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In this proof-of-concept study we report the use of <15nm, water soluble, inorganic nanoparticles as a vaccine delivery system for a blood stage malaria vaccine. The recombinant malarial antigen, Merozoite Surface Protein 1 (rMSP1) of Plasmodium falciparum served as the model vaccine. The rMSP1 was covalently conjugated to polymer-coated quantum dot CdSe/ZnS nanoparticles (QDs) via surface carboxyl groups, forming rMSP1-QDs. Anti-MSP1 antibody responses induced by rMSP1-QDs were found to have 2-3log higher titers than those obtained with rMSP1 administered with the conventional adjuvants, Montanide ISA51 and CFA. Moreover, the immune responsiveness and the induction of parasite inhibitory antibodies were significantly superior in mice injected with rMSP1-QDs. The rMSP1-QDs delivered via intra-peritoneal (i.p.), intra-muscular (i.m.), and subcutaneous (s.c.) routes were equally efficacious. The high level of immunogenicity exhibited by the rMSP1-QDs was achieved without further addition of other adjuvant components. Bone marrow derived dendritic cells were shown to efficiently take up the nanoparticles leading to their activation and the expression/secretion of key cytokines, suggesting that this may be a mode of action for the enhanced immunogenicity. This study provides promising results for the use of water soluble, inorganic nanoparticles (<15nm) as potent vehicles/platforms to enhance the immunogenicity of polypeptide antigens in adjuvant-free immunizations.
University of Hawaii, School of Medicine, Department of Tropical Medicine, 651 Ilalo Street, BSB320 Honolulu, HI 96813, USA.
This article was published in the following journal.
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A layer of protein coating adsorbed by NANOPARTICLES upon entry into PLASMA or other protein-containing biological fluids, which affects how nanoparticles are internalized by cells and cleared from the body.
A surface protein found on Plasmodium species which induces a T-cell response. The antigen is polymorphic, sharing amino acid sequence homology among PLASMODIUM FALCIPARUM; PLASMODIUM CHABAUDI; PLASMODIUM VIVAX; and PLASMODIUM YOELII.
Nanometer-sized particles that are nanoscale in three dimensions. They include nanocrystaline materials; NANOCAPSULES; METAL NANOPARTICLES; DENDRIMERS, and QUANTUM DOTS. The uses of nanoparticles include DRUG DELIVERY SYSTEMS and cancer targeting and imaging.
Cells or feeding stage in the life cycle of sporozoan protozoa. In the malarial parasite, the trophozoite develops from the MEROZOITE and then splits into the SCHIZONT. Trophozoites that are left over from cell division can go on to form gametocytes.
A trisaccharide antigen expressed on glycolipids and many cell-surface glycoproteins. In the blood the antigen is found on the surface of NEUTROPHILS; EOSINOPHILS; and MONOCYTES. In addition, CD15 antigen is a stage-specific embryonic antigen.
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