Age-related buildup of humoral immunity against epitopes for rosette formation and agglutination in African areas of malaria endemicity.

In this report, we show an age-related buildup of agglutinating activity as well as serum activity against rosette formation in children living in areas of Kenya and Gabon where malaria is endemic. Sera from Kenyans in general exhibited a stronger and wider immune response toward the epitopes, probably reflecting a difference in transmission patterns between the two areas. Thus, our results indicate that repeated malaria attacks in areas of endemicity, and consequently exposure to different isolate-specific antigens, will elicit an antibody-mediated response eventually enabling recognition of the majority of rosetting and agglutinating antigens. The correlation between antirosetting and agglutinating capacity was poor in individual cases, indicating that the rosetting epitopes are only a minor part of the highly diverse surface-exposed antigens (mainly PfEMP1) on the surface of parasitized erythrocytes toward which antibodies may react. These data together with our previous findings that the protection against cerebral malaria correlates with presence of antirosetting antibodies shed new light on our understanding of the gradual acquisition of immunity toward severe complications of malarial infection which children reared in areas of endemicity attain.