title: Repeat sequences in block 2 of Plasmodium falciparum merozoite surface protein 1 are targets of antibodies associated with protection from malaria.
abstract: Human antibodies to the block 2 region of Plasmodium falciparum merozoite surface protein 1 (MSP1) are associated with a reduced prospective risk of clinical malaria. Block 2 is highly polymorphic, but all known alleles can be grouped into three major types. Two of these types (the K1-like and MAD20-like types) contain type-specific sequences (found in all alleles of a particular type) that flank polymorphic tripeptide repeats. These repeats contain both type-specific and subtype-specific sequences. To evaluate the antibody recognition of these parts of block 2, a new panel of six recombinant proteins was used (fused type-specific flanking sequences and two representative repeat sequences for each of the K1-like and MAD20-like types separately). Extensive testing of these antigens and full-length block 2 antigens showed that human serum immunoglobulin G antibodies induced by infection can recognize (i) type-specific epitopes in the repeats, (ii) subtype-specific epitopes in the repeats, or (iii) type-specific epitopes in flanking sequences. A large prospective study in The Gambia showed that antibodies to the repeats are strongly associated with protection from clinical malaria. The results are important for design of a vaccine to induce protective antibodies, and they address hypotheses about repeat sequences in malaria antigens.
authors.affiliation: London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
authors.forename: Spencer D
authors.initials: SD
authors.lastname: Polley
authors.forename: Kevin K A
authors.initials: KK
authors.lastname: Tetteh
authors.forename: David R
authors.initials: DR
authors.lastname: Cavanagh
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Pearce
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Lloyd
authors.forename: Kalifa A
authors.initials: KA
authors.lastname: Bojang
authors.forename: Daniel M N
authors.initials: DM
authors.lastname: Okenu
authors.forename: Brian M
authors.initials: BM
authors.lastname: Greenwood
authors.forename: Jana S
authors.initials: JS
authors.lastname: McBride
authors.forename: David J
authors.initials: DJ
authors.lastname: Conway
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D000918:Antibody Specificity; D000953:Antigens, Protozoan / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control; D020066:Merozoite Surface Protein 1 / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000276:immunology; D012091:Repetitive Sequences, Nucleic Acid / Q000276:immunology*; D014611:Vaccination
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1