title: Induction of humoral and cellular immune responses against hepatitis C virus by vaccination with replicon particles derived from Sindbis-like virus XJ-160.
abstract: A replication-defective, recombinant Sindbis virus vector was utilized in a novel immunization strategy to induce humoral and cellular responses against hepatitis C virus (HCV). The recombinant vector, pVaXJ-E1E2, expressing the gene for HCV glycoproteins E2 and E1, was constructed by inserting the E1E2 gene into the replicon pVaXJ, a DNA vector derived from Sindbis-like virus XJ-160. The defective replicon particles, XJ-E1E2, were produced by transfecting BHK-21(E+Capsid) cells, the packaging cell lines for the vector from XJ-160 virus, with pVaXJ-E1E2. Both glycoproteins, E2 and E1, were stably expressed, as indicated by immunofluorescence assay (IFA) and Western blotting. Mice were vaccinated using a prime-boost strategy with XJ-E1E2 particles combined with Freund's incomplete adjuvant via intramuscular injection at 0 and 2 weeks. HCV-specific IgG antibody levels and cellular immune responses were evaluated by IFA and IFN-γ ELISPOT, respectively. The results showed that the defective XJ-E1E2 particles in combination with Freund's incomplete adjuvant induced effective humoral and cellular immune responses against HCV glycoprotein E1 or E2, suggesting that a defective Sindbis particle vaccine is capable of eliciting an effective immune response. These findings have important implications for the development of HCV vaccine candidates.
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, The Department of Viral Encephalitis, National Institute for Viral Disease Control and Prevention, Chinese Center for Viral Disease Control and Prevention China CDC, Changbai Road 155, Changping District, Beijing, 102206, People's Republic of China. zhuwuyang1971@sohu.com
authors.forename: Wuyang
authors.initials: W
authors.lastname: Zhu
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Fu
authors.forename: Jian
authors.initials: J
authors.lastname: Lu
authors.forename: Yao
authors.initials: Y
authors.lastname: Deng
authors.forename: Huanqin
authors.initials: H
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wei
authors.forename: Lingling
authors.initials: L
authors.lastname: Deng
authors.forename: Wenjie
authors.initials: W
authors.lastname: Tan
authors.forename: Guodong
authors.initials: G
authors.lastname: Liang
mesh_terms: D000818:Animals; D004337:Drug Carriers; D005260:Female; D005620:Freund's Adjuvant / Q000008:administration & dosage; D005822:Genetic Vectors; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000097:blood; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D012845:Sindbis Virus / Q000235:genetics*; D014611:Vaccination / Q000379:methods; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D004337:Drug Carriers; C087035:E1 protein, Hepatitis C virus; D018937:Hepatitis C Antibodies; D007074:Immunoglobulin G; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C091015:glycoprotein E2, Hepatitis C virus; D005620:Freund's Adjuvant