DNA vaccination for cervical cancer; a novel technology platform of RALA mediated gene delivery via polymeric microneedles.

Aham A. Ali, Cian M. McCrudden, Joanne McCaffrey, John W. McBride, Grace Cole, Nicholas J. Dunne, Tracy Robson, Adrien Kissenpfennig, Ryan F. Donnelly, Helen O. McCarthy

Research output: Contribution to journalArticle

40 Citations (Scopus)
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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.
Original languageEnglish
Pages (from-to)921-932
Number of pages12
JournalNanomedicine: Nanotechnology, Biology and Medicine
Volume13
Issue number3
Early online date12 Dec 2016
DOIs
Publication statusPublished - Apr 2017

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