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FASEB J. 2013 Mar;27(3):1153-66. doi: 10.1096/fj.12-218362. Epub 2012 Nov 29.

Iron oxide nanoparticles as a clinically acceptable delivery platform for a recombinant blood-stage human malaria vaccine.

Author information

1
University of Hawaii, School of Medicine, Department of Tropical Medicine, 651 Ilalo St., BSB320, Honolulu, Hawaii 96813, USA. kae@hawaii.edu

Abstract

This study explored the novel use of iron oxide (IO) nanoparticles (<20 nm) as a vaccine delivery platform without additional adjuvants. A recombinant malaria vaccine antigen, the merozoite surface protein 1 (rMSP1), was conjugated to IO nanoparticles (rMSP1-IO). Immunizations in outbred mice with rMSP1-IO achieved 100% responsiveness with antibody titers comparable to those obtained with rMSP1 formulated with a clinically acceptable adjuvant, Montanide ISA51 (2.7×10 vs. 1.6×10; respectively). Only rMSP1-1O could induce significant levels (80%) of parasite inhibitory antibodies. The rMSP1-IO was highly stable at 4°C and was amenable to lyophilization, maintaining its antigenicity, immunogenicity, and ability to induce inhibitory antibodies. Further testing in nonhuman primates, Aotus monkeys, also elicited 100% immune responsiveness and high levels of parasite inhibitory antibodies (55-100% inhibition). No apparent local or systemic toxicity was associated with IO immunizations. Murine macrophages and dendritic cells efficiently (>90%) internalized IO nanoparticles, but only the latter were significantly activated, with elevated expression/secretion of CD86, cytokines (IL-6, TNF-α, IL1-b, IFN-γ, and IL-12), and chemokines (CXCL1, CXCL2, CCL2, CCL3, CCL4, and CXCL10). Thus, the IO nanoparticles is a novel, safe, and effective vaccine platform, with built-in adjuvancy, that is highly stable and field deployable for cost-effective vaccine delivery.

PMID:
23195035
PMCID:
PMC3574285
DOI:
10.1096/fj.12-218362
[Indexed for MEDLINE]
Free PMC Article
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