当前位置: X-MOL 学术J. Hepatol. › 论文详情
IFNL3-adjuvanted HCV DNA vaccine reduces regulatory T-cell frequency and increases virus-specific T-cell responses.
Journal of Hepatology ( IF 18.946 ) Pub Date : 2020-02-20 , DOI: 10.1016/j.jhep.2020.02.009
Ji Won Han,Pil Soo Sung,Seon-Hui Hong,Hoyoung Lee,June Young Koh,Hyojin Lee,Scott White,Joel N Maslow,David B Weiner,Su-Hyung Park,Moonsup Jeong,Jeong Heo,Sang Hoon Ahn,Eui-Cheol Shin

BACKGROUND & AIMS Although direct-acting antiviral (DAA) treatment results in a sustained virologic response (SVR) in most patients with chronic hepatitis C virus (HCV) infection, they are at risk of re-infection. Moreover, the immune system is not completely normalized even after SVR (e.g. increased regulatory T (Treg) cell frequency). We developed a DNA vaccine, GLS-6150, to prevent re-infection of patients with DAA-induced SVR and evaluated its safety and immunogenicity in persons with chronic HCV infection (NCT02027116). METHODS GLS-6150 consists of plasmids encoding HCV non-structural proteins (NS3-NS5A) and adjuvant IFNL3. The vaccine was administered four times at 4-week intervals to three groups (1, 3, or 6 mg/vaccination; n=6 per group), followed by a 6 mg boost at 24 weeks (n=14). Peripheral blood T-cell responses were evaluated by IFN-γ enzyme-linked immunospot assays, intracellular cytokine staining, and MHC-I dextramer staining. Treg cell frequency was assessed by flow cytometry. RESULTS Severe adverse events or vaccine discontinuation were not reported. The IFN-γ spot-forming cells specific to NS3-NS5A were increased by GLS-6150. Both CD4+ and CD8+ T cells produced multiple cytokines. However, the frequency and phenotype of HCV-specific MHC-I dextramer+CD8+ T cells were not changed. Interestingly, frequency of Treg cells, particularly activated Treg cells, was decreased by GLS-6150, as expected from previous reports that IFNL3 adjuvants decrease Treg cell frequency. Ex vivo IFN-λ3 treatment reduced Treg frequency in pre-vaccination PBMCs. Finally, Treg cell frequency inversely correlated with HCV-specific, IFN-γ-producing T-cell responses in the study subjects. CONCLUSIONS We demonstrate that GLS-6150 decreases Treg cell frequency and enhances HCV-specific T-cell responses without significant side effects. A phase I clinical trial of GLS-6150 is currently underway in subjects with DAA-induced SVR (NCT03674125).
更新日期:2020-02-21

 

全部期刊列表>>
智控未来
聚焦商业经济政治法律
跟Nature、Science文章学绘图
控制与机器人
招募海内外科研人才,上自然官网
隐藏1h前已浏览文章
课题组网站
新版X-MOL期刊搜索和高级搜索功能介绍
ACS材料视界
x-mol收录
湖南大学化学化工学院刘松
上海有机所
李旸
南方科技大学
西湖大学
伊利诺伊大学香槟分校
徐明华
中山大学化学工程与技术学院
试剂库存
天合科研
down
wechat
bug