title: Tricomponent immunopotentiating system as a novel molecular design strategy for malaria vaccine development.
abstract: The creation of subunit vaccines to prevent malaria infection has been hampered by the intrinsically weak immunogenicity of the recombinant antigens. We have developed a novel strategy to increase immune responses by creating genetic fusion proteins to target specific antigen-presenting cells (APCs). The fusion complex was composed of three physically linked molecular entities: (i) a vaccine antigen, (ii) a multimeric α-helical coiled-coil core, and (iii) an APC-targeting ligand linked to the core via a flexible linker. The vaccine efficacy of the tricomponent complex was evaluated using an ookinete surface protein of Plasmodium vivax, Pvs25, and merozoite surface protein-1 of Plasmodium yoelii. Immunization of mice with the tricomponent complex induced a robust antibody response and conferred substantial levels of P. vivax transmission blockade as evaluated by a membrane feed assay, as well as protection from lethal P. yoelii infection. The observed effect was strongly dependent on the presence of all three components physically integrated as a fusion complex. This system, designated the tricomponent immunopotentiating system (TIPS), onto which any recombinant protein antigens or nonproteinaceous substances could be loaded, may be a promising strategy for devising subunit vaccines or adjuvants against various infectious diseases, including malaria.
authors.affiliation: Molecular Microbiology Group, Tropical Biosphere Research Center, COMB, University of the Ryukyus, Okinawa Japan. tarakawa@comb.u-ryukyu.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyata
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Harakuni
authors.forename: Takafumi
authors.initials: T
authors.lastname: Tsuboi
authors.forename: Jetsumon
authors.initials: J
authors.lastname: Sattabongkot
authors.forename: Ayumu
authors.initials: A
authors.lastname: Ikehara
authors.forename: Mayumi
authors.initials: M
authors.lastname: Tachibana
authors.forename: Motomi
authors.initials: M
authors.lastname: Torii
authors.forename: Goro
authors.initials: G
authors.lastname: Matsuzaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Arakawa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000953:Antigens, Protozoan / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D000954:Antigens, Surface / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D015195:Drug Design; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation; D008288:Malaria / Q000276:immunology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D016780:Malaria, Vivax / Q000276:immunology / Q000517:prevention & control; D064235:Matrilin Proteins; D020066:Merozoite Surface Protein 1 / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010966:Plasmodium vivax / Q000235:genetics / Q000276:immunology*; D010967:Plasmodium yoelii / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; D000954:Antigens, Surface; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D008024:Ligands; D017780:Malaria Vaccines; C577540:Matn1 protein, mouse; D064235:Matrilin Proteins; D020066:Merozoite Surface Protein 1; C121473:Pvs25 protein, P vivax; D011993:Recombinant Fusion Proteins; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic