title: Identification of a novel merozoite surface antigen of Plasmodium vivax, PvMSA180.
abstract: Although a number of Plasmodium vivax proteins have been identified, few have been investigated as potential vaccine candidates. This study characterized the Plasmodium vivax merozoite surface antigen 180 (PvMSA180, PVX_094920), a novel P. vivax antigenic protein.
  
  
  
  The target gene was amplified as four overlapping domains (D1, D2, D3 and D4) to enable expression of the recombinant protein using cell-free and bacterial expression systems. The recombinant PvMSA180 proteins were used in protein microarrays to evaluate the humoral immune response of 72 vivax-infected patients and 24 vivax-naïve individuals. Antibodies produced in mice against the PvMSA180-D1 and -D4 domains were used to assess the subcellular localization of schizont-stage parasites with immunofluorescence assays. A total of 51 pvmsa180 sequences from 12 countries (41 sequences from PlasmoDB and 6 generated in this study) were used to determine the genetic diversity and genealogical relationships with DNAsp and NETWORK software packages, respectively.
  
  
  
  PvMSA180 consists of 1603 amino acids with a predicted molecular mass of 182 kDa, and has a signal peptide at the amino-terminus. A total of 70.8% of patients (51/72) showed a specific antibody response to at least one of the PvMSA180 domains, and 20.8% (15/72) exhibited a robust antibody response to at least three of the domains. These findings suggest that PvMSA180 is targeted by the humoral immune response during natural infection with P. vivax. Immunofluorescence analysis demonstrated that PvMSA180 is localized on the merozoite surface of schizont-stage parasites, and pvmsa180 sequences originating from various geographic regions worldwide showed low genetic diversity. Twenty-two haplotypes were found, and haplotype 6 (Hap_6, 77%) of pvmsa180 was detected in isolates from six countries.
  
  
  
  A novel P. vivax surface protein, PvMSA180, was characterized in this study. Most of P. vivax-infected patients had specific antibodies against particular antigenic domains, indicating that this protein is immunogenic in naturally exposed populations. Genetic analysis of worldwide isolates showed that pvmsa180 is less polymorphic than other well-known candidates and that some haplotypes are common to several countries. However, additional studies with a larger sample size are necessary to evaluate the antibody responses in geographically separated populations, and to identify the function of PvMSA180 during parasite invasion.
authors.affiliation: Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, Republic of Korea.
authors.forename: Fauzi
authors.initials: F
authors.lastname: Muh
authors.affiliation: Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, Republic of Korea.
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Han
authors.affiliation: Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, Republic of Korea.|Department of Medical Research, Yangon, Republic of the Union of Myanmar.
authors.forename: Myat Htut
authors.initials: MH
authors.lastname: Nyunt
authors.affiliation: Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, Republic of Korea.
authors.forename: Seong-Kyun
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Department of Cellular and Molecular Biology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, Republic of Korea.
authors.forename: Hye-Yoon
authors.initials: HY
authors.lastname: Jeon
authors.affiliation: Department of Cellular and Molecular Biology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, Republic of Korea.
authors.forename: Kwon-Soo
authors.initials: KS
authors.lastname: Ha
authors.affiliation: Department of Physiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, Republic of Korea.
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, Republic of Korea.
authors.forename: Seok-Ho
authors.initials: SH
authors.lastname: Hong
authors.affiliation: Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, Republic of Korea.
authors.forename: Md Atique
authors.initials: MA
authors.lastname: Ahmed
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, Republic of Korea.
authors.forename: Sunghun
authors.initials: S
authors.lastname: Na
authors.affiliation: Division of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, Ehime, 790-8577, Japan.
authors.forename: Eizo
authors.initials: E
authors.lastname: Takashima
authors.affiliation: Division of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, Ehime, 790-8577, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Tsuboi
authors.affiliation: Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, Republic of Korea. ethan@kangwon.ac.kr.
authors.forename: Eun-Taek
authors.initials: ET
authors.lastname: Han
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000032:analysis* / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D000954:Antigens, Surface / Q000032:analysis* / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D052940:Merozoites / Q000737:chemistry* / Q000276:immunology; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D008970:Molecular Weight; D058974:Phylogeography; D010966:Plasmodium vivax / Q000737:chemistry* / Q000276:immunology; D021382:Protein Sorting Signals / Q000235:genetics; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D021382:Protein Sorting Signals
keywords: Haplotype; Humoral immune response; MSA180; Merozoite surface protein; Plasmodium vivax