title: In vivo delivery of bovine viral diahorrea virus, E2 protein using hollow mesoporous silica nanoparticles.
abstract: Our work focuses on the application of mesoporous silica nanoparticles as a combined delivery vehicle and adjuvant for vaccine applications. Here we present results using the viral protein, E2, from bovine viral diarrhoea virus (BVDV). BVDV infection occurs in the target species of cattle and sheep herds worldwide and is therefore of economic importance. E2 is a major immunogenic determinant of BVDV and is an ideal candidate for the development of a subunit based nanovaccine using mesoporous silica nanoparticles. Hollow type mesoporous silica nanoparticles with surface amino functionalisation (termed HMSA) were characterised and assessed for adsorption and desorption of E2. A codon-optimised version of the E2 protein (termed Opti-E2) was produced in Escherichia coli. HMSA (120 nm) had an adsorption capacity of 80 μg Opti-E2 per mg HMSA and once bound E2 did not dissociate from the HMSA. Immunisation studies in mice with a 20 μg dose of E2 adsorbed to 250 μg HMSA was compared to immunisation with Opti-E2 (50 μg) together with the traditional adjuvant Quillaja saponaria Molina tree saponins (QuilA, 10 μg). The humoral responses with the Opti-E2/HMSA nanovaccine although slightly lower than those obtained for the Opti-E2 + QuilA group demonstrated that HMSA particles are an effective adjuvant that stimulated E2-specific antibody responses. Importantly the cell-mediated immune responses were consistently high in all mice immunised with Opti-E2/HMSA nanovaccine formulation. Therefore we have shown the Opti-E2/HMSA nanoformulation acts as an excellent adjuvant that gives both T-helper 1 and T-helper 2 mediated responses in a small animal model. This study has provided proof-of-concept towards the development of an E2 subunit nanoparticle based vaccine.
authors.affiliation: Queensland Alliance for Agriculture and Food Innovation, The University of Queensland, St Lucia, QLD 4072, Australia. n.mitter@uq.edu.au.
authors.forename: D
authors.initials: D
authors.lastname: Mahony
authors.forename: A S
authors.initials: AS
authors.lastname: Cavallaro
authors.forename: K T
authors.initials: KT
authors.lastname: Mody
authors.forename: L
authors.initials: L
authors.lastname: Xiong
authors.forename: T J
authors.initials: TJ
authors.lastname: Mahony
authors.forename: S Z
authors.initials: SZ
authors.lastname: Qiao
authors.forename: N
authors.initials: N
authors.lastname: Mitter
mesh_terms: D000327:Adsorption; D000818:Animals; D004058:Diffusion; D008422:Materials Testing; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D012822:Silicon Dioxide / Q000737:chemistry*; D014759:Viral Envelope Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology
chemical_list: D053769:Nanocapsules; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C076551:gp53, bovine viral diarrhea virus; D012822:Silicon Dioxide