Malaria Parasite Ligands And Host Cell Receptors

目的：1.鉴定疟原虫红细胞侵入受体和感染红细胞粘附于内皮和胎盘的受体。2.识别每种寄生虫配体的红细胞受体。3.鉴定与胎盘结合的变异抗原的最小结构域。4.测试变异抗原上的一个区域，用于诱导Aotus猴对恶性疟原虫的保护和克服变异。本年度取得的成绩：1。在世界范围内，在一种恶性疟原虫受体中发现了六种突变。每个突变都与红细胞上不同的受体结合。该家族其他成员的寄生虫受体显示结合红细胞2。在胎盘中结合硫酸软骨素A的变体抗原上的最小结构域已被鉴定。由于胎盘中受感染红细胞的结合与胎儿和新生儿死亡率有关，因此用疫苗阻断这种结合可能会减少疾病。这个区域的抗体似乎与世界各地的寄生虫有交叉反应.我们正在研究这个领域作为候选疫苗。3.已经开发了一种方法来诱导免疫力，该免疫力将克服变异抗原的多样性。

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 minimal domain in the variant antigen for binding to placenta. 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. Six mutations were identified worldwide in one of the P. falciparum parasite receptor. Each mutation binds to a different receptor on the red cell. The parasite receptor for other members of this family are shown to bind red cells 2. The minimal 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. 3. A method has been developed to induce immunity that will overcome diversity in the variant antigen.