Suresh, Manasa, et al. 2017. Antiviral Efficacy and Host Immune Response Induction during Sequential Treatment with SB 9200 Followed by Entecavir (ETV) in Woodchucks (January 5, 2017)
Manasa Suresh is a second year PhD student in the Department of Microbiology & Immunology. She is mentored by Dr. Stephan Menne, Associate Professor of Microbiology & Immunology. A focus of the laboratory research in the Menne lab is new treatments against hepatitis B virus (HBV). In this newly published paper, the research team evaluated a dinucloeotide (SB 9200) for an antiviral response in a woodchuck model of HBV. Two groups of animals were used to evaluate SB9200. Group 1 received ETV for 4 weeks followed by SB 9200 for 12 weeks. Group 2 received SB 9200 for 12 weeks followed by ETV for 4 weeks. At the end of treatment in Group 2, average reductions of 6.4 log10 in serum woodchuck (WHV) DNA and 3.3 log10 in WHV surface antigen were observed whereas in Group 1, average reductions of 4.2 log10 and 1.1 log10 in viremia and antigenemia were noted. Both groups demonstrated marked reductions in hepatic WHV nucleic acid levels which were more pronounced in Group 2. Following treatment cessation and an 8-week follow-up, recrudescence of viral replication was observed in Group 1 while viral relapse in Group 2 was significantly delayed. The antiviral effects observed in both groups were associated with temporally different induction of IFN-α, IFN-β, and IFN-stimulated genes in blood and liver. These results suggest that the induction of host immune responses by pretreatment with SB 9200 followed by ETV resulted in antiviral efficacy that was superior to that obtained using the strategy of viral reduction with ETV followed by immunomodulation.