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Title: Discovery of GAMA, a plasmodium falciparum merozoite micronemal protein, as a novel blood-stage vaccine candidate antigen
Authors: 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
Ehime University
Burapha University
National Institute of Allergy and Infectious Diseases
Tottori University
Armed Forces Research Institute of Medical Sciences, Thailand
The Walter and Eliza Hall Institute for Medical Research
Burnet Institute
Mahidol University
Keywords: Immunology and Microbiology;Medicine
Issue Date: 1-Nov-2011
Citation: Infection and Immunity. Vol.79, No.11 (2011), 4523-4532
Abstract: 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 pl ays 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. © 2011, American Society for Microbiology.
ISSN: 10985522
Appears in Collections:Scopus 2011-2015

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