Schistosome Calpain as a Vaccine Candidates

血吸虫钙蛋白酶作为候选疫苗

• 批准号: 6413303
• 负责人: Afzal A Siddiqui
• 金额: $ 14.8万
• 依托单位: TEXAS TECH UNIVERSITY HEALTH SCIS CENTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6413303
• 关键词: antigen antibody reaction; biotechnology; calpain; complementary DNA; confocal scanning microscopy; cytokine; drug screening /evaluation; enzyme linked immunosorbent assay; gene delivery system; immunofluorescence technique; intramuscular injections; laboratory mouse; molecular shape; nonhuman therapy evaluation; schistosomiasis; transfection /expression vector; transmission electron microscopy; vaccine development; vector vaccine

DESCRIPTION (Provided by Applicant): Schistosomiasis is a chronic, often debilitating, disease afflicting over 200 million people, an additional 600 million are at risk in 74 countries. Although schistosomicidal agents and other control measures, including public hygiene and snail control exist, the advent of an efficacious vaccine still remains the most potentially powerful means for control of this disease. Schistosomes interact closely with their host, performing functions such as nutrient uptake, immune avoidance and attachment. Our goal is to test the hypothesis that host-exposed, schistosome proteins that undertake such essential functions can be effective targets of a schistosomiasis vaccine. In this proposal, we focus on one host interactive protein and utilize the latest technologies to stimulate and modulate immune responses so as to definitively test the hypothesis that these proteins will be effective targets of a highly protective schistosomiasis vaccine. Our vaccine candidate is calcium activated neutral protease (= calpain, =sm-p80), which plays a pivotal role in the surface membrane renewal of schistosomes, a phenomenon which is considered to be a mechanism employed by hemo-helminths to evade host immunity. The protein has been shown to be exposed at the host parasite interface and to be naturally immunogenic. Therefore if an immune response is induced against this protein, it should cause substantial harm to the worm. In this application we propose to construct expression vectors containing cDNA encoding calpain and cytokines for DNA immunization. We will test DNA immunization protocols using these constructs containing calpain and also vectors directing co-expression of cytokines to enhance immune recognition of calpain for its ability to elicit a damaging effect on the survival of schistosomes. In addition to testing the hypothesis that functionally important schistosome host interactive proteins make effective vaccine targets, the results of the proposed experiments should offer additional benefits. Our studies will provide new data on how these strategies and cytokines succeed in modifying immune responses to amphitropic proteins. Of greater importance, these studies should provide new insight into immune mechanisms which can damage worm parasites and establish a model by which to subsequently study the effector mechanisms.

描述（由申请人提供）：血吸虫病是一种慢性，通常 使人衰弱的疾病折磨着2亿多人，另有600人 在74个国家中，有100万人处于危险之中。虽然杀线虫剂和其他 控制措施，包括公共卫生和控制蜗牛存在， 有效的疫苗仍然是最有效的手段， 控制这种疾病。 血吸虫与宿主密切相互作用，执行诸如 营养吸收、免疫回避和附着。我们的目标是测试 假设暴露于宿主的，进行这种 基本功能可以成为血吸虫病疫苗的有效靶点。在 在这个建议中，我们专注于一种宿主相互作用蛋白，并利用最新的 刺激和调节免疫反应的技术， 测试假设，这些蛋白质将是有效的目标， 血吸虫病保护性疫苗 我们的候选疫苗是钙激活的中性蛋白酶（=钙蛋白酶， =sm-p80），其在细胞表面膜更新中起关键作用。 这种现象被认为是一种机制， 血蠕虫逃避宿主免疫这种蛋白质已经被证明是暴露在 并具有天然免疫原性。因此，如果 免疫反应是针对这种蛋白质诱导的，它应该引起大量的 对蠕虫的伤害。 在本申请中，我们提出构建含有cDNA的表达载体， 编码用于DNA免疫的钙蛋白酶和细胞因子。我们会检测DNA 使用这些含有钙蛋白酶的构建体的免疫方案， 引导细胞因子共表达以增强免疫识别的载体 钙蛋白酶，因为它能够引起对生存的破坏性影响， 讨厌鬼除了测试功能重要性的假设 与宿主相互作用的蛋白质是有效的疫苗靶点， 拟议实验的结果应提供额外的好处。我们 研究将提供关于这些策略和细胞因子如何成功的新数据， 修饰对两亲性蛋白质的免疫反应。更重要的是， 这些研究将为免疫机制提供新的见解， 破坏蠕虫寄生虫，并建立模型，随后研究 效应器机制