title: The successful immune response against hepatitis C nonstructural protein 5A (NS5A) requires heterologous DNA/protein immunization.
abstract: The aim of this study was to evaluate the immunogenicity of NS5A protein of human hepatitis C virus (HCV) when delivered as naked DNA (NS5A DNA), or recombinant protein (rNS5A). DBA/2J mice received NS5A DNA, rNS5A, or NS5A DNA/rNS5A in different prime-boost combinations with a peptidoglycan Immunomax((R)). The weakest response was induced after rNS5A prime and NS5A DNA boost; rNS5A alone induced an immune response with a strong Th2-component; and NS5A DNA alone, a relatively weak secretion of IL-2 and IFN-gamma. The most efficient was co-injection of NS5A DNA and rNS5A, which induced a significant increase in CD4(+) and CD8(+) T-cell counts, anti-NS5A antibodies, specific T-cell proliferation, and proinflammatory cytokine production in vitro against a broad spectrum of NS5A epitopes. Administration of the mixture of adjuvanted DNA and protein immunogens can be selected as the best regimen for further preclinical HCV-vaccine trials.
authors.affiliation: D.I. Ivanovsky Institute of Virology, Russian Academy of Medical Sciences, Gamaleya str. 16, 123098 Moscow, Russian Federation. ol.mas@mail.ru
authors.forename: Olga V
authors.initials: OV
authors.lastname: Masalova
authors.forename: Ekaterina I
authors.initials: EI
authors.lastname: Lesnova
authors.forename: Alexei V
authors.initials: AV
authors.lastname: Pichugin
authors.forename: Tatiana M
authors.initials: TM
authors.lastname: Melnikova
authors.forename: Vadim V
authors.initials: VV
authors.lastname: Grabovetsky
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Petrakova
authors.forename: Olga A
authors.initials: OA
authors.lastname: Smirnova
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Ivanov
authors.forename: Alexei D
authors.initials: AD
authors.lastname: Zaberezhny
authors.forename: Ravshan I
authors.initials: RI
authors.lastname: Ataullakhanov
authors.forename: Maria G
authors.initials: MG
authors.lastname: Isaguliants
authors.forename: Alla A
authors.initials: AA
authors.lastname: Kushch
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation; D000939:Epitopes / Q000276:immunology; D005260:Female; D006526:Hepatitis C / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D051379:Mice; D008811:Mice, Inbred DBA; D010457:Peptidoglycan / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000276:immunology*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000276:Adjuvants, Immunologic; D000956:Antigens, Viral; D000939:Epitopes; D007371:Interferon-gamma; D007376:Interleukin-2; D010457:Peptidoglycan; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D014761:Viral Hepatitis Vaccines; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase