Cellular immunogenicity of a multi-epitope peptide vaccine candidate based on hepatitis C virus NS5A, NS4B and core proteins in HHD-2 mice

• Published in: Journal of virological methods 2013-04, Vol.189 (1), p.47-52
• Main Authors: Huang, Xiao-jun, Lü, Xin, Lei, Ying-feng, Yang, Jing, Yao, Min, Lan, Hai-yun, Zhang, Jian-min, Jia, Zhan-sheng, Yin, Wen, Xu, Zhi-kai
• Format: Article
• Language: English
• Subjects: Adult; Amino Acid Sequence; Animals; CD4-positive T-lymphocytes; CD4-Positive T-Lymphocytes - immunology; CD8-positive T-lymphocytes; CD8-Positive T-Lymphocytes - immunology; Cell Line; Cell Proliferation; cell-mediated immunity; CTL; epitopes; Epitopes, T-Lymphocyte - immunology; Female; Hepacivirus - immunology; hepatitis C; Hepatitis C virus; HHD-2 mice; HLA-A2; Humans; immune response; Immunization; interferon-gamma; Interferon-gamma - metabolism; interleukin-2; Interleukin-2 - metabolism; Leukocytes, Mononuclear - immunology; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Middle Aged; patients; Peptide vaccine; secretion; T-Lymphocytes - immunology; vaccine development; vaccines; Vaccines, Subunit - immunology; Vaccines, Synthetic; Viral Hepatitis Vaccines - immunology; viral nonstructural proteins; Viral Nonstructural Proteins - immunology; Young Adult
• ISSN: 0166-0934; 1879-0984
• DOI: 10.1016/j.jviromet.2013.01.003

► Our engineered vaccine candidate, VAL-44, consists of multiple epitopes from HCV NS5A, NS4B and core proteins. ► VAL-44 induced antigen-specific IFN-γ-producing CD4+ T cells and CD8+ T cells. ► VAL-44 elicited a Th1-biased immune response with secretion of high amounts of IFN-γ and IL-2. ► Our findings suggest that VAL-44 may be developed as a potential HCV multi-epitope peptide vaccine. To develop a vaccine against hepatitis C virus (HCV), a multi-epitope peptide was synthesized from nonstructural proteins containing HLA-A2 epitopes inducing mainly responses in natural infection. The engineered vaccine candidate, VAL-44, consists of multiple epitopes from the HCV NS5A, NS4B and core proteins. Immunization with the VAL-44 peptide induced higher CTL responses than those by the smaller VL-20 peptide. VAL-44 induced antigen-specific IFN-γ-producing CD4+ T cells and CD8+ T cells. VAL-44 elicited a Th1-biased immune response with secretion of high amounts of IFN-γ and IL-2, compared with VL-20. These results suggest that VAL-44 can elicit strong cellular immune responses. The VAL-44 peptide stimulated IFN-γ production from viral-specific peripheral blood mononuclear cells (PBMCs) of patients infected with HCV. These results suggest that VAL-44 could be developed as a potential HCV multi-epitope peptide vaccine.