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Journal of Virology, November 2008, p. 10896-10905, Vol. 82, No. 21
0022-538X/08/$08.00+0     doi:10.1128/JVI.01179-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Evidence for Protection against Chronic Hepatitis C Virus Infection in Chimpanzees by Immunization with Replicating Recombinant Vaccinia Virus{triangledown}

Jin-Won Youn,1,{dagger} Yu-Wen Hu,2 Nancy Tricoche,1 Wolfram Pfahler,1,3 Mohamed Tarek Shata,4 Marlene Dreux,5 François-Loic Cosset,5 Antonella Folgori,6 Dong-Hun Lee,1,{ddagger} Betsy Brotman,1 and Alfred M. Prince1*

Laboratory of Virology, The Lindsley F. Kimball Research Institute of the New York Blood Center, 310 East 67th St., New York, New York 10065,1 Canadian Blood Services, Ottawa, Ontario, Canada,2 Vilab II, The Liberian Institute for Biomedical Research, Robertsfield, Liberia,3 Department of Medicine, University of Cincinnati School of Medicine, Cincinnati, Ohio,4 Department U758, Human Virology Department, Inserm, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, F-69007 Lyon, France,5 Okairòs, via dei Castelli Romani, 22 00040 Pomezia, Rome, Italy6

Received 5 June 2008/ Accepted 19 August 2008

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.

* Corresponding author. Present address: Hepatitis Research Foundation, 349 Stone Hill Rd., Pound Ridge, NY 10576. Phone: (914) 764-8337. Fax: (914) 764-1921. E-mail: amprince00{at}optonline.net

{triangledown} Published ahead of print on 27 August 2008.

{dagger} Present address: MOGAM Biotechnology Research Institute, 341 Bojeong-Dong, Giheung-Gu, Yongin-Si, Gyeonggi-Do, 449-799, South Korea.

{ddagger} Present address: Clinical Molecular Biology Lab, BioTech Development Department, Schering-Plough, Union, NJ.

Journal of Virology, November 2008, p. 10896-10905, Vol. 82, No. 21
0022-538X/08/$08.00+0     doi:10.1128/JVI.01179-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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