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    Cytolytic DNA vaccine encoding lytic perforin augments the maturation of- and antigen presentation by- dendritic cells in a time-dependent manner

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    Author
    Wijesundara, DK; Yu, W; Quah, BJC; Eldi, P; Hayball, JD; Diener, KR; Voskoboinik, I; Gowans, EJ; Grubor-Bauk, B
    Date
    2017-08-17
    Source Title
    Scientific Reports
    Publisher
    NATURE PUBLISHING GROUP
    University of Melbourne Author/s
    Voskoboinik, Ilia
    Affiliation
    Sir Peter MacCallum Department of Oncology
    Metadata
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    Document Type
    Journal Article
    Citations
    Wijesundara, D. K., Yu, W., Quah, B. J. C., Eldi, P., Hayball, J. D., Diener, K. R., Voskoboinik, I., Gowans, E. J. & Grubor-Bauk, B. (2017). Cytolytic DNA vaccine encoding lytic perforin augments the maturation of- and antigen presentation by- dendritic cells in a time-dependent manner. SCIENTIFIC REPORTS, 7 (1), https://doi.org/10.1038/s41598-017-08063-1.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/256745
    DOI
    10.1038/s41598-017-08063-1
    Abstract
    The use of cost-effective vaccines capable of inducing robust CD8+ T cell immunity will contribute significantly towards the elimination of persistent viral infections and cancers worldwide. We have previously reported that a cytolytic DNA vaccine encoding an immunogen and a truncated mouse perforin (PRF) protein significantly augments anti-viral T cell (including CD8+ T cell) immunity. Thus, the current study investigated whether this vaccine enhances activation of dendritic cells (DCs) resulting in greater priming of CD8+ T cell immunity. In vitro data showed that transfection of HEK293T cells with the cytolytic DNA resulted in the release of lactate dehydrogenase, indicative of necrotic/lytic cell death. In vitro exposure of this lytic cell debris to purified DCs from naïve C57BL/6 mice resulted in maturation of DCs as determined by up-regulation of CD80/CD86. Using activation/proliferation of adoptively transferred OT-I CD8+ T cells to measure antigen presentation by DCs in vivo, it was determined that cytolytic DNA immunisation resulted in a time-dependent increase in the proliferation of OT-I CD8+ T cells compared to canonical DNA immunisation. Overall, the data suggest that the cytolytic DNA vaccine increases the activity of DCs which has important implications for the design of DNA vaccines to improve their translational prospects.

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