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 a n area of low-intensity, seasonal, and unstable malaria transmission in eas tern Sudan, and we have used this database to study the acquisition, specif icity, and duration of the antibody response to variant parasitized erythro cyte surface antigens. Both the levels and the spectrum of reactivity of th ese antibodies varied considerably among individuals, ranging from low leve ls of antibodies recognizing only few parasitized erythrocyte surface antig ens to high levels of broad-specificity antibodies. In general, episodes of clinical malaria were associated with increases in the levels of parasitiz ed erythrocyte surface-specific antibodies that subsided within months of t he attack This response was often, but not always, specific for the antigen ic variants expressed by the parasite isolate causing disease. Our study pr ovides evidence that Palciparum falciparum malaria is associated with a sho rt-lived, variant-specific antibody response to PfEMP1-like antigens expose d 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 co nditions of low-intensity, seasonal, and unstable malaria transmission. Fin ally, we demonstrate the existence of persistent differences among individu als in the capacity to mount antibody responses to variant surface antigens .