Research Article Comparative Immunogenicity in Rabbits of the Polypeptides Encoded by the 5  Terminus of Hepatitis C Virus RNA Irina Sominskaya, 1 Juris Jansons, 1 Anastasija Dovbenko, 1 Natalia Petrakova, 2 Ilva Lieknina, 1 Marija Mihailova, 1 Oleg Latyshev, 2 Olesja Eliseeva, 2 Irina Stahovska, 1 Inara Akopjana, 1 Ivars Petrovskis, 1 and Maria Isaguliants 2,3,4 1 Latvian Biomedical Research and Study Center, Ratsupites Street 1, Riga LV-1067, Latvia 2 N. F. Gamaleja Research Center of Epidemiology and Microbiology, Gamaleja Street 18, Moscow 123098, Russia 3 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels V¨ ag 16, 17177 Stockholm, Sweden 4 Riga Stradins University, Dzirciema Street 16, Riga LV-1007, Latvia Correspondence should be addressed to Maria Isaguliants; maria.issagouliantis@ki.se Received 22 July 2015; Accepted 29 September 2015 Academic Editor: Masha Fridkis-Hareli Copyright © 2015 Irina Sominskaya et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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 difcult 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 specifc 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. Te C-terminally truncated core was also weakly immunogenic on the T-cell level. To enhance core-specifc 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 specifcity confrming 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. 1. Introduction Nucleocapsid (core) protein of hepatitis C virus (HCV) is the most conserved HCV antigen capable of inducing strong broadly cross-reactive responses, and therefore an attractive component of a genotype-non-restricted HCV vaccine. As such, it has been included in a number of HCV vaccine candidates including ones reaching primate trials [1]. Te responses observed were described as limited. In immuniza- tions, HCV core demonstrated features of a weak immunogen capable of inducing mainly CTL and low or no CD4+ T-cell responses with moderate IFN-gamma, weak IL-2 production, and no antibodies [2, 3]. In primate trials, HCV core induced stable low-level T-cell response of CD4+ and CD8+ T-cells manifested by IFN-gamma, but no IL-2 or IL-4 responses, weak T-cell proliferation, and low titer of core-specifc anti- bodies [4–8]. Attempts to achieve a more efcient anticore immune response met with difculties [9–11] even when using viral vectors [12]. Interestingly, in natural infection HCV core acts as a strong humoral immunogen inducing an early potent anti- body production, but limited cellular response. Furthermore, in patients developing chronic infection, antibody response to HCV core protein continues to expand, whereas the cellular responses shrink [13]. Tis scenario points at a limited (low to no) protective potential of core-specifc humoral Hindawi Publishing Corporation Journal of Immunology Research Volume 2015, Article ID 762426, 12 pages http://dx.doi.org/10.1155/2015/762426