Nine-year longitudinal study of antibodies to variant antigens on the surface of Plasmodium falciparum-infected erythrocytes

PfEMP1 is an antigenically variable molecule which mediates the adhesion of parasitized erythrocytes to a variety of cell types and which is believed to constitute an important target for naturally acquired protective immune responses in malaria. For 9 years we have monitored individuals living in an area of low-intensity, seasonal, and unstable malaria transmission in eastern Sudan, and we have used this database to study the acquisition, specificity, and duration of the antibody response to variant parasitized erythrocyte surface antigens. Both the levels and the spectrum of reactivity of these antibodies varied considerably among individuals, ranging from low levels of antibodies recognizing only few parasitized erythrocyte surface antigens to high levels of broad-specificity antibodies. In general, episodes of clinical malaria were associated with increases in the levels of parasitized erythrocyte surface-specific antibodies that subsided within months of the attack This response was often, but not always, specific for the antigenic variants expressed by the parasite isolate causing disease. Our study provides evidence that Palciparum falciparum malaria is associated with a short-lived, variant-specific antibody response to PfEMP1-like antigens exposed on the surface of parasitized erythrocytes. Furthermore, our data suggest that the antigenic repertoires of variant antigens expressed by different parasite isolates show considerable overlapping, at least under Sahelian conditions of low-intensity, seasonal, and unstable malaria transmission. Finally, we demonstrate the existence of persistent differences among individuals in the capacity to mount antibody responses to variant surface antigens.