Scientists discover protein targets critical to developing malaria vaccines for pregnant women and children
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Tanzanian women and their children may one-day benefit from a malaria pregnancy vaccine.
Credit: Voices for a Malaria Free Future/Bonnie Gillespie |
NIAID grantee Patrick Duffy, M.D. directs the malaria program at Seattle Biomedical Research Institute (SBRI), Department of Global Health, University of Washington, leads an international malaria research and training program for African scientists, and coordinates malaria vaccine trials in Tanzania. He and his colleagues have described the pathogenesis of pregnancy malaria and severe malaria in children; pioneered the use of functional genomics tools to study malaria parasites in the field; and established the first DNA microarray facility in east Africa, the Genome Science Center at Sokoine University in Morogoro, Tanzania.
Placental malaria occurs though a complex set of interactions between the malaria parasite, the pregnant woman, and her fetus. Parasites sequester in the human placenta by binding to a novel receptor, known as chondroitin sulfate A (CSA), which does not commonly support binding of other parasites. Dr. Duffy led the first studies of the human immune response to sequestered parasites and defined the molecular basis for preeclampsia—pregnancy-induced hypertension—caused by placental malaria.
Preeclampsia, like placental malaria, occurs most often among women having their first child. It accounts for a large proportion of maternal deaths in women under age 20. Dr. Duffy used genomic tools to characterize the distinct features of placental parasites, and identified protein targets for preeclampsia-infected red cells, a key step in developing vaccines.
He has built upon his work by assessing parasite proteins as candidates for a malaria vaccine that will protect the new mothers and their babies from placental malaria. Dr. Duffy collected parasites from Tanzanian women with pregnancy malaria. He examined whole-genome profiles of the parasites and identified six genes associated with the development of the placental parasites. The finding suggests these genes are important in the placental binding of malaria parasites and that targeting the genes may lead to novel therapeutic intervention for pregnant woman and their offspring.
African children under the age of five are the hardest hit by severe malaria. Earlier studies have shown that antibodies purified from the blood of immune adult Africans could effectively treat young children with malaria. Dr. Duffy and his colleagues are working to identify the human immune responses in children that will protect them. The work is being conducted onsite in Tanzania, using the services of the Mother-Offspring Malaria Study (MOMS) laboratory and the Genome Science Center at Sokoine University.
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