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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Public Library of Science (PLoS)
2013
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oai:doaj.org-article:ea094f7d4bfb48cf9ac352f2617c01e12021-11-18T07:52:24ZThe chemotherapeutic agent DMXAA as a unique IRF3-dependent type-2 vaccine adjuvant.1932-620310.1371/journal.pone.0060038https://doaj.org/article/ea094f7d4bfb48cf9ac352f2617c01e12013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23555875/?tool=EBIhttps://doaj.org/toc/1932-62035,6-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.Choon Kit TangTaiki AoshiNao JounaiJunichi ItoKeiichi OhataKouji KobiyamaBenoit H DessaillyEtsushi KurodaShizuo AkiraKenji MizuguchiCevayir CobanKen J IshiiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e60038 (2013) |
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DOAJ |
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DOAJ |
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EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Choon Kit Tang Taiki Aoshi Nao Jounai Junichi Ito Keiichi Ohata Kouji Kobiyama Benoit H Dessailly Etsushi Kuroda Shizuo Akira Kenji Mizuguchi Cevayir Coban Ken J Ishii The chemotherapeutic agent DMXAA as a unique IRF3-dependent type-2 vaccine adjuvant. |
| 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. |
| format |
article |
| author |
Choon Kit Tang Taiki Aoshi Nao Jounai Junichi Ito Keiichi Ohata Kouji Kobiyama Benoit H Dessailly Etsushi Kuroda Shizuo Akira Kenji Mizuguchi Cevayir Coban Ken J Ishii |
| author_facet |
Choon Kit Tang Taiki Aoshi Nao Jounai Junichi Ito Keiichi Ohata Kouji Kobiyama Benoit H Dessailly Etsushi Kuroda Shizuo Akira Kenji Mizuguchi Cevayir Coban Ken J Ishii |
| author_sort |
Choon Kit Tang |
| title |
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_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_sort |
chemotherapeutic agent dmxaa as a unique irf3-dependent type-2 vaccine adjuvant. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/ea094f7d4bfb48cf9ac352f2617c01e1 |
| work_keys_str_mv |
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