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Electroporation as a "prime/boost" strategy for naked DNA vaccination against a tumor antigen

Electroporation as a "prime/boost" strategy for naked DNA vaccination against a tumor antigen
Electroporation as a "prime/boost" strategy for naked DNA vaccination against a tumor antigen
We have developed novel DNA fusion vaccines encoding tumor Ags fused to pathogen-derived sequences. This strategy activates linked T cell help and, using fragment C of tetnus toxin, amplification of anti-tumor Ab, CD4+, and CD8+ T cell responses is achievable in mice. However, there is concern that simple DNA vaccine injection may produce inadequate responses in larger humans. To overcome this, we tested electroporation as a method to increase the transfection efficiency and immune responses by these tumor vaccines in vivo in mice. Using a DNA vaccine expressing the CTL epitope AH1 from colon carcinoma CT26, we confirmed that effective priming and tumor protection in mice are highly dependent on vaccine dose and volume. However, suboptimal vaccination was rendered effective by electroporation, priming higher levels of AH1-specific CD8+ T cells able to protect mice from tumor growth. Electroporation during priming with our optimal vaccination protocol did not improve CD8+ T cell responses. In contrast, electroporation during boosting strikingly improved vaccine performance. The prime/boost strategy was also effective if electroporation was used at both priming and boosting. For Ab induction, DNA vaccination is generally less effective than protein. However, prime/boost with naked DNA followed by electroporation dramatically increased Ab levels. Thus, the priming qualities of DNA fusion vaccines, integrated with the improved Ag expression offered by electroporation, can be combined in a novel homologous prime/boost approach, to generate superior antitumor immune responses. Therefore, boosting may not require viral vectors, but simply a physical change in delivery, facilitating application to the cancer clinic.
0022-1767
6292-6298
Buchan, Sarah
9ade187d-f127-45de-ad90-9d544d64718a
Gronevik, Eirik
9a1acbf4-e824-4f6c-a41e-74b192771122
Mathiesen, Iacob
fd96fb25-21e0-411d-b4b5-f2a3169de8ae
King, Catherine A.
8239cea6-bbe4-4031-bf3e-8deb5a3dab7f
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Rice, Jason
d58d4fcd-8dc0-4599-bf96-62323d579227
Buchan, Sarah
9ade187d-f127-45de-ad90-9d544d64718a
Gronevik, Eirik
9a1acbf4-e824-4f6c-a41e-74b192771122
Mathiesen, Iacob
fd96fb25-21e0-411d-b4b5-f2a3169de8ae
King, Catherine A.
8239cea6-bbe4-4031-bf3e-8deb5a3dab7f
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Rice, Jason
d58d4fcd-8dc0-4599-bf96-62323d579227

Buchan, Sarah, Gronevik, Eirik, Mathiesen, Iacob, King, Catherine A., Stevenson, Freda K. and Rice, Jason (2005) Electroporation as a "prime/boost" strategy for naked DNA vaccination against a tumor antigen. Journal of Immunology, 174 (10), 6292-6298.

Record type: Article

Abstract

We have developed novel DNA fusion vaccines encoding tumor Ags fused to pathogen-derived sequences. This strategy activates linked T cell help and, using fragment C of tetnus toxin, amplification of anti-tumor Ab, CD4+, and CD8+ T cell responses is achievable in mice. However, there is concern that simple DNA vaccine injection may produce inadequate responses in larger humans. To overcome this, we tested electroporation as a method to increase the transfection efficiency and immune responses by these tumor vaccines in vivo in mice. Using a DNA vaccine expressing the CTL epitope AH1 from colon carcinoma CT26, we confirmed that effective priming and tumor protection in mice are highly dependent on vaccine dose and volume. However, suboptimal vaccination was rendered effective by electroporation, priming higher levels of AH1-specific CD8+ T cells able to protect mice from tumor growth. Electroporation during priming with our optimal vaccination protocol did not improve CD8+ T cell responses. In contrast, electroporation during boosting strikingly improved vaccine performance. The prime/boost strategy was also effective if electroporation was used at both priming and boosting. For Ab induction, DNA vaccination is generally less effective than protein. However, prime/boost with naked DNA followed by electroporation dramatically increased Ab levels. Thus, the priming qualities of DNA fusion vaccines, integrated with the improved Ag expression offered by electroporation, can be combined in a novel homologous prime/boost approach, to generate superior antitumor immune responses. Therefore, boosting may not require viral vectors, but simply a physical change in delivery, facilitating application to the cancer clinic.

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Published date: 15 May 2005

Identifiers

Local EPrints ID: 26228
URI: https://eprints.soton.ac.uk/id/eprint/26228
ISSN: 0022-1767
PURE UUID: 598ae0d6-4ad5-42c9-af3c-220aacee5407
ORCID for Freda K. Stevenson: ORCID iD orcid.org/0000-0002-0933-5021

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Date deposited: 21 Apr 2006
Last modified: 06 Jun 2018 13:01

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Contributors

Author: Sarah Buchan
Author: Eirik Gronevik
Author: Iacob Mathiesen
Author: Catherine A. King
Author: Jason Rice

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