IMMUNOLOGICAL STUDY OF THE CS LIGAND AND ITS LIVER CELL RECEPTOR

基于诱导中和抗体的免疫预防， 抑制病毒、细菌或细菌毒素与 相应的宿主细胞受体，形成了许多疫苗的基础 目前在世界各地使用。 在项目3中，CS蛋白配体， 和该区域侧翼的氨基酸序列，将用作 抗原，以努力产生单克隆抗体，可以抑制 子孢子与肝细胞的结合。 啮齿动物疟疾模型将是 用于测定含有所述抗体的合成构建体的免疫原性。 最佳CS配体或侧翼序列，以确定是否 旨在抑制寄生虫/宿主细胞相互作用的疫苗可以保护 对抗体内子孢子攻击。 我们还将筛选免疫血清， 确定抗体是否在人体内诱导，无论是自然的， 感染或子孢子免疫，其可以结合肽 代表恶性疟原虫CS蛋白的II+区配体，和 亲和纯化的这种特异性的人抗体是否可以抑制 体外子孢子/肝细胞相互作用。 是否容忍 宿主或寄生虫的免疫逃避，调节对这些抗体的反应。 还将检查CS蛋白的非重复区域，因为这些区域 这些因素将决定疫苗的效力。 互惠研究将侧重于 产生多克隆和单克隆抗体， 肝细胞上的CS结合硫酸乙酰肝素蛋白聚糖， 在分子和细胞水平上表征这种受体。

Immunoprophylaxis based on the induction of neutralizing antibodies to inhibit the interaction of virus, bacteria or bacterial toxins, with the corresponding host cellular receptors, forms the basis of numerous vaccines in current use throughout the world. In Project 3, the CS protein ligand, and the amino acid sequences which flank this region, will be used as antigens in an effort to produce monoclonal antibodies that can inhibit the binding of sporozoites to liver cells. The rodent malaria model will be used to assay the immunogenicity of synthetic constructs containing the optimal CS ligand, or flanking sequences, in order to determine whether vaccines designed to inhibit parasite/host cell interactions can protect against sporozoite challenge in vivo. We will also screen immune sera to determine whether antibodies are induced in man, either by natural infection or sporozoite immunization, which can bind to peptides representing the region II-plus ligand of the P. falciparum CS protein, and whether affinity purified human antibodies of this specificity can inhibit sporozoite/hepatocyte interactions in vitro. Whether tolerance of the host, or immune evasion by the parasite, modulate the response to these non-repeat regions of the CS protein will also be examined, since these factors will determine vaccine efficacy. The reciprocal studies will focus on the generation of polyclonal and monoclonal antibodies that recognize the CS-binding heparan sulfate proteoglycan on the liver cell, in order to characterize this receptor at the molecular and cellular level.