Novel Adenovirus-Based Vaccines Induce Broad and Sustained T Cell Responses to HCV in Man

Citations Over TimeTop 1% of 2012 papers

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-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.

Related Papers

• → Opportunities for the Use of Lentiviral Vectors in Human Gene Therapy(2002)71 cited
• → Gene therapy for neurodegenerative and ocular diseases using lentiviral vectors(2005)35 cited
• → Gene therapy for cardiovascular applications(2005)
• [Improvements of lentiviral vector and its application in gene therapy of hematological diseases].(2003)
• → 501. Porcine Adenoviral Vectors as Promising Supplement to Human Adenoviral Vectors for Gene Therapy(2003)