title: Naturally acquired antibodies to polymorphic and conserved epitopes of Plasmodium falciparum merozoite surface protein 3.
abstract: 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.
authors.affiliation: London School of Hygiene and Tropical Medicine, Keppel Street, London, UK. fosier@kilifi.kemri-wellcome.org
authors.forename: F H A
authors.initials: FH
authors.lastname: Osier
authors.forename: S D
authors.initials: SD
authors.lastname: Polley
authors.forename: T
authors.initials: T
authors.lastname: Mwangi
authors.forename: B
authors.initials: B
authors.lastname: Lowe
authors.forename: D J
authors.initials: DJ
authors.lastname: Conway
authors.forename: K
authors.initials: K
authors.lastname: Marsh
mesh_terms: D000483:Alleles; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology*; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007630:Kenya; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000097:blood / Q000276:immunology* / Q000469:parasitology; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000939:Epitopes; D007074:Immunoglobulin G; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; C089133:merozoite surface protein 3, Plasmodium