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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 ?-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.

SUBMITTER: Miyata T 

PROVIDER: S-EPMC3187242 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Tricomponent immunopotentiating system as a novel molecular design strategy for malaria vaccine development.

Miyata Takeshi T   Harakuni Tetsuya T   Tsuboi Takafumi T   Sattabongkot Jetsumon J   Ikehara Ayumu A   Tachibana Mayumi M   Torii Motomi M   Matsuzaki Goro G   Arakawa Takeshi T  

Infection and immunity 20110801 10


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 co  ...[more]

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