Schistosome Calpain as a Vaccine Candidates

血吸虫钙蛋白酶作为候选疫苗

• 批准号: 6570481
• 负责人: Afzal A Siddiqui
• 金额: $ 4.22万
• 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 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6570481
• 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病，通常 使人衰弱的疾病困扰着超过 2 亿人，另有 600 人 74 个国家有 100 万人面临风险。尽管杀血吸虫剂和其他 控制措施，包括公共卫生和蜗牛控制存在，出现 有效的疫苗仍然是最有可能最有力的手段 控制这种疾病。 血吸虫与其宿主密切相互作用，执行以下功能： 营养吸收、免疫回避和依恋。我们的目标是测试 假设宿主暴露的血吸虫蛋白承担这种 基本功能可以成为血吸虫病疫苗的有效目标。在 在这个提案中，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，以便最终 检验这些蛋白质将成为高度有效靶标的假设 保护性血吸虫病疫苗。 我们的候选疫苗是钙激活中性蛋白酶（=钙蛋白酶， =sm-p80)，它在表面膜更新中起着关键作用 血吸虫，一种被认为是血吸虫所采用的机制的现象 血液蠕虫逃避宿主免疫。该蛋白质已被证明已暴露 位于宿主寄生虫界面并具有天然免疫原性。因此，如果一个 针对这种蛋白质诱导免疫反应，它应该会引起大量的 对蠕虫的伤害。 在此应用中，我们建议构建含有 cDNA 的表达载体 编码用于 DNA 免疫的钙蛋白酶和细胞因子。我们将测试DNA 使用这些含有钙蛋白酶的构建体的免疫方案 载体指导细胞因子共表达以增强免疫识别 钙蛋白酶因其能够对生物的生存产生破坏性影响 血吸虫。除了检验功能上重要的假设之外 血吸虫宿主相互作用蛋白成为有效的疫苗靶标 所提出的实验结果应该会带来额外的好处。我们的 研究将提供有关这些策略和细胞因子如何成功的新数据 改变对两性蛋白的免疫反应。更重要的是， 这些研究应该为免疫机制提供新的见解，从而可以 损害蠕虫寄生虫并建立模型，随后研究 效应器机制。