Development of an oral vaccine against strongyloidiasis

我们发现，在小鼠感染委内瑞拉圆线虫时，委内瑞拉圆线虫成虫在肠粘膜内积极移动，反复进出，委内瑞拉圆线虫排出的机制是肥大细胞糖胺聚糖抑制成虫再次侵入肠上皮。肠道肥大细胞增多症。阻止手术植入的成虫侵入肠粘膜，肥大细胞糖胺聚糖如硫酸软骨素A、硫酸软骨素E和肝素也抑制体内成虫的入侵。成虫通过口腔分泌的肝素结合黏附物质附着在肠上皮细胞上。肥大细胞糖胺聚糖以剂量依赖的方式抑制分泌黏附物质与肠上皮细胞的结合，从而阻断附着和随后的侵袭。小鼠抗分泌黏附物质（286…More -3D7, IgG1, κ）单克隆抗体显示，蠕虫在感染期间持续分泌这些物质，并在其周围形成隧道壁。因此，分泌黏附物质可能在委内瑞拉螺感染肠道寄生中起主要作用。286-3D7抑制成虫对塑料表面的粘附以及分泌的粘附物质与肠上皮细胞的结合。因此，抗体可以抑制成虫的入侵。兔抗分泌黏附物质的多克隆抗体识别可溶性成虫抗原中的2-3个蛋白，包括一个42.0 kDa的肝素结合蛋白，该蛋白在感染过程中在成虫体内一致表达。因此，这种蛋白似乎是肝素结合黏附物质的可能成分。对分泌性黏附物质的蛋白直接测序显示，即使在秀丽隐杆线虫中也没有明显的同源蛋白。这些重要蛋白cDNA的分子克隆将使我们进一步了解肠道线虫生物学，并为诱导对类圆线虫病的保护性免疫提供有力的工具。少

We demonstrated that, in Strongyloides venezuelensis infection in mice, adult worms of S.venezuelensis were actively moving in the intestinal mucosa, exiting and re-entering repeatedly, and that the mechanism for S.venezuelensis expulsion is the inhibition by mast cell glycosaminoglycans of re-invasion of adult worms into intestinal epithelium. Intestinal mastocytosis. prevented surgically implanted adult worms from invading into the intestinal mucosa, and mast cell glycosaminoglycans such as chondroitin sulfate A, chondroitin sulfate E,and heparin, also inhibited invasion of adult worms in vivo. Adult S.venezuelensis worms attach to the intestinal epithelial cells upon invasion by orally secreted heparin-binding adhesion substances. Mast cell glycosaminoglycans inhibited binding of secreted adhesion substances to intestinal epithelial cells in a dose-dependent manner, thus blocking attachment and subsequent invasion.A mouse monoclonal antibody against secreted adhesion substances (286 … More -3D7, IgG1, κ) revealed that worms continuously secreted the substances during infection, forming tunnel wall around them. Secreted adhesion substances, therefore, might play a major role in intestinal parasitism in S.venezuelensis infection. 286-3D7 inhibited adhesion of adult worms to plastic surface as well as binding of secreted adhesion substances to intestinal epithelial cells. Antibodies thus could be inhibitory to adult worm invasion. Rabbit polyclonal antibodies against secreted adhesion substances recognized 2-3 proteins in soluble adult antigens, including a heparin-binding protein of 42.0 kDa, which was consistently expressed by adult worms during infection. This protein therefore seemed a possible component of heparin-binding adhesion substances.Direct sequencing of proteins in secreted adhesion substances revealed no apparent homologous proteins even in Caenorhabditis elegans. Molecular cloning of cDNA for these important proteins would bring us further understanding of intestinal nematode biology and a strong tool to induce protective immunity against strongyloidiasis. Less