Malaria Parasite Ligands And Host Cell Receptors

目的:1。目的：鉴定疟原虫红细胞入侵受体和感染红细胞粘附内皮和胎盘受体。2. 确定每个寄生虫配体的红细胞受体。3.确定结合胎盘的寄生虫和结合内皮的寄生虫的二分法的基础。4. 对变异抗原的一个区域进行测试，以诱导猴对恶性疟原虫的保护并克服变异。一年内取得的成绩：恶性疟原虫与红细胞结合的新受体及其与红细胞结合的受体的鉴定。2. 已经确定了胎盘中结合硫酸软骨素A的变异抗原的结构域。由于受感染的红细胞在胎盘中的结合与胎儿和新生儿的死亡率有关，用疫苗阻断这种结合可能会减少疾病。该结构域的抗体似乎对来自世界各地的寄生虫有交叉反应。我们正在研究这个域作为候选疫苗。我们已经确定了与CD36或CIDR1的二分类结合的基础。3. 第一个针对红细胞表面的一种用于结合内皮的变异抗原域（CIDR1）的疫苗试验已用于在猕猴身上接种的疫苗，该疫苗对同源株具有保护作用，而对异源株没有保护作用。

Purpose: 1. To identify the receptors on malaria parasites for red cell invasion and on infected red cells for adhesion to endothelium and to placenta. 2. To identify the red cell receptors for each parasite ligand. 3.To identify the basis of the dichotomy between parasites that bind placenta and parasites that bind to endothelium. 4. Test a region on the variant antigen for inducing protection against P. falciparum in Aotus monkeys and for overcoming variation. Accomplishments during the year: 1. Identification of a new receptor on P. falciparum malaria parasites for binding to red cells and the receptor on the red cell to which it binds. 2. The domain on the variant antigen for binding chondroitin sulfate A in placenta has been identified. As the binding of infected red cells in placenta is associated with fetal and newborn mortality, blocking this with a vaccine may reduce disease. Antibodies to this domain appear to be cross- reactive to parasites from around the world. We are working on this domain as a vaccine candidate. We have identified the basis of the dichotomous binding to CD36 or CIDR1. 3. The first vaccine trial against one of the domain of the variant antigen (CIDR1) on the red cell surface for binding endothelium has been used in a vaccine in Aotus monkeys that protected against the homologous strain but not the heterologous one.