The functionality of virus-specific CD8 T cells in male mice was suppressed by intrahepatic Tregs and inversely correlated with levels of hepadnaviral DNA and viral protein; the induction of intrahepatic Tregs by viral replication and/or protein levels may explain the gender-related differences in the outcomes of HBV infection and limit the success of immunotherapeutic strategies in male patients. (Hepatology 2017;66:69-83).

Asian Pac J Cancer Prev, 15 (9), [4061][4062][4063][4064][4065] IntroductionBreast cancer is the second most common cancer in the world, accounts for 25% of all cancers (excluding nonmelanoma skin cancers) in women (GLOBOCAN, 2012). According to recently published data, the overall cancer incidence in Iran has been 110 per 100,000 in men and 98 per 100,000 in women in 2006. Among Iranian women, breast cancer is the leading cause of cancer morbidity and mortality, even though its incidence is among the lowest in the world, i.e., 25 per 100,000 (Mousavi et al., 2008).Breast cancer affects Iranian women at least one decade younger than their counterparts in developed countries (Harirchi et al., 2004). There are many published studies about breast cancer in Iran, but the epidemiological aspects of Iranian breast cancer are uncertain.Well known risk factors of breast cancer are genetic and epigenetic factors including: mutations in breast cancer susceptibility genes BRCA1 and BRCA2, TP53, sex-steroid hormones and lifestyle factors (Hulka and Moorman, 2008;Derks-Smeets et al., 2014).

Background:Hypervariability of HCV proteins is an important obstacle to design an efficient vaccine for HCV infection. Multi-epitope vaccines containing conserved epitopes of the virus could be a promising approach for protection against HCV.Objectives:Cellular and humoral immune responses against multi-epitope DNA and peptide vaccines were evaluated in BALB/c mice.Materials and Methods:In this experimental study, multi-epitope DNA- and peptide-based vaccines for HCV infection harboring immunodominant CD8+ T cell epitopes (HLA-A2 and H2-Dd) from Core (132-142), NS3 (1073-1081) and NS5B (2727-2735), a Th CD4+ epitope from NS3 (1248-1262) and a B-cell epitope from E2 (412-426) were designed. Multi-epitope DNA and peptide vaccines were tested in two regimens as heterologous DNA/peptide (group 1) and homologous peptide/peptide (group 2) prime/boost vaccine in BALB/c mice model. Electroporation was used for delivery of the DNA vaccine. Peptide vaccine was formulated with Montanide ISA 720 (M720) as adjuvant. Cytokine assay and antibody detection were performed to analyze the immune responses.Results:Mice immunized with multi-epitope peptide formulated with M720 developed higher HCV-specific levels of total IgG, IgG1 and IgG2a than those immunized with multi-epitope DNA vaccine. IFN-γ levels in group 2 were significantly higher than group 1 (i.e. 3 weeks after the last immunization; 37.61 ± 2.39 vs. 14.43 ± 0.43, P < 0.05). Moreover, group 2 had a higher IFN-γ/IL-4 ratio compared to group 1, suggesting a shift toward Th1 response. In addition, in the present study, induced immune responses were long lasting and stable after 9 weeks of the last immunization.Conclusions:Evaluation of multi-epitope DNA and peptide-vaccines confirmed their specific immunogenicity in BALB/c mice. However, lower Th1 immune responses in mice immunized with DNA vaccine suggests further investigations to improve the immunogenicity of the multi-epitope DNA vaccine through immune enhancers.