Preclinical evaluation of multi antigenic HCV DNA vaccine for the prevention of Hepatitis C virus infection

• Published in: Scientific reports Vol. 7; no. 1; p. 43531
• Main Authors: Lee, Hyojin, Jeong, Moonsup, Oh, Jooyeon, Cho, Youngran, Shen, Xuefei, Stone, John, Yan, Jian, Rothkopf, Zachary, Khan, Amir S., Cho, Byung Mun, Park, Young K., Weiner, David B., Son, Woo-Chan, Maslow, Joel N.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.03.2017; Nature Publishing Group
• Subjects: 42/44; 45/22; 631/250/590/1991; 692/699/255/2514; 96/21; Animals; Antigens; CD4 antigen; CD8 antigen; Cytokines - biosynthesis; Disease Models, Animal; DNA vaccines; Dose-Response Relationship, Immunologic; Electroporation; Female; Hepacivirus - genetics; Hepacivirus - immunology; Hepatitis; Hepatitis C; Hepatitis C - immunology; Hepatitis C - prevention & control; Hepatitis C Antigens - genetics; Hepatitis C Antigens - immunology; Humanities and Social Sciences; Humans; Immune response; Immunity, Cellular; Immunization; Immunization Schedule; Infections; Injection; Lethal dose; Lymphocytes; Lymphocytes T; Male; Mice; Mice, Inbred C57BL; multidisciplinary; Plasmids; Science; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Time Factors; Tissue Distribution; Vaccination; Vaccines; Vaccines, DNA - administration & dosage; Vaccines, DNA - adverse effects; Vaccines, DNA - immunology; Viral Hepatitis Vaccines - administration & dosage; Viral Hepatitis Vaccines - adverse effects; Viral Hepatitis Vaccines - genetics; Viral Hepatitis Vaccines - immunology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep43531

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 14 th vaccination. 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.