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Journal of Virology, October 2007, p. 10614-10624, Vol. 81, No. 19
0022-538X/07/$08.00+0     doi:10.1128/JVI.00691-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Chemoimmunotherapy of Chronic Hepatitis B Virus Infection in the Woodchuck Model Overcomes Immunologic Tolerance and Restores T-Cell Responses to Pre-S and S Regions of the Viral Envelope Protein{triangledown}

Stephan Menne,1* Bud C. Tennant,1 John L. Gerin,2 and Paul J. Cote2

Gastrointestinal Unit, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York,1 Division of Molecular Virology and Immunology, Department of Microbiology and Immunology, Georgetown University Medical Center, Rockville, Maryland2

Received 30 March 2007/ Accepted 16 July 2007

Treatment of chronic hepatitis B virus (HBV) infection could combine potent antiviral drugs and therapeutic vaccines to overcome immunological tolerance and induce the recovery phenotype to protect against disease progression. Conventional vaccination of woodchucks chronically infected with the woodchuck hepatitis virus (WHV) elicited differential T-cell response profiles depending on whether or not carriers were treated with the potent antiviral drug clevudine (CLV), which significantly reduces viral and antigen loads. The differential T-cell responses defined both CLV-dependent and CLV-independent epitopes of the pre-S and S regions of the WHV envelope protein. Only combined treatment involving CLV and conventional vaccine therapeutically restored the T-cell response profile of chronic WHV carrier woodchucks to that seen in prophylactic vaccination and in recovery from acute WHV infection. The results have implications for mechanisms of immunological tolerance operating in chronic HBV infection and suggest that such combined chemoimmunotherapy may be useful for treatment of humans with chronic HBV infection.

* Corresponding author. Mailing address: Gastrointestinal Unit, Department of Clinical Sciences, College of Veterinary Medicine, Room C-2005 VMC, Cornell University, Ithaca, New York 14853. Phone: (607) 253-3596. Fax: (607) 253-3289. E-mail: sm119{at}cornell.edu

{triangledown} Published ahead of print on 25 July 2007.

Journal of Virology, October 2007, p. 10614-10624, Vol. 81, No. 19
0022-538X/07/$08.00+0     doi:10.1128/JVI.00691-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Rodriguez-Madoz, J. R., Liu, K. H., Quetglas, J. I., Ruiz-Guillen, M., Otano, I., Crettaz, J., Butler, S. D., Bellezza, C. A., Dykes, N. L., Tennant, B. C., Prieto, J., Gonzalez-Aseguinolaza, G., Smerdou, C., Menne, S. (2009). Semliki Forest Virus Expressing Interleukin-12 Induces Antiviral and Antitumoral Responses in Woodchucks with Chronic Viral Hepatitis and Hepatocellular Carcinoma. J. Virol. 83: 12266-12278 [Abstract] [Full Text]  


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