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与内皮细胞和胎盘黏附的受体。2.确定每个寄生虫配体的红细胞受体。3.确定变异抗原中与胎盘结合的最小结构域。4.在变异抗原上测试一个区域，以诱导对恶性疟原虫的保护和克服变异。一年来取得的成就：1.在全球范围内发现了恶性疟原虫一种受体的六个突变。每个突变都与红细胞上的不同受体结合。该家族其他成员的寄生虫受体被证明能结合红细胞2。已确定了与胎盘中的硫酸软骨素A结合的变异抗原上的最小结构域。由于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，用疫苗阻止这一点可能会减少疾病。这个区域的抗体似乎对来自世界各地的寄生虫有交叉反应。作为候选疫苗，我们正在研究这一领域。3.已经开发出一种方法来诱导免疫，以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.