title: Effect of route of delivery on heterologous protection against HCV induced by an adenovirus vector carrying HCV structural genes.
abstract: BACKGROUND
  An effective vaccine and new therapeutic methods for hepatitis C virus (HCV) are needed, and a potent HCV vaccine must induce robust and sustained cellular-mediated immunity (CMI). Research has indicated that adenoviral and vaccinia vectors may have the ability to elicit strong B and T cell immune responses to target antigens.
  
  
  RESULTS
  A recombinant replication-defective adenovirus serotype 5 (rAd5) vector, rAd5-CE1E2, and a recombinant Tian Tan vaccinia vector, rTTV-CE1E2, were constructed to express the HCV CE1E2 gene (1-746 amino acid HCV 1b subtype). Mice were prime-immunised with rAd5-CE1E2 delivered via intramuscular injection (i.m.), intranasal injection (i.n.), or intradermal injection (i.d.) and boosted using a different combination of injection routes. CMI was evaluated via IFN-γ ELISPOT and ICS 2 weeks after immunisation, or 16 weeks after boost for long-term responses. The humoral response was analysed by ELISA. With the exception of priming by i.n. injection, a robust CMI response against multiple HCV antigens (core, E1, E2) was elicited and remained at a high level for a long period (16 weeks post-vaccination) in mice. However, i.n. priming elicited the highest anti-core antibody levels. Priming with i.d. rAd5-CE1E2 and boosting with i.d. rTTV-CE1E2 carried out simultaneously enhanced CMI and the humoral immune response, compared to the homologous rAd5-CE1E2 immune groups. All regimens demonstrated equivalent cross-protective potency in a heterologous surrogate challenge assay based on a recombinant HCV (JFH1, 2a) vaccinia virus.
  
  
  CONCLUSIONS
  Our data suggest that a rAd5-CE1E2-based HCV vaccine would be capable of eliciting an effective immune response and cross-protection. These findings have important implications for the development of T cell-based HCV vaccine candidates.
authors: State Key Laboratory for Molecular Virology and Genetic Engineering, National Institute for Viral Disease Control and Prevention, Chinese Centre for Disease Control and Prevention, Changbai Road 155, Changping District, Beijing 102206, People's Republic of China.
authors: Jie
authors: J
authors: Guan
authors: Bo
authors: B
authors: Wen
authors: Yao
authors: Y
authors: Deng
authors: Ke
authors: K
authors: Zhang
authors: Hong
authors: H
authors: Chen
authors: Xiaobing
authors: X
authors: Wu
authors: Li
authors: L
authors: Ruan
authors: Wenjie
authors: W
authors: Tan
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D056738:Cross Protection; D004337:Drug Carriers / Q000008:administration & dosage; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005822:Genetic Vectors; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology* / Q000517:prevention & control*; D018937:Hepatitis C Antibodies / Q000097:blood; D007117:Immunization, Secondary / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D014611:Vaccination / Q000379:methods; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D015678:Viral Structural Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D004337:Drug Carriers; D018937:Hepatitis C Antibodies; D014614:Vaccines, Synthetic; D015678:Viral Structural Proteins; D014765:Viral Vaccines; D007371:Interferon-gamma