Immunogenic Effects of Woodchuck Hepatitis Virus Surface Antigen Vaccine in Combination with Antiviral Therapy: Breaking of Humoral and Cellular Immune Tolerance in Chronic Woodchuck Hepatitis Virus Infection

Intervirology ◽  
2002 ◽  
Vol 45 (4-6) ◽  
pp. 237-250 ◽  
Author(s):  
Stephan Menne ◽  
Carol A. Roneker ◽  
Bud C. Tennant ◽  
Brent E. Korba ◽  
John L. Gerin ◽  
...  
Keyword(s):  
Virus Infection ◽  
Antiviral Therapy ◽  
Surface Antigen ◽  
Immune Tolerance ◽  
Hepatitis Virus ◽  
Woodchuck Hepatitis Virus ◽  
Virus Surface ◽  
Antigen Vaccine ◽  
Cellular Immune ◽  
Hepatitis Virus Infection

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

2002 ◽  
Vol 76 (11) ◽  
pp. 5305-5314 ◽  
Author(s):  
Stephan Menne ◽  
Carol A. Roneker ◽  
Brent E. Korba ◽  
John L. Gerin ◽  
Bud C. Tennant ◽  
...  
Keyword(s):  
Virus Infection ◽  
Antibody Response ◽  
Surface Antigen ◽  
Immune Tolerance ◽  
Hepatitis Virus ◽  
Woodchuck Hepatitis Virus ◽  
Cell Mediated Immunity ◽  
Low Level ◽  
Antigen Vaccine ◽  
Chronic Hepatitis B Virus

ABSTRACT Woodchucks chronically infected with the woodchuck hepatitis virus (WHV) were treated with the antiviral drug 1-(2-fluoro-5-methyl-β-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.

scholarly journals Antiviral Activities of Oral 1-O-Hexadecylpropanediol-3-Phosphoacyclovir and Acyclovir in Woodchucks with Chronic Woodchuck Hepatitis Virus Infection

2000 ◽  
Vol 44 (7) ◽  
pp. 1964-1969 ◽  
Author(s):  
Karl Y. Hostetler ◽  
James R. Beadle ◽  
William E. Hornbuckle ◽  
Christine A. Bellezza ◽  
Ilia A. Tochkov ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Virus Infection ◽  
Hepatitis B ◽  
Hepatitis Virus ◽  
Response To Therapy ◽  
Hydroxyl Group ◽  
Woodchuck Hepatitis Virus ◽  
Acyclovir Treatment ◽  
B Virus ◽  
Hepatitis Virus Infection

ABSTRACT Acyclovir triphosphate is a potent inhibitor of hepatitis B virus DNA polymerase, but acyclovir treatment provides no benefit in patients with hepatitis B virus infection. This is due in part to the fact that hepatitis B virus, unlike herpes simplex virus, does not code for a viral thymidine kinase which catalyzes the initial phosphorylation of acyclovir. We synthesized 1-O-octadecyl-sn-glycero-3-phospho (3-P)-acyclovir and found that it was highly active in reducing hepatitis B virus replication in 2.2.15 cells, while acyclovir was inactive. The greater antiviral activity of 1-O-octadecyl-sn-glycero-3-P-acyclovir appeared to be due to liver cell metabolism of the compound to acyclovir monophosphate (K. Y. Hostetler et al., Biochem. Pharmacol. 53:1815–1822, 1997). However, a closely related compound without a hydroxyl group at the sn-2 position of glycerol, 1-O-hexadecylpropanediol-3-P-acyclovir, was more active and selective in 2.2.15 cells in vitro. In this study, we treated woodchucks chronically infected with woodchuck hepatitis virus with increasing oral doses of 1-O-hexadecylpropanediol-3-P-acyclovir and assessed the response to therapy versus acyclovir or a placebo. At a dosage of 10 mg/kg of body weight twice a day, the test compound significantly inhibited viral replication in vivo, as indicated by a 95% reduction in serum woodchuck hepatitis virus DNA levels and by a 54% reduction in levels of woodchuck hepatitis virus replicative intermediates in the liver. Higher doses were somewhat less effective. In contrast, 20 mg of acyclovir/kg twice daily, a 5.3-fold-higher molar dosage, had no demonstrable activity against woodchuck hepatitis virus. Oral 1-O-hexadecylpropanediol-3-P-acyclovir appeared to be safe and effective in chronic woodchuck hepatitis virus infection.

scholarly journals Therapeutic vaccination of woodchucks against chronic woodchuck hepatitis virus infection

1997 ◽  
Vol 27 (4) ◽  
pp. 726-737 ◽  
Author(s):  
Sandra Hervás-Stubbs ◽  
Juan-José Lasarte ◽  
Pablo Sarobe ◽  
Jesús Prieto ◽  
John Cullen ◽  
...  
Keyword(s):  
Virus Infection ◽  
Hepatitis Virus ◽  
Woodchuck Hepatitis Virus ◽  
Therapeutic Vaccination ◽  
Hepatitis Virus Infection

scholarly journals Innate and adaptive immunity associated with resolution of acute woodchuck hepatitis virus infection in adult woodchucks

2019 ◽  
Vol 15 (12) ◽  
pp. e1008248 ◽  
Author(s):  
Manasa Suresh ◽  
Stefanie Czerwinski ◽  
Marta G. Murreddu ◽  
Bhaskar V. Kallakury ◽  
Ashika Ramesh ◽  
...  
Keyword(s):  
Virus Infection ◽  
Adaptive Immunity ◽  
Hepatitis Virus ◽  
Woodchuck Hepatitis Virus ◽  
Innate And Adaptive Immunity ◽  
Hepatitis Virus Infection

Effects of age and viral determinants on chronicity as an outcome of experimental woodchuck hepatitis virus infection

Hepatology ◽  
2000 ◽  
Vol 31 (1) ◽  
pp. 190-200 ◽  
Author(s):  
Paul J. Cote ◽  
Brent E. Korba ◽  
Roger H. Miller ◽  
James R. Jacob ◽  
Betty H. Baldwin ◽  
...  
Keyword(s):  
Virus Infection ◽  
Hepatitis Virus ◽  
Woodchuck Hepatitis Virus ◽  
Viral Determinants ◽  
Hepatitis Virus Infection
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