title: Discovery of GAMA, a Plasmodium falciparum merozoite micronemal protein, as a novel blood-stage vaccine candidate antigen.
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 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.
authors: Cell-Free Science and Technology Research Center, Ehime University, 3 Bunkyo-cho, Matsuyama, Ehime 790-8577, Japan.
authors: Thangavelu U
authors: TU
authors: Arumugam
authors: Satoru
authors: S
authors: Takeo
authors: Tsutomu
authors: T
authors: Yamasaki
authors: Amporn
authors: A
authors: Thonkukiatkul
authors: Kazutoyo
authors: K
authors: Miura
authors: Hitoshi
authors: H
authors: Otsuki
authors: Hong
authors: H
authors: Zhou
authors: Carole A
authors: CA
authors: Long
authors: Jetsumon
authors: J
authors: Sattabongkot
authors: Jennifer
authors: J
authors: Thompson
authors: Danny W
authors: DW
authors: Wilson
authors: James G
authors: JG
authors: Beeson
authors: Julie
authors: J
authors: Healer
authors: Brendan S
authors: BS
authors: Crabb
authors: Alan F
authors: AF
authors: Cowman
authors: Motomi
authors: M
authors: Torii
authors: Takafumi
authors: T
authors: Tsuboi
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan / Q000276:immunology*; D002474:Cell-Free System; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D017780:Malaria Vaccines / Q000276:immunology*; D008565:Membrane Proteins / Q000378:metabolism; D052940:Merozoites / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D009439:Neuraminidase; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D008565:Membrane Proteins; D015800:Protozoan Proteins; D009439:Neuraminidase