Antigenic drift in the ligand domain of Plasmodium vivax duffy binding protein confers resistance to inhibitory antibodies.
Interaction of the Duffy binding protein (DBP) with its erythrocyte receptor is critical for maintaining Plasmodium vivax blood-stage infections, making DBP an appealing vaccine candidate. The cysteine-rich region II is the ligand domain of DBP and a target of vaccine development. Interestingly, most of the allelic diversity observed in DBP is due to the high rate of nonsynonymous polymorphisms in this critical domain for receptor recognition. Similar to the hypervariability in influenza hemagglutinin, this pattern of polymorphisms in the DBP ligand domain suggests that this variation is a mechanism to evade antibody neutralization. To evaluate the role that dbp allelic diversity plays in strain-specific immunity, we examined the ability of an anti-Sal1 DBP serum to inhibit the erythrocyte-binding function of variant dbp alleles expressed on COS cells. We observed that the PNG-7.18 allele was significantly less sensitive to immune inhibition of its erythrocyte-binding activity than were the Sal1 and PNG-27.16 alleles. This result suggested that the unique polymorphisms of resistant PNG-7.18 were part of a protective epitope on the DBP ligand. To confirm this, Sal1 was converted to the refractory phenotype by introduction of 3 polymorphisms unique to PNG-7.18, via site-directed mutagenesis. The results of the present study indicate that linked polymorphisms have an additive, synergistic effect on DBP antigenic character.
Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556-0369, USA.
Kelley M
KM
VanBuskirk
Jennifer L
JL
Cole-Tobian
Moses
M
Baisor
Elitza S
ES
Sevova
Moses
M
Bockarie
Christopher L
CL
King
John H
JH
Adams
D000483:Alleles; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D004375:Duffy Blood-Group System; D040961:Genetic Drift; D014644:Genetic Variation; D006801:Humans; D008024:Ligands; D016780:Malaria, Vivax / Q000276:immunology; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010219:Papua New Guinea; D010966:Plasmodium vivax / Q000235:genetics / Q000276:immunology*; D011110:Polymorphism, Genetic; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D004375:Duffy Blood-Group System; C066001:Duffy antigen binding protein, Plasmodium; D008024:Ligands; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface