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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

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 mot...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5860099/
https://www.ncbi.nlm.nih.gov/pubmed/29330557
http://dx.doi.org/10.1007/s00262-017-2111-y
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author 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
author_facet 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
author_sort Allen, Alex
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00262-017-2111-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-58600992018-03-22 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 Cancer Immunol Immunother Original Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00262-017-2111-y) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2018-01-12 2018 /pmc/articles/PMC5860099/ /pubmed/29330557 http://dx.doi.org/10.1007/s00262-017-2111-y Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
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
Linear doggybone DNA vaccine induces similar immunological responses to conventional plasmid DNA independently of immune recognition by TLR9 in a pre-clinical model
title Linear doggybone DNA vaccine induces similar immunological responses to conventional plasmid DNA independently of immune recognition by TLR9 in a pre-clinical model
title_full Linear doggybone DNA vaccine induces similar immunological responses to conventional plasmid DNA independently of immune recognition by TLR9 in a pre-clinical model
title_fullStr Linear doggybone DNA vaccine induces similar immunological responses to conventional plasmid DNA independently of immune recognition by TLR9 in a pre-clinical model
title_full_unstemmed Linear doggybone DNA vaccine induces similar immunological responses to conventional plasmid DNA independently of immune recognition by TLR9 in a pre-clinical model
title_short Linear doggybone DNA vaccine induces similar immunological responses to conventional plasmid DNA independently of immune recognition by TLR9 in a pre-clinical model
title_sort linear doggybone dna vaccine induces similar immunological responses to conventional plasmid dna independently of immune recognition by tlr9 in a pre-clinical model
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5860099/
https://www.ncbi.nlm.nih.gov/pubmed/29330557
http://dx.doi.org/10.1007/s00262-017-2111-y
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