title: DNA vaccination for cervical cancer; a novel technology platform of RALA mediated gene delivery via polymeric microneedles.
abstract: HPV subtypes (16, 18) are associated with the development of cervical cancer, with oncoproteins E6 and E7 responsible for pathogenesis. The goal of this study was to evaluate our 'smart system' technology platform for DNA vaccination against cervical cancer. The vaccination platform brings together two main components; a peptide RALA which condenses DNA into cationic nanoparticles (NPs), and a polymeric polyvinylpyrrolidone (PVP) microneedle (MN) patch for cutaneous delivery of the loaded NPs. RALA condensed E6/E7 DNA into NPs not exceeding 100nm in diameter, and afforded the DNA protection from degradation in PVP. Sera from mice vaccinated with MN/RALA-E6/E7 were richer in E6/E7-specific IgGs, displayed a greater T-cell-mediated TC-1 cytotoxicity and contained more IFN-γ than sera from mice that received NPs intramuscularly. More importantly, MN/RALA-E6/E7 delayed TC-1 tumor initiation in a prophylactic model, and slowed tumor growth in a therapeutic model of vaccination, and was more potent than intramuscular vaccination.
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.
authors.forename: Ahlam A
authors.initials: AA
authors.lastname: Ali
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.
authors.forename: Cian M
authors.initials: CM
authors.lastname: McCrudden
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.
authors.forename: Joanne
authors.initials: J
authors.lastname: McCaffrey
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.
authors.forename: John W
authors.initials: JW
authors.lastname: McBride
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.
authors.forename: Grace
authors.initials: G
authors.lastname: Cole
authors.affiliation: School of Mechanical and Manufacturing Engineering, Dublin City University, Dublin, Ireland.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Dunne
authors.affiliation: Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
authors.forename: Tracy
authors.initials: T
authors.lastname: Robson
authors.affiliation: The Centre for Infection and Immunity, The Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, UK.
authors.forename: Adrien
authors.initials: A
authors.lastname: Kissenpfennig
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.
authors.forename: Ryan F
authors.initials: RF
authors.lastname: Donnelly
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK. Electronic address: h.mccarthy@qub.ac.uk.
authors.forename: Helen O
authors.initials: HO
authors.lastname: McCarthy
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D002460:Cell Line; D002584:Cervix Uteri / Q000276:immunology / Q000473:pathology / Q000821:virology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D005260:Female; D018014:Gene Transfer Techniques / Q000295:instrumentation*; D052162:Human papillomavirus 16 / Q000235:genetics / Q000276:immunology; D052161:Human papillomavirus 18 / Q000235:genetics / Q000276:immunology; D006801:Humans; D056724:Immunity, Humoral; D008810:Mice, Inbred C57BL; D009339:Needles; D009842:Oligopeptides / Q000737:chemistry*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology; D030361:Papillomavirus Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D011205:Povidone / Q000737:chemistry*; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D014611:Vaccination / Q000295:instrumentation*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use
chemical_list: D019496:Cancer Vaccines; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; D009842:Oligopeptides; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D019444:Vaccines, DNA; D011205:Povidone
keywords: Cervical cancer; DNA vaccination; Microneedles; RALA peptide