Development of PfEMP1 based malaria vaccines


PfEMP1 are a class of parasite proteins expressed on the surface of Plamosium falciparum-infected erythrocytes, where they function as adhesion receptors interacting with a range of host tissue ligands. Tissue adhesion of infected erythrocytes is a significant factor in the virulence of P. falciparum malaria and PfEMP1 antigens are the major target of naturally acquired protective immunity to the disease. Both the adhesive interaction and immune recognition of PfEMP1 are critically dependent on presentation of PfEMP1 as an antigenic structure on the surface membrane of infected human red blood cells. However the molecular topology of PfEMP1 - the structural relationships between antigen and protective antibodies and between host cell receptor and parasite membrane ligand - are not understood. The objective of this program is to identify and characterise the PfEMP1 epitobes that are targeted by protective immune responses to guide the development of malaria vaccines based on these antigens. The project will be conducted in collaboration between researchers at University of Copenhagen, Kilimanjaro Christian Medical College and Tanga Centre, National Institute of Medical Research. The strategy is to obtain malaria parasites from children and pregnant women suffering from severe malaria and to use immunological molecular biological techniques to identify and characterise the PfEMP1 expressed by these parasites. We will go on to characterise which PfEMP1 domains that are targeted by protective antibodies and define which parts of these domains that harbour antibody epitobes targeted by protective antibodies.


Project Completion Report:

During this project we have: developed the first vaccine to protect women for pregnancy associated malaria planned to undergo clinical testing with the next years, defined the parasite proteins which precipitates severe malaria in children, participated in phase 2 and 3 clinical testing of a malaria vaccine to protect children from malaria, monitored and documented a dramatic decrease in the malaria burden in North Eastern Tanzania.