Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/124217
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Type: Journal article
Title: Safety profile of a multi-antigenic DNA vaccine against hepatitis C virus
Author: Gummow, J.
Masavuli, M.
Mekonnen, Z.A.
Li, Y.
Wijesundara, D.K.
Shrestha, A.C.
Voskoboinik, I.
Gowans, E.J.
Grubor-Bauk, B.
Citation: Vaccines, 2020; 8(1):1-15
Publisher: MDPI
Issue Date: 2020
ISSN: 2076-393X
2076-393X
Statement of
Responsibility: 
Jason Gummow, Makutiro G. Masavuli, Zelalem A. Mekonnen, Yanrui Li, Danushka K. Wijesundara, Ashish C. Shrestha, Ilia Voskoboinik, Eric J. Gowans and Branka Grubor-Bauk
Abstract: Despite direct acting antivirals (DAAs) curing >95% of individuals infected with hepatitis C (HCV), in order to achieve the World Health Organization HCV Global Elimination Goals by 2030 there are still major challenges that need to be overcome. DAAs alone are unlikely to eliminate HCV in the absence of a vaccine that can limit viral transmission. Consequently, a prophylactic HCV vaccine is necessary to relieve the worldwide burden of HCV disease. DNA vaccines are a promising vaccine platform due to their commercial viability and ability to elicit robust T-cell-mediated immunity (CMI). We have developed a novel cytolytic DNA vaccine that encodes non-structural HCV proteins and a truncated mouse perforin (PRF), which is more immunogenic than the respective canonical DNA vaccine lacking PRF. Initially we assessed the ability of the HCV pNS3-PRF and pNS4/5-PRF DNA vaccines to elicit robust long-term CMI without any adverse side-effects in mice. Interferon-γ (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assay was used to evaluate CMI against NS3, NS4 and NS5B in a dose-dependent manner. This analysis showed a dose-dependent bell-curve of HCV-specific responses in vaccinated animals. We then thoroughly examined the effects associated with reactogenicity of cytolytic DNA vaccination with the multi-antigenic HCV DNA vaccine (pNS3/4/5B). Hematological, biochemical and histological studies were performed in male Sprague Dawley rats with a relative vaccine dose 10–20-fold higher than the proposed dose in Phase I clinical studies. The vaccine was well tolerated, and no toxicity was observed. Thus, the cytolytic multi-antigenic DNA vaccine is safe and elicits broad memory CMI.
Keywords: DNA vaccine; Hepatitis C Virus; immune breadth; Pre-clinical; pathology; perforin; toxicology
Rights: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
RMID: 1000013542
DOI: 10.3390/vaccines8010053
Grant ID: http://purl.org/au-research/grants/nhmrc/1026293
http://purl.org/au-research/grants/nhmrc/543139
http://purl.org/au-research/grants/nhmrc/543143
Appears in Collections:Medicine publications

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