Differential immune transcriptomic profiles between vaccinated and resolved HCV reinfected subjects.
Differential immune transcriptomic profiles between vaccinated and resolved HCV reinfected subjects.
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DOI：
10.1371/journal.ppat.1010968
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发表时间：
2022-11
期刊：
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
--
作者：
丙型肝炎病毒 (HCV) 感染的连续发作代表了一种独特的自然再攻击实验，可确定长期保护性免疫的相关性并为疫苗开发提供信息。我们应用系统免疫学方法来表征八名受试者外周血转录组特征的纵向变化，这些受试者自发地解决了两次连续的 HCV 感染。此外，我们将这些特征与基于 HCV T 细胞的疫苗方案诱导的特征进行了比较。我们在早期急性 HCV 再感染期间鉴定了浆细胞转录组特征。在原发感染和 HCV 疫苗加强接种后，该特征不存在。 HCV 再感染的自发消退与 3 名受试者中糖蛋白 E2 特异性记忆 B 细胞的快速扩增以及 6 名受试者中 E2 特异性中和抗体的短暂增加有关。同时，8 名受试者中有 7 名的 HCV 特异性 T 细胞的广度和数量有所增加。这些结果表明抗体和 T 细胞在清除 HCV 再感染中发挥协同作用，并支持开发针对这两个免疫系统的下一代 HCV 疫苗。在这项研究中，我们检查了再次暴露和再感染后自发清除后针对丙型肝炎病毒（HCV）的记忆免疫反应。这代表了一个模型，用于定义疫苗应引起的长期保护性免疫的关键免疫特征。我们观察到，大多数研究对象都诱导了抗体和白细胞（淋巴细胞）反应，这表明它们在预防 HCV 方面发挥着协同作用。实验性 HCV 疫苗方案缺乏这种协调反应。总而言之，这些数据表明，针对 HCV 的新疫苗应将免疫系统的这两个分支结合起来。
Successive episodes of hepatitis C virus (HCV) infection represent a unique natural rechallenge experiment to define correlates of long-term protective immunity and inform vaccine development. We applied a systems immunology approach to characterize longitudinal changes in the peripheral blood transcriptomic signatures in eight subjects who spontaneously resolved two successive HCV infections. Furthermore, we compared these signatures with those induced by an HCV T cell-based vaccine regimen. We identified a plasma cell transcriptomic signature during early acute HCV reinfection. This signature was absent in primary infection and following HCV vaccine boost. Spontaneous resolution of HCV reinfection was associated with rapid expansion of glycoprotein E2-specifc memory B cells in three subjects and transient increase in E2-specific neutralizing antibodies in six subjects. Concurrently, there was an increase in the breadth and magnitude of HCV-specific T cells in 7 out of 8 subjects. These results suggest a cooperative role for both antibodies and T cells in clearance of HCV reinfection and support the development of next generation HCV vaccines targeting these two arms of the immune system. In this study we examined the memory immune response against hepatitis C virus (HCV) upon re-exposure and reinfection followed by spontaneous clearance. This represents a model to define the key immune signatures that should be elicited by a vaccine for long-term protective immunity. We observed that antibodies as well as white blood cells (lymphocyte) responses were induced in the majority of the subjects studied suggesting their cooperative role in protection against HCV. Such a coordinated response was lacking in an experimental HCV vaccine regimen. Altogether, these data suggest that new vaccines against HCV should combine these two arms of the immune system.
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
29.4
作者：
Osburn WO;Fisher BE;Dowd KA;Urban G;Liu L;Ray SC;Thomas DL;Cox AL
通讯作者：
Cox AL
影响因子：
30.3
作者：
Kinchen VJ;Zahid MN;Flyak AI;Soliman MG;Learn GH;Wang S;Davidson E;Doranz BJ;Ray SC;Cox AL;Crowe JE Jr;Bjorkman PJ;Shaw GM;Bailey JR
通讯作者：
Bailey JR