This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Menne, S. Articles by Cote, P. J. Search for Related Content PubMed PubMed Citation Articles by Menne, S. Articles by Cote, P. J.

 Previous Article  |  Next Article 

Journal of Virology, June 2002, p. 5305-5314, Vol. 76, No. 11
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.11.5305-5314.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Immunization with Surface Antigen Vaccine Alone and after Treatment with 1-(2-Fluoro-5-Methyl-ß-L-Arabinofuranosyl)-Uracil (L-FMAU) Breaks Humoral and Cell-Mediated Immune Tolerance in Chronic Woodchuck Hepatitis Virus Infection

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

Received 18 December 2001/ Accepted 26 February 2002

Woodchucks chronically infected with the woodchuck hepatitis virus (WHV) were treated with the antiviral drug 1-(2-fluoro-5-methyl-ß-L-arabinofuranosyl)-uracil (L-FMAU) or placebo for 32 weeks. Half the woodchucks in each group then received four injections of surface antigen vaccine during the next 16 weeks. Vaccination alone elicited a low-level antibody response to surface antigen in most carriers but did not affect serum WHV DNA and surface antigen. Carriers treated first with L-FMAU to reduce serum WHV DNA and surface antigen and then vaccinated had a similar low-level antibody response to surface antigen. Following vaccinations, cell-mediated immunity to surface antigen was demonstrated in both groups, independent of serum viral and antigen load, but was significantly enhanced in woodchucks treated with L-FMAU and was broadened to include other viral antigens (core, e, and x antigens and selected core peptides). Cell-mediated immunity and antibody responses to surface antigen were observed after drug discontinuation in half of the carriers that received L-FMAU alone. Surface antigen vaccine alone or in combination with drug broke humoral and cell-mediated immune tolerance in chronic WHV infection, but the combination with drug was more effective. This suggested that a high viral and antigen load in carriers is important in maintaining immunologic tolerance during chronicity. The humoral and cellular immunity associated with the combination of L-FMAU and vaccine resembled that observed in self-limited WHV infection. Such combination therapy represents a potentially useful approach to the control of chronic hepatitis B virus infection in humans.

This article has been cited by other articles:

• Menne, S., Butler, S. D., George, A. L., Tochkov, I. A., Zhu, Y., Xiong, S., Gerin, J. L., Cote, P. J., Tennant, B. C. (2008). Antiviral Effects of Lamivudine, Emtricitabine, Adefovir Dipivoxil, and Tenofovir Disoproxil Fumarate Administered Orally Alone and in Combination to Woodchucks with Chronic Woodchuck Hepatitis Virus Infection. Antimicrob. Agents Chemother. 52: 3617-3632 [Abstract] [Full Text]  
• Lu, M., Yao, X., Xu, Y., Lorenz, H., Dahmen, U., Chi, H., Dirsch, O., Kemper, T., He, L., Glebe, D., Gerlich, W. H., Wen, Y., Roggendorf, M. (2008). Combination of an Antiviral Drug and Immunomodulation against Hepadnaviral Infection in the Woodchuck Model. J. Virol. 82: 2598-2603 [Abstract] [Full Text]  
• Cooksley, H., Chokshi, S., Maayan, Y., Wedemeyer, H., Andreone, P., Gilson, R., Warnes, T., Paganin, S., Zoulim, F., Frederick, D., Neumann, A. U., Brosgart, C. L., Naoumov, N. V. (2008). Hepatitis B Virus e Antigen Loss during Adefovir Dipivoxil Therapy Is Associated with Enhanced Virus-Specific CD4+ T-Cell Reactivity. Antimicrob. Agents Chemother. 52: 312-320 [Abstract] [Full Text]  
• Dougherty, A. M., Guo, H., Westby, G., Liu, Y., Simsek, E., Guo, J.-T., Mehta, A., Norton, P., Gu, B., Block, T., Cuconati, A. (2007). A Substituted Tetrahydro-Tetrazolo-Pyrimidine Is a Specific and Novel Inhibitor of Hepatitis B Virus Surface Antigen Secretion. Antimicrob. Agents Chemother. 51: 4427-4437 [Abstract] [Full Text]  
• Menne, S., Tennant, B. C., Gerin, J. L., Cote, P. J. (2007). 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. J. Virol. 81: 10614-10624 [Abstract] [Full Text]  
• Menne, S., Asif, G., Narayanasamy, J., Butler, S. D., George, A. L., Hurwitz, S. J., Schinazi, R. F., Chu, C. K., Cote, P. J., Gerin, J. L., Tennant, B. C. (2007). Antiviral Effect of Orally Administered ( )-{beta}-D-2-Aminopurine Dioxolane in Woodchucks with Chronic Woodchuck Hepatitis Virus Infection. Antimicrob. Agents Chemother. 51: 3177-3184 [Abstract] [Full Text]  
• Casey, J., Cote, P. J., Toshkov, I. A., Chu, C. K., Gerin, J. L., Hornbuckle, W. E., Tennant, B. C., Korba, B. E. (2005). Clevudine Inhibits Hepatitis Delta Virus Viremia: a Pilot Study of Chronically Infected Woodchucks. Antimicrob. Agents Chemother. 49: 4396-4399 [Abstract] [Full Text]  
• Menne, S., Cote, P. J., Korba, B. E., Butler, S. D., George, A. L., Tochkov, I. A., Delaney, W. E. IV, Xiong, S., Gerin, J. L., Tennant, B. C. (2005). Antiviral Effect of Oral Administration of Tenofovir Disoproxil Fumarate in Woodchucks with Chronic Woodchuck Hepatitis Virus Infection. Antimicrob. Agents Chemother. 49: 2720-2728 [Abstract] [Full Text]  
• Lu, M., Isogawa, M., Xu, Y., Hilken, G. (2005). Immunization with the Gene Expressing Woodchuck Hepatitis Virus Nucleocapsid Protein Fused to Cytotoxic-T-Lymphocyte-Associated Antigen 4 Leads to Enhanced Specific Immune Responses in Mice and Woodchucks. J. Virol. 79: 6368-6376 [Abstract] [Full Text]  
• Zoulim, F. (2005). Combination of nucleoside analogues in the treatment of chronic hepatitis B virus infection: lesson from experimental models. J Antimicrob Chemother 55: 608-611 [Abstract] [Full Text]