弓形虫多价疫苗研究近况

弓形虫疫苗研制已经历了全虫疫苗、抗原组份疫苗、基因工程亚单位疫苗和核酸疫苗发展阶段,结果表明基因工程多价疫苗具有较大的前景。本文综述了弓形虫多价疫苗的研制、应用和目前存在的问题及解决策略。     

我国血吸虫疫苗研究进展及应用前景

血吸虫病疫苗研究一直是WHO/TDR热带病防治和我国血防研究的热点内容,近年来我国有关血吸虫病疫苗的研究取得了重要进展。随着蛋白质组学和分子生物学技术的发展,我国血吸虫病疫苗研究已发展到基因工程疫苗研制阶段。其中DNA疫苗已成为当前我国血吸虫病疫苗研究的主流方向。同时,新的有效疫苗抗原分子的筛选鉴定及其配伍与优化,混合疫苗、多价疫苗的构建及其与佐剂的联用,为提高疫苗免疫保护效果提供了新的途径。     

寄生虫14-3-3基因工程疫苗研究进展

寄生虫病是危害人和动物的重要传染病之一,疫苗是目前控制寄生虫病最为经济有效的方式。近年来,免疫学及生物工程的迅速发展极大的促进了寄生虫基因工程疫苗的研究。14-3-3蛋白是一种广泛存在于真核生物中的高度保守蛋白,已被国内外学者运用于多种寄生虫基因工程疫苗的研究。本文则对国内外寄生虫14-3-3基因工程疫苗的研究进展做一综述。     

新型乙型肝炎核酸疫苗pVAX1-C3d-S2S的免疫预防效应

既往的乙型肝炎（乙肝）血源疫苗和目前使用的基因工程多肽疫苗已在很大程度上控制了乙肝的流行。众多研究表明，接种乙肝核酸疫苗后能长时间诱导特异性抗体的产生和较强的细胞毒T淋巴细胞（CTL）应答，有望用于HBV感染的预防和治疗。但目前仍存在一些问题，如血源疫苗的安全性，现有基因工程多肽疫苗的部分接种者无应答，以及所诱导的免疫应答效率偏低等。     

淋病奈瑟菌基因工程疫苗研究概况

淋病奈瑟菌是性传播疾病淋病的致病菌,为预防和控制淋病奈瑟菌的感染,淋病奈瑟菌的疫苗已经进行了深入的研究。其中淋病奈瑟菌基因工程疫苗越来越受到关注,其能诱导机体产生特异性细胞和体液免疫应答,且是安全性最高的疫苗。本文概述了淋病奈瑟菌PorA、PorB、NspA和Tbp基因相关的基因工程疫苗的研究进展。     

疟原虫传播阻断免疫的研究进展

疟疾疫苗的研究已经深入到分子水平,基因工程疫苗、合成肽疫苗、亚单位疫苗以及复合多价疫苗的研究进展迅速。本文概述了对疟原虫传播阻断靶抗原研究的进展,并对传播阻断疫苗的研制及佐剂的应用进行了探讨。     

我国血吸虫疫苗研究进展和展望

疫苗是控制传染性疾病的有效手段，20世纪初人们曾设想研制血吸虫疫苗来预防和控制血吸虫病。血吸虫疫苗研究的历史，经历了从死疫苗、致弱活疫苗、亚单位疫苗到基因工程疫苗等的探索过程。     

疟原虫传播阻断免疫的研究进展

疟疾疫苗的研究已经深入到分子水平，基因工程疫苗、合成肽疫苗、亚单位疫苗以及复合多价疫苗的研究进展迅速。本文概述了对疟原虫传播阻断靶抗原研究的进展，并对传播阻断疫苗的研制及佐剂的应用进行了探讨。     

我国首个基因工程戊型肝炎疫苗进入临床试验

据医学空间网1月12日报道，我国首个拥有核心自主知识产权的基因工程疫苗-戊型肝炎疫苗，日前正式获准进入Ⅰ／Ⅱ期临床试验，该疫苗有望成为世界上继乙肝疫苗之后的第二个基因工程病毒疫苗。     

BCAP37-hIL-18基因疫苗抗乳腺癌作用研究

目的 为乳腺癌基因工程疫苗的临床应用奠定基础。方法 采用MTT法检测经高能X线照射灭活BCAP37-hIL-18基因疫苗（下简称基因疫苗）的生存曲线，以及其刺激T细胞增殖的能力。结果 经过高能X线照射后，BCAP37-hIL-18细胞生长停滞。基因疫苗作用T细胞的反应值及刺激率提高，荷瘤小鼠的肿瘤缩小，生存时间延长，生存率提高。结论 BCAP37-hIL-18疫苗具有明显抗肿瘤作用；本研究为乳腺癌基因工程肿瘤疫苗的研制及临床应用提供了实验基础。     

布鲁氏菌病疫苗研究进展

使用疫苗免疫是防控布氏菌病(简称布病)的重要措施之一,但对人群使用疫苗免疫一直存有争议,世界上主要是俄罗斯(前苏联)和中国使用19-BA疫苗和104M疫苗对布病高危人群进行免疫.对于动物布病,早期曾使用灭活疫苗进行免疫,目前主要使用S19,Rev.1,RB51,S2和M5等弱毒活疫苗,其中Rev.1和S19是预防小反刍动物和奶牛布病最有效的疫苗,其它疫苗的使用也比较广泛.初步研究表明基因工程疫苗等新型布病疫苗具有良好的应用前景,但尚未被官方认可用于人和动物的布病免疫.特对人布病疫苗和动物布病疫苗进行介绍,并对基因工程疫苗以及其它新型布病疫苗的最新研究进展进行概述.     

Recombinant allergens for immunotherapy.

Many of the problems associated with using natural allergenic products for allergy diagnosis and treatment can be overcome using genetically engineered recombinant allergens. Over the past 10 years, the most important allergens from mites, pollens, animal dander, insects, and foods have been cloned, sequenced, and expressed. Allergens have diverse biological functions (they may be enzymes, enzyme inhibitors, lipocalins, or structural proteins). High-level expression systems have been developed to produce recombinant allergens in bacteria, yeast, or insect cells. Recombinant allergens show comparable immunoglobulin E (IgE) antibody binding to natural allergens and show excellent reactivity on skin testing and in in vitro diagnostic tests. Recombinant allergens will enable innovative new strategies for allergen immunotherapy to be developed. These include peptide-based vaccines, engineered hypoallergens with reduced reactivity for IgE antibodies, nucleotide-conjugated vaccines that promote Th1 responses, and the possibility of developing prophylactic allergen vaccines.     

Now and future influenza vaccines

Influenza is a modern day plague. In the young, the clinical picture is classical, but in the elderly, the disease may go unsuspected until complications such as pneumonia develop. Influenza A and B viruses are responsible, and these viruses mutate with great regularity. Antibodies to the HA and NA surface antigens of influenza viruses, both naturally and vaccine induced, are protective. The earliest influenza vaccines were crude, toxic, and ineffective. With modern purification techniques, the egg-grown viruses have been turned into safe, immunogenic, and effective killed-virus vaccines--whole virus and split virus. Surveillance permits the correct virus strains to be incorporated into each new vaccine. Those who have been experiencing the worst effects of influenza have been identified. These individuals need to be immunized each year. In the future, live influenza virus vaccines may offer the benefits of ease of administration and longer-lasting protection. Synthetic peptides, genetically engineered antigens, and even nonantigen (anti-idiotype) vaccines are possible, but such vaccines will require adjuvant enhancement. For the present, greater efforts must be made to use existing influenza vaccines.     

乙肝表面抗原载体多价重组核酸疫苗研究进展

研究表明,乙肝病毒的包膜蛋白HBsAg不仅可以作为疫苗的理想候选分子,还可作为基因工程疫苗的理想载体,用来成功构建多种重组核酸疫苗。本文概述了以乙肝表面抗原为载体,重组或联合其他病毒、寄生虫、细胞因子等其他基因制作多价核酸疫苗的研究进展。     

Cancer vaccines: the interleukin 2 dosage effect.

Cancer vaccines genetically engineered to produce interleukin 2 have been investigated intensively in a series of animal models and are at the point of entering into clinical trials. In this study we demonstrate a strong correlation between the rate of interleukin 2 production and the protection efficiency of murine S91 melanoma cell (clone M-3) vaccines. Best immunization is achieved with vaccines producing medium interleukin 2 levels of 1000-3000 units per 10(5) cells per day. Reduced interleukin 2 production evokes a corresponding decline in the number of successfully treated animals. Unexpectedly, when interleukin 2 expression is raised to high levels of 5000-7500 units per 10(5) cells per day, protection is completely absent because of impaired generation of tumor-specific cytotoxic T lymphocytes. In comparison, granulocyte-macrophage colony-stimulating factor as immunomodulator induces substantial immunization even at a moderate level of secretion and protects all animals at the maximal obtainable level of secretion. Our findings demonstrate the importance of the interleukin 2 level produced by genetically modified tumor cells and may have substantial impact for the clinical application of cancer vaccines.     

All sites up and running on AIDS vaccine trials

Three-year Phase III AIDS vaccine trials are underway at approximately 50 sites for AIDSVAX, one of the most promising vaccines. This vaccine is a genetically engineered compound developed by VaxGen, and is made from a copy of a protein on the surface of HIV. It contains no HIV DNA, so there is no chance the vaccine would cause infection. The randomized, double-blind, placebo-controlled trial will enroll 5,000 people who do not have HIV-1 infection but are at risk of acquiring it through sexual contact. So far, study volunteers have reported no allergic reactions, and the participation level has remained high. Volunteers receive seven shots over a 3-year period, and they have blood work done 14 days after each injection to assess their tolerability to the drug. They are tested for HIV infection at 6-month intervals. Research on the vaccine began in 1984, with the initial clinical trials of a first-generation vaccine beginning in 1992. Researchers are hopeful that AIDSVAX, or another vaccine, will become as common as other immunizations given to children.     

Expression of Norwalk virus capsid protein in transgenic tobacco and potato and its oral immunogenicity in mice.

Alternatives to cell culture systems for production of recombinant proteins could make very safe vaccines at a lower cost. We have used genetically engineered plants for expression of candidate vaccine antigens with the goal of using the edible plant organs for economical delivery of oral vaccines. Transgenic tobacco and potato plants were created that express the capsid protein of Norwalk virus, a calicivirus that causes epidemic acute gastroenteritis in humans. The capsid protein could be extracted from tobacco leaves in the form of 38-nm Norwalk virus-like particles. Recombinant Norwalk virus-like particle (rNV) was previously recovered when the same gene was expressed in recombinant baculovirus-infected insect cells. The capsid protein expressed in tobacco leaves and potato tubers cosedimented in sucrose gradients with insect cell-derived rNV and appeared identical to insect cell-derived rNV on immunoblots of SDS/polyacrylamide gels. The plant-expressed rNV was orally immunogenic in mice. Extracts of tobacco leaf expressing rNV were given to CD1 mice by gavage, and the treated mice developed both serum IgG and secretory IgA specific for rNV. Furthermore, when potato tubers expressing rNV were fed directly to mice, they developed serum IgG specific for rNV. These results indicate the potential usefulness of plants for production and delivery of edible vaccines. This is an appropriate technology for developing countries where vaccines are urgently needed.     

Adjuvant effect of human growth hormone with an inactivated flavivirus vaccine

Vaccines made by inactivating pathogenic microorganisms have been dramatically successful in controlling diseases in humans and animals. Despite their successes, they have a major disadvantage in that several inoculations are required for them to be effective. To overcome this problem, a commercial inactivated vaccine preparation against tickborne encephalitis was combined with human growth hormone (HGH). This formulation produced complete protection in a murine model with only one dose of vaccine, apparently by binding hormone and antigen to an insoluble matrix containing aluminium hydroxide. Thus it is postulated that when virus-specific lymphocytes are attracted to the site of injection, the hormone is at a high local concentration and stimulates the clonal expansion of antigen-specific T cells. The development of genetically engineered HGH now gives unlimited supplies of hormone, potentially resulting in an increase in efficacy of a wide variety of vaccines, especially those needing prolonged immunization schedules such as those being developed to combat human immunodeficiency virus infection.     

The straw that stirs the drink: insight into the pathogenesis of inflammatory bowel disease revealed through the study of microflora-induced inflammation in genetically modified mice

Abnormal response to enteric microflora is a critical factor driving bowel inflammation in patients with inflammatory bowel disease (IBD). Mice with genetically engineered mutations have played a central role in both formulating this hypothesis and elucidating the mechanism that normally protect the host from excessive inflammation within the bowel. One emerging theme is the importance of regulation within the innate immune system in protecting from microflora-driven pathology. In this review, I describe how genetically engineered mice have played a crucial role in shaping our conceptual understanding of pathways that regulate the development of chronic bowel inflammation, and furthermore, explore data derived from the study of genetically engineered mice that implicates the fundamental importance of regulation within the innate immune system in the control of this process.     

Non-Hodgkin lymphomas of mice

Studies of lymphoid neoplasms occurring in normal or genetically engineered mice have revealed parallels and differences to non-Hodgkin lymphomas (NHL) of humans. Some mouse lymphomas have strong histologic similarities to the human NHL subsets including precursor B- and T-cell lymphoblastic, small lymphocytic, splenic marginal zone, and diffuse large-cell B-cell lymphomas (DLCL); whether molecular parallels also exist is under study. Others mouse types such as sIg+ lymphoblastic B-cell lymphoma have no histologic equivalent in human NHL even though they share molecular deregulation of BCL6 with human DLCL. Finally, Burkitt lymphoma does not appear to occur naturally in mice, but it can be induced with appropriately engineered transgenes.