title: Evidence for protection against chronic hepatitis C virus infection in chimpanzees by immunization with replicating recombinant vaccinia virus.
abstract: Given the failures of nonreplicating vaccines against chronic hepatitis C virus (HCV) infection, we hypothesized that a replicating viral vector may provide protective immunity. Four chimpanzees were immunized transdermally twice with recombinant vaccinia viruses (rVV) expressing HCV genes. After challenge with 24 50% chimpanzee infective doses of homologous HCV, the two control animals that had received only the parental VV developed chronic HCV infection. All four immunized animals resolved HCV infection. The difference in the rate of chronicity between the immunized and the control animals was close to statistical significance (P = 0.067). Immunized animals developed vigorous gamma interferon enzyme-linked immunospot responses and moderate proliferative responses. To investigate cross-genotype protection, the immunized recovered chimpanzees were challenged with a pool of six major HCV genotypes. During the acute phase after the multigenotype challenge, all animals had high-titer viremia in which genotype 4 dominated (87%), followed by genotype 5 (13%). However, after fluctuating low-level viremia, the viremia finally turned negative or persisted at very low levels. This study suggests the potential efficacy of replicating recombinant vaccinia virus-based immunization against chronic HCV infection.
authors.affiliation: Laboratory of Virology, The Lindsley F Kimball Research Institute of the New York Blood Center, New York, New York 10065, USA.
authors.forename: Jin-Won
authors.initials: JW
authors.lastname: Youn
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Hu
authors.forename: Nancy
authors.initials: N
authors.lastname: Tricoche
authors.forename: Wolfram
authors.initials: W
authors.lastname: Pfahler
authors.forename: Mohamed Tarek
authors.initials: MT
authors.lastname: Shata
authors.forename: Marlene
authors.initials: M
authors.lastname: Dreux
authors.forename: François-Loic
authors.initials: FL
authors.lastname: Cosset
authors.forename: Antonella
authors.initials: A
authors.lastname: Folgori
authors.forename: Dong-Hun
authors.initials: DH
authors.lastname: Lee
authors.forename: Betsy
authors.initials: B
authors.lastname: Brotman
authors.forename: Alfred M
authors.initials: AM
authors.lastname: Prince