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The Chemotherapeutic Agent DMXAA as a Unique IRF3-Dependent Type-2 Vaccine Adjuvant

5,6-Dimethylxanthenone-4-acetic acid (DMXAA), a potent type I interferon (IFN) inducer, was evaluated as a chemotherapeutic agent in mouse cancer models and proved to be well tolerated in human cancer clinical trials. Despite its multiple biological functions, DMXAA has not been fully characterized...

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Autores principales: Tang, Choon Kit, Aoshi, Taiki, Jounai, Nao, Ito, Junichi, Ohata, Keiichi, Kobiyama, Kouji, Dessailly, Benoit H., Kuroda, Etsushi, Akira, Shizuo, Mizuguchi, Kenji, Coban, Cevayir, Ishii, Ken J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605442/
https://www.ncbi.nlm.nih.gov/pubmed/23555875
http://dx.doi.org/10.1371/journal.pone.0060038
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author Tang, Choon Kit
Aoshi, Taiki
Jounai, Nao
Ito, Junichi
Ohata, Keiichi
Kobiyama, Kouji
Dessailly, Benoit H.
Kuroda, Etsushi
Akira, Shizuo
Mizuguchi, Kenji
Coban, Cevayir
Ishii, Ken J.
author_facet Tang, Choon Kit
Aoshi, Taiki
Jounai, Nao
Ito, Junichi
Ohata, Keiichi
Kobiyama, Kouji
Dessailly, Benoit H.
Kuroda, Etsushi
Akira, Shizuo
Mizuguchi, Kenji
Coban, Cevayir
Ishii, Ken J.
author_sort Tang, Choon Kit
collection PubMed
description 5,6-Dimethylxanthenone-4-acetic acid (DMXAA), a potent type I interferon (IFN) inducer, was evaluated as a chemotherapeutic agent in mouse cancer models and proved to be well tolerated in human cancer clinical trials. Despite its multiple biological functions, DMXAA has not been fully characterized for the potential application as a vaccine adjuvant. In this report, we show that DMXAA does act as an adjuvant due to its unique property as a soluble innate immune activator. Using OVA as a model antigen, DMXAA was demonstrated to improve on the antigen specific immune responses and induce a preferential Th2 (Type-2) response. The adjuvant effect was directly dependent on the IRF3-mediated production of type-I-interferon, but not IL-33. DMXAA could also enhance the immunogenicity of influenza split vaccine which led to significant increase in protective responses against live influenza virus challenge in mice compared to split vaccine alone. We propose that DMXAA can be used as an adjuvant that targets a specific innate immune signaling pathway via IRF3 for potential applications including vaccines against influenza which requires a high safety profile.
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spelling pubmed-36054422013-04-03 The Chemotherapeutic Agent DMXAA as a Unique IRF3-Dependent Type-2 Vaccine Adjuvant Tang, Choon Kit Aoshi, Taiki Jounai, Nao Ito, Junichi Ohata, Keiichi Kobiyama, Kouji Dessailly, Benoit H. Kuroda, Etsushi Akira, Shizuo Mizuguchi, Kenji Coban, Cevayir Ishii, Ken J. PLoS One Research Article 5,6-Dimethylxanthenone-4-acetic acid (DMXAA), a potent type I interferon (IFN) inducer, was evaluated as a chemotherapeutic agent in mouse cancer models and proved to be well tolerated in human cancer clinical trials. Despite its multiple biological functions, DMXAA has not been fully characterized for the potential application as a vaccine adjuvant. In this report, we show that DMXAA does act as an adjuvant due to its unique property as a soluble innate immune activator. Using OVA as a model antigen, DMXAA was demonstrated to improve on the antigen specific immune responses and induce a preferential Th2 (Type-2) response. The adjuvant effect was directly dependent on the IRF3-mediated production of type-I-interferon, but not IL-33. DMXAA could also enhance the immunogenicity of influenza split vaccine which led to significant increase in protective responses against live influenza virus challenge in mice compared to split vaccine alone. We propose that DMXAA can be used as an adjuvant that targets a specific innate immune signaling pathway via IRF3 for potential applications including vaccines against influenza which requires a high safety profile. Public Library of Science 2013-03-21 /pmc/articles/PMC3605442/ /pubmed/23555875 http://dx.doi.org/10.1371/journal.pone.0060038 Text en © 2013 Tang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Tang, Choon Kit
Aoshi, Taiki
Jounai, Nao
Ito, Junichi
Ohata, Keiichi
Kobiyama, Kouji
Dessailly, Benoit H.
Kuroda, Etsushi
Akira, Shizuo
Mizuguchi, Kenji
Coban, Cevayir
Ishii, Ken J.
The Chemotherapeutic Agent DMXAA as a Unique IRF3-Dependent Type-2 Vaccine Adjuvant
title The Chemotherapeutic Agent DMXAA as a Unique IRF3-Dependent Type-2 Vaccine Adjuvant
title_full The Chemotherapeutic Agent DMXAA as a Unique IRF3-Dependent Type-2 Vaccine Adjuvant
title_fullStr The Chemotherapeutic Agent DMXAA as a Unique IRF3-Dependent Type-2 Vaccine Adjuvant
title_full_unstemmed The Chemotherapeutic Agent DMXAA as a Unique IRF3-Dependent Type-2 Vaccine Adjuvant
title_short The Chemotherapeutic Agent DMXAA as a Unique IRF3-Dependent Type-2 Vaccine Adjuvant
title_sort chemotherapeutic agent dmxaa as a unique irf3-dependent type-2 vaccine adjuvant
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605442/
https://www.ncbi.nlm.nih.gov/pubmed/23555875
http://dx.doi.org/10.1371/journal.pone.0060038
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