SCHISTOSOME HOST/INTERACTIVE SURFACE MEMBRANE PROTEINS

血吸虫是细胞外的血吸虫，可以存活很多年。 在人体血管系统内存活数年。因为这些蠕虫密切地相互作用 与它们的宿主一起执行诸如营养吸收和 通常由整体表面膜执行的附着 蛋白质，寄生虫一定已经形成了避免 针对这些蛋白质的免疫攻击。我们的目标是确定 这些有功能的、宿主暴露的血吸虫膜蛋白是否可以 成为血吸虫病疫苗的有效靶点。如果成功，这将是 新的疫苗接种策略也应该对其他 由蠕虫寄生虫引起的疾病。 朝着我们的目标，我们已经获得了几个全长血吸虫 Mansoni的cdna克隆，其中三个编码表膜蛋白， 我们已经证明在生活中存在于宿主/寄生虫的界面 虫子。其中包括葡萄糖转运体，一种氨基酸渗透酶 同源物和表面抗原SM23。所有这些都被表达到了高水平 重组昆虫细胞内的水平。在此应用程序中，我们建议 把我们的努力集中在三个真正的血吸虫宿主互动上 膜蛋白(HIMP)，并进行最终研究 确定HIMP是否可以成为有效血吸虫病的目标 疫苗。我们将使用构象天然的重组蛋白 和裸露DNA表达质粒作为免疫原诱导细胞和/或 针对宿主暴露的HIMP表位的体液免疫反应。 免疫成功的小鼠将被测试它们的抵抗能力 血吸虫感染。重组抗体库(RAB)将 从免疫成功的小鼠的脾中提取并筛选 用于显示表面表位识别的克隆。精制兔抗菌药物 阳性克隆将接受测试，以确定其被动转移的能力 防止尾蚴感染。宿主暴露的表位将是 确定并用于设计改进的候选疫苗。

Schistosomes are extracellular blood flukes that can survive for many years within the human vascular system. Since the worms interact closely with their host, performing functions such as nutrient uptake and attachment that are normally performed by integral surface membrane proteins, the parasites must have developed mechanisms for avoiding immune attack directed at these proteins. Our goal is to determine whether these functional, host-exposed, schistosome membrane proteins can be effective targets of a schistosomiasis vaccine. If successful, this novel vaccination strategy should also be effective against other diseases caused by helminth parasites. Towards our goal, we have obtained several full-length Schistosoma mansoni cDNA clones, three of which encode surface membrane proteins that we have shown to be present at the host/parasite interface in living worms. These include a glucose transporter, an amino acid permease homologue and the surface antigen, SM23. All have been expressed to high levels within recombinant insect cells. In this application, we propose to focus our efforts on the three bona fide schistosome host-interactive membrane proteins (HIMPs) and perform the definitive studies that win ascertain whether HIMPs can be targets of an effective schistosomiasis vaccine. We will use both conformationally native, recombinant protein and naked DNA expression plasmids as immunogens to induce cellular and/or humoral immune responses against host-exposed epitopes on the HIMPs. Successfully immunized mice will be tested for their ability to resist schistosome infection. A library of recombinant antibodies (rAbs) will be generated from the spleens of successfully immunized mice and screened for clones that display surface epitope recognition. Purified rAbs from positive clones will be tested for their ability to passively transfer protection against cercariaI infection. Host-exposed epitopes will be determined and used to design improved vaccine candidates.