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Linear doggybone DNA vaccine induces similar immunological responses to conventional plasmid DNA independently of immune recognition by TLR9 in a pre-clinical model.
Allen, Alex; Wang, Chuan; Caproni, Lisa J; Sugiyarto, Gessa; Harden, Elena; Douglas, Leon R; Duriez, Patrick J; Karbowniczek, Kinga; Extance, Jon; Rothwell, Paul J; Orefo, Ifeayinwa; Tite, John P; Stevenson, Freda K; Ottensmeier, Christian H; Savelyeva, Natalia.
Afiliação
  • Allen A; Cancer Sciences Unit and Cancer Research UK and Experimental Cancer Medicine Centre Protein Core Facility, Faculty of Medicine, University of Southampton, Tremona road, Southampton, SO16 6YD, UK.
  • Wang C; Cancer Sciences Unit and Cancer Research UK and Experimental Cancer Medicine Centre Protein Core Facility, Faculty of Medicine, University of Southampton, Tremona road, Southampton, SO16 6YD, UK.
  • Caproni LJ; Touchlight Genetics Ltd, Morelands and Riverdale Buildings, Lower Sunbury Road, Hampton, London, TW12 2ER, UK.
  • Sugiyarto G; Cancer Sciences Unit and Cancer Research UK and Experimental Cancer Medicine Centre Protein Core Facility, Faculty of Medicine, University of Southampton, Tremona road, Southampton, SO16 6YD, UK.
  • Harden E; Cancer Sciences Unit and Cancer Research UK and Experimental Cancer Medicine Centre Protein Core Facility, Faculty of Medicine, University of Southampton, Tremona road, Southampton, SO16 6YD, UK.
  • Douglas LR; Cancer Sciences Unit and Cancer Research UK and Experimental Cancer Medicine Centre Protein Core Facility, Faculty of Medicine, University of Southampton, Tremona road, Southampton, SO16 6YD, UK.
  • Duriez PJ; Cancer Sciences Unit and Cancer Research UK and Experimental Cancer Medicine Centre Protein Core Facility, Faculty of Medicine, University of Southampton, Tremona road, Southampton, SO16 6YD, UK.
  • Karbowniczek K; Touchlight Genetics Ltd, Morelands and Riverdale Buildings, Lower Sunbury Road, Hampton, London, TW12 2ER, UK.
  • Extance J; Touchlight Genetics Ltd, Morelands and Riverdale Buildings, Lower Sunbury Road, Hampton, London, TW12 2ER, UK.
  • Rothwell PJ; Touchlight Genetics Ltd, Morelands and Riverdale Buildings, Lower Sunbury Road, Hampton, London, TW12 2ER, UK.
  • Orefo I; Touchlight Genetics Ltd, Morelands and Riverdale Buildings, Lower Sunbury Road, Hampton, London, TW12 2ER, UK.
  • Tite JP; Touchlight Genetics Ltd, Morelands and Riverdale Buildings, Lower Sunbury Road, Hampton, London, TW12 2ER, UK.
  • Stevenson FK; Cancer Sciences Unit and Cancer Research UK and Experimental Cancer Medicine Centre Protein Core Facility, Faculty of Medicine, University of Southampton, Tremona road, Southampton, SO16 6YD, UK.
  • Ottensmeier CH; Cancer Sciences Unit and Cancer Research UK and Experimental Cancer Medicine Centre Protein Core Facility, Faculty of Medicine, University of Southampton, Tremona road, Southampton, SO16 6YD, UK.
  • Savelyeva N; Cancer Sciences Unit and Cancer Research UK and Experimental Cancer Medicine Centre Protein Core Facility, Faculty of Medicine, University of Southampton, Tremona road, Southampton, SO16 6YD, UK. ns1@soton.ac.uk.
Cancer Immunol Immunother ; 67(4): 627-638, 2018 Apr.
Article em En | MEDLINE | ID: mdl-29330557
ABSTRACT
Vaccination with DNA that encodes cancer antigens is a simple and convenient way to raise immunity against cancer and has already shown promise in the clinical setting. Conventional plasmid DNA is commonly used which together with the encoded antigen also includes bacterial immunostimulatory CpG motifs to target the DNA sensor Toll-like receptor 9. Recently DNA vaccines using doggybone DNA (dbDNA™), have been developed without the use of bacteria. The cell-free process relies on the use of Phi29 DNA polymerase to amplify the template followed by protelomerase TelN to complete individual closed linear DNA. The resulting DNA contains the required antigenic sequence, a promoter and a poly A tail but lacks bacterial sequences such as an antibiotic resistance gene, prompting the question of immunogenicity. Here we compared the ability of doggybone DNA vaccine with plasmid DNA vaccine to induce adaptive immunity using clinically relevant oncotargets E6 and E7 from HPV. We demonstrate that despite the inability to trigger TLR9, doggybone DNA was able to induce similar levels of cellular and humoral immunity as plasmid DNA, with suppression of established TC-1 tumours.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Plasmídeos / Células Dendríticas / Linfócitos T CD8-Positivos / Vacinas de DNA / Receptor Toll-Like 9 / Imunidade Celular / Neoplasias Pulmonares Limite: Animals Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Plasmídeos / Células Dendríticas / Linfócitos T CD8-Positivos / Vacinas de DNA / Receptor Toll-Like 9 / Imunidade Celular / Neoplasias Pulmonares Limite: Animals Idioma: En Ano de publicação: 2018 Tipo de documento: Article