Scientists have discovered a powerful strategy to combat malaria that may be described as the most effective next-generation vaccination approach for the disease. The new approach works by eliciting an immune response that can combat the malarial parasite during multiple stages of its complex life cycle. "Halting Plasmodium infection during the clinically silent liver stage represents an attractive goal of antimalarial vaccination, but is challenging because, if not complete, some parasites can get into the blood and cause disease," noted study co-author Stefan Kappe, from the Seattle Biomedical Research Institute.
Irradiating the parasites elicits extensive and random DNA damage that arrests the parasite early in the liver and provides the immune system with an opportunity to develop an immune response that can combat the native parasite. However, very high irradiated-sporozoites doses are needed to generate full liver-stage protection and there is no protection against blood stages.
"In our study, we examined whether genetically attenuated parasites (GAP) generated by targeted gene deletions to stop replication late in liver-stage development were a better vaccine option," said co-author John Harty from the University of Iowa. Using mouse malaria models, the researchers discovered that immunization with late-liver-stage-arresting GAP provided superior and long-lasting protection against liver-stage infection when compared with irradiated parasites or early-liver-stage arresting GAP.
Importantly, late-liver-stage-arresting GAP also provided protection at the blood stage of infection and across different malaria parasite species, as well as by the route of immunization that can be used in humans. The research was published online in the journal Cell Host and Microbe , June 15.