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Many studies on the role of merozoite surface protein 3 (MSP3) in immunity against malaria have focused on a conserved section of MSP3. New evidence suggests that polymorphic sequences within MSP3 are under immune selection. We report a detailed analysis of naturally-acquired antibodies to allele-specific and conserved parts of MSP3 in a Kenyan cohort. Indirect and competition ELISA to heterologous recombinant MSP3 proteins were used for antibody assays, and parasites were genotyped for msp3 alleles. Antibody reactivity to allele-specific and conserved epitopes of MSP3 was heterogeneous between individuals. Overall, the prevalence of allele-specific antibody reactivity was significantly higher (3D7-specific 54%, K1-specific 41%) than that to a recombinant protein representing a conserved portion of C-terminal MSP3 (24%, P < 0.01). The most abundant IgG subclass was IgG3, followed by IgG1. Allele-specific reactivity to the K1-type of MSP3 was associated with a lower risk of clinical malaria episodes during a 6-month follow-up in individuals who were parasitized at the start of the malaria transmission season (Relative risk 0.41 with 95% confidence interval 0.20-0.81, P = 0.011). The potential importance of allele-specific immunity to MSP3 should be considered in addition to immunity to conserved epitopes, in the development of an MSP3 malaria vaccine.

Original publication

DOI

10.1111/j.1365-3024.2007.00951.x

Type

Journal article

Journal

Parasite Immunol

Publication Date

08/2007

Volume

29

Pages

387 - 394

Keywords

Alleles, Animals, Antibodies, Protozoan, Antigens, Protozoan, Cohort Studies, Enzyme-Linked Immunosorbent Assay, Epitopes, Humans, Immunoglobulin G, Kenya, Longitudinal Studies, Malaria, Falciparum, Plasmodium falciparum, Protozoan Proteins, Recombinant Fusion Proteins