title: Mesoporous silica nanoparticles act as a self-adjuvant for ovalbumin model antigen in mice.
abstract: Immunization to the model protein antigen ovalbumin (OVA) is investigated using MCM-41 mesoporous silica nanoparticles as a novel vaccine delivery vehicle and adjuvant system in mice. The effects of amino surface functionalization and adsorption time on OVA adsorption to nanoparticles are assessed. Amino-functionalized MCM-41 (AM-41) shows an effect on the amount of OVA binding, with 2.5-fold increase in binding capacity (72 mg OVA/g AM-41) compared to nonfunctionalized MCM-41 (29 mg OVA/g MCM-41). Immunization studies in mice with a 10 μg dose of OVA adsorbed to AM-41 elicits both antibody and cell-mediated immune responses following three subcutaneous injections. Immunizations at a lower 2 μg dose of OVA adsorbed to AM-41 particles results in an antibody response but not cell-mediated immunity. The level of antibody responses following immunization with nanoformulations containing either 2 μg or 10 μg of OVA are only slightly lower than that in mice which receive 50 μg OVA adjuvanted with QuilA, a crude mixture of saponins extracted from the bark of the Quillaja saponaria Molina tree. This is a significant result, since it demonstrates that AM-41 nanoparticles are self-adjuvanting and elicit immune responses at reduced antigen doses in vivo compared to a conventional delivery system. Importantly, there are no local or systemic negative effects in animals injected with AM-41. Histopathological studies of a range of tissue organs show no changes in histopathology of the animals receiving nanoparticles over a six week period. These results establish the biocompatible MCM-41 silica nanoparticles as a new method for vaccine delivery which incorporates a self-adjuvant effect.
authors.affiliation: Queensland Alliance for Agriculture and Food Innovation, The University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Donna
authors.initials: D
authors.lastname: Mahony
authors.forename: Antonino S
authors.initials: AS
authors.lastname: Cavallaro
authors.forename: Frances
authors.initials: F
authors.lastname: Stahr
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Mahony
authors.forename: Shi Zhang
authors.initials: SZ
authors.lastname: Qiao
authors.forename: Neena
authors.initials: N
authors.lastname: Mitter
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000818:Animals; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010047:Ovalbumin / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D000276:Adjuvants, Immunologic; C509968:MCM-41; D012822:Silicon Dioxide; D010047:Ovalbumin
keywords: adjuvants; drug delivery; mesoporous silica nanoparticles; vaccines