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Infect Immun. 2011 Oct;79(10):4260-75. doi: 10.1128/IAI.05214-11. Epub 2011 Aug 1.

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

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1
Molecular Microbiology Group, Tropical Biosphere Research Center, COMB, University of the Ryukyus, Okinawa Japan. tarakawa@comb.u-ryukyu.ac.jp

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.

PMID:
21807905
PMCID:
PMC3187242
DOI:
10.1128/IAI.05214-11
[Indexed for MEDLINE]
Free PMC Article

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