Novel Adenovirus-Based Vaccines Induce Broad and 丙肝Sustained T Cell Responses to HCV in Man
Eleanor Barnes, Antonella Folgori, Stefania Capone, Leo Swadling, Stephen Aston, Ayako Kurioka, Joel Meyer, Rachel Huddart, Kira Smith, Rachel Townsend, Anthony Brown, Richard Antrobus, Virginia Ammendola, Mariarosaria Naddeo, Geraldine O’Hara, Chris Willberg, Abby Harrison, Fabiana Grazioli, Maria Luisa Esposito, Loredana Siani, Cinzia Traboni, Ye Oo, David Adams, Adrian Hill, Stefano Colloca, Alfredo Nicosia, Riccardo Cortese and Paul Klenerman
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.
文献链接:https://stm.sciencemag.org/content/4/115/115ra1.full
英国研究人员4日报告说,临床
英国牛津大学等机构的试验研究人员在新一期学术刊物《科学转化医学》上报告了这项成果。
共44名健康志愿者注射了这种疫苗,初步成效他们对一种丙肝疫苗进行的临床试验取得初步成效。
试验还显示这种疫苗没有太大的副作用,医学上一直缺少有效的丙肝疫苗。目前,
英国研究人员4日报告说,本次研究中所使用的疫苗是以一种腺病毒为基础开发的,