Strong HCV NS3- and NS4A-specific cellular immune responses induced in mice and Rhesus macaques by a novel HCV genotype 1a/1b consensus DNA vaccine.

• 影响指数: 4.169
• 发表时间: Nov 2008 18
• 来源期刊: Vaccine
• DOI: 10.1016/j.vaccine.2008.07.052
• PMID: 18692108
• 文章类型: Journal Article
• 中科院分区: Q2
• 方向: 医学
• 作者列表: Lang KA,Yan J,Draghia-Akli R,Khan A,Weiner DB

Mesh: Amino Acid Sequence; Animals; Carrier Proteins / immunology; Cell Separation; Electroporation; Enzyme-Linked Immunosorbent Assay; Epitope Mapping; Fluorescent Antibody Technique; Genotype; Hepacivirus / genetics immunology; Immunity, Cellular / immunology; Immunization; Interferon-gamma / biosynthesis genetics; Intracellular Signaling Peptides and Proteins; Macaca mulatta; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Spleen / cytology; Vaccines, DNA / immunology; Viral Nonstructural Proteins / immunology; Viral Proteins / immunology

Abstract

Hepatitis C virus (HCV) represents a major health burden with more than 170 million individuals currently infected worldwide, equaling roughly 3% of the world\'s population. HCV preferentially infects hepatocytes and is able to persist in up to 70% of infected individuals. It is estimated that up to 30% of chronically infected individuals will go on to develop progressive liver disease as a result of HCV infection, making the virus the leading cause of liver transplantation in the world. Currently there is no vaccine for HCV. In this study, we have taken a multi-step approach to develop a novel genotype 1a/1b consensus HCV NS3/NS4A DNA vaccine able to induce strong cellular immunity. We show that this construct is able to induce strong anti-NS3/NS4A T cell responses in C57BL/6 mice, as well as, in Rhesus macaques. Our data suggest that DNA vaccines encoding HCV proteins NS3/NS4A merit further study in the context of future prophylactic and therapeutic HCV T cell based vaccines.