title: DNA prime-canarypox boost with polycistronic hepatitis C virus (HCV) genes generates potent immune responses to HCV structural and nonstructural proteins.
abstract: DNA vaccination was employed to study immune responses to hepatitis C virus (HCV) proteins. As an immunizing strategy, we studied immune responses of BALB/c (H-2d) and C57BL/6 mice (H-2b) to HCV genes delivered intramuscularly as a polycistronic construct capsid/E1/E2/NS2/NS3 (pRC/C-NS3) encoding 5 structural and nonstructural proteins. We also evaluated canarypox virus containing the same HCV genes as a means for potentiating immune responses to naked DNA. Our results indicate that mice that received a polycistronic pRC/C-NS3 with canarypox booster had enhanced antibody and cellular responses to HCV proteins. Immunodominant CD8(+) T cell responses to several HCV structural and nonstructural proteins, characterized by cytotoxicity and interferon (IFN)-gamma production or IFN-gamma production without significant cytotoxicity, were observed in both strains of mice. The combination of naked DNA with a nonreplicating canarypox booster encoding HCV polycistronic pRC/C-NS3 genes appears to diversify and enhance T cell responses to HCV proteins.
authors.affiliation: Laboratory of Virology, The Lindlsey F. Kimball Research Institute of the New York Blood Center, New York, NY 10021, USA. ppanchol@nybc.org
authors.forename: P
authors.initials: P
authors.lastname: Pancholi
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
authors.forename: N
authors.initials: N
authors.lastname: Tricoche
authors.forename: P
authors.initials: P
authors.lastname: Zhang
authors.forename: M E
authors.initials: ME
authors.lastname: Perkus
authors.forename: A M
authors.initials: AM
authors.lastname: Prince
mesh_terms: D000818:Animals; D000917:Antibody Formation; D018150:Avipoxvirus / Q000235:genetics / Q000276:immunology*; D017931:DNA Primers; D004279:DNA, Viral / Q000276:immunology; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D007111:Immunity, Cellular; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010641:Phenotype; D010957:Plasmids / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D019444:Vaccines, DNA; D014761:Viral Hepatitis Vaccines / Q000235:genetics / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000276:immunology*; D015678:Viral Structural Proteins / Q000276:immunology*
chemical_list: D017931:DNA Primers; D004279:DNA, Viral; D019444:Vaccines, DNA; D014761:Viral Hepatitis Vaccines; D017361:Viral Nonstructural Proteins; D015678:Viral Structural Proteins; D007371:Interferon-gamma