Identification of a novel antigenic domain of Plasmodium falciparum merozoite surface protein-1 that specifically binds to human erythrocytes and inhibits parasite invasion, in vitro.
Merozoite surface protein 1 (MSP-1) of Plasmodium falciparum is a promising candidate for vaccine development against malaria. Identification of protective epitopes within MSP-1 is an important step towards the elucidation of mechanisms of parasitic invasion and for the creation of a multi-subunit vaccine. In this study, we show that a 115 amino acid region (p115MSP-1) within the p38 domain of MSP-1 can: (i) specifically bind to human erythrocytes, independent of glycophorin A; (ii) inhibit parasite invasion at significant levels, in vitro; and (iii) be recognized by human sera of individuals from malaria-endemic regions of Africa. More importantly, we also show that polyclonal antibodies specific to this region prevent parasite invasion at levels approaching 90%, in vitro. Our data illustrate that not only is p115MSP-1 involved in parasite recognition/invasion of human erythrocytes, but that this region is highly antigenic, producing high titer antibodies. The delineation of the role of MSP-1 in parasite invasion is an important component of the development of a multi-subunit malaria vaccine, and this study identifies a candidate antigen in this context.
Nikodem
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Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, Washington, DC, USA.
Davidson
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D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology*; D006801:Humans; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology; D020066:Merozoite Surface Protein 1 / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D008969:Molecular Sequence Data; D018512:Parasitemia / Q000469:parasitology; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D011485:Protein Binding
D000913:Antibodies, Protozoan; D000939:Epitopes; D020066:Merozoite Surface Protein 1