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。     

日本血吸虫DNA疫苗的研究进展

血吸虫病是严重危害人类健康的人畜共患寄生虫病,疫苗是预防控制血吸虫病的重要手段。该文概述了日本血吸虫DNA疫苗的优点、候选抗原、联合免疫、免疫机制及DNA疫苗存在的问题和展望。     

提高血吸虫疫苗保护性效果的研究进展

对血吸虫感染产生的特异性免疫应答表现为非消除性免疫。当前 ,血吸虫疫苗的研究仍是世界性难题。迄今为止 ,还没有一种理想的疫苗可用于免疫预防以阻断血吸虫病的传播。基于国内外学者近几年在血吸虫病疫苗研究领域中取得的成就 ,本文在核酸疫苗、甘露糖化抗原、鸡尾酒式疫苗、免疫佐剂选用及改变免疫微环境等方面 ,就如何提高血吸虫病疫苗保护效果作一综述。     

日本血吸虫病核酸疫苗研究进展

血吸虫病是严重危害人类健康的寄生虫病,寻找新的杀虫药物和开发研制有效抗血吸虫疫苗已成为刻不容缓的工作。随着现代分子生物学及免疫学的发展,血吸虫病疫苗已由减毒活疫苗、基因重组抗原疫苗发展到核酸疫苗等阶段[1-2]。疫苗是20世纪最重要的公共卫生成就之一[3]。传统的疫苗研究策略是模拟自然感染,成功的疫苗多依赖于中和抗体的产生;虽然减毒活疫苗的免疫保护作用效果显著,但缺乏足够的虫源,且多种抗原成分不一定全部产生保护力,甚至可能导致免疫性病变或免疫抑制。基因重组抗原疫苗应用安全,但只能引起体液免疫,且蛋白的提取纯化步骤…     

提高血吸虫疫苗保护性效果的研究进展

对血吸虫感染产生的特异性免疫应答表现为非消除性免疫。当前，血吸虫疫苗的研究仍是世界性难题。迄今为止，还没有一种理想的疫苗可用于免疫预防以阻断血吸虫病的传播。基于国内外学者近几年在血吸虫病疫苗研究领域中取得的成就，本文在核酸疫苗、甘露糖化抗原、鸡尾酒式疫苗、免疫佐剂选用及改变免疫微环境等方面，就如何提高血吸虫病疫苗保护效果作一综述。     

紫外线致弱尾蚴免疫兔血清筛选日本血吸虫童虫cDNA文库

目的筛选紫外线致弱尾蚴中起免疫保护作用的抗原分子,分析其主要表位,为血吸虫病疫苗研究提供新的候选抗原。方法以紫外线照射致弱尾蚴免疫兔血清筛选日本血吸虫童虫cDNA文库,对阳性克隆插入片段的核苷酸进行序列分析,并利用软件Antheprot对所筛基因编码的抗原分子进行表位预测。结果经三轮筛选,共获20个阳性克隆,序列同源性分析表明其中有5种已知基因(GST、副肌球蛋白、肌球蛋白、钙离子激活蛋白和3-磷酸甘油醛脱氢酶),6种未知基因,软件分析显示不同抗原分子分别具有多个不同的抗原表位。结论获得的阳性克隆插入基因片段可能为潜在的日本血吸虫病疫苗分子,可能是多抗原、多表位在照射致弱尾蚴中起免疫保护作用。     

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。     

人体对血吸虫感染的抵抗力:年龄还是经历?

从Fisher最早进行的人体暴露感染实验到近期周密细致的重复感染研究,都证明在血吸虫病流行区成人的再感染发生率低于儿童。 免疫流行病学研究表明获得性免疫在血吸虫病流行中有十分重要的作用,但是适当的免疫应答系统的建立可能需要很多年。其作用机制尚不十分明了。近几年可望研制出针对一种或几种抗原的疫苗,这些工作都将建立在一个假设之上,即早期疫苗注射可加速获得性免疫的建立。     

日本血吸虫候选疫苗研究现状与展望

血吸虫病疫苗的研制工作已纳入WHO和我国主要疾病防治规划并取得了显著进展。近年来开展的血吸虫免疫机制和血吸虫基因组研究对血吸虫疫苗的研制起了积极的推动作用。本文主要对血吸虫蛋白疫苗、DNA疫苗和多价疫苗候选抗原的研究进展作综述。     

核酸疫苗研究状况及其在寄生虫病方面的应用

目前用于寄生虫病预防和治疗的疫苗种类很多。在血吸虫病、弓形虫病、疟疾、利什曼病等病种方面,已有多种疫苗,如减毒活疫苗、重组抗原疫苗、合成肽疫苗、抗独特型疫苗、基因工程重组疫苗和核酸疫苗等。不论疫苗的组成如何,设计新疫苗应致力于充分表达免疫原性和诱发免疫记忆的能力;进一步改善抗原决定簇的质量、密度和位置,以诱导预防疾病所需要的免疫应答。在设计新疫苗的各种方法中,很难预测最佳方法。用DNA重组技术或化学合成得到的亚单位疫苗的大小有限,限制了它们表达免疫原性的能力,选用几种对T、B细胞有适当活性的肽段结合起来,可…     

日本血吸虫Sj97疫苗研究进展

日本血吸虫疫苗研制已作为我国防治该病的重要组成部分。副肌球蛋白是WHO提出的血吸虫疫苗较为理想的候选抗原之一,已用于日本血吸虫疫苗的研究。本文主要对日本血吸虫副肌球蛋白的概况、重组蛋白疫苗和DNA疫苗研究进展进行综述。     

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。     

Qualitative and quantitative assessment of meningococcal antigens to evaluate the potential strain coverage of protein-based vaccines

A unique multicomponent vaccine against serogroup B meningococci incorporates the novel genome-derived proteins fHbp, NHBA, and NadA that may vary in sequence and level of expression. Measuring the effectiveness of such vaccines, using the accepted correlate of protection against invasive meningococcal disease, could require performing the serum bactericidal assay (SBA) against many diverse strains for each geographic region. This approach is impractical, especially for infants, where serum volumes are very limited. To address this, we developed the meningococcal antigen typing system (MATS) by combining a unique vaccine antigen-specific ELISA, which detects qualitative and quantitative differences in antigens, with PorA genotyping information. The ELISA correlates with killing of strains by SBA and measures both immunologic cross-reactivity and quantity of the antigens NHBA, NadA, and fHbp. We found that strains exceeding a threshold value in the ELISA for any of the three vaccine antigens had ≥80% probability of being killed by immune serum in the SBA. Strains positive for two or more antigens had a 96% probability of being killed. Inclusion of multiple different antigens in the vaccine improves breadth of coverage and prevents loss of coverage if one antigen mutates or is lost. The finding that a simple and high-throughput assay correlates with bactericidal activity is a milestone in meningococcal vaccine development. This assay allows typing of large panels of strains and prediction of coverage of protein-based meningococcal vaccines. Similar assays may be used for protein-based vaccines against other bacteria.     

Comparative analysis of different vaccine constructs expressing defined antigens from Mycobacterium tuberculosis

BACKGROUND: Studies of different vaccine constructs have demonstrated variable efficacy against Mycobacterium tuberculosis in animal models. Despite the fact that these vaccines have used one or another of a very small number of immunodominant antigens, a direct comparison of the relative efficacy of the antigens and delivery systems has been difficult, because the studies have used different parameters for assessment. METHODS: We compared the efficacies of the most commonly used vaccine constructs--adjuvanted protein, plasmid DNA, and live bacterial vectors--bearing the immunodominant secreted antigens early secreted antigen target-6 and antigen 85B, either alone or as a fusion protein. Mice were vaccinated with these constructs, and the effects of different delivery systems on protective efficacy (as assessed by survival studies and by monitoring bacterial load) and antigen-specific responses (including the contribution of CD4 and CD8 T cells to these responses) were assayed by various methods. RESULTS: The relative efficacy of different vaccines is dependent on the delivery system, the antigen, and the animal model. Likewise, the relative immunodominance of individual antigens in the fusion molecule is altered by the choice of delivery system. CONCLUSION: These results clearly demonstrate the importance of assessing vaccine function by use of multiple parameters and indicate which parameters are most reliable for assessing vaccine efficacy.     

Live oral Salmonella vaccines: potential use of attenuated strains as carriers of heterologous antigens to the immune system

Live attenuated strains of salmonellae are showing promise as live oral vaccines against human typhoid fever and other Salmonella infections of man and animals. Attenuation can be achieved by introducing genetically defined, non-reverting mutations into specific genes on the Salmonella chromosome. Mutations in the gal E or aroA genes of Salmonella inhibit the ability of the bacteria to grow in vivo, and strains carrying such lesions are effective vaccines against salmonellosis. Genetic determinants encoding for the expression of potentially protective antigens from heterologous, non-Salmonella pathogens can be readily introduced into these attenuated Salmonella strains. Expression of the heterologous antigen does not affect the ability of the Salmonella host to be used as a Salmonella vaccine. Mice infected orally with a Salmonella typhimurium aroA vaccine expressing the Escherichia coli heat-labile toxin B subunit developed both a secretory and serum antibody response to this antigen. These serum antibodies were able to neutralise the activity of E. coli heat-labile toxin in tissue culture assays. A humoral and cell-mediated (DTH) immune response was detected against beta galactosidase, an intracellular antigen, in mice infected with an aroA vaccine expressing this cloned antigen. The prospects for the development of live Salmonella vaccines as a method for delivering heterologous antigens derived from bacteria, viruses and parasites is discussed.     

Schistosomiasis Elimination Strategies and Potential Role of a Vaccine in Achieving Global Health Goals

In March 2013, the National Institute of Allergy and Infectious Diseases and the Bill and Melinda Gates Foundation co-sponsored a meeting entitled “Schistosomiasis Elimination Strategy and Potential Role of a Vaccine in Achieving Global Health Goals” to discuss the potential role of schistosomiasis vaccines and other tools in the context of schistosomiasis control and elimination strategies. It was concluded that although schistosomiasis elimination in some focal areas may be achievable through current mass drug administration programs, global control and elimination will face several significant scientific and operational challenges, and will require an integrated approach with other, additional interventions. These challenges include vector (snail) control; environmental modification; water, sanitation, and hygiene; and other future innovative tools such as vaccines. Defining a clear product development plan that reflects a vaccine strategy as complementary to the existing control programs to combat different forms of schistosomiasis will be important to develop a vaccine effectively.     

Bacterial enteric infections and vaccine development.

There is a great need for effective vaccines against the major bacterial enteropathogens. Bacterial enteric infections resulting in diarrhea, dysentery, or enteric fever constitute a huge public health problem, with more than a billion episodes of disease and several million deaths annually in developing countries. Diarrhea caused by a bacterial enteric infection is also the commonest illness experienced by international travellers. Studies of pathogenesis have established the importance of specific ligand-receptor interactions between the enteropathogens and the intestinal epithelium, resulting in attachment and colonization of the bacteria and production of disease through either invasive mechanisms or production of toxins. Studies of protective immune mechanisms have emphasized the importance of secretory IgA antibodies and mucosal memory for protection against noninvasive, enterotoxigenic infections such as cholera and ETEC diarrhea and also drawn attention to the possible protective role of IFN-gamma production by intestinal T cells in these secretory diarrheas. In invasive dysenteric and enteric-fever infections caused by such organisms as Shigella and Salmonella, optimal protection may depend on a combination of mucosal and systemic immunity. On the basis of this knowledge, several new vaccines have been developed and proved to be efficacious in large field tests. These include an oral killed B-WC vaccine and a killed WC-alone vaccine against cholera, and both a live attenuated oral vaccine (Ty21a) and an injectable Vi antigen vaccine against typhoid fever. In addition, a killed oral ETEC vaccine and live attenuated oral Shigella vaccines have begun to be tested in phase 1 and phase 2 studies in humans. The properties of the new vaccines against bacterial enteric infections give promise that these vaccines should be useful both in control programs in developing countries and for immunoprophylaxis against travellers' diarrhea.     

HspX的功能及其在结核疫苗研制中的应用进展

研制安全有效的结核疫苗一直是结核病研究的重点,因此,有必要对其主要致病菌结核分枝杆菌(Mycobacterium tuberculosis,Mtb)抗原进行科学合理的评价。本文综述了潜伏性结核感染重要抗原HspX的致病机制及其在结核疫苗研制中的应用进展,探讨了HspX抗原在不同类型疫苗研制中的作用,旨在为将来研制有效的结核疫苗提供较准确的信息。     

血吸虫感染抗性人血清筛选日本血吸虫童虫cDNA文库

目的分析血吸虫感染抗性人血清中起免疫保护作用抗体针对的日本血吸虫蛋白抗原谱,为日本血吸虫病疫苗研究提供新的候选抗原分子。方法采集血吸虫流行病区感染抗性人血清,免疫学方法筛选日本血吸虫童虫cDNA文库,对获得的阳性克隆核苷酸进行序列分析,并利用软件对所筛基因编码的抗原分子进行表位预测。结果共筛选出29个持续阳性克隆,对其进行测序,获得25个基因,包括5种已知基因(其中日本血吸虫肌球蛋白12个、丝氨酸蛋白酶抑制剂2个、细胞色素b1个、延伸因子1-α1个和线粒体编码区1个)和5个未知基因,软件分析显示不同抗原分别具有多个不同的抗原表位。结论获得的阳性克隆插入基因片段可能编码潜在的日本血吸虫病疫苗分子,其中日本血吸虫肌球蛋白为主要抗感染蛋白分子。