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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

Linear doggybone DNA vaccine induces similar immunological responses to conventional plasmid DNA independently of immune recognition by TLR9 in a pre-clinical model
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 motifs to target the DNA sensor Toll like receptor 9. Recently DNA vaccines using doggybone DNA (dbDNATM), have been developed without the use of bacteria. The cell free process relies on 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 tumours.
0340-7004
1-12
Allen, Alexandra J.
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Wang, Chuan
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Caproni, Lisa J.
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Sugiyarto, Gessa
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Harden, Elena L.
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Douglas, Leon R.
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Duriez, Patrick J.
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Karbowniczek, Kinga
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Extance, Jon
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Rothwell, Paul J.
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Orefo, Ifeayinwa
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Tite, John P.
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Stevenson, Freda K.
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Ottensmeier, Christian H.
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Savelyeva, Natalia
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Allen, Alexandra J.
660f61b5-0ccc-46f6-a638-4495d7ae7686
Wang, Chuan
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Caproni, Lisa J.
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Sugiyarto, Gessa
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Harden, Elena L.
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Douglas, Leon R.
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Duriez, Patrick J.
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Karbowniczek, Kinga
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Extance, Jon
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Rothwell, Paul J.
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Orefo, Ifeayinwa
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Tite, John P.
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Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Ottensmeier, Christian H.
42b8a398-baac-4843-a3d6-056225675797
Savelyeva, Natalia
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Allen, Alexandra J., Wang, Chuan, Caproni, Lisa J., Sugiyarto, Gessa, Harden, Elena L., Douglas, Leon R., Duriez, Patrick J., Karbowniczek, Kinga, Extance, Jon, Rothwell, Paul J., Orefo, Ifeayinwa, Tite, John P., Stevenson, Freda K., Ottensmeier, Christian H. and Savelyeva, Natalia (2018) Linear doggybone DNA vaccine induces similar immunological responses to conventional plasmid DNA independently of immune recognition by TLR9 in a pre-clinical model. Cancer Immunology Immunotherapy, 1-12. (doi:10.1007/s00262-017-2111-y).

Record type: Article

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 (dbDNATM), have been developed without the use of bacteria. The cell free process relies on 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 tumours.

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Accepted/In Press date: 20 December 2017
e-pub ahead of print date: 12 January 2018

Identifiers

Local EPrints ID: 416900
URI: https://eprints.soton.ac.uk/id/eprint/416900
ISSN: 0340-7004
PURE UUID: 518b235e-c6f3-4ddc-ae27-1a4c84aa2aa4
ORCID for Freda K. Stevenson: ORCID iD orcid.org/0000-0002-0933-5021

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Date deposited: 12 Jan 2018 17:30
Last modified: 04 Apr 2018 16:30

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Contributors

Author: Alexandra J. Allen
Author: Chuan Wang
Author: Lisa J. Caproni
Author: Gessa Sugiyarto
Author: Elena L. Harden
Author: Leon R. Douglas
Author: Patrick J. Duriez
Author: Kinga Karbowniczek
Author: Jon Extance
Author: Paul J. Rothwell
Author: Ifeayinwa Orefo
Author: John P. Tite

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