title: Construction and physiochemical characterisation of a multi-composite, potential oral vaccine delivery system (VDS).
abstract: An increasing human population requires a secure food supply and a cost effective, oral vaccine delivery system for livestock would help facilitate this end. Recombinant antigen adsorbed onto silica beads and coated with myristic acid, was released (∼15% (w/v)) over 24 h at pH 8.8. At pH 2, the myristic acid acted as an enteric coating, protecting the antigen from a variety of proteases. The antigen adsorbed onto silica particles, coated in myristic acid had a conserved secondary structure (measured by circular dichroism (CD) spectroscopy) following its pH-triggered release. Small angle neutron scattering (SANS) was used to measure the thickness of the adsorbed antigen, finding that its adsorbed conformation was slightly greater than its solution radius of gyration, i.e. 120-160 Å. The addition of myristic acid led to a further increase in particle size, with scattering data consistent with an acid thickness slightly greater than a monolayer of fully extended alkyl chains and a degree of hydration of around 50%. Whilst adsorbed onto the silica and coated in myristic acid, the protein was stable over 14 days at 42 °C, indicating a reduced need for cold chain storage. These data indicate that further investigation is warranted into the development of this technology.
authors.affiliation: Faculty of Engineering and Science, University of Greenwich, Central Avenue, Chatham Maritime, Kent ME4 4TB, UK.
authors.forename: Marie W
authors.initials: MW
authors.lastname: Pettit
authors.affiliation: Faculty of Engineering and Science, University of Greenwich, Central Avenue, Chatham Maritime, Kent ME4 4TB, UK.
authors.forename: Paul D R
authors.initials: PD
authors.lastname: Dyer
authors.affiliation: Medway Centre for Pharmaceutical Sciences, Faculty of Engineering and Science, University of Greenwich, Central Avenue, Chatham Maritime, Kent, ME4 4TB, UK.
authors.forename: John C
authors.initials: JC
authors.lastname: Mitchell
authors.affiliation: Faculty of Engineering and Science, University of Greenwich, Central Avenue, Chatham Maritime, Kent ME4 4TB, UK.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Griffiths
authors.affiliation: Faculty of Engineering and Science, University of Greenwich, Central Avenue, Chatham Maritime, Kent ME4 4TB, UK.
authors.forename: Bruce
authors.initials: B
authors.lastname: Alexander
authors.affiliation: Faculty of Engineering and Science, University of Greenwich, Central Avenue, Chatham Maritime, Kent ME4 4TB, UK.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Cattoz
authors.affiliation: ISIS Facility, STFC Rutherford Appleton Laboratory, Harwell Oxford, Didcot OX11 0QX, UK.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Heenan
authors.affiliation: ISIS Facility, STFC Rutherford Appleton Laboratory, Harwell Oxford, Didcot OX11 0QX, UK.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: King
authors.affiliation: Institut Laue - Langevin, DS/LSS, CS 20 156, Grenoble CEDEX 9 F-38042, France.
authors.forename: Ralf
authors.initials: R
authors.lastname: Schweins
authors.affiliation: Faculty of Engineering and Science, University of Greenwich, Central Avenue, Chatham Maritime, Kent ME4 4TB, UK.
authors.forename: Frank
authors.initials: F
authors.lastname: Pullen
authors.affiliation: Medway Centre for Pharmaceutical Sciences, Faculty of Engineering and Science, University of Greenwich, Central Avenue, Chatham Maritime, Kent, ME4 4TB, UK.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Wicks
authors.affiliation: Faculty of Engineering and Science, University of Greenwich, Central Avenue, Chatham Maritime, Kent ME4 4TB, UK. Electronic address: S.C.W.Richardson@Greenwich.ac.uk.
authors.forename: Simon C W
authors.initials: SC
authors.lastname: Richardson
mesh_terms: D000284:Administration, Oral; D000327:Adsorption; D000941:Antigens / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D002942:Circular Dichroism; D004337:Drug Carriers; D004355:Drug Stability; D004356:Drug Storage; D005982:Glutathione Transferase / Q000737:chemistry; D049452:Green Fluorescent Proteins / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D019814:Myristic Acid / Q000737:chemistry*; D033363:Neutron Diffraction; D010316:Particle Size; D055550:Protein Stability; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D053838:Scattering, Small Angle; D012822:Silicon Dioxide / Q000737:chemistry*; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D000941:Antigens; D004337:Drug Carriers; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D019814:Myristic Acid; D049452:Green Fluorescent Proteins; D012822:Silicon Dioxide; D005982:Glutathione Transferase
keywords: Enteric; Immobilisation; Silica; Synthetic protein; Vaccine