{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T13:35:43Z","timestamp":1765546543774,"version":"build-2065373602"},"reference-count":71,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,29]],"date-time":"2020-01-29T00:00:00Z","timestamp":1580256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1026293","543143"],"award-info":[{"award-number":["APP1026293","543143"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Health and Medical Research Council :","award":["543139"],"award-info":[{"award-number":["543139"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Despite direct acting antivirals (DAAs) curing &gt;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-\u03b3 (IFN-\u03b3) 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\u201320-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.<\/jats:p>","DOI":"10.3390\/vaccines8010053","type":"journal-article","created":{"date-parts":[[2020,1,29]],"date-time":"2020-01-29T10:51:07Z","timestamp":1580295067000},"page":"53","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Safety Profile of a Multi-Antigenic DNA Vaccine Against Hepatitis C Virus"],"prefix":"10.3390","volume":"8","author":[{"given":"Jason","family":"Gummow","sequence":"first","affiliation":[{"name":"Virology Laboratory, Discipline of Surgery, The University of Adelaide and Basil Hetzel Institute for Translational Health Research, Adelaide 5011, Australia"},{"name":"Gene Silencing and Expression Laboratory, Robinson Research Institute, The University of Adelaide, Adelaide 5000, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makutiro G.","family":"Masavuli","sequence":"additional","affiliation":[{"name":"Virology Laboratory, Discipline of Surgery, The University of Adelaide and Basil Hetzel Institute for Translational Health Research, Adelaide 5011, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3705-4526","authenticated-orcid":false,"given":"Zelalem A.","family":"Mekonnen","sequence":"additional","affiliation":[{"name":"Virology Laboratory, Discipline of Surgery, The University of Adelaide and Basil Hetzel Institute for Translational Health Research, Adelaide 5011, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanrui","family":"Li","sequence":"additional","affiliation":[{"name":"Virology Laboratory, Discipline of Surgery, The University of Adelaide and Basil Hetzel Institute for Translational Health Research, Adelaide 5011, Australia"},{"name":"International Centre for Allied Health Evidence and Sansom Institute for Health Research, University of South Australia, Adelaide 5000, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danushka K.","family":"Wijesundara","sequence":"additional","affiliation":[{"name":"Virology Laboratory, Discipline of Surgery, The University of Adelaide and Basil Hetzel Institute for Translational Health Research, Adelaide 5011, Australia"},{"name":"School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5049-8351","authenticated-orcid":false,"given":"Ashish C.","family":"Shrestha","sequence":"additional","affiliation":[{"name":"Virology Laboratory, Discipline of Surgery, The University of Adelaide and Basil Hetzel Institute for Translational Health Research, Adelaide 5011, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilia","family":"Voskoboinik","sequence":"additional","affiliation":[{"name":"Killer Cell Biology Laboratory, Cancer Immunology Research, Peter MacCallum Cancer Centre, Victoria 3000, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric J.","family":"Gowans","sequence":"additional","affiliation":[{"name":"Virology Laboratory, Discipline of Surgery, The University of Adelaide and Basil Hetzel Institute for Translational Health Research, Adelaide 5011, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Branka","family":"Grubor-Bauk","sequence":"additional","affiliation":[{"name":"Virology Laboratory, Discipline of Surgery, The University of Adelaide and Basil Hetzel Institute for Translational Health Research, Adelaide 5011, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/j.1469-0691.2010.03432.x","article-title":"Evolving epidemiology of hepatitis C virus","volume":"17","author":"Lavanchy","year":"2011","journal-title":"Clin. 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