Journal
SCIENCE TRANSLATIONAL MEDICINE
Volume 4, Issue 115, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.3003155
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Funding
- European Union
- Medical Research Council (UK)
- Wellcome Trust
- Oxford NIHR Biomedical Research Centre
- James Martin School for 21st Century, Oxford
- Wellcome Trust Clinical Research Facility, Birmingham
- National Institute for Health and Research Liver Biomedical Research Unit, Birmingham
- NIH grant 1U19AI082630-01
- MRC [G0901723, G1002552] Funding Source: UKRI
- Medical Research Council [G1002552, G0901723] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0510-10204] Funding Source: researchfish
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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-gamma, and tumor necrosis factor-alpha; 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.
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