title: Functional anti-polysaccharide IgG titres induced by unadjuvanted pneumococcal-conjugate vaccine when delivered by microprojection-based skin patch.
abstract: Adequate access to effective and affordable vaccines is essential for the prevention of mortality due to infectious disease. Pneumonia--a consequence of Streptococcus pneumoniae infection--is the world's leading cause of death in children aged under 5 years. The development of a needle-free, thermostable pneumococcal-conjugate vaccine (PCV) could revolutionise the field by reducing cold-chain and delivery constraints. Skin patches have been used to deliver a range of vaccines, with some inducing significantly higher vaccine-specific immunogenicity than needle-injected controls in pre-clinical models, though they have yet to be used to deliver a PCV. We dry-coated a licensed PCV onto a microprojection-based patch (the Nanopatch) and delivered it to mouse skin. We analysed resulting anti-polysaccharide IgG responses. With and without adjuvant, anti-polysaccharide IgG titres induced by Nanopatch immunisation were significantly higher than dose-matched intramuscular controls. These improved responses were primarily obtained against pneumococcal serotypes 4 and 14. Importantly, capsule-specific IgG correlated with functionality in an opsonophagocytic killing assay. We demonstrate enhanced anti-PCV immunogenicity when delivered by Nanopatch over intramuscular injection. As the first study of a PCV delivered by a skin vaccination technology, this report indicates the potential for reduced costs and greater global distribution of such a vaccine.
authors.affiliation: University of Queensland, Delivery of Drugs and Genes Group, Australian Institute for Bioengineering and Nanotechnology, Building 75, St Lucia, Queensland 4072, Australia.
authors.forename: Frances E
authors.initials: FE
authors.lastname: Pearson
authors.affiliation: University of Queensland, Delivery of Drugs and Genes Group, Australian Institute for Bioengineering and Nanotechnology, Building 75, St Lucia, Queensland 4072, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Muller
authors.affiliation: WHO Pneumococcal Serology Reference Laboratory, Immunobiology Section, University College London, Institute of Child Health, 30 Guildford Street, London WC1N 1EH, United Kingdom.
authors.forename: Lucy
authors.initials: L
authors.lastname: Roalfe
authors.affiliation: WHO Pneumococcal Serology Reference Laboratory, Immunobiology Section, University College London, Institute of Child Health, 30 Guildford Street, London WC1N 1EH, United Kingdom.
authors.forename: Marta
authors.initials: M
authors.lastname: Zancolli
authors.affiliation: WHO Pneumococcal Serology Reference Laboratory, Immunobiology Section, University College London, Institute of Child Health, 30 Guildford Street, London WC1N 1EH, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Goldblatt
authors.affiliation: University of Queensland, Delivery of Drugs and Genes Group, Australian Institute for Bioengineering and Nanotechnology, Building 75, St Lucia, Queensland 4072, Australia; Faculty of Medicine and Biomedical Sciences, University of Queensland, Centre for Clinical Research, Royal Brisbane and Women's Hospital, Herston, Queensland 4029, Australia. Electronic address: m.kendall@uq.edu.au.
authors.forename: Mark A F
authors.initials: MA
authors.lastname: Kendall
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000279:Administration, Cutaneous; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D005260:Female; D007074:Immunoglobulin G / Q000097:blood*; D007273:Injections, Intramuscular; D008807:Mice, Inbred BALB C; D009895:Opsonin Proteins / Q000097:blood; D010587:Phagocytosis; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D009895:Opsonin Proteins; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; D018074:Vaccines, Conjugate
keywords: Microprojection; Opsonophagocytic killing assay; Pneumococcal-conjugate vaccine; Polysaccharide; Skin vaccination; Vaccine delivery