Sequential, ordered acquisition of antibodies to Plasmodium falciparum erythrocyte membrane protein 1 domains

TY - JOUR

T1 - Sequential, ordered acquisition of antibodies to Plasmodium falciparum erythrocyte membrane protein 1 domains

AU - Cham, Gerald K K

AU - Turner, Louise

AU - Lusingu, John

AU - Vestergaard, Lasse

AU - Mmbando, Bruno P

AU - Kurtis, Jonathan D

AU - Jensen, Anja T R

AU - Salanti, Ali

AU - Lavstsen, Thomas

AU - Theander, Thor G

N1 - Keywords: Adolescent; Adult; Age Factors; Animals; Antibodies, Protozoan; Antigens, Protozoan; Child; Child, Preschool; Cross-Sectional Studies; Erythrocyte Membrane; Humans; Infant; Infant, Newborn; Malaria, Falciparum; Middle Aged; Parasitemia; Plasmodium falciparum; Prevalence; Protein Structure, Tertiary; Protozoan Proteins; Young Adult

PY - 2009

Y1 - 2009

N2 - The binding of erythrocytes infected with mature blood stage parasites to the vascular bed is key to the pathogenesis of malignant malaria. The binding is mediated by members of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family. PfEMP1s can be divided into groups, and it has previously been suggested that parasites expressing group A or B/A PfEMP1s are most pathogenic. To test the hypothesis that the first malaria infections in infants and young children are dominated by parasites expressing A and B/A PfEMP1s, we measured the plasma Ab level against 48 recombinant PfEMP1 domains of different groupings in 1342 individuals living in five African villages characterized by markedly different malaria transmission. We show that children progressively acquire a broader repertoire of anti-PfEMP1 Abs, but that the rate of expansion is governed by transmission intensity. However, independently of transmission intensity, Abs are first acquired to particular Duffy binding ligand-like domains belonging to group A or B/A PfEMP1s. The results support the view that anti-PfEMP1 Ab responses effectively structure the expenditure of the repertoire of PfEMP1 maintained by the parasite. Parasites expressing certain group A and B/A PfEMP1s are responded to first by individuals with limited previous exposure, and the resulting Abs reduce the fitness and pathogenicity of these parasites during subsequent infections. This allows parasites expressing less pathogenic PFEMP1s to dominate during later infections. The identification of PfEMP1 domains expressed by parasites causing disease in infants and young children is important for development of vaccines protecting against severe malaria.

AB - The binding of erythrocytes infected with mature blood stage parasites to the vascular bed is key to the pathogenesis of malignant malaria. The binding is mediated by members of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family. PfEMP1s can be divided into groups, and it has previously been suggested that parasites expressing group A or B/A PfEMP1s are most pathogenic. To test the hypothesis that the first malaria infections in infants and young children are dominated by parasites expressing A and B/A PfEMP1s, we measured the plasma Ab level against 48 recombinant PfEMP1 domains of different groupings in 1342 individuals living in five African villages characterized by markedly different malaria transmission. We show that children progressively acquire a broader repertoire of anti-PfEMP1 Abs, but that the rate of expansion is governed by transmission intensity. However, independently of transmission intensity, Abs are first acquired to particular Duffy binding ligand-like domains belonging to group A or B/A PfEMP1s. The results support the view that anti-PfEMP1 Ab responses effectively structure the expenditure of the repertoire of PfEMP1 maintained by the parasite. Parasites expressing certain group A and B/A PfEMP1s are responded to first by individuals with limited previous exposure, and the resulting Abs reduce the fitness and pathogenicity of these parasites during subsequent infections. This allows parasites expressing less pathogenic PFEMP1s to dominate during later infections. The identification of PfEMP1 domains expressed by parasites causing disease in infants and young children is important for development of vaccines protecting against severe malaria.

U2 - 10.4049/jimmunol.0901331

DO - 10.4049/jimmunol.0901331

M3 - Journal article

C2 - 19675168

SN - 0022-1767

VL - 183

SP - 3356

EP - 3363

JO - Journal of Immunology

JF - Journal of Immunology

IS - 5

ER -