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https://hdl.handle.net/2440/83621
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Type: | Journal article |
Title: | Discovery of GAMA, a Plasmodium falciparum merozoite micronemal protein, as a novel blood-stage vaccine candidate antigen |
Author: | Arumugam, T. Takeo, S. Yamasaki, T. Thonkukiatkul, A. Miura, K. Otsuki, H. Zhou, H. Long, C. Sattabongkot, J. Thompson, J. Wilson, D. Beeson, J. Healer, J. Crabb, B. Cowman, A. Torii, M. Tsuboi, T. |
Citation: | Infection and Immunity, 2011; 79(11):4523-4532 |
Publisher: | Amer Soc Microbiology |
Issue Date: | 2011 |
ISSN: | 0019-9567 1098-5522 |
Editor: | Adams, J.H. |
Statement of Responsibility: | 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 and Takafumi Tsuboi |
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. |
Keywords: | Erythrocytes Cell-Free System Animals Plasmodium falciparum Neuraminidase Membrane Proteins Protozoan Proteins Malaria Vaccines Antibodies, Protozoan Antigens, Protozoan Microscopy, Immunoelectron Gene Expression Regulation Protein Binding Protein Transport Merozoites |
Rights: | Copyright © 2011, American Society for Microbiology. All Rights Reserved. |
DOI: | 10.1128/IAI.05412-11 |
Published version: | http://dx.doi.org/10.1128/iai.05412-11 |
Appears in Collections: | Aurora harvest 4 Molecular and Biomedical Science publications |
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