論文

国際誌
2011年11月

Discovery of GAMA, a Plasmodium falciparum Merozoite Micronemal Protein, as a Novel Blood-Stage Vaccine Candidate Antigen

INFECTION AND IMMUNITY
  • Thangavelu U. Arumugam
  • Satoru Takeo
  • Tsutomu Yamasaki
  • Amporn Thonkukiatkul
  • Kazutoyo Miura
  • Hitoshi Otsuki
  • Hong Zhou
  • Carole A. Long
  • Jetsumon Sattabongkot
  • Jennifer Thompson
  • Danny W. Wilson
  • James G. Beeson
  • Julie Healer
  • Brendan S. Crabb
  • Alan F. Cowman
  • Motomi Torii
  • Takafumi Tsuboi
  • 全て表示

79
11
開始ページ
4523
終了ページ
4532
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1128/IAI.05412-11
出版者・発行元
AMER SOC MICROBIOLOGY

One of the solutions for reducing the global mortality and morbidity due to malaria is multivalent vaccines comprising antigens of several life cycle stages of the malarial parasite. Hence, there is a need for supplementing the current set of malaria vaccine candidate antigens. Here, we aimed to characterize glycosylphosphatidylinositol (GPI)-anchored micronemal antigen (GAMA) encoded by the PF08_0008 gene in Plasmodium falciparum. Antibodies were raised against recombinant GAMA synthesized by using a wheat germ cell-free system. Immunoelectron microscopy demonstrated for the first time that GAMA is a microneme protein of the merozoite. Erythrocyte binding assays revealed that GAMA possesses an erythrocyte binding epitope in the C-terminal region and it binds a nonsialylated protein receptor on human erythrocytes. Growth inhibition assays revealed that anti-GAMA antibodies can inhibit P. falciparum invasion in a dose-dependent manner and GAMA plays a role in the sialic acid (SA)-independent invasion pathway. Anti-GAMA antibodies in combination with anti-erythrocyte binding antigen 175 exhibited a significantly higher level of invasion inhibition, supporting the rationale that targeting of both SA-dependent and SA-independent ligands/pathways is better than targeting either of them alone. Human sera collected from areas of malaria endemicity in Mali and Thailand recognized GAMA. Since GAMA in P. falciparum is refractory to gene knockout attempts, it is essential to parasite invasion. Overall, our study indicates that GAMA is a novel blood-stage vaccine candidate antigen.

リンク情報
DOI
https://doi.org/10.1128/IAI.05412-11
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/21896773
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257921
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000296352400023&DestApp=WOS_CPL
ID情報
  • DOI : 10.1128/IAI.05412-11
  • ISSN : 0019-9567
  • eISSN : 1098-5522
  • PubMed ID : 21896773
  • PubMed Central 記事ID : PMC3257921
  • Web of Science ID : WOS:000296352400023

エクスポート
BibTeX RIS