Characterizing Hepatitis C Virus-Specific CD4(+) T Cells Following Viral-Vectored Vaccination, Directly Acting Antivirals, and Spontaneous Viral Cure.
Characterizing Hepatitis C Virus-Specific CD4(+) T Cells Following Viral-Vectored Vaccination, Directly Acting Antivirals, and Spontaneous Viral Cure.
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DOI：
10.1002/hep.31160
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发表时间：
2020-11
期刊：
影响因子：
--
通讯作者：
Klenerman P
中科院分区：
文献类型：
--
作者：
Hartnell F;Esposito I;Swadling L;Brown A;Phetsouphanh C;de Lara C;Gentile C;Turner B;Dorrell L;Capone S;Folgori A;Barnes E;Klenerman P
功能性辅助性CD 4 + T细胞的诱导是针对丙型肝炎病毒（HCV）的保护性免疫应答的标志，与自发的病毒清除相关。Heteroimmune prime/boost病毒载体疫苗接种已证明在健康志愿者中诱导广泛和多功能的HCV特异性CD 8 + T细胞;然而，对疫苗接种后的CD 4 + T细胞亚群知之甚少。我们使用主要组织相容性复合物II类四聚体分析了接受重组HCV腺病毒/修饰的安卡拉牛痘病毒载体HCV疫苗接种的志愿者中的HCV特异性CD 4 + T细胞群。随着时间的推移跟踪肽特异性T细胞应答，并使用流式细胞术评估功能（增殖和细胞因子分泌）和表型（细胞表面和核内）标志物。这些进行了比较，在10个人类白细胞抗原匹配的人与丙型肝炎病毒的自发决议和21例慢性感染患者直接作用抗病毒（DAA）治疗的CD 4+反应。疫苗接种诱导的四聚体阳性CD 4 + T细胞在加强后1 - 4周最高（平均值为0.06%）。在疾病自发消退后追踪的患者中获得了相似的频率（平均值为0.04%）。此外，疫苗接种后表征的细胞表面表型（CD 28、CD 127）记忆亚群标志物和核内转录因子以及肽特异性CD 4 + T细胞应答的功能能力与病毒自发消退后相当。相比之下，慢性感染中的辅助反应很少被检测到，而且功能较差，并且在HCV治愈后并没有持续恢复。HCV病毒载体疫苗接种后辅助CD 4 + T细胞表型和功能类似于HCV自发清除后观察到的“保护性记忆”。DAA治疗不会促进慢性感染中耗尽的CD 4 + T细胞记忆的复苏。
Induction of functional helper CD4+ T cells is the hallmark of a protective immune response against hepatitis C virus (HCV), associated with spontaneous viral clearance. Heterologous prime/boost viral vectored vaccination has demonstrated induction of broad and polyfunctional HCV‐specific CD8+ T cells in healthy volunteers; however, much less is known about CD4+ T‐cell subsets following vaccination. We analyzed HCV‐specific CD4+ T‐cell populations using major histocompatibility complex class II tetramers in volunteers undergoing HCV vaccination with recombinant HCV adenoviral/modified vaccinia Ankara viral vectors. Peptide‐specific T‐cell responses were tracked over time, and functional (proliferation and cytokine secretion) and phenotypic (cell surface and intranuclear) markers were assessed using flow cytometry. These were compared to CD4+ responses in 10 human leukocyte antigen–matched persons with HCV spontaneous resolution and 21 chronically infected patients treated with directly acting antiviral (DAA) therapy. Vaccination induced tetramer‐positive CD4+ T cells that were highest 1‐4 weeks after boosting (mean, 0.06%). Similar frequencies were obtained for those tracked following spontaneous resolution of disease (mean, 0.04%). In addition, the cell‐surface phenotype (CD28, CD127) memory subset markers and intranuclear transcription factors, as well as functional capacity of peptide‐specific CD4+ T‐cell responses characterized after vaccination, are comparable to those following spontaneous viral resolution. In contrast, helper responses in chronic infection were infrequently detected and poorly functional and did not consistently recover following HCV cure. Helper CD4+ T‐cell phenotype and function following HCV viral vectored vaccination resembles “protective memory” that is observed following spontaneous clearance of HCV. DAA cure does not promote resurrection of exhausted CD4+ T‐cell memory in chronic infection.
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影响因子：
4.4
作者：
Capone, Stefania;Zampaglione, Immacolata;Folgori, Antonella
通讯作者：
Folgori, Antonella
影响因子：
82.9
作者：
Gattinoni L;Lugli E;Ji Y;Pos Z;Paulos CM;Quigley MF;Almeida JR;Gostick E;Yu Z;Carpenito C;Wang E;Douek DC;Price DA;June CH;Marincola FM;Roederer M;Restifo NP
通讯作者：
Restifo NP
影响因子：
6.7
作者：
Buggert M;Tauriainen J;Yamamoto T;Frederiksen J;Ivarsson MA;Michaëlsson J;Lund O;Hejdeman B;Jansson M;Sönnerborg A;Koup RA;Betts MR;Karlsson AC
通讯作者：
Karlsson AC
影响因子：
15.9
作者：
Missale, G;Bertoni, R;Ferrari, C
通讯作者：
Ferrari, C
影响因子：
30.5
作者：
Kaech, SM;Tan, JT;Ahmed, R
通讯作者：
Ahmed, R