Membrane transport during liver-stage growth and development of a potent and safe live whole-parasite vaccine
Annie Yang works on several aspects of Plasmodium falciparum liver-stage biology including whole-parasite live vaccine development. Larger-scale generation of loss-of-function mutants and streamlined profiling of their life cycle progression provides a wealth of data that will help us understand malaria parasite biology, but it can also lead to the generation of promising late-arresting genetically attenuated parasites (LA-GAPs) that may be used as whole-organism vaccines. LA-GAPs provide more potent protection in mice than early arresting vaccines, however, breakthrough infections of the current LA-GAPs prohibit a translation to P. falciparum. Interestingly, many of these GAP candidates lack genes with roles in the apicoplast, a plastid of red algal origin. Indeed, many apicoplast proteins appear to play an important role during liver-stage development. Annie will continue to develop some of our most promising LA-GAP candidates, by combining multiple gene deletions and including newly identified targets in the vaccine development pipeline, while further functional characterization of these LA-GAP candidates will help us understand host switching leading to a new infection.
Taco Kooij 