Designer Parasites: Genetically Engineered Plasmodium as Vaccines To Prevent Malaria Infection

A highly efficacious malaria vaccine that prevents disease and breaks the cycle of infection remains an aspirational goal of medicine. Whole parasite vaccines based on the sporozoite forms of the parasite that target the clinically silent pre-erythrocytic stages of infection have emerged as one of the leading candidates. In animal models of malaria, these vaccines elicit potent neutralizing Ab responses against the sporozoite stage and cytotoxic T cells that eliminate parasite-infected hepatocytes. Among whole-sporozoite vaccines, immunization with live, replication-competent whole parasites engenders superior immunity and protection when compared with live replication-deficient sporozoites. As such, the genetic design of replication-competent vaccine strains holds the promise for a potent, broadly protective malaria vaccine. In this report, we will review the advances in whole-sporozoite vaccine development with a particular focus on genetically attenuated parasites both as malaria vaccine candidates and also as valuable tools to interrogate protective immunity against infection.