title: 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.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, 505 Stellar-Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Krystle A
authors.initials: KA
authors.lastname: Lang
authors.forename: Jian
authors.initials: J
authors.lastname: Yan
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Draghia-Akli
authors.forename: Amir
authors.initials: A
authors.lastname: Khan
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000276:immunology*; D002469:Cell Separation; D018274:Electroporation; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D005455:Fluorescent Antibody Technique; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology*; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008253:Macaca mulatta; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D013154:Spleen / Q000166:cytology; D019444:Vaccines, DNA / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D002352:Carrier Proteins; D007371:Interferon-gamma; D047908:Intracellular Signaling Peptides and Proteins; D019444:Vaccines, DNA; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C455041:NS4A cofactor peptide, Hepatitis C virus