title: AIC649 Induces a Bi-Phasic Treatment Response in the Woodchuck Model of Chronic Hepatitis B.
abstract: AIC649 has been shown to directly address the antigen presenting cell arm of the host immune defense leading to a regulated cytokine release and activation of T cell responses. In the present study we analyzed the antiviral efficacy of AIC649 as well as its potential to induce functional cure in animal models for chronic hepatitis B. Hepatitis B virus transgenic mice and chronically woodchuck hepatitis virus (WHV) infected woodchucks were treated with AIC649, respectively. In the mouse system AIC649 decreased the hepatitis B virus titer as effective as the "gold standard", Tenofovir. Interestingly, AIC649-treated chronically WHV infected woodchucks displayed a bi-phasic pattern of response: The marker for functional cure--hepatitis surface antigen--first increased but subsequently decreased even after cessation of treatment to significantly reduced levels. We hypothesize that the observed bi-phasic response pattern to AIC649 treatment reflects a physiologically "concerted", reconstituted immune response against WHV and therefore may indicate a potential for inducing functional cure in HBV-infected patients.
authors.affiliation: AiCuris GmbH & Co KG., Wuppertal, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Paulsen
authors.affiliation: Bayer Aktiengesellschaft, Leverkusen, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Weber
authors.affiliation: AiCuris GmbH & Co KG., Wuppertal, Germany.
authors.forename: Helga
authors.initials: H
authors.lastname: Ruebsamen-Schaeff
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, United States of America.
authors.forename: Bud C
authors.initials: BC
authors.lastname: Tennant
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, United States of America.
authors.forename: Stephan
authors.initials: S
authors.lastname: Menne
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001691:Biological Therapy; D015415:Biomarkers / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D006514:Hepatitis B Surface Antigens / Q000378:metabolism*; D017919:Hepatitis B Virus, Woodchuck / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology; D016898:Interferon-alpha / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008392:Marmota / Q000276:immunology* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D018157:Parapoxvirus / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D000068698:Tenofovir / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D015164:Vaccines, Inactivated / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D006514:Hepatitis B Surface Antigens; D016898:Interferon-alpha; D014409:Tumor Necrosis Factor-alpha; D015164:Vaccines, Inactivated; D007371:Interferon-gamma; D000068698:Tenofovir