title: Within-population genetic diversity of Plasmodium falciparum vaccine candidate antigens reveals geographic distance from a Central sub-Saharan African origin.
abstract: Populations of Plasmodium falciparum, the most virulent human malaria parasite, are diverse owing to wide levels of transmission and endemicity of infection. Genetic diversity of P. falciparum antigens, within and between parasite populations, remains a confounding factor in malaria pathogenesis as well as clinical trials of vaccine candidates. Variation of target antigens in parasite populations may arise from immune pressure depending on the levels of acquired immunity. Alternatively, similar to our study in housekeeping genes [Tanabe et al. Curr Biol 2010;70:1-7], within-population genetic diversity of vaccine candidate antigens may also be determined by geographical distance from a postulated origin in Central sub-Saharan Africa. To address this question, we obtained full-length sequences of P. falciparum genes, apical membrane antigen 1 (ama1) (n=459), circumsporozoite protein (csp) (n=472) and merozoite surface protein 1 (msp1) (n=389) from seven geographically diverse parasite populations in Africa, Southeast Asia and Oceania; and, together with previously determined sequences (n=13 and 15 for csp and msp1, respectively) analyzed within-population single nucleotide polymorphism (SNP) diversity. The three antigen genes showed SNP diversity that supports a model of isolation-by-distance. The standardized number of polymorphic sites per site, expressed as θ(S), indicates that 77-83% can be attributed by geographic distance from the African origin, suggesting that geographic distance plays a significant role in variation in target vaccine candidate antigens. Furthermore, we observed that a large proportion of SNPs in the antigen genes were shared between African and non-African parasite populations, demonstrating long term persistence of those SNPs. Our results provide important implications for developing effective malaria vaccines and better understanding of acquired immunity against falciparum malaria.
authors.affiliation: Laboratory of Malariology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan. kztanabe@biken.osaka-u.ac.jp
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tanabe
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Mita
authors.forename: Nirianne M Q
authors.initials: NM
authors.lastname: Palacpac
authors.forename: Nobuko
authors.initials: N
authors.lastname: Arisue
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tougan
authors.forename: Satoru
authors.initials: S
authors.lastname: Kawai
authors.forename: Thibaut
authors.initials: T
authors.lastname: Jombart
authors.forename: Fumie
authors.initials: F
authors.lastname: Kobayashi
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Horii
mesh_terms: D000349:Africa; D000953:Antigens, Protozoan / Q000235:genetics* / Q000276:immunology*; D001210:Asia, Southeastern; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D006801:Humans; D017780:Malaria Vaccines / Q000235:genetics* / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D020066:Merozoite Surface Protein 1 / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D044349:Oceania; D058974:Phylogeography; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D017422:Sequence Analysis, DNA
chemical_list: D000953:Antigens, Protozoan; D016054:DNA, Protozoan; D017780:Malaria Vaccines; D008565:Membrane Proteins; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium; C041595:circumsporozoite protein, Protozoan