title: Comparative Immunogenicity in Rabbits of the Polypeptides Encoded by the 5' Terminus of Hepatitis C Virus RNA.
abstract: Recent studies on the primate protection from HCV infection stressed the importance of immune response against structural viral proteins. Strong immune response against nucleocapsid (core) protein was difficult to achieve, requesting further experimentation in large animals. Here, we analyzed the immunogenicity of core aa 1-173, 1-152, and 147-191 and of its main alternative reading frame product F-protein in rabbits. Core aa 147-191 was synthesized; other polypeptides were obtained by expression in E. coli. Rabbits were immunized by polypeptide primes followed by multiple boosts and screened for specific anti-protein and anti-peptide antibodies. Antibody titers to core aa 147-191 reached 10(5); core aa 1-152, 5 × 10(5); core aa 1-173 and F-protein, 10(6). Strong immunogenicity of the last two proteins indicated that they may compete for the induction of immune response. The C-terminally truncated core was also weakly immunogenic on the T-cell level. To enhance core-specific cellular response, we immunized rabbits with the core aa 1-152 gene forbidding F-protein formation. Repeated DNA immunization induced a weak antibody and sustained proliferative response of broad specificity confirming a gain of cellular immunogenicity. Epitopes recognized in rabbits overlapped those in HCV infection. Our data promotes the use of rabbits for the immunogenicity tests of prototype HCV vaccines.
authors.affiliation: Latvian Biomedical Research and Study Center, Ratsupites Street 1, Riga LV-1067, Latvia.
authors.forename: Irina
authors.initials: I
authors.lastname: Sominskaya
authors.affiliation: Latvian Biomedical Research and Study Center, Ratsupites Street 1, Riga LV-1067, Latvia.
authors.forename: Juris
authors.initials: J
authors.lastname: Jansons
authors.affiliation: Latvian Biomedical Research and Study Center, Ratsupites Street 1, Riga LV-1067, Latvia.
authors.forename: Anastasija
authors.initials: A
authors.lastname: Dovbenko
authors.affiliation: N. F. Gamaleja Research Center of Epidemiology and Microbiology, Gamaleja Street 18, Moscow 123098, Russia.
authors.forename: Natalia
authors.initials: N
authors.lastname: Petrakova
authors.affiliation: Latvian Biomedical Research and Study Center, Ratsupites Street 1, Riga LV-1067, Latvia.
authors.forename: Ilva
authors.initials: I
authors.lastname: Lieknina
authors.affiliation: Latvian Biomedical Research and Study Center, Ratsupites Street 1, Riga LV-1067, Latvia.
authors.forename: Marija
authors.initials: M
authors.lastname: Mihailova
authors.affiliation: N. F. Gamaleja Research Center of Epidemiology and Microbiology, Gamaleja Street 18, Moscow 123098, Russia.
authors.forename: Oleg
authors.initials: O
authors.lastname: Latyshev
authors.affiliation: N. F. Gamaleja Research Center of Epidemiology and Microbiology, Gamaleja Street 18, Moscow 123098, Russia.
authors.forename: Olesja
authors.initials: O
authors.lastname: Eliseeva
authors.affiliation: Latvian Biomedical Research and Study Center, Ratsupites Street 1, Riga LV-1067, Latvia.
authors.forename: Irina
authors.initials: I
authors.lastname: Stahovska
authors.affiliation: Latvian Biomedical Research and Study Center, Ratsupites Street 1, Riga LV-1067, Latvia.
authors.forename: Inara
authors.initials: I
authors.lastname: Akopjana
authors.affiliation: Latvian Biomedical Research and Study Center, Ratsupites Street 1, Riga LV-1067, Latvia.
authors.forename: Ivars
authors.initials: I
authors.lastname: Petrovskis
authors.affiliation: N. F. Gamaleja Research Center of Epidemiology and Microbiology, Gamaleja Street 18, Moscow 123098, Russia ; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels Väg 16, 17177 Stockholm, Sweden ; Riga Stradins University, Dzirciema Street 16, Riga LV-1007, Latvia.
authors.forename: Maria
authors.initials: M
authors.lastname: Isaguliants
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D004195:Disease Models, Animal; D018604:Epitope Mapping; D015870:Gene Expression; D016174:Hepacivirus / Q000235:genetics* / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology / Q000821:virology; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007114:Immunization; D010455:Peptides / Q000235:genetics* / Q000276:immunology*; D012367:RNA, Viral; D011817:Rabbits; D014758:Viral Core Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D010455:Peptides; D012367:RNA, Viral; D014758:Viral Core Proteins; C433031:hepatitis C protein F, Hepatitis C virus