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

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 perfori...

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Bibliographic Details
Published in:Scientific reports 2017-08, Vol.7 (1), p.8530-8, Article 8530
Main Authors: Wijesundara, Danushka K., Yu, Wenbo, Quah, Ben J. C., Eldi, Preethi, Hayball, John D., Diener, Kerrilyn R., Voskoboinik, Ilia, Gowans, Eric J., Grubor-Bauk, Branka
Format: Article
Language:English
Subjects:
13
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631/250/590/1991
631/250/590/2291
Antigen presentation
Antiviral agents
CD8 antigen
CD80 antigen
CD86 antigen
Cell activation
Cell death
Cell proliferation
Dendritic cells
Deoxyribonucleic acid
DNA
DNA vaccines
Humanities and Social Sciences
Immunization
L-Lactate dehydrogenase
Lactic acid
Lymphocytes
Lymphocytes T
multidisciplinary
Perforin
Science
Science (multidisciplinary)
Transfection
Vaccines
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-08063-1