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- Title
Novel Adenovirus-Based Vaccines Induce Broad and Sustained T Cell Responses to HCV in Man.
- Authors
Barnes, Eleanor; Folgori, Antonella; Capone, Stefania; Swadling, Leo; Aston, Stephen; Kurioka, Ayako; Meyer, Joel; Huddart, Rachel; Smith, Kira; Townsend, Rachel; Brown, Anthony; Antrobus, Richard; Ammendola, Virginia; Naddeo, Mariarosaria; O'Hara, Geraldine; Willberg, Chris; Harrison, Abby; Grazioli, Fabiana; Esposito, Maria Luisa; Siani, Loredana
- Abstract
Currently, no vaccine exists for hepatitis C virus (HCV), a major pathogen thought to infect 170 million people globally. Many studies suggest that host T cell responses are critical for spontaneous resolution of disease, and preclinical studies have indicated a requirement for T cells in protection against challenge. We aimed to elicit HCV-specific T cells with the potential for protection using a recombinant adenoviral vector strategy in a phase 1 study of healthy human volunteers. Two adenoviral vectors expressing NS proteins from HCV genotype 1B were constructed based on rare serotypes [human adenovirus 6 (Ad6) and chimpanzee adenovirus 3 (ChAd3)]. Both vectors primed T cell responses against HCV proteins; these T cell responses targeted multiple proteins and were capable of recognizing heterologous strains (genotypes 1A and 3A). HCV-specific T cells consisted of both CD4+ and CD8+ T cell subsets; secreted interleukin-2, interferon-β, and tumor necrosis factor-α; and could be sustained for at least a year after boosting with the heterologous adenoviral vector. Studies using major histocompatibility complex peptide tetramers revealed long-lived central and effector memory pools that retained polyfunctionality and proliferative capacity. These data indicate that an adenoviral vector strategy can induce sustained T cell responses of a magnitude and quality associated with protective immunity and open the way for studies of prophylactic and therapeutic vaccines for HCV.
- Publication
Science Translational Medicine, 2012, Vol 4, Issue 115, p1
- ISSN
1946-6234
- Publication type
Article
- DOI
10.1126/scitranslmed.3003155