4.4 Article

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

期刊

INFECTION AND IMMUNITY
卷 79, 期 11, 页码 4523-4532

出版社

AMER SOC MICROBIOLOGY
DOI: 10.1128/IAI.05412-11

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资金

  1. Bill and Melinda Gates Foundation
  2. Ministry of Education, Culture, Sports, Science and Technology [21249028, 21022034, 23406007, 23117008]
  3. Ministry of Health, Labor, and Welfare, Japan [H21-Chikyukibo-ippan-005]
  4. National Institute of Allergy and Infectious Diseases/NIH
  5. PATH/Malaria Vaccine Initiative
  6. Grants-in-Aid for Scientific Research [21022034, 23406007, 21249028] Funding Source: KAKEN

向作者/读者索取更多资源

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.

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