Targeting Plasmodium sporozoite-Kupffer cell interactions with a phage display library

After inoculation by the bite of an infected mosquito, Plasmodium sporozoites enter the blood stream and infect the liver with unique specificity. Previous evidence suggests that specific sporozoite-Kupffer cell interactions are required for liver invasion to occur but the molecular determinants of these interactions are unknown. By use of a phage display library we identified three peptides that bind to the surface of Kupffer cells. Importantly, these peptides strongly inhibited Plasmodium berghei sporozoite invasion of Kupffer cells in vitro and of the mouse liver in vivo. In a separate set of experiments we determined that antibodies against one of the peptides binds to the surface of sporozoites and protects mice from Plasmodium infection. The results suggest that the selected peptides interact with specific Kupffer cell surface receptor(s) and structurally mimic sporozoite ligands of liver invasion. These findings may lead to the development of novel protective vaccines. Role:I designed the project with assistance of my advisor and almost all of the experiments were done by me.