含抗HIV广谱中和抗体2F5、4E10靶基因载体的构建及鉴定

目的:构建含HIV gp120,gp41序列中广谱中和抗体2F5,4E10作用靶基因的载体并进行鉴定,为后期重组载体表达产物诱导产生中和抗体及抗HIV亚单位疫苗的研究奠定基础.方法:根据NCBI中HIV gp120,gp41基因序列中可与2F5、4E10结合的区域设计引物并进行PCR反应,将PCR得到的目的片段插入到载体pET28a中,对重组载体进行PCR鉴定、酶切鉴定及DNA测序.结果:PCR鉴定、酶切鉴定及DNA测序结果证实重组载体构建成功.结论:成功构建了含HIV gp120,gp41序列中广谱中和抗体2F5,4E10作用靶基因的载体.     

艾滋病疫苗的研究进展

2005年初,在全球六大州19个国家共有35个艾滋病疫苗候选进入了人体早期临床实验。选用的抗原一般均着眼于诱导细胞免疫和体液免疫双重效果。从疫苗的存在形式上看,可供选择的HIV候选疫苗包括下列几种:传统疫苗(灭活疫苗和减毒活疫苗)、合成肽和蛋白亚单位疫苗、DNA疫苗以及活载体疫苗。目前新型疫苗研究策略包括抗原改造加强免疫原性、免疫佐剂协同以提高疫苗免疫反应强度;新型免疫策略包括初免/加强免疫策略和粘膜免疫策略。由于粘膜感染是艾滋病病毒感染的主要途径之一,因而,探索经粘膜免疫是未来疫苗发展的重要方向。中国艾滋病疫苗研究领域的现状是挑战与机遇并存,需要相关领域专家的共同努力,以促进我国艾滋病疫苗研究的发展。     

基因工程疫苗的研究进展

随着分子生物学及重组DNA技术的发展,基因工程疫苗的研究不断深入,传统疫苗已体现出诸多缺陷,利用基因工程开发新疫苗是当前解决这个问题的最好途径之一.目前开发的主要有基因工程亚单位疫苗,基因工程活载体疫苗、核酸疫苗、合成肽疫苗、转基因植物可食疫苗、抗独特型疫苗等.本文对新型疫苗发展方向及进展情况作以综述.     

第四代人类免疫缺陷病毒HIV(Ⅰ+Ⅱ)型抗体酶免检测试剂

<正> 该项成果属于现代生物技术方面免疫生物工程领域。艾滋病由一种嗜人类淋巴细胞病毒感染而引起的疾病,该病传播快,死亡率极高。迄今尚无特效的药物及疫苗来治愈和预防该病。切断其传播途径是防治该病传播的可行有效的措施。艾滋病病毒(人类免疫缺陷病毒,缩写“HIV”)检测盒是我们诊断HIV感染和杜绝经血液     

pH-responsive vaccine delivery systems for improving cellular immunity

Immune vaccination is a critically important strategy in disease prevention and treatment. In vaccination, efficient vaccine carriers are necessary to augment the immune response initiated by vaccines generally with weak immunogenecity. Nowadays, commercially available vaccine/carrier formulations induce effective humoral immunity but weak or none cellular immunity. However, in practice, cellular rather than humoral immunity plays the key role in treating some intractable diseases such as AIDS and cancers, in which the elicited cytotoxic T lymphocytes can directly kill HIV-infected or cancer cells. To trigger potent cellular immunity, the carriers should help antigens escape from endosomal/lysosomal degradation and release them directly into the cytosol of antigen presenting cells. To this aim, such kind of vaccine carriers should be rationally designed and prepared in terms of their structure and physiochemical properties. Here, we summarized the recent advances in pH-responsive vaccine carriers exclusively developed for improving cellular immunity.     

免疫系统人源化小鼠模型的现状及应用

摘要: 实验动物模型在医学生命科学发展中发挥着重要作用。某些病原微生物仅仅特异对人类具有易感性及致病 性。由于缺乏理想的实验动物模型限制了人们对疾病发病机理的理解及预防治疗。因动物种属差异,许多对小鼠 有效的药物及疫苗不能有效地用于人类疾病的治疗或预防。通过将人的胚胎胸腺、造血干细胞等移植到免疫缺陷 小鼠可有效地建立人类天然与适应性免疫系统,即免疫系统人源化小鼠。该小鼠的成功建立为免疫系统相关疾病 研究及免疫药物研发提供了良好实验模型。本文主要对免疫系统人源化小鼠模型的建立、发展及其在感染等研究 中的应用进行简要综述。     

Development of a preventive vaccine for Ebola virus infection in primates

Outbreaks of haemorrhagic fever caused by the Ebola virus are associated with high mortality rates that are a distinguishing feature of this human pathogen. The highest lethality is associated with the Zaire subtype, one of four strains identified to date. Its rapid progression allows little opportunity to develop natural immunity, and there is currently no effective anti-viral therapy. Therefore, vaccination offers a promising intervention to prevent infection and limit spread. Here we describe a highly effective vaccine strategy for Ebola virus infection in non-human primates. A combination of DNA immunization and boosting with adenoviral vectors that encode viral proteins generated cellular and humoral immunity in cynomolgus macaques. Challenge with a lethal dose of the highly pathogenic, wild-type, 1976 Mayinga strain of Ebola Zaire virus resulted in uniform infection in controls, who progressed to a moribund state and death in less than one week. In contrast, all vaccinated animals were asymptomatic for more than six months, with no detectable virus after the initial challenge. These findings demonstrate that it is possible to develop a preventive vaccine against Ebola virus infection in primates.     

HIV的病原学研究进展

人类免疫缺陷病毒(Human Immunodeficiency Virus,简称HIV)是导致艾滋病的病原体。研究HIV的病原学是认识HIV的致病机理、寻找有效的抗病毒治疗的靶位、设计HIV疫苗和诊断方法并最终控制艾滋病的基础。自从1983年HIV被分离出以来,HIV的病原学研究取得了长足进展：阐明了HIV的形态、结构以及病毒各个组成部分的功能;了解了HIV的复制和生命周期,并对病毒复制的调控有了基本的认识;对HIV在体内的动态和变异规律有了深入的了解;在上述认识的基础上,对HIV的致病机理以及病毒与宿主细胞的相互作用进行了深入的研究并取得了良好的进展。但是,艾滋病的抗病毒治疗和特异性免疫预防还远没有解决。开展深入的艾滋病病原学和致病机理研究,进一步揭示病毒复制、调控和致病的分子机制,阐明病毒与宿主细胞的相互作用,是发展新型抗药物、设计有效的HIV疫苗的前提和保证。本文概括了HIV病原学研究领域的主要进展,并提出了今后研究的展望。     

Immune responses of a designed HIV-1 DNA vaccine on rhesus monkeys

According to the UNAIDS/WHO report (http:// www.unaids.org/Epi2005/doc/report.html), there are about 40.3 million HIV/AIDS survivors, and the new HIV infection number amounts to about 4.9 million, while the death number is some 3.1 million in the world in…     

Prevention of HIV-2 and SIVsm infection by passive immunization in cynomolgus monkeys.

Infection of macaques with simian immunodeficiency virus (SIV) and human immunodeficiency virus type 2 (HIV-2) are useful models for studies of immunotherapy and vaccination against HIV as well as for testing of antiviral drugs. Vaccine research showing protective immunity in immunized monkeys has indicated that it will be possible to develop a vaccine for prevention of human HIV infection, although many hurdles remain. The design of an HIV vaccine would be helped if the basis of the protective immunity could be elucidated. Passive immune prophylaxis offers a means to determine the relative role of antibodies in protection against infection. We have studied whether a transfer of antibodies can prevent HIV-2 and SIVsm (SIV of sooty mangabey origin) infection in cynomolgus monkeys. Sera with high antibody titres were collected, heat-treated and injected into naive animals 6 h before challenge with 10-100 monkey-infectious doses of live homologous virus. All control animals treated with normal monkey serum (n = 6) or no serum (n = 39) became infected by the challenge virus, whereas five out of seven animals pretreated with antibody-containing serum at a dose of 9 ml kg-1 resisted infection. Thus passively transferred antibodies can protect against a low-dose lentivirus challenge in a nonhuman primate.     

Prospects for a vaccine against the hepatitis C virus

The recent discovery of natural immunity to the hepatitis C virus and vaccine efficacy in the chimpanzee challenge model has allowed optimism about the development of at least a partly effective vaccine against this heterogeneous pathogen that is responsible for much of the chronic liver disease around the world. The immune systems of some infected individuals can spontaneously clear the virus, whereas other people need treatment with antivirals that work partly by stimulating humoral and cellular immune responses. Therefore, therapeutic vaccine strategies are also being pursued to improve treatment outcome.     

Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine

The acquired immunodeficiency syndrome (AIDS)-causing lentiviruses human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) effectively evade host immunity and, once established, infections with these viruses are only rarely controlled by immunological mechanisms. However, the initial establishment of infection in the first few days after mucosal exposure, before viral dissemination and massive replication, may be more vulnerable to immune control. Here we report that SIV vaccines that include rhesus cytomegalovirus (RhCMV) vectors establish indefinitely persistent, high-frequency, SIV-specific effector memory T-cell (T(EM)) responses at potential sites of SIV replication in rhesus macaques and stringently control highly pathogenic SIV(MAC239) infection early after mucosal challenge. Thirteen of twenty-four rhesus macaques receiving either RhCMV vectors alone or RhCMV vectors followed by adenovirus 5 (Ad5) vectors (versus 0 of 9 DNA/Ad5-vaccinated rhesus macaques) manifested early complete control of SIV (undetectable plasma virus), and in twelve of these thirteen animals we observed long-term (≥1 year) protection. This was characterized by: occasional blips of plasma viraemia that ultimately waned; predominantly undetectable cell-associated viral load in blood and lymph node mononuclear cells; no depletion of effector-site CD4(+) memory T cells; no induction or boosting of SIV Env-specific antibodies; and induction and then loss of T-cell responses to an SIV protein (Vif) not included in the RhCMV vectors. Protection correlated with the magnitude of the peak SIV-specific CD8(+) T-cell responses in the vaccine phase, and occurred without anamnestic T-cell responses. Remarkably, long-term RhCMV vector-associated SIV control was insensitive to either CD8(+) or CD4(+) lymphocyte depletion and, at necropsy, cell-associated SIV was only occasionally measurable at the limit of detection with ultrasensitive assays, observations that indicate the possibility of eventual viral clearance. Thus, persistent vectors such as CMV and their associated T(EM) responses might significantly contribute to an efficacious HIV/AIDS vaccine.     

鸭病毒性肝炎综合防制措施的研究

肉鸭养殖场采取严格消毒、隔离饲养、加强种鸭免疫和雏鸭免疫、利用血清或抗体对雏鸭被动预防、药物预防等综合防制措施,对选定养殖户的养殖跟踪表明,在20日龄的鸭病毒性肝炎发生率从60%降低到20%。对来自非免疫种鸭和免疫种鸭的雏鸭群分别采用雏鸭疫苗接种、免疫血清注射和喂中药“鸭肝灵”,结果表明,疫苗的免疫接种是防制DVH所必须的,且与中草药“鸭肝灵”配合应用防制效果明显;注射血清能起到一定的防制作用,但其效价维持的时间较短,至少要经过两次注射才可能起到有效的保护作用。而对来自规则免疫种鸭的健康雏鸭其母源抗体有一定的保护作用,对预防DHV的早期感染起关键的作用,但保护不到15日龄,最早需在5日龄进行首免,15日龄才能达到有效的保护作用,同时饲喂中药“鸭肝灵”保护效果明显。无论雏鸭的母源抗体如何,隔离饲养、严格消毒,疫苗免疫(首免时间依种鸭免疫情况而定),并同时饲喂中药“鸭肝灵”保护效果明显。