Malaria Parasite Ligands And Host Cell Receptors

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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.