PARASITE ANTIGENS ON THE INFECTED RED-CELL SURFACE ARE TARGETS FOR NATURALLY ACQUIRED-IMMUNITY TO MALARIA

The feasibility of a malaria vaccine is supported by the fact that chi ldren in endemic areas develop naturally acquired immunity to disease. Development of disease immunity is characterized by a decrease in the frequency and severity of disease episodes over several years despite almost continuous infection(1), suggesting that immunity may develop through the acquisition of a repertoire of specific, protective antibo dies directed against polymorphic target antigens(1-3). Plasmodium fal ciparum erythrocyte membrane protein 1 (PfEMP1) is a potentially impor tant family of target antigens, because these proteins are inserted in to the red cell surface and are prominently exposed(4-6) and because t hey are highly polymorphic and undergo clonal antigenic variation(7,8, 18), a mechanism of immune evasion maintained by a large family of vor genes(9-11). In a large prospective study of Kenyan children, we have used the fact that anti-PfEMP1 antibodies agglutinate infected erythr ocytes in a variant-specific manner(10,12-16), to show that the PfEMP1 variants expressed during episodes of clinical malaria were less like ly to be recognized by the corresponding child's own preexisting antib ody response than by that of children of the same age from the same co mmunity. In contrast, a heterologous parasite isolate was just as like ly to be recognized. The apparent selective pressure exerted by establ ished anti-PfEMP1 antibodies on infecting parasites supports the idea that such responses provide variant-specific protection against diseas e.