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  • American Society for Microbiology  (2)
  • Lin, Chih-Wei  (2)
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  • American Society for Microbiology  (2)
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  • 1
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 60, No. 3 ( 2016-03), p. 1546-1555
    Abstract: ABT-493 is a hepatitis C virus (HCV) nonstructural (NS) protein 3/4A protease inhibitor, and ABT-530 is an HCV NS5A inhibitor. These direct-acting antivirals (DAAs) demonstrated potent antiviral activity against major HCV genotypes and high barriers to resistance in vitro . In this open-label dose-ranging trial, antiviral activity and safety were assessed during 3 days of monotherapy with ABT-493 or ABT-530 in treatment-naive adults with HCV genotype 1 infection, with or without compensated cirrhosis. The presence of baseline resistance-associated variants (RAVs) was also evaluated. The mean maximal decreases in HCV RNA levels from baseline were approximately 4 log 10 IU/ml for all ABT-493 doses ranging from 100 mg to 700 mg and for ABT-530 doses of ≥40 mg. There were no meaningful differences in viral load declines for patients with versus without compensated cirrhosis. Twenty-four (50%) of the baseline samples from patients treated with ABT-493 had RAVs to NS3/4A protease inhibitors. Among 40 patients treated with ABT-530, 6 (15%) carried baseline RAVs to NS5A inhibitors. Viral load declines in patients with single baseline NS5A RAVs were similar to those in patients without RAVs. One patient harbored baseline RAVs at 3 NS5A positions and appeared to have a slightly less robust viral load decline on day 3 of monotherapy. No serious or grade 3 (severe) or higher adverse events and no clinically relevant laboratory abnormalities were observed with either compound. ABT-493 and ABT-530 demonstrated potent antiviral activity and acceptable safety during 3-day monotherapy in patients with HCV genotype 1 infection, with or without compensated cirrhosis. Based on these results, phase II studies assessing the combination of these DAAs for the treatment of chronic HCV infection in patients with or without compensated cirrhosis have been initiated. (This study has been registered at ClinicalTrials.gov under registration no. NCT01995071.)
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    RVK:
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2016
    detail.hit.zdb_id: 1496156-8
    detail.hit.zdb_id: 217602-6
    SSG: 12
    SSG: 15,3
    Location Call Number Limitation Availability
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  • 2
    Online Resource
    Online Resource
    American Society for Microbiology ; 2004
    In:  Journal of Virology Vol. 78, No. 3 ( 2004-02), p. 1333-1343
    In: Journal of Virology, American Society for Microbiology, Vol. 78, No. 3 ( 2004-02), p. 1333-1343
    Abstract: Previously, we identified human papillomavirus type 16 (HPV-16) E5 as a tumor rejection antigen that can induce cytotoxic T lymphocytes (CTLs) to protect against tumor growth (D. W. Liu et al., J. Virol. 74: 9083-9089, 2000). In the present study, we further mapped the CTL epitope of E5 protein by analyzing E5-specific CD8 + gamma interferon-positive (IFN-γ + ) double-positive cells in C57BL/6 mice with flow cytometry. The results showed the region spanning amino acids 25 to 33 (VCLLIRPLL) contained the potential D b -restricted CTL epitope. Subsequently, to determine whether peptide E5 25-33-based vaccination could induce E5-specific CTL activity, syngeneic animals received E5 25-33 emulsified with either CpG oligodeoxynucleotide (CpG ODN 1826) or Freund's adjuvant, and the growth of the tumors was monitored. The results showed that although both adjuvants induced E5-specific CD8 + IFN-γ + T cells and eradicated E5-containing tumor growth, CpG ODN was found to stimulate stronger CTL response than Freund's adjuvant. We also compared the immune response of the effector/memory/recall phase induced by E5 25-33 peptide or by E5 protein that was synthesized in vivo by adenovirus-based E5 gene delivery. E5 25-33 peptide plus CpG ODN was shown to be a superior vaccine compared to the adenovirus-based E5 gene. Interestingly, their chronological patterns of immune response were similar, suggesting that E5 25-33 is a major CTL peptide of E5 protein.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2004
    detail.hit.zdb_id: 1495529-5
    detail.hit.zdb_id: 80174-4
    Location Call Number Limitation Availability
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