title: The structure of Plasmodium yoelii merozoite surface protein 119, antibody specificity and implications for malaria vaccine design.
abstract: Merozoite surface protein 1 (MSP1) has been identified as a target antigen for protective immune responses against asexual blood stage malaria, but effective vaccines based on MSP1 have not been developed so far. We have modified the sequence of Plasmodium yoelii MSP119 (the C-terminal region of the molecule) and examined the ability of the variant proteins to bind protective monoclonal antibodies and to induce protection by immunization. In parallel, we examined the structure of the protein and the consequences of the amino acid changes. Naturally occurring sequence polymorphisms reduced the binding of individual protective antibodies, indicating that they contribute to immune evasion, but immunization with these variant proteins still provided protective immunity. One variant that resulted in the localized distortion of a loop close to the N-terminus of MSP119 almost completely ablated protection by immunization, indicating the importance of this region of MSP119 as a target for protective immunity and in vaccine development.
authors.affiliation: Divisions of Parasitology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Rachel D
authors.initials: RD
authors.lastname: Curd
authors.forename: Berry
authors.initials: B
authors.lastname: Birdsall
authors.forename: Madhusudan
authors.initials: M
authors.lastname: Kadekoppala
authors.forename: Solabomi A
authors.initials: SA
authors.lastname: Ogun
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Kelly
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Holder
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000913:Antibodies, Protozoan / Q000276:immunology*; D004926:Escherichia coli / Q000378:metabolism; D017780:Malaria Vaccines / Q000276:immunology; D020066:Merozoite Surface Protein 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D010967:Plasmodium yoelii / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins
keywords: MSP1 structure; malaria vaccine; plasmodium