Immunity to liver stage malaria: considerations for vaccine design

Malaria is the world's deadliest parasitic disease and effective control measures are a public health priority. Most deaths in humans from malaria are caused by one species of the protozoa, Plasmodium falciparum. An efficacious and cost-effective vaccine against this parasite is considered a holy grail of modern molecular medicine. A vaccine that targets liver stage parasites would prevent infection from reaching the blood and causing clinical disease. Among known P. falciparum antigens, liver stage antigen-1 (LSA-1) is the only protein expressed exclusively by infected hepatocytes. Several independent studies in humans have consistently related immune responses to LSA-1 with resistance to infection or disease, providing a powerful rationale for the development of liver stage vaccines. Investigations by ourselves and others aim to dissect the mechanism of cellular immunity to LSA-1 and to evaluate in different delivery systems epitopes associated with protection as components of a multiantigen malaria vaccine. The first clinical trials are already being conducted, the results of which are eagerly awaited.