title: The novel replication-defective vaccinia virus (Tiantan strain)-based hepatitis C virus vaccine induces robust immunity in macaques.
abstract: The induction of a robust neutralizing antibody (nAb) response is likely to be as essential as specific cell-mediated immunity (CMI) against multiple antigens for the development of effective preventive and therapeutic vaccines against hepatitis C virus (HCV) infection in humans. To date, no data on the immunogenicity of the replication-defective vaccinia virus (derived from the Tiantan strain) (rNTV)-based HCV vaccine in primates have been reported. This study describes in detail the immunogenicity of various vaccine candidates in rhesus macaques, including rNTV-based and replication-defective recombinant adenoviral (rAd)-based HCV vaccines, as well as HCV pseudotyped virus-like particles (HCVpp). Our data showed that rAd-HCV vaccine boosting induced robust CMI, while priming or boosting with HCVpp enhanced the antigen-specific nAb response after rAd-HCV vaccination; however, CMI was not enhanced. Vaccination includes rNTV-HCV priming induced robust antigen-specific antibody, particularly nAbs, and CMI responses. Furthermore, more robust and longer-lasting CMI and higher cytokine levels (both Th1 and Th2 types, especially IFN-γ) resulted from boosting with rAd-HCV. We conclude that the rNTV-based HCV vaccine induces robust nAbs and CMI when combined with a heterogeneous primer-booster strategy, which shows promise for development of a human HCV vaccine.
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, Changchun, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wen
authors.forename: Yao
authors.initials: Y
authors.lastname: Deng
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.forename: Jie
authors.initials: J
authors.lastname: Guan
authors.forename: Xia
authors.initials: X
authors.lastname: Chuai
authors.forename: Li
authors.initials: L
authors.lastname: Ruan
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
authors.forename: Wenjie
authors.initials: W
authors.lastname: Tan
mesh_terms: D000256:Adenoviridae; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D016207:Cytokines / Q000097:blood*; D003673:Defective Viruses / Q000235:genetics / Q000276:immunology; D005260:Female; D005822:Genetic Vectors; D016174:Hepacivirus / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000097:blood*; D007111:Immunity, Cellular; D007117:Immunization, Secondary; D008251:Macaca / Q000276:immunology; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D058425:Vaccines, Virus-Like Particle / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D014761:Viral Hepatitis Vaccines / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication
chemical_list: D057134:Antibodies, Neutralizing; D016207:Cytokines; D018937:Hepatitis C Antibodies; D014614:Vaccines, Synthetic; D058425:Vaccines, Virus-Like Particle; D014761:Viral Hepatitis Vaccines