Biologically informed design of CD8+ T cell-dependent pre-erythrocytic stage malaria vaccines

Live-attenuated Plasmodium parasite vaccines confer sterilizing immune protection against liver infection via CD8+ T cells, yet their molecular biological and immunological features that elicit this response and the target MHC class I epitopes of liver stage parasites remain largely unknown. We will elucidate protective features of replication-competent parasite vaccines and directly identify MHCI-restricted liver stage antigens from the surface of infected hepatocytes. This will allow us to build next generation vectored subunit vaccines as well genetically engineer optimally safe and potent live-attenuated vaccines.

Inducing durable, protective immune memory against malaria, this research will reveal the types of innate immune responses that are associated with the differentiation and maintenance of memory lymphocyte populations that will ultimately help aid future vaccine development against malaria and other global infectious diseases.