Preclinical evaluation of multi antigenic HCV DNA vaccine for the prevention of Hepatitis C virus infection
| Autor: | Woo-Chan Son, Byung Mun Cho, David B. Weiner, Hyojin Lee, Youngran Cho, Moonsup Jeong, Amir S. Khan, Joel N. Maslow, Jooyeon Oh, Jian Yan, John E. Stone, Zachary Rothkopf, Xuefei Shen, Young Kyoung Park |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Viral Hepatitis Vaccines Time Factors Hepatitis C virus T cell T-Lymphocytes Dose-Response Relationship Immunologic Hepacivirus medicine.disease_cause Article DNA vaccination 03 medical and health sciences Mice Immune system Antigen Immunity Vaccines DNA Medicine Animals Humans Tissue Distribution Immunization Schedule Immunity Cellular Multidisciplinary business.industry Lethal dose Virology Hepatitis C Vaccination Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure Cytokines Female Immunization Hepatitis C Antigens business |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep43531 |
| Popis: | 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 14th 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|