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Age-Dependent Cellular Immune Responses to Plasmodium vivax Duffy Binding Protein in Humans¹

Jia Xainli^*, Moses Baisor, Will Kastens^*, Moses Bockarie, John H. Adams and Christopher L. King^2,*,

^* Division of Geographic Medicine, Case Western Reserve University and Veterans Affairs Medical Center, Cleveland, OH 44106; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea; and University of Notre Dame, South Bend, IN 46556

The Plasmodium vivax merozoite Duffy binding protein (DBP) contains a cysteine-rich region II (DBPII) that binds to the Duffy Ag receptor for chemokines on erythrocytes, which is essential for parasite invasion. Cellular immune responses to DBPII have not been reported in P. vivax endemic populations, although they may contribute to partial acquired immunity. To examine host cellular immunity to DBPII and identify major T cell epitopes, PBMCs from 107 individuals (2–68 years old) were examined for cytokine production by ELISPOT and/or ELISA to rDBP and overlapping peptides (displaced by 2 aa spanning a 170-aa region of DBPII corresponding to the critical binding motif to the Duffy Ag receptor for chemokines). In P. vivax-exposed subjects, 60 and 71% generated significant rDBP-induced IFN- and IL-10 production, respectively, 11% stimulated IL-2, and IL-5 and IL-13 were not detected. Children <5 years of age had reduced levels and frequency of rDBP-induced IL-10 and IFN- production compared with partially immune older children and adults (p < 0.01). Five major T cell epitopes were identified. Three of these T cell epitopes contained polymorphic residues present in the population. Peptides synthesized corresponding to these variants induced IFN- and IL-10 production to one variant and little response to the other variant in the same individual. These results demonstrate age-dependent and variant-specific cellular immune responses to DBPII and implicate this molecule in partial acquired immunity to P. vivax in endemic populations.

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				J. Xainli, J. L. Cole-Tobian, M. Baisor, W. Kastens, M. Bockarie, S. S. Yazdani, C. E. Chitnis, J. H. Adams, and C. L. King Epitope-Specific Humoral Immunity to Plasmodium vivax Duffy Binding Protein Infect. Immun., May 1, 2003; 71(5): 2508 - 2515. [Abstract] [Full Text] [PDF]