Centre de Recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, Québec, Canada.
Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, Québec, Canada.
PLoS Pathog. 2022 Nov 15;18(11):e1010968. doi: 10.1371/journal.ppat.1010968. eCollection 2022 Nov.
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.
连续的丙型肝炎病毒（HCV）感染代表了一个独特的自然再挑战实验，以确定长期保护免疫的相关性，并为疫苗开发提供信息。我们应用系统免疫学方法来描述在 8 名自发清除两次连续 HCV 感染的受试者中，外周血转录组特征的纵向变化。此外，我们将这些特征与 HCV T 细胞疫苗方案诱导的特征进行了比较。我们在早期急性 HCV 再感染期间发现了浆细胞转录组特征。该特征在原发性感染和 HCV 疫苗加强后均不存在。在 3 名受试者中，HCV 再感染的自发清除与糖蛋白 E2 特异性记忆 B 细胞的快速扩增有关，在 6 名受试者中，E2 特异性中和抗体短暂增加。同时，在 8 名受试者中的 7 名中，HCV 特异性 T 细胞的广度和幅度均增加。这些结果表明抗体和 T 细胞在清除 HCV 再感染中具有协同作用，并支持开发针对这两个免疫系统分支的下一代 HCV 疫苗。
