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Type: Journal article
Title: Intradermal delivery of DNA encoding HCV NS3 and perforin elicits robust cell-mediated immunity in mice and pigs
Author: Grubor-Bauk, B.
Yu, W.
Wijesundara, D.
Gummow, J.
Garrod, T.
Brennan, A.
Voskoboinik, I.
Gowans, E.
Citation: Gene Therapy (Basingstoke), 2016; 23(1):26-37
Publisher: Nature Publishing Group
Issue Date: 2016
ISSN: 0969-7128
Statement of
B Grubor-Bauk, W Yu, D Wijesundara, J Gummow, T Garrod, AJ Brennan, I Voskoboinik and EJ Gowans
Abstract: Currently, no vaccine is available against hepatitis C virus (HCV), and although DNA vaccines have considerable potential, this has not been realised. Previously, the efficacy of DNA vaccines for human immunodeficiency virus (HIV) and HCV was shown to be enhanced by including the gene for a cytolytic protein, viz. perforin. In this study, we examined the mechanism of cell death by this bicistronic DNA vaccine, which encoded the HCV non-structural protein 3 (NS3) under the control of the CMV promoter and perforin is controlled by the SV40 promoter. Compared with a canonical DNA vaccine and a bicistronic DNA vaccine encoding NS3 and the proapoptotic gene NSP4, the perforin-containing vaccine elicited enhanced cell-mediated immune responses against the NS3 protein in vaccinated mice and pigs, as determined by ELISpot and intracellular cytokine staining, whereas a mouse challenge model suggested that the immunity was CD8(+) T-cell-dependent. The results of the study showed that the inclusion of perforin in the DNA vaccine altered the fate of NS3-positive cells from apoptosis to necrosis, and this resulted in more robust immune responses in mice and pigs, the latter of which represents an accepted large animal model in which to test vaccine efficacy.
Keywords: CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cell Line, Tumor
Disease Models, Animal
Vaccines, DNA
Viral Nonstructural Proteins
DNA, Viral
Immunity, Cellular
Toxins, Biological
Promoter Regions, Genetic
HEK293 Cells
Enzyme-Linked Immunospot Assay
Description: Advance online publication, 1 October 2015
Rights: © 2016 Macmillan Publishers Limited All rights reserved.
DOI: 10.1038/gt.2015.86
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