title: Sustained E2 antibody response correlates with reduced peak viremia after hepatitis C virus infection in the chimpanzee.
abstract: Immune correlates of protection against hepatitis C virus (HCV) infection are not well understood. Here we investigated 2 naive and 6 immunized chimpanzees before and after intravenous challenge, 12 weeks after the last immunization, with 100 50% chimpanzee infectious doses (CID(50)) of heterologous genotype 1b HCV. Vaccination with recombinant DNA and adenovirus vaccines expressing HCV core, E1E2, and NS3-5 genes induced long-term HCV-specific antibody and T-cell responses and reduced peak viral load about 100 times compared with controls (5.91 +/- 0.38 vs. 3.81 +/- 0.71 logs, respectively). There was a statistically significant inverse correlation between peak viral loads and envelope glycoprotein 2 (E2)-specific antibody responses at the time of challenge. Interestingly, one vaccinee that had sterilizing immunity against slightly heterologous virus generated the highest level of E2-specific total and neutralizing antibody responses as well as strong NS3/NS5-specific T-cell proliferative responses. The other four vaccinees with low levels of E2-specific antibody had about 44-fold reduced peak viral loads but eventually developed persistent infections. In conclusion, vaccine-induced E2-specific antibody plays an important role in prevention from nonhomologous virus infection and may provide new insight into the development of an effective HCV vaccine.
authors.affiliation: National Research Laboratory of DNA Medicine, Division of Molecular and Life Science, POSTECH Biotech Center, Pohang University of Science and Technology, Republic of Korea.
authors.forename: Jin-Won
authors.initials: JW
authors.lastname: Youn
authors.forename: Su-Hyung
authors.initials: SH
authors.lastname: Park
authors.forename: Dimitri
authors.initials: D
authors.lastname: Lavillette
authors.forename: Francois-Loic
authors.initials: FL
authors.lastname: Cosset
authors.forename: Se-Hwan
authors.initials: SH
authors.lastname: Yang
authors.forename: Chang Geun
authors.initials: CG
authors.lastname: Lee
authors.forename: Hyun-Tak
authors.initials: HT
authors.lastname: Jin
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Kim
authors.forename: Mohamed Tarek M
authors.initials: MT
authors.lastname: Shata
authors.forename: Dong-Hun
authors.initials: DH
authors.lastname: Lee
authors.forename: Wolfram
authors.initials: W
authors.lastname: Pfahler
authors.forename: Alfred M
authors.initials: AM
authors.lastname: Prince
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Sung
mesh_terms: D000818:Animals; D006526:Hepatitis C / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000097:blood*; D007371:Interferon-gamma / Q000096:biosynthesis; D002679:Pan troglodytes; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D014759:Viral Envelope Proteins / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000276:immunology; D014766:Viremia / Q000276:immunology*
chemical_list: D018937:Hepatitis C Antibodies; D014759:Viral Envelope Proteins; D014761:Viral Hepatitis Vaccines; C091015:glycoprotein E2, Hepatitis C virus; D007371:Interferon-gamma