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

Ahlam 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

doi:10.1016/j.nano.2016.11.019

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

Nanomedicine. 2017 Apr;13(3):921-932. doi: 10.1016/j.nano.2016.11.019. Epub 2016 Dec 12.

Authors

Affiliations

¹ School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.
² School of Mechanical and Manufacturing Engineering, Dublin City University, Dublin, Ireland.
³ Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
⁴ The Centre for Infection and Immunity, The Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, UK.
⁵ School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK. Electronic address: [email protected].

PMID: 27979747
DOI: 10.1016/j.nano.2016.11.019

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.

Keywords: Cervical cancer; DNA vaccination; Microneedles; RALA peptide.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Cutaneous
Animals
Cancer Vaccines / administration & dosage*
Cancer Vaccines / genetics
Cancer Vaccines / immunology
Cancer Vaccines / therapeutic use
Cell Line
Cervix Uteri / immunology
Cervix Uteri / pathology
Cervix Uteri / virology
DNA-Binding Proteins / genetics
DNA-Binding Proteins / immunology
Female
Gene Transfer Techniques / instrumentation*
Human papillomavirus 16 / genetics
Human papillomavirus 16 / immunology
Human papillomavirus 18 / genetics
Human papillomavirus 18 / immunology
Humans
Immunity, Humoral
Mice, Inbred C57BL
Needles
Oligopeptides / chemistry*
Oncogene Proteins, Viral / genetics
Oncogene Proteins, Viral / immunology
Papillomavirus Infections / immunology
Papillomavirus Infections / pathology
Papillomavirus Infections / prevention & control*
Papillomavirus Infections / virology
Povidone / chemistry*
Repressor Proteins / genetics
Repressor Proteins / immunology
Uterine Cervical Neoplasms / immunology
Uterine Cervical Neoplasms / pathology
Uterine Cervical Neoplasms / prevention & control*
Uterine Cervical Neoplasms / virology
Vaccination / instrumentation*
Vaccines, DNA / administration & dosage*
Vaccines, DNA / genetics
Vaccines, DNA / immunology
Vaccines, DNA / therapeutic use

Substances

Cancer Vaccines
DNA-Binding Proteins
E6 protein, Human papillomavirus type 16
E6 protein, Human papillomavirus type 18
Oligopeptides
Oncogene Proteins, Viral
Repressor Proteins
Vaccines, DNA
Povidone