The erythrocytic stage of Plasmodium falciparum kills an estimated 2 million children annually. The parasite invades erythrocytes (RBCs) by attaching to surface receptors, one of which involves sialic acids. The 175 kD P. falciparum protein, erythrocyte binding antigen (BBA-175), binds to RBCs in a sialic acid dependent, receptor-specific fashion. The ability of EBA-l75 to bind to RBCs correlates with the ability of these RBCs to be invaded by parasites. The actual sialic acid binding domain of EBA-175 (region ll) has recently been identified.
The specific aim of this Phase l proposal is to determine if antibodies against region ll of EBA- 175 will block merozoite invasion of RBCs indicating that region H should be developed as a malaria vaccine. To accomplish this goal, a plasmid construct with region H of EBA-175 will be expressed by 2 methods in mammalian cells, and in prokaryotic cells, and the expressed proteins assessed for their capacity to produce functionally active antibodies. The short term goals of this proposal are, l) to determine if region ll can induce functional antibodies, and 2) to determine which expression method induces the most functionally active antibodies. The long term goal is to assess the safety, immunogenicity, and protective efficacy of the best immunogen first in Aotus monkeys, and then in humans.
| Ambroggio, Xavier; Jiang, Lubin; Aebig, Joan et al. (2013) The epitope of monoclonal antibodies blocking erythrocyte invasion by Plasmodium falciparum map to the dimerization and receptor glycan binding sites of EBA-175. PLoS One 8:e56326 |
| Sim, B Kim Lee; Narum, David L; Chattopadhyay, Rana et al. (2011) Delineation of stage specific expression of Plasmodium falciparum EBA-175 by biologically functional region II monoclonal antibodies. PLoS One 6:e18393 |
