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中級會員·17年
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丙肝疫苗臨床試驗獲初步成效

2012-8-13  閱讀(1506)

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近日,雜志《科學—轉化醫學》Sci Transl Med刊登了英國牛津大學等機構的研究人員的研究成果“Novel Adenovirus-Based Vaccines Induce Broad and Sustained T Cell Responses to HCV in Man。”,文章中,英國研究人員報告說,他們對一種丙肝疫苗進行的臨床試驗取得初步成效。這種疫苗的效果能至少持續一年,并且沒有太大副作用。

目前,醫學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種腺病毒為基礎開發的,它沒有模仿丙肝病毒易變的外殼,而是模仿了其內部相對長期穩定不變的結構。

共41名健康志愿者注射了這種疫苗,結果顯示在用該疫苗“培訓”過一種名為T細胞的免疫細胞后,T細胞能夠長期對丙肝病毒進行攻擊,這種效果在為期一年的跟蹤研究期間內都有效。

試驗還顯示這種疫苗沒有太大的副作用,受試者zui多出現輕微頭痛或局部疼痛等癥狀。

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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