The chemotherapeutic agent DMXAA as a unique IRF3-dependent type-2 vaccine adjuvant.
Tang, CK; Aoshi, T; Jounai, N; Ito, J; Ohata, K; Kobiyama, K; Dessailly, BH; Kuroda, E; Akira, S; Mizuguchi, K; Coban, C; Ishii, KJ
PloS one
8
e60038
2013
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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. | 23555875
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Convenient assay for interferons.
Rubinstein, S, et al.
J. Virol., 37: 755-8 (1981)
1981
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A convenient assay for interferons based on reduction of cytopathic effect was developed. The number of manipulations and the lengths of the various incubation steps were reduced to a minimum. The assay is simple to perform and can be completed within 16 h. Moreover, it can be used with various types of cells and a variety of viruses. | 6163873
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