title: Preclinical evaluation of multi antigenic HCV DNA vaccine for the prevention of Hepatitis C virus infection.
abstract: Direct-acting antiviral treatment for hepatitis C virus (HCV) infection is costly and does not protect from re-infection. For human and chimpanzees, recovery from acute HCV infection correlates with host CD4+ and CD8+ T cell responses. DNA plasmids targeting the HCV non-structural antigens NS3, NS4, and NS5, were previously reported to induce robust and sustained T cell responses in mice and primates. These plasmids were combined with a plasmid encoding cytokine IL-28B, together named as VGX-6150. The dose-dependent T cell response and safety of VGX-6150 administered intramuscularly and followed by electroporation was assessed in mice. Immune responses plateaued at 20 μg/dose with IL-28B demonstrating significant immunoadjuvant activity. Mice administered VGX-6150 at 40, 400, and 800 μg given either as a single injection or as 14 injections given bi-weekly over 26 weeks showed no vaccine related changes in any clinical parameter compared to placebo recipients. There was no evidence of VGX-6150 accumulation at the injection site or in any organ 1 month following the 14thvaccination. Based on these studies, the approximate lethal dose (ALD) exceeds 800 μg/dose and the NOAEL was 800 μg/dose in mouse. In conclusion, VGX-6150 appears safe and a promising preventive vaccine candidate for HCV infection.
authors.affiliation: GeneOne Life Science, Seoul, Korea.|Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: Hyojin
authors.initials: H
authors.lastname: Lee
authors.affiliation: GeneOne Life Science, Seoul, Korea.
authors.forename: Moonsup
authors.initials: M
authors.lastname: Jeong
authors.affiliation: GeneOne Life Science, Seoul, Korea.
authors.forename: Jooyeon
authors.initials: J
authors.lastname: Oh
authors.affiliation: GeneOne Life Science, Seoul, Korea.
authors.forename: Youngran
authors.initials: Y
authors.lastname: Cho
authors.affiliation: Inovio Pharmaceuticals, Plymouth Meeting, PA, USA.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Shen
authors.affiliation: Inovio Pharmaceuticals, Plymouth Meeting, PA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Stone
authors.affiliation: Inovio Pharmaceuticals, Plymouth Meeting, PA, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Medicine, Morristown Medical Center, Morristown, NJ, USA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Rothkopf
authors.affiliation: Inovio Pharmaceuticals, Plymouth Meeting, PA, USA.
authors.forename: Amir S
authors.initials: AS
authors.lastname: Khan
authors.affiliation: GeneOne Life Science, Seoul, Korea.
authors.forename: Byung Mun
authors.initials: BM
authors.lastname: Cho
authors.affiliation: GeneOne Life Science, Seoul, Korea.
authors.forename: Young K
authors.initials: YK
authors.lastname: Park
authors.affiliation: Wistar Institute, Philadelphia, PA, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: Woo-Chan
authors.initials: WC
authors.lastname: Son
authors.affiliation: GeneOne Life Science, Seoul, Korea.
authors.forename: Joel N
authors.initials: JN
authors.lastname: Maslow
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D016174:Hepacivirus / Q000235:genetics* / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology* / Q000517:prevention & control*; D018936:Hepatitis C Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007114:Immunization; D007115:Immunization Schedule; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D007378:Interleukins; D000095022:Interferon Lambda
chemical_list: D016207:Cytokines; D018936:Hepatitis C Antigens; D019444:Vaccines, DNA; D014761:Viral Hepatitis Vaccines; C511668:interferon-lambda protein, mouse; D007378:Interleukins; D000095022:Interferon Lambda