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

Abstract

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.

FIG. 1

Percentage of Kenyan individuals in each age group exhibiting ≥50% antirosetting serum activity (A) and agglutination (≥1+ on the semiquantitative scale) (B) toward the P. falciparum laboratory strain FCR3S1 (■) or TM284 (░⃞). Sera from 22 to 24 individuals in each age group were tested in assays performed as indicated in Materials and Methods.

FIG. 2

Sera from 12 Kenyan children selected for high antirosetting activity tested against nine Gabonese P. falciparum isolates for antirosetting (A) and agglutinating (B) activities. Antirosetting activity (percent inhibition of rosetting) and agglutinating activity (for semiquantitative scoring scale, see Materials and Methods) are depicted in a five-level grey scale as indicated. A serum obtained from a nonimmune Swede (n/i) was used as a control.

FIG. 3

Sera from 15 Gabonese adults tested against the two laboratory strains FCR3S1 and TM284 and against six Gabonese P. falciparum isolates for antirosetting (A) and agglutinating (B) activities. Antirosetting activity (percent inhibition of rosetting) and agglutinating activity (for semiquantitative scoring scale, see Materials and Methods) are depicted in a five-level grey scale as indicated. A highly rosette disrupting and agglutinating Kenyan serum (K14) and serum obtained from a nonimmune Swede (n/i) were used as controls.

FIG. 4

Percentage of Gabonese individuals in each age group exhibiting ≥50% antirosetting serum activity (A) and agglutination (≥1+ on the semiquantitative scale) (B) toward the P. falciparum laboratory strain FCR3S1 (■) or TM284 (░⃞) and toward the Gabonese isolate G168 (). Sera from 10 to 14 individuals in each age group were tested.