Novel adenovirus-based vaccines induce broad and sustained T cell responses to HCV in man

• Published in: Science translational medicine Vol. 4; no. 115; p. 115ra1
• Main 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, Traboni, Cinzia, Oo, Ye, Adams, David, Hill, Adrian, Colloca, Stefano, Nicosia, Alfredo, Cortese, Riccardo, Klenerman, Paul
• Format: Journal Article
• Language: English
• Published: United States 04.01.2012
• Subjects: Adenoviridae - metabolism; CD4-Positive T-Lymphocytes - virology; CD8-Positive T-Lymphocytes - virology; Cell Proliferation; Genotype; HEK293 Cells; Hepacivirus - genetics; Hepatitis C - prevention & control; Hepatitis C - virology; Humans; Interferon-gamma - biosynthesis; Interleukin-2 - biosynthesis; Leukocytes, Mononuclear - cytology; T-Lymphocytes - virology; Time Factors; Tumor Necrosis Factor-alpha - metabolism; Viral Hepatitis Vaccines - therapeutic use
• ISSN: 1946-6242
• DOI: 10.1126/scitranslmed.3003155

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-γ, 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.