title: Allele-specific antibodies to Plasmodium falciparum merozoite surface protein-2 and protection against clinical malaria.
abstract: IgG and IgG3 antibodies to merozoite surface protein-2 (MSP-2) of Plasmodium falciparum have been associated with protection from clinical malaria in independent studies. We determined whether this protection was allele-specific by testing whether children who developed clinical malaria lacked IgG/IgG3 antibodies specific to the dominant msp2 parasite genotypes detected during clinical episodes. We analysed pre-existing IgG and IgG1/IgG3 antibodies to antigens representing the major dimorphic types of MSP-2 by ELISA. We used quantitative real-time PCR to determine the dominant msp2 alleles in parasites detected in clinical episodes. Over half (55%, 80/146) of infections contained both allelic types. Single or dominant IC1- and FC27-like alleles were detected in 46% and 42% of infections respectively, and both types were equally dominant in 12%. High levels of IgG/IgG3 antibodies to the FC27-like antigen were not significantly associated with a lower likelihood of clinical episodes caused by parasites bearing FC27-like compared to IC1-like alleles, and vice versa for IgG/IgG3 antibodies to the IC1-like antigen. These findings were supported by competition ELISAs which demonstrated the presence of IgG antibodies to allele-specific epitopes within both antigens. Thus, even for this well-studied antigen, the importance of an allele-specific component of naturally acquired protective immunity to malaria remains to be confirmed.
authors.affiliation: KEMRI-Centre for Geographic Medicine Research, Coast, Kilifi, Kenya. fosier@kilifi.kemri-wellcome.org
authors.forename: F H A
authors.initials: FH
authors.lastname: Osier
authors.forename: L M
authors.initials: LM
authors.lastname: Murungi
authors.forename: G
authors.initials: G
authors.lastname: Fegan
authors.forename: J
authors.initials: J
authors.lastname: Tuju
authors.forename: K K
authors.initials: KK
authors.lastname: Tetteh
authors.forename: P C
authors.initials: PC
authors.lastname: Bull
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*; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D002675:Child, Preschool; D016054:DNA, Protozoan / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control*; D010963:Plasmodium falciparum / Q000276:immunology*; D016133:Polymerase Chain Reaction; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D016054:DNA, Protozoan; D007074:Immunoglobulin G; D015800:Protozoan Proteins; C065974:merozoite surface protein 2, Plasmodium
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