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Candidacy of liver stage antigen-1 for Plasmodium falciparum vaccine development

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Malaria is the world's most important parasitic disease, imposing a massive health burden on people living in the tropics, often in the poorest countries. The vast majority of deaths in humans from malaria are caused by one species of the hemoprotozoan, Plasmodium falciparum., against which effective control measures are urgently needed. The global situation has deteriorated in recent times due to increased resistance of the anopheline mosquitoes that transmit P. falciparum to insecticides, and of the parasites themselves to drug therapy. An efficacious and cost-effective vaccine against this parasite is considered a public health priority. A vaccine that targets pre-erythrocytic parasites in the liver could potentially prevent clinical disease by blocking development of the pathogenic erythrocytic stage of the parasite's life cycle. Among around 40 known P. falciparum antigens, liver stage antigen-1 (LSA-1) is the only protein expressed exclusively by liver stage parasites. Independent studies in humans have consistently related immune responses to LSA-1 with resistance to malaria infection or disease, providing a powerful rationale for the development of liver stage vaccines based on LSA-1. By dissecting the mechanism(s) of immunity to this antigen, epitopes associated with protection can be evaluated in different delivery systems as components of a focused and coordinated multi-antigen malaria vaccine strategy.

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