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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 ofPlasmodium vivax , Pvs25, and merozoite surface protein-1 ofPlasmodium yoelii . Immunization of mice with the tricomponent complex induced a robust antibody response and conferred substantial levels ofP. vivax transmission blockade as evaluated by a membrane feed assay, as well as protection from lethalP. 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.

Tricomponent Immunopotentiating System as a Novel Molecular Design Strategy for Malaria Vaccine Development