title: Iron oxide nanoparticles as a clinically acceptable delivery platform for a recombinant blood-stage human malaria vaccine.
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.
authors.affiliation: University of Hawaii, School of Medicine, Department of Tropical Medicine, 651 Ilalo St., BSB320, Honolulu, Hawaii 96813, USA. kae@hawaii.edu
authors.forename: Kae
authors.initials: K
authors.lastname: Pusic
authors.forename: Zoraida
authors.initials: Z
authors.lastname: Aguilar
authors.forename: Jaclyn
authors.initials: J
authors.lastname: McLoughlin
authors.forename: Sophie
authors.initials: S
authors.lastname: Kobuch
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.forename: Mazie
authors.initials: M
authors.lastname: Tsang
authors.forename: Andrew
authors.initials: A
authors.lastname: Wang
authors.forename: George
authors.initials: G
authors.lastname: Hui
mesh_terms: D000818:Animals; D016645:Aotidae; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology*; D005290:Ferric Compounds / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007114:Immunization; D008264:Macrophages / Q000276:immunology; D008288:Malaria / Q000276:immunology / Q000517:prevention & control; D017780:Malaria Vaccines / Q000276:immunology / Q000494:pharmacology*; D020066:Merozoite Surface Protein 1 / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D053758:Nanoparticles; D014614:Vaccines, Synthetic / Q000494:pharmacology
chemical_list: D016207:Cytokines; D004337:Drug Carriers; D005290:Ferric Compounds; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D014614:Vaccines, Synthetic; C000499:ferric oxide