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丙肝疫苗临床试验获初步成效
2012-8-13 阅读(1521)
近日，杂志《科学—转化医学》Sci Transl Med刊登了英国牛津大学等机构的研究人员的研究成果“Novel Adenovirus-Based Vaccines Induce Broad and Sustained T Cell Responses to HCV in Man。”，文章中，英国研究人员报告说，他们对一种丙肝疫苗进行的临床试验取得初步成效。这种疫苗的效果能至少持续一年，并且没有太大副作用。
目前，医学上一直缺少有效的丙肝疫苗。本次研究中所使用的疫苗是以一种腺病毒为基础开发的，它没有模仿丙肝病毒易变的外壳，而是模仿了其内部相对长期稳定不变的结构。
共41名健康志愿者注射了这种疫苗，结果显示在用该疫苗“培训”过一种名为T细胞的免疫细胞后，T细胞能够长期对丙肝病毒进行攻击，这种效果在为期一年的跟踪研究期间内都有效。
试验还显示这种疫苗没有太大的副作用，受试者zui多出现轻微头痛或局部疼痛等症状。
Novel Adenovirus-Based Vaccines Induce Broad and Sustained T Cell Responses to HCV in Man
Eleanor Barnes1,2,*, Antonella Folgori3,*, Stefania Capone3, Leo Swadling1, Stephen Aston1, Ayako Kurioka1, Joel Meyer1, Rachel Huddart1, Kira Smith1, Rachel Townsend1, Anthony Brown1, Richard Antrobus1, Virginia Ammendola3, Mariarosaria Naddeo3, Geraldine O’Hara1, Chris Willberg1, Abby Harrison1, Fabiana Grazioli4, Maria Luisa Esposito4, Loredana Siani3, Cinzia Traboni3, Ye Oo5, David Adams5, Adrian Hill1,2, Stefano Colloca3, Alfredo Nicosia3, Riccardo Cortese3 and Paul Klenerman1,2,†
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.
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