Malaria

We posit that the structures of important vaccine targets will reveal both interesting biology, and enable rational development of vaccines. These vaccines will focus the immune response on conserved epitopes, and avoid masking by polymorphic epitopes that pathogens often use to evade immune responses. Proteins on sporozoites are candidates for vaccines that prevent infection. We are interested in determining the structure of the sheath that surrounds sporozoites, its main component the circumsporozoite protein, and the motility protein TRAP. Proteins on gametocytes are targets for vaccines that prevent Plasmodium fertilization and infection in mosquitoes, and prevent transmission to other humans. These proteins include a family unique to Apicomplexans with 6-Cys domains, and HAP2, a putative gamete fusogen conserved in many eukaryotic phyla.