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Contribution of IRF-3 mediated IFN beta production to DNA vaccine dependent cellular immune responses

  1. Author:
    Shirota, H.
    Petrenko, L.
    Hattori, T.
    Klinman, D. M.

  2. Author Address

    Shirota, Hidekazu, Petrenko, Lev, Klinman, Dennis M.] NCI, Expt Immunol Lab, Frederick, MD 21702 USA. [Shirota, Hidekazu, Hattori, Toshio] Tohoku Univ, Sch Med, Dept Resp & Infect Dis, Sendai, Miyagi 980, Japan.
    1. Year: 2009
  2. Journal: Vaccine
    1. 27
    2. 15
    3. Pages: 2144-2149
  4. Type of Article: Article
  1. Abstract:

    The mechanism(s) by which DNA vaccines activate Ag-specific cellular immune responses is incompletely understood. Current findings indicate that IRF-3 plays an important role in this process. The IRF-3 dependent signaling pathway is triggered by the presence of intracytoplasmic DNA, and culminates in the production of type 1 IFNs. DNA vaccination of IRF-3 KO mice elicits a strong Ag-specific humoral response, yet CD4 and CD8 T cell responses (including the production of Th1, Th2 and Th17 cytokines) are severely impaired. Although expression of the immunogenic protein encoded by the DNA vaccine was similar in IRF-3 KO vs wild type mice, antigen presentation was severely impaired in the KO animals. This defect was remedied by the co-delivery of an IFN beta encoding plasmid. These findings suggest that the IRF-3/IFN beta pathways are key to the induction of cellular immunity following DNA vaccination. Published by Elsevier Ltd.

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  2. DOI: 10.1016/j.vaccine.2009.01.134
  3. PMID: 19356618

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