title: Priming with two DNA vaccines expressing hepatitis C virus NS3 protein targeting dendritic cells elicits superior heterologous protective potential in mice.
abstract: Development an effective vaccine may offer an alternative preventive and therapeutic strategy against HCV infection. DNA vaccination has been shown to induce robust humoral and cellular immunity and overcome many problems associated with conventional vaccines. In this study, mice were primed with either conventional pVRC-based or suicidal pSC-based DNA vaccines carrying DEC-205-targeted NS3 antigen (DEC-NS3) and boosted with type 5 adenoviral vectors encoding the partial NS3 and core antigens (C44P). The prime boost regimen induced a marked increase in antigen-specific humoral and T-cell responses in comparison with either rAd5-based vaccines or DEC-205-targeted DNA immunization in isolation. The protective effect against heterogeneous challenge was correlated with high levels of anti-NS3 IgG and T-cell-mediated immunity against NS3 peptides. Moreover, priming with a suicidal DNA vaccine (pSC-DEC-NS3), which elicited increased TNF-α-producing CD4+ and CD8+ T-cells against NS3-2 peptides (aa 1245-1461), after boosting, showed increased heterogeneous protective potential compared with priming with a conventional DNA vaccine (pVRC-DEC-NS3). In conclusion, a suicidal DNA vector (pSC-DEC-NS3) expressing DEC-205-targeted NS3 combined with boosting using an rAd5-based HCV vaccine (rAd5-C44P) is a good candidate for a safe and effective vaccine against HCV infection.
authors.affiliation: Central Laboratory, Meitan General Hospital, Beijing, 100028, China.|Key Laboratory of Medical Virology, Ministry of Health; National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, ChangPing District, Beijing, 102206, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Guan
authors.affiliation: Key Laboratory of Medical Virology, Ministry of Health; National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, ChangPing District, Beijing, 102206, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Key Laboratory of Medical Virology, Ministry of Health; National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, ChangPing District, Beijing, 102206, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Key Laboratory of Medical Virology, Ministry of Health; National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, ChangPing District, Beijing, 102206, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yin
authors.affiliation: Key Laboratory of Medical Virology, Ministry of Health; National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, ChangPing District, Beijing, 102206, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Medical Virology, Ministry of Health; National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, ChangPing District, Beijing, 102206, China. tanwj28@163.com.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Tan
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology* / Q000821:virology; D006801:Humans; D007111:Immunity, Cellular; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D014409:Tumor Necrosis Factor-alpha; D019444:Vaccines, DNA; D014761:Viral Hepatitis Vaccines; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases