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

dc.contributor.authorWijesundara, D.
dc.contributor.authorYu, W.
dc.contributor.authorQuah, B.
dc.contributor.authorEldi, P.
dc.contributor.authorHayball, J.
dc.contributor.authorDiener, K.
dc.contributor.authorVoskoboinik, I.
dc.contributor.authorGowans, E.
dc.contributor.authorGrubor-Bauk, B.
dc.date.issued2017
dc.description.abstractThe 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.
dc.description.statementofresponsibilityDanushka K. Wijesundara, Wenbo Yu, Ben J. C. Quah, Preethi Eldi, John D. Hayball, Kerrilyn R. Diener, Ilia Voskoboinik, Eric J. Gowans, and Branka Grubor-Bauk
dc.identifier.citationScientific Reports, 2017; 7(1):8530-1-8530-8
dc.identifier.doi10.1038/s41598-017-08063-1
dc.identifier.issn2045-2322
dc.identifier.issn2045-2322
dc.identifier.orcidHayball, J. [0000-0002-3089-4506]
dc.identifier.orcidDiener, K. [0000-0001-8417-5542]
dc.identifier.orcidGowans, E. [0000-0002-4274-8311]
dc.identifier.orcidGrubor-Bauk, B. [0000-0002-4642-105X]
dc.identifier.urihttp://hdl.handle.net/2440/110127
dc.language.isoen
dc.publisherNature Publishing Group
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1026293
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/543139
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/543143
dc.rights© The Author(s) 2017. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.source.urihttps://doi.org/10.1038/s41598-017-08063-1
dc.subjectDendritic Cells
dc.subjectT-Lymphocytes, Cytotoxic
dc.subjectAnimals
dc.subjectMice, Inbred C57BL
dc.subjectHumans
dc.subjectVaccines, DNA
dc.subjectAntigens
dc.subjectCell Proliferation
dc.subjectAntigen Presentation
dc.subjectTime Factors
dc.subjectPerforin
dc.subjectHEK293 Cells
dc.titleCytolytic DNA vaccine encoding lytic perforin augments the maturation of- and antigen presentation by- dendritic cells in a time-dependent manner
dc.typeJournal article
pubs.publication-statusPublished

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