BOG初次免疫联合结核分枝杆菌Ag85A DNA疫苗加强免疫效果的研究

为探讨BCG初次免疫,结核分枝杆菌Ag85A DNA疫苗加强免疫的序贯免疫策略对小鼠的免疫效果。采用BCG及结核分枝杆菌Ag85A DNA疫苗依次免疫小鼠,在末次免疫后的4、6、8周通过检测小鼠血清总IgG抗体、特异性淋巴细胞增殖．细胞因子的水平,观测BCG初次免疫,Ag85A DNA疫苗加强免疫的策略对小鼠的免疫效果。结果显示,采用BCG初次免疫,结核分枝杆菌Ag85A DNA疫苗加强免疫的策略组的小鼠与其它免疫方式组相比,IgG明显升高（P〈0．05）、特异性淋巴细胞明显增殖、IFN7、IL-2、IL-4水平明显增高（P〈0．05）。由此可知,在采用BCG初次免疫,结核分枝杆菌Ag85A DNA疫苗加强的免疫策略后,能增强对小鼠的免疫效应,尤其是Thl型细胞免疫反应增强明显,为进一步在动物体内进行保护性效应试验的研究提供了实验依据。     

新型细菌幽灵疫苗的研究进展

细菌幽灵是革兰氏阴性菌被噬菌体PhiX174的裂解基因E裂解后形成的完整细菌空壳,可以作为一种候选疫苗.细菌幽灵是一种新的研发疫苗的策略,其本身所具有的佐剂性质可以加强免疫反应,包括T细胞的活化和黏膜免疫.因为细菌幽灵本身的和外源的抗原可以在细菌裂解之前就表达于膜复合物的表面,所以不同来源的抗原可以同时通过细菌幽灵呈递给免疫系统.细菌幽灵具有多种优势,包括生产方便、安全和可作为多价联合疫苗.     

基因疫苗及影响其免疫效果的因素

基因疫苗被视为“第3代疫苗“,是目前疫苗研究领域的热点.本文回顾了基因疫苗的诞生,阐述了其优越性,重点讨论了增强其免疫效应的策略包括合理的载体设计、细胞因子及共刺激因子与抗原的共表达及适宜的接种途径等.     

表达结核杆菌抗原的重组酿酒酵母免疫小鼠研究

近年来研究显示全细胞重组酿酒酵母疫苗具有治疗性疫苗潜能.为了研究重组酿酒酵母结核病候选疫苗的免疫效果,将IFN-γ基因与结核杆菌抗原蛋白Ag85B、ESAT6的基因融合,利用pHR酿酒酵母表达系统和同源重组方法,成功构建了以酿酒酵母Y16为宿主的表达融合蛋白IF-γ-Ag85B和IF-γ-ESAT6-Ag85B的重组酿...     

抗感染免疫——中国科学家谈科学

抗感染免疫研究与严重威胁人类健康的疾病的攻克休戚相关。急性和慢性病毒感染免疫应答规律的研究突破，可直接指导艾滋病疫苗和乙型肝炎特异性药物的研制，在临床上可以帮助发展新型有效的免疫治疗方案，同时准确地判断疾病转归、预后等。     

基因疫苗研究与进展

基因疫苗代表了新的、具有潜力的疫苗发展途径和研究方向，它取得成功主要归功于基因治疗技术的发展．基因疫苗是直接将抗原的编码基因注入动物体内，并在动物细胞中表达抗原蛋白以诱导动物产生免疫保护作用．基因疫苗研究有可能为当今人类无法控制的一些严重传染疾病，提供新的免疫防治途径和手段．本文回顾了基因疫苗发展历史和研究进展，与传统疫苗相比较，对基因疫苗的作用原理、构造以及技术方法等方面的初步研究和进展情况进行了概述。     

新艾滋病疫苗雌猕猴实验获成功

法国研究人员日前报告说,他们研制的一种新型艾滋病疫苗在雌性猕猴身上实验成功。实验结果表明,疫苗能够有效防止艾滋病通过性途径传播。 法国国家科研中心以及国家健康与医学研究所的研究人员在美国最新一期《免疫》杂志上报告说,为了验证疫苗的有效性,研究人员对5只雌性猕猴进行了鼻部和肌肉注射。     

表达结核分枝杆菌融合抗原TB10.4-HspX的重组酵母免疫效果研究

结核病是一种严重危害人类健康的传染病,其防治难点主要在于抗药性菌株的出现以及唯一的抗结核疫苗——卡介苗的效果不理想.为发展新型抗结核疫苗,本研究中构建了表达结核分枝杆菌融合抗原TB10.4-HspX(TB10H)的重组酿酒酵母,分别以皮下注射和滴鼻两种方式免疫小鼠,检测免疫效果.结果显示,该重组酿酒酵母通过皮下注射的方式免疫后刺激小鼠产生TB10H特异性抗体IgG,分泌Th1型细胞因子IFN-γ,而且重组酵母免疫后在一定程度上刺激小鼠树突状细胞的成熟分化和抗原递呈作用.一系列结果表明,表达融合抗原TB10H的重组酿酒酵母能够有效激发小鼠抗原特异性免疫应答.     

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.     

我国艾滋病实验室网络、检测技术及其质量保证体系进展

艾滋病实验室检测在艾滋病防治工作中起着举足轻重的作用。我国艾滋病实验室网络及其质量保证体系已经建立并不断完善,截至2004年底全国共验收批准3707个筛查实验室,53个确证实验室,已经开展的实验室检测能力验证包括血清学和免疫学检测,病毒学检测能力的验证将于2005年启动。目前艾滋病实验室使用的常规检测技术包括HIV抗体检测、核酸检测和CD4细胞计数。正在研究和评价的新策略、新技术包括：确认试验替代策略、抗原检测、多亚型新感染酶联检测技术（BED-EIA）、滤纸于血片检测HIV抗体及核酸技术、集合RT-PCR方法等。这些研究工作紧跟国际步伐、符合中国国情。     

A group specific anamnestic immune reaction against HIV-1 induced by a candidate vaccine against AIDS

The first experimental immunization of humans against the AIDS retrovirus, HIV-1, was started in a series of HIV seronegative, healthy volunteers in November 1986. For the primary vaccination recombinant vaccinia virus (V25) expressing the complete gp160 env protein of the HTLV-IIIB strain of HIV-1 was introduced by scarification. This elicited a weak primary response which we subsequently attempted to enhance by additional immunizations (boosting), using four different immunization protocols. We report here that intravenous injection of paraformaldehyde-fixed autologous cells infected in vitro with V25 (individual D.Z.) gave the best results. This individual received second and third boosts of intramuscular gp160 derived from an HTLV-IIIB clone using the hybrid vaccinia virus/bacteriophage T7 expression system. An anamnestic humoral and cellular immune reaction was achieved for over one year after the original vaccination, with high levels of antibodies to the viral envelope, and neutralizing antibodies against divergent HIV-1 strains such as HTLV-IIIB and HTLV-IIIRF (also called HTLV-III HAT) after the first boost. In addition, group-specific cell-mediated immunity and cell-mediated cytotoxicity against infected T4 cells were obtained after the primary vaccine and enhanced by the boosts. Finally, skin tests showed both immediate and delayed hypersensitivity to gp160 in vivo. Although this protocol is not practical for a large scale vaccine trial, our results show for the first time that an immune state against HIV can be obtained in man.     

胚期接种IBD疫苗对雏鸡ND4倍剂量免疫接种效果之影响

为了研究用IBD疫苗进行鸡胚免疫的可行性，探讨了胚期接种IBD疫苗对雏鸡ND4倍剂量免疫接种效果的影响．将IBD中等毒力疫苗接种18日龄鸡胚，出壳后采用4倍剂量ND疫苗进行免疫，通过抗体水平、免疫细胞数量及功能和免疫保护力等的检测，结果表明：胚期接种IBD中等毒力疫苗对雏鸡4倍剂量免疫仍具有免疫抑制作用．     

Challenges in the development of an HIV-1 vaccine

The development of a safe and effective human immunodeficiency virus (HIV)-1 vaccine is a critically important global health priority. Despite recent advances in our understanding of HIV-1 pathogenesis and immunology, however, major scientific obstacles remain. Prototype HIV-1 vaccine candidates aimed at eliciting humoral and cellular immune responses have so far failed to protect against HIV-1 infection or to reduce viral loads after infection in clinical efficacy studies. A renewed and coordinated commitment to basic discovery research, preclinical studies and clinical trials will therefore be required to overcome the hurdles currently facing the field. Here I review key challenges and future prospects in the quest to develop a prophylactic HIV-1 vaccine.     

鸭疫里默氏杆菌三价灭活疫苗的免疫保护期研究

选择免疫原性好的血清1,2,4型鸭疫里默氏杆菌（RA）分离株制备三价灭活油乳剂苗,疫苗抗原含量为5×109CFU/ml,分别用0.5,1.0和1.5ml/只剂量接种7日龄樱桃谷肉鸭以检验器其安全性;用0.25ml/只的剂量接种樱桃谷肉雏鸭,分别于免疫后第1、2、3,4、5和9周攻毒,以检验其免疫效果.安全性检验结果显示,肉雏鸭接种后未见局部和全身异常反应;攻毒保护试验结果显示,免疫后2～9周雏鸭对3个血清型的RA的攻毒保护率达70％ ～ 100％.证明该三价灭活疫苗具有良好的安全性免疫保护力,免疫保护期不少于9周.     

HIV-1C亚型DNA疫苗诱导小鼠免疫反应的研究

 构建含中国流行株HIV-1 C亚型核心蛋白gag基因的重组质粒pVAX-gag,并在体外进行了表达与鉴定.同时构建了含此gag基因的原核表达质粒pGEX-gag,表达纯化并鉴定重组蛋白Gag.以质粒pVAX-gag免疫Balb/C小鼠后,用ELISpot和流式细胞仪检测其细胞免疫反应.再以纯化后的重组蛋白Gag作为包被抗原,用ELISA检测其体液免疫反应.结果显示重组质粒pVAX-gag免疫小鼠后可有效地诱导机体产生细胞免疫和体液免疫反应,且免疫剂量和免疫效果存在一定的正相关性.重组原核表达质粒pGEX-gag的表达产物能与抗p24单克隆抗体发生特异性反应,可用于抗HIV抗体检测.     

Induction of protective immunity against experimental infection with malaria using synthetic peptides

Synthetic peptides are potential vaccine candidates because they may be able to induce high antibody titres and specific cellular immune responses against native proteins and thus the whole invading organism. In a previous study we showed that immunization with molecules of relative molecular mass (Mr) 155,000 (155K) 83K, 55K and 35K, specific for the late schizont and merozoite stages of Plasmodium falciparum, could elicit either partial or total protection in Aotus trivirgatus monkeys experimentally infected with P. falciparum. Here we have chemically synthesized 18 peptides corresponding to different fragments of these proteins to immunize Aotus trivirgatus monkeys. Some peptides gave partial protection from challenge with P. falciparum parasites, but none provided complete protection individually. A combination of three partially protective peptides gave complete or almost complete protection, however, suggesting that this particular combination of peptides is a good candidate for a malaria vaccine.     

Effect of immunization with a vaccinia-HIV env recombinant on HIV infection of chimpanzees

Acquired immunodeficiency syndrome (AIDS) is caused by human immunodeficiency virus (HIV) and is now recognized as a worldwide epidemic for which there is no cure or vaccine. Chimpanzees are the only other animals that can be infected by HIV, and therefore the chimpanzee-HIV model system is useful for testing potential HIV vaccines. However, with one exception, there have been no reports of clinical manifestations of AIDS in chimpanzees. We report here results of an HIV vaccine trial in which nine chimpanzees were first immunized with either a recombinant vaccinia virus expressing the envelope glycoproteins of HIV strain LAV-1 (v-env5) or a control recombinant vaccinia virus and were then challenged with a high or low dose of LAV-1. Although HIV-specific antibody and T-cell responses were elicited by immunization, virus was isolated from lymphocytes of all challenged chimpanzees, indicating that immunization did not prevent infection by HIV. Among the animals that received a higher dose of LAV-1, one of two control chimpanzees, but none of the four v-env5-immunized chimpanzees developed substantial and persistent lymphadenopathy.     

鸡新城疫水－油－水型活性复乳的研制和免疫研究

水－油－水（Ｗ／Ｏ／Ｗ）型活性复乳是将油包水初乳（Ｗ／Ｏ）进一步分散在水相中经过二次乳化，使用时并配以新城疫弱毒疫苗联合制成。采用透析法测定复乳的形成率分别为９５．０％，８９．３％，８８．０％和８４．４％，雏鸡免疫后４ｄＨＩ抗体即明显升高，井持续２个月以上；对育成鸡的加强免疫持续期达１４个月，滴鼻或肌注攻毒全保护，证实新城疫Ｗ／Ｏ／Ｗ活性复乳已达到实用要求。     

鸡新城疫水-油-水型活性复乳的研制和免疫研究

水－油－水（Ｗ／Ｏ／Ｗ）型活性复乳是将油包水初乳（Ｗ／Ｏ）进一步分散在水相中经过二次乳化，使用时并佤以新城疫弱疫苗联合制成，有杉透析法测定复乳的形成率分别为９５．０％，８９．３％，８８．０％和８４．４％，雏鸡免疫后４天ＨＩ抗体即明显升高，并持续２个月以上，对育成鸡的加强免疫持续期达１４个月，滴鼻或肌注攻毒全保护，实新城疫Ｗ／Ｏ／Ｗ活性复乳已达到实用要求。     

Gulliver's travels in HIVland

The emergence of HIV and AIDS is narrated here through the eyes of the legendary Irish traveller Gulliver, observing the replication, cross-species origin, evolution, diversity and transmission of HIV. Ethical problems of vaccine trials, the social impact of AIDS, and prospects for its prevention, including the development of topical virucidal lotions, are discussed. The existence of a growing proportion of HIV-infected, immunocompromised children and adults may significantly affect current immunization programmes and the evolution of opportunistic infections.